JerMa88/BMC_Gastroenterology_Peer_Reviews huggingface dataset:
Review for 10.1186/s12876-025-03620-9 (2025)

Title: The Serum Hepcidin and the Hepcidin/Ferritin ratio in NAFLD: A Systematic Review
and Meta-Analysis
Version: 3 Date: 01 Dec 2024
Reviewer's report:
The authors conducted a systematic search to investigate " The Serum Hepcidin and the
Hepcidin/Ferritin ratio in NAFLD: A Systematic Review and Meta-Analysis". The manuscript
is scientifically valid; nonetheless, it requires substantial editing prior to consideration for
publication in the journal.
1-Web of Science is not a database; it is a platform. Kindly rectify the abstract and the text.
2-In the methods part of the abstract, please specify the variables utilized in the analysis.
3-What was the rationale for sub-grouping the results? Was it due to identifying the source of
heterogeneity in the studies?
4-What is your recommendation in the study's conclusion? Kindly provide further clarification.
5-Accurately define the research PICOTs and include the search strategy table as a
supplementary file.
6-There appears to be a publishing bias among the research from a visual perspective. Kindly
investigate this matter concerning the Trim and fill Test and provide the related figure.
7-Enhance the conclusion for comprehensiveness in both the abstract and the article's body, and
as a researcher, please articulate your recommendations for future investigations in this domain.
Review for 10.1186/s12876-025-03620-9 (2025)

Title: The Serum Hepcidin and the Hepcidin/Ferritin ratio in NAFLD: A Systematic Review
and Meta-Analysis
Version: 3 Date: 06 Dec 2024
Reviewer's report:
The Serum Hepcidin and the Hepcidin/Ferritin ratio in NAFLD: A Systematic Review and Meta-
Analysis
Abstract:
The introduction is long and confusing. Use up-to-date statistics.
Introduction
The gap of knowledge is not well mentioned.
There are many typographical and grammatical errors. The entire text needs to be rewritten. For
example, conducted by the PRISA guideline........ probably means PRISMA.
To structure the eligibility criteria, the PEO...??or PICO
Methods:
I expect the discussion to begin with the key findings of the study.
It is necessary to provide a publication bias funnel plot.
The authors justify the difference between their study and that of Sharma R, Zhao W, Zafar
Y, Murali AR, Brown KE. Serum hepcidin levels in chronic liver disease: a systematic
review and meta-analysis. Clinical Chemistry and Laboratory Medicine (CCLM). 2024 Feb
26;62(3):373-84.
The authors have registered the study in Prospero. If yes, please provide the code.
Review for 10.1186/s12876-025-03620-9 (2025)

Title: The Serum Hepcidin and the Hepcidin/Ferritin ratio in NAFLD: A Systematic Review
and Meta-Analysis
Version: 5 Date: 02 Jan 2025
Reviewer:  Ehsan Amini-Salehi
Reviewer's report:
Authors have addressed my comments. I have no further concerns.
Review for 10.1186/s12876-025-03653-0 (2025)

Title: Optimization of the Cholesterol Gallstone Model in C57BL/6 Mice and Evaluation of
Lactobacillus Intervention Effects
Version: 2 Date: 13 Jan 2025
Reviewer's report:
In the study, authors optimized the cholesterol gallstone model of C57BL/6 mice and evaluated
the effect of probiotic intervention on the formation of cholestol stones, focusing on determining
the optimal feeding time for gallstone induction under a high-fat diet, as well as the optimal
timing and efficacy of probiotic intervention. Through a phased experimental design, this
study showed that the probiotic intervention significantly reduced the incidence and severity of
gallstones and improved liver pathology. The results suggest that the beneficial bacteria may
play a protective role by regulating bile acid and cholesterol metabolism, which has important
scientific innovation and clinical relevance.
The effect of intestinal probiotics on the formation of gallstones is the focus of current research,
but the literature on gallstone models is still limited. By inducing gallstone formation with a
high-fat diet, combined with probiotic interventions at different time periods (2 and 4 weeks of
preconditioning), this study provides data supporting time-dependent and dose-response effects
of probiotics. The protective effect of probiotics was systematically validated by a variety of
parameters, including body weight, liver pathology, and gallstone score. This study provides an
important basis for optimizing gallstone models and probiotic intervention strategies, and has
certain clinical translational potential.
Although studies have mentioned the regulatory role of probiotics on bile acid and cholesterol
metabolism, specific molecular pathways, such as key metabolic pathways and related
molecules, have not been mentioned. Despite the clinical relevance of probiotic preconditioning
and different doses of the study, the findings are based only on mouse models.
This study has certain innovative and scientific value, reasonable experimental design and
reliable data, and provides valuable insights for optimizing the mouse model of cholsterol
stone and probiotic preventive intervention. Based on its scientific value and potential clinical
relevance, I recommend this study for publication.
Review for 10.1186/s12876-025-03653-0 (2025)

Title: Optimization of the Cholesterol Gallstone Model in C57BL/6 Mice and Evaluation of
Lactobacillus Intervention Effects
Version: 2 Date: 15 Jan 2025
Reviewer's report:
Comments to the Authors
I recommend its potential publication. Some comments are as follows.
1. In the second phase of experiment, how many C57BL/6 mice were included?
2. In the whole experimental stage, how many C57BL/6 mice had cholesterol gallstone
formation?
3. In the section “Liver Pathology in Mice”, the authors should explain which group corresponds
to the Figure 6E.
4. In this study, the authors used only one strain of Lactobacillus to evaluate the effects on
cholesterol gallstone formation. The word “systematically” is misfit.
5. In this study, the authors used only one strain of Lactobacillus to evaluate the effects on
cholesterol gallstone formation. “Probiotic” should be revised as “Lactobacillus” in the text and
title.
6. The word “First” appears twice in the discussion section, and the authors should change the
“First” to “Second” in the second paragraph.
7. The words “with the goal of …” are meaningless in the introduction section. Delete them.
Review for 10.1186/s12876-025-03651-2 (2025)

Title: Short-term endoscopic alterations of early gastric cancer after successful eradication of
Helicobacter pylori
Version: 2 Date: 04 Nov 2024
Reviewer's report:
Comments to Author
This study was well revised according to Reviewer’s recommendation and suggestion. However,
this version has any problems to be an acceptable level of this journal, as below.
General:
In this study, the authors investigated the endoscopic alterations of early-stage gastric cancer
within 3 months after eradication. Authors showed that the confidence level of demarcation
line and invasion depth and histopathological classification were significantly improved after
eradication. Authors concluded that eradication therapy is necessary even shortly prior to
endoscopic procedure to help precise pre-procedure diagnosis and avoid incomplete resection
Major comments:
1. As authors mention, endoscopists do not recommend eradication therapy before ESD.
However, in this study, the confidence level of demarcation line and invasion depth and
histopathological classification were significantly improved after eradication. What is this
discrepancy with this result and previous?
2. Authors showed significant endoscopic improvement for gastric cancer after eradication.
However, in Japan and Korea, cure rate of ESD for early-stage gastric cancer is high, irrespective
with patients infect currently in H. pylori or not. Therefore, it is unknown whether eradication
therapy before ESD is required or not.
3. In addition, this strategy takes 4-5 months after detection of gastric cancer. If gastric cancer is
diffuse type or borderline lesion for ESD, tumor may advance. Are there any cases that should
not be on this strategy?
4. This is prospective study. Therefore, sample power should be shown.
5. What is second option for gastric cancer patients failed eradication? Second-line eradication
treatment or endoscopic procedure, ESD?
6. Please show approved number in IRB and put it in the revised version.
7. Please show a registration number for clinical trial.
8. In the section of statistical analysis, authors put that continuous variables were expressed as
the mean ± Standard deviation (SD). Please check.
9. Please show information of endoscope used. Was endoscope used same among before
eradication and after eradication?
Review for 10.1186/s12876-025-03651-2 (2025)

Title: Short-term endoscopic alterations of early gastric cancer after successful eradication of
Helicobacter pylori
Version: 3 Date: 20 Dec 2024
Reviewer's report:
The revised manuscript has addressed the reviewers' comments well. However, several concerns
remain.
#1, Tumor Size Measurement
The response states that "the tumor size was measured with tools like calibrated forceps to
ensure accuracy." However, given the retrospective nature of the study, it is unclear if this
was consistently performed across all cases. With a small difference in tumor size (17.9 ± 8.8
mm before eradication vs. 16.2 ± 8.0 mm after eradication), the accuracy and reliability of the
measurements are critical. If the measurement method was not uniformly applied, it would be
more appropriate to remove discussions on tumor size differences. Alternatively, please describe
the measurement method in detail in the Methods section.
#2, Adverse Effects (Diarrhea)
Diarrhea is the most common adverse effect of eradication therapy and should be added to the
list of adverse effects (line 286), alongside nausea and skin rash.
#3, Figure 3 Labeling
In Figure 3, all images are labeled as "a." Please revise the labels to "a" through "f" to correspond
with the figure legends and ensure clarity.
Review for 10.1186/s12876-025-03660-1 (2025)

Title: Emodin Protects Against Severe Acute Pancreatitis-associated Acute Lung Injury by
Activating Nrf2/HO-1/GPX4 Signal and Inhibiting Ferroptosis in Vivo and in Vitro
Version: 2 Date: 04 Jan 2025
Reviewer's report:
This is a revised version of a manuscript by Shen et al. in which a research article to explore how
EMO protects against lung injury in SAP rats and alveolar epithelial cells, concentrating on the
classical ferroptosis pathway. The authors show relevant data in vitro and in vivo. The study is
sound, and the protocol detailed enough for others to replicate. In my opinion, the authors have
addressed the concerns raised by my colleague reviewers, but I do have some minor concerns/
comments for the authors:
I found a couple of petty typos and minor comments for the authors to fix:
Minor Comments:
1. Line 107-line 109: “The SO group, SAP group, SAP+EMO group, SAP+Nrf2 inhibitor
group (SAP+ML385 group), and SAP+ML385+EMO group were randomly assigned to forty
SD rats” should be written as “Forty SD rats were randomly assigned into five groups: SO
group, SAP group, SAP+EMO group, SAP+Nrf2 inhibitor group (SAP+ML385 group), and
SAP+ML385+EMO group”.
2. In future study, it would be better to include both male and female subjects.
3. Line 131: the title of Figure 1 should be changed to “Experimental design schematic diagram.
(A) In vivo study design. (B) In vitro study design.”
4. Line 133: it should be changed to “Chemicals and Reagents.”
5. Line 193: “PyMol” instead of “Pymol”
6. Line 256: the title of “3.1” is a little bit confused, and please rewrite it.
Review for 10.1186/s12876-025-03660-1 (2025)

Title: Emodin Protects Against Severe Acute Pancreatitis-associated Acute Lung Injury by
Activating Nrf2/HO-1/GPX4 Signal and Inhibiting Ferroptosis in Vivo and in Vitro
Version: 2 Date: 06 Jan 2025
Reviewer:  Longfei Pan
Reviewer's report:
The experimental design of this study is rigorous, and the conclusions are reliable. In the revised
manuscript, the authors have reasonably addressed the reviewers' comments. I recommend that
this manuscript be accepted for publication.
Review for 10.1186/s12876-025-03660-1 (2025)

Title: Emodin Protects Against Severe Acute Pancreatitis-associated Acute Lung Injury by
Activating Nrf2/HO-1/GPX4 Signal and Inhibiting Ferroptosis in Vivo and in Vitro
Version: 2 Date: 06 Jan 2025
Reviewer:  Chuanhai Cao
Reviewer's report:
The manuscript submitted by Shen et al. to BMC Gastroenterology, titled “Emodin Protects
Against Severe Acute Pancreatitis-associated Acute Lung Injury by Activating Nrf2/HO-1/
GPX4 Signal and Inhibiting Ferroptosis in Vivo and in Vitro” presents findings on the use of
Emodin (EMO) as a preventive agent against SAP-ALI in both in vitro and in vivo models.
The study concludes that EMO effectively inhibits ferroptosis and modulates the Nrf2/HO-1/
GPX4 signaling pathway, thereby providing protection against SAP-ALI. This research is well-
structured, using both animal and cell models, with methods described that are clearly articulated
and easy to replicate. The results are presented comprehensively, accompanied by adequate
explanation and the conclusions are strictly adhered to the results. Overall, this is a very
nice research study and aligns well with the journal very well. I recommend accepting it for
publication, after making revision to the following points:
1. Change “This research was conducted to explore how EMO protects against lung injury in
SAP rats and alveolar epithelial cells, concentrating on the classical ferroptosis pathway” to
“This study was undertaken to investigate the protective effects of EMO against lung injury
in SAP rats and alveolar epithelial cells, with a particular focus on the classical ferroptosis
pathway”
2. Modify “In an in vivo study, forty male SD rats were split into five groups on average” to
“Forty SD rats were evenly split into five groups”
3. Revised the conclusions from” This study confirmed that EMO inhibited in vivo and in vitro
ferroptosis and modulated Nrf2/HO-1/GPX4 signaling to protect against SAP-ALI” to “Our
results demonstrated that EMO effectively inhibited ferroptosis both in vivo and in vitro, while
also modulating the Nrf2/HO-1/GPX4 signaling pathway to provide protection against SAP-
ALI”
4. Please ensure that all animal numbers are included in each figure legend, along with
indications of significance.
Review for 10.1186/s12876-025-03633-4 (2025)

Title: The Patient Perspective on Transanal Irrigation Treatment for Low Anterior Resection
Syndrome after Rectal Cancer Surgery -A Qualitative and Quantitative Study
Version: 1 Date: 10 Dec 2024
Reviewer:  Audrius Dulskas
Reviewer's report:
Dear Authors,
I would like to thank you with this great study.
Few comments
ABSTRACT
--well written
INTRODUCTION
--well written. Just, I would include the long-term effect of LARS (ulskas A, Kavaliauskas P,
Pilipavicius L, Jodinskas M, Mikalonis M, Samalavicius NE. Long-term bowel dysfunction
following low anterior resection. Sci Rep. 2020 Jul 17;10(1):11882.  and  Chen TY, Wiltink LM,
Nout RA, Meershoek-Klein Kranenbarg E, Laurberg S, Marijnen CA, van de Velde CJ. Bowel
function 14 years after preoperative short-course radiotherapy and total mesorectal excision for
rectal cancer: report of a multicenter randomized trial. Clin. Colorectal Cancer. 2015;14:106–
114.)
METHODS
--was anybody blinded for the results? I suppose during the interviewing process it could not
be done.
--what was the treatment for control group?
RESULTS
--why was the ileostomy take down so late?
--were patients using any other treatment after the initial study: biofeedback, medication, diet,
etc
--what was the percentage of drop off?
DISCUSSION
--well written
--drop off is a significant  limitation
Review for 10.1186/s12876-025-03633-4 (2025)

Title: The Patient Perspective on Transanal Irrigation Treatment for Low Anterior Resection
Syndrome after Rectal Cancer Surgery -A Qualitative and Quantitative Study
Version: 1 Date: 11 Dec 2024
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-The authors highlight the lack of a direct randomized control group during the follow-up
period, which is an important limitation. While the study builds on a previous RCT, without an
active comparison group during this stage, it is difficult to definitively attribute the observed
improvements to TAI alone. The authors mention this as a limitation but do not explore
alternative ways in which the control group could have been better incorporated into the analysis
(e.g., by directly comparing baseline and follow-up data in both groups).
-While the discussion highlights many positive outcomes of TAI, such as improved bowel
regularity and enhanced social participation, the analysis could benefit from a more nuanced
discussion of the negative aspects or limitations of TAI. Although the authors do mention
discomfort and pain during the procedure, they could have further expanded on how these issues
affect patient adherence, especially in the long term. For instance, a deeper exploration of the
psychological challenges or physical discomfort faced by some patients (e.g., pain, anxiety, or
inconvenience) would provide a more balanced view of the treatment. Discussing strategies to
mitigate these challenges would be helpful for clinicians considering TAI as a treatment option.
-Although the authors acknowledge the small sample size and dropout, they do not sufficiently
address the potential biases introduced by dropout. Given that only 28 out of 39 patients were
included in the final quantitative analysis, it is essential to explore whether the dropout was
random or if there were systematic differences between those who dropped out and those
who remained in the study. This could provide additional context for interpreting the results,
particularly regarding the generalizability of the findings.
Review for 10.1186/s12876-025-03633-4 (2025)

Title: The Patient Perspective on Transanal Irrigation Treatment for Low Anterior Resection
Syndrome after Rectal Cancer Surgery -A Qualitative and Quantitative Study
Version: 1 Date: 17 Dec 2024
Reviewer:  Alimohammad Bananzadeh
Reviewer's report:
Dear Author(s)
I've carefully reviewed your article, and I'm impressed with the quality of your work. The content
is well-researched, the writing is clear and concise, and the overall structure is strong. Your
efforts have resulted in a valuable contribution to the field.
Review for 10.1186/s12876-025-03633-4 (2025)

Title: The Patient Perspective on Transanal Irrigation Treatment for Low Anterior Resection
Syndrome after Rectal Cancer Surgery -A Qualitative and Quantitative Study
Version: 2 Date: 30 Dec 2024
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Changes are satisfactory, can be accepted for publication
Review for 10.1186/s12876-025-03633-4 (2025)

Title: The Patient Perspective on Transanal Irrigation Treatment for Low Anterior Resection
Syndrome after Rectal Cancer Surgery -A Qualitative and Quantitative Study
Version: 2 Date: 31 Dec 2024
Reviewer:  Audrius Dulskas
Reviewer's report:
Dear Authors,
Thank you once again for great study. The manuscript improved and now it can be accepted.
Good luck with the publication.
Review for 10.1186/s12876-025-03600-z (2025)

Title: Therapeutic effects of reduced glutathione on liver function, fibrosis, and HBV DNA
clearance in chronic hepatitis b patients
Version: 2 Date: 21 Oct 2024
Reviewer's report:
The authors tried to explore the potential of the administration of reduced glutathione in HBV
patients. My technical concerns are:
1. Grammatical constructions and used expressions in the whole manuscript should be looked
through and improved. Structures like 'a ordinary' must be corrected.
1. According to the abstract results do not correspond to methodology. The character of the study
should be described in a more detailed way. Results consist of several comparisons, nevertheless
used markers are not presented before.
Review for 10.1186/s12876-025-03600-z (2025)

Title: Therapeutic effects of reduced glutathione on liver function, fibrosis, and HBV DNA
clearance in chronic hepatitis b patients
Version: 2 Date: 03 Nov 2024
Reviewer's report:
Dear sir,
thank you to select  me to review an article "The curative impact of reduced glutathione on
chronic hepatitis B sufferers and liver function and fibrosis" written by Wei and Zhao. The
authors compared reduced glutathione and entecavir in chronic hepatitis B patients after surgery.
Design of the study is not correctly chosen, because HBV patients need to be treated by
nucleot(s)ide analogues.  Patients treated with reduced glutathione (which isn´t antiviral drug
for HBV infection) didn´t receive antiviral treatment. Design of the study is not described in
detail (type of surgery etc..).  Although liver decompensation was an exclusion criterion in this
study, mean bilirubin level in both arms was about 60 µmol /L.  Reduced glutathione had worse
effect on HBV DNA  loss compared to entecavir.
My final decision is rejection.
Review for 10.1186/s12876-025-03600-z (2025)

Title: Therapeutic effects of reduced glutathione on liver function, fibrosis, and HBV DNA
clearance in chronic hepatitis b patients
Version: 2 Date: 19 Nov 2024
Reviewer:  Panagiotis Tsibouris
Reviewer's report:
The title seems incoherent Abstract Numerical values should be provided apart from the p-values
All abbreviations should be explained in their first appearance in the text Abstract results are a
bit confusing concerning time point of various measurements Methods Why had 100 IU and not
2000IU limit selected? Which antibiotic have been used as anti-infective treatment What were
the limits for PT, APTT or Fib accepted? In what way was fibrosis evaluated? Has liver biopsy
been performed or transient elastography? Immunodeficiency should be also defined Were all
patients with other liver diseases apart from chronic hepatitis B excluded? What about HDV
co-infection? In what extent was MASLD accepted? What quantity of alcohol was accepted?
Description of the study population belongs in the results The time-points of liver function
evaluation should be defined Statistics Power of the study should be calculated Multi-variated
analysis is advisable Results Side effects should be graded
Review for 10.1186/s12876-025-03600-z (2025)

Title: Therapeutic effects of reduced glutathione on liver function, fibrosis, and HBV DNA
clearance in chronic hepatitis b patients
Version: 3 Date: 14 Dec 2024
Reviewer's report:
Dear sir,
thank you to select me to review manuscript Therapeutic effects of reduced glutathione on liver
function, fibrosis, and HBV dna clearance in chronic hepatitis b patients. Authors improved
quality of the manuscript, but there are still flaws.
1) Abstract is too long and data from abstract are not matching with data from Table 3. Please
revise and correct.
2)Please add entecavir dose
3) If mean bilirubin level is 60 µmol /L and mean albumin level is 29 g/l, some patients need to
be decompensated. Please exclude liver decompensation from exclusion criteria - line 120.
4) Line 186: please clearly define therapeutic effect
5) Grade of fibrosis is F0-F4, nor S0-S4.
6) English needs revision.
Review for 10.1186/s12876-025-03600-z (2025)

Title: Therapeutic effects of reduced glutathione on liver function, fibrosis, and HBV DNA
clearance in chronic hepatitis b patients
Version: 6 Date: 26 Dec 2024
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
The responses are satisfactory, can be accepted for publication
Review for 10.1186/s12876-025-03650-3 (2025)

Title: Risk factors for Clostridioides difficile infection among patients diagnosed with
inflammatory intestinal and rheumatological diseases in the biologic era
Version: 3 Date: 24 Dec 2024
Reviewer's report:
The authors have taken a large cohort of patients on biologics with the aim of determining risk
factors for CDI particularly in the IBD cohort. I do have some concerns regarding adjustment
for confounding factors and therefore some of the results and discussion statements. Please see
the points below.
1)  The two cohorts chosen are vastly different. And I think makes it very difficult to
compare beyond saying that biologic therapy does not appear to have an increased risk. This
is acknowledged in the opening discussion sentence, however I don't think all of table 1
information is required. I would also exlcude rheumatology cohort from the reset of the data.
Differences in traditional risk factors, i.e. antibiotic use and PPI use should be included in this
table 1. Given I suspect the skewing of data, median rather than mean should be used to describe
the number of biologics used.
Table 2 should exclude the rheumatology cohort given small numbers and could just add to
skewing - I would keep this to just the IBD cohort.
2) Each table needs a legend. for example, multvariate logistic regression needs the variables
that were included in the multivariable analysis. This appears in the body of the text but also
needs to be in the table. Before presenting multivariable analysis, univariable analysis with all
important variables should also be included.
3) Table 5 and body of the text results: I think there has been a misinterpretation of the data.
referrence appears to be UC, and then the odds ratio is 2? Therefore CD compared to UC has
higher risk? Or is the table the wrong way around?
4) It is interesting that vedolizumab and ustekinumab have the higher incidence of c. diff -
these two biologicals are used infrequently in the rheumatology cohort. Hence another reason
to exclude the rheumatological cohort from further analysis post the initial one.
5) Appropriate adjustment for known confounders needs to happen - i.e. antibiotics and PPI.
Some of the findings here could all be related to confounders. Please redo statistics with listed
confounders.
6) Regarding the discussion point of the number of biologics. Could this not be an indication of
severity of their IBD and therefore potentially more disruption of the gut integrity?
Review for 10.1186/s12876-025-03650-3 (2025)

Title: Risk factors for Clostridioides difficile infection among patients diagnosed with
inflammatory intestinal and rheumatological diseases in the biologic era
Version: 3 Date: 29 Dec 2024
Reviewer:  Sasha R. Fehily
Reviewer's report:
This is very useful data in improving the understanding of CDI risk in a large IBD cohort.
Some revision considerations:
Please include how the medication data was collected ?prescriptions. Was dosing variability
across cohorts assessed ie was dosing/frequency and compassionate drug access recorded as
cumulative exposure may have been higher in IBD cohorts.
Asymptomatic carriage is higher in IBD patients likely due to more frequent stool testing. Were
specific criteria used to differentiate infections from colonization? Were asymptomatic carriers
excluded from the analysis?
Details on rationale for choosing the CDI severity score. Has this been validated in IBD cohorts.
You have tabulated more data that could have been included in more comprehensive CDI
severity score.
Re vedolizumab and ustekinumab, these drugs are widely recognized as options for first-line
therapy in international guidelines. Details surrounding the rationale for these agents not being
used first line / in refractory patients should be included as this impact’s the generalisability of
the data.
Were the patients in the "without biologics" group using immunomodulators, 5-asa,
corticosteroids? A subgroup analysis (biologic therapy vs. vs. immunomodulator vs.
corticosteroids vs. 5-ASA vs. no therapy) may demonstrate a difference.
While disease severity was not assessed, retrospective evaluation of disease severity within 3-6
months before CDI would provide valuable context as to whether the drug or disease activity
is driving the risk, an important distinction.
The current Montreal classification could be used to compare whether there is a difference in risk
between UC and Crohn's colitis. The statement about colonic involvement and CDI risk appears
overstated if it is not directly presented in the data. Clarification is needed, or the language
should be revised to indicate that this was an assumption rather than a finding.
Review for 10.1186/s12876-025-03644-1 (2025)

Title: Efficacy analysis of folic acid in chronic atrophic gastritis with Helicobacter pylori
Infection: a systematic review and meta-analysis
Version: 3 Date: 06 Dec 2024
Reviewer's report:
Efficacy analysis of folic acid in chronic atrophic gastritis with Helicobacter pylori Infection:
a systematic review and meta-analysis
Abstract:
In the meta-analysis reporting method, the conventional odds ratio is not used and the RR is used.
In the results, the effect of folic acid on reducing complications is not significant and the authors
should check the new ones. Also, based on this, they have concluded that it is associated with
reducing complications (safety), which I think is wrong.
Introduction
There are many sentences in the introduction without references. Please review.
The gap of knowledge is not well mentioned.
Methods:
Statistical analyzes are not valid. Was met regression not done?
Result
The heterogeneity of the studies was high in a number of outcomes. How was heterogeneity
resolved? Why was meta-regression not performed?
I expect the characteristics of the studies to be presented in a table (not an Excel spreadsheet).
Why hasn't the publication bias assessment and its results been presented?
Review for 10.1186/s12876-025-03644-1 (2025)

Title: Efficacy analysis of folic acid in chronic atrophic gastritis with Helicobacter pylori
Infection: a systematic review and meta-analysis
Version: 3 Date: 08 Dec 2024
Reviewer's report:
The review might be limited by the exclusive inclusion of studies from one country , potentially
affecting the generalizability of the findings to populations in other geographical areas.
Additionally, the decision to exclude non-English studies could miss significant data from non-
English publications, especially from countries where Helicobacter pylori infection is prevalent.
The total number of patients (1088) across 13 studies raises concerns about the statistical power
of individual studies to detect clinically meaningful differences. The small sample size in some
included trials might also contribute to a high risk of type II errors.  There is inadequate
discussion about how the risk of bias within individual studies might affect the overall meta-
analysis results. The document mentions most studies are of low risk but does not elaborate on
the criteria or specifics of the risk assessments.  The application of fixed-effect models where
moderate heterogeneity exists (I2 > 50% in some outcomes) may not be appropriate as it assumes
that all variability between studies is due to sampling error rather than actual differences in study
populations or interventions.
Review for 10.1186/s12876-025-03644-1 (2025)

Title: Efficacy analysis of folic acid in chronic atrophic gastritis with Helicobacter pylori
Infection: a systematic review and meta-analysis
Version: 6 Date: 02 Jan 2025
Reviewer:  Ehsan Amini-Salehi
Reviewer's report:
Authors have applied my comments. I have no further concerns.
Review for 10.1186/s12876-025-03631-6 (2025)

Title: Helicobacter pylori CagA+ strains modulate colorectal pathology by regulating intestinal
flora
Version: 1 Date: 28 Nov 2024
Reviewer's report:
The paper by Dr. Shasha Cui describes Helicobacter pylori CagA+ strain infection induced
inflammation and histological disorganization as well as dysbiosis. This study might shed light
on investigation therapy of colorectal lesion but some of the methods need to be clarified.
1. It is general understanding Helicobacter pylori CagA+ strain induce inflammation and
colorectal cancer. Please clarify what significance is in figure 1 and 2.
2. Giemsa control staining histology looks different location compared with other staining.
3. It is unclear MHC2 positive cells.
4. Please add p value in figure 3 and 5.
5. It seems there are not difference between 2 cluster. (figure 4b)
Review for 10.1186/s12876-025-03631-6 (2025)

Title: Helicobacter pylori CagA+ strains modulate colorectal pathology by regulating intestinal
flora
Version: 1 Date: 02 Dec 2024
Reviewer's report:
The author demonstrated the role of HP CagA+ strains to modulate colorectal pathology
by regulating intestinal flora. It is interesting study, but there are several difficulties in this
manuscript.
1. There is no mention of what “GC” stands for.
2. The author states that HP CagA+ strains have an effect on intestinal bacteria, but HP CagA-
strains should be used as control.
3. The author indicates that HP CagA+ strains may cause abnormalities in the intestinal
microbiota and thus influence colon carcinogenesis. However, epidemiological studies need to
be cited to see if this is the case. Based on the data from the present study, it would be an
overstatement to refer to an association between HP CagA+ strains and colorectal cancer.
4. The author states that HP CagA+ strains cause abnormalities in the intestinal microbiota and
progress destruction of the intestinal barrier. However, data on the disruption of the intestinal
barrier are not included in the results of this study, and the author should not discuss this
conclusion.
5. The author has measured serum cytokines in mice infected with HP CagA+ strains. However,
cytokine expression in the colonic mucosa needs to be compared to controls in order to assess
colonic inflammation.
Review for 10.1186/s12876-025-03631-6 (2025)

Title: Helicobacter pylori CagA+ strains modulate colorectal pathology by regulating intestinal
flora
Version: 2 Date: 19 Dec 2024
Reviewer's report:
The authors have made substantial revisions in response to the original critique.  However the
authors need to resolve a problem.
There are not significances difference in figure 3E and F. However, the authors described
Shannon and Chao1 indexes were significantly reduced in HP CagA + group. That is wrong.
Please correct it.
Review for 10.1186/s12876-025-03655-y (2025)

Title: Machine Learning-Based Plasma Metabolomics for Improved Cirrhosis Risk
Stratification
Version: 2 Date: 05 Jan 2025
Reviewer's report:
This UK Biobank-based study utilizes serum metabolomics for cirrhosis classification
improvement. Using 1H-NMR data, the authors developed and validated models integrating
metabolomics with known NIT-based models like APRI and FIB-4 indices.  A key strength
is the large dataset and the machine learning approach, which identifies specific metabolites
associated with cirrhosis risk and shows the merit in diagnostic improvement. Despite several
weaknesses, the study offers a promising optimization.
Concerns:
-The “fasting state” requires more elaboration on the mechanic reasons and potential
improvement in future studies, e.g. elaboration on publications relevant to the impact of fasting
state, etc. Please concisely elaborate on possible mitigations, solutions, evaluations for this
factor-- status of fasting or not-- in later studies, as concerned by hepatologists.
- Elaborate by adding one more sentence of statement for the following method-“All metabolites
were log-normalized and standardized to a mean of 0 and standard deviation of 1."
- "The cohort was then divided into derivation (80%) and validation (20%) cohorts." This
statement needs concise, additional statement explaining why stratified splitting were not
applied in this context.
- "incomplete parameters, such as missing data on age or liver enzymes" and "We further
excluded individuals with incomplete parameters, such as missing data on age or liver
enzymes..." raise concerns and worries. Please clarify concisely.
- "To identify the most predictive metabolites, we applied a Cox-PH model with EN
regularization to the training set, optimizing model discrimination using 10-fold cross-
validation..." Please concisely address the parameters and expand the expected statement.
- Common, obvious understanding and concerns regarding the variable selection bias, healthy
volunteer bias, data imbalance, batch effect correction, multiple comparison correction, etc.
in current context needs to be concisely discussed as well.
- The current presentation in technical details and titles and footnotes of tables and figures
of the promising study still needs to be acknowledged and improved for expected clarity,
transparency, and reproducibility, as compared with relevant reports including Guo et al.
Machine-learning-based plasma metabolomic profiles for predicting long-term complications
of cirrhosis. Hepatology 2024.
- For example, hepatologists are concerned about the self-explaining clarity of Table 1. Please
clarify “Yes”, “incident liver fibrosis”, in Table 1.
- Regarding the core target: “cirrhosis status”, please concisely expand and elaborate the
biomarkers selected for facilitating discrimination, in terms of the biomolecular perspectives,
in relation to the defined cirrhosis.
Review for 10.1186/s12876-025-03641-4 (2025)

Title: TITLE: The Association Between Blood Pressure and Gallstones and the Age of First
Cholecystectomy in U.S. Adults: Results from a Cross-Sectional Study
Version: 0 Date: 16 Nov 2024
Reviewer:  Bahtiyar Muhammedo#lu
Reviewer's report:
The authors have written a good study. In the past, textbooks had said that there
was cholecystocardial syndrome. The authors' studies contain academic information and
suggestions.
Review for 10.1186/s12876-025-03641-4 (2025)

Title: TITLE: The Association Between Blood Pressure and Gallstones and the Age of First
Cholecystectomy in U.S. Adults: Results from a Cross-Sectional Study
Version: 0 Date: 20 Nov 2024
Reviewer:  Sandeep S. Nayak
Reviewer's report:
Review for 10.1186/s12876-025-03641-4 (2025)

Title: TITLE: The Association Between Blood Pressure and Gallstones and the Age of First
Cholecystectomy in U.S. Adults: Results from a Cross-Sectional Study
Version: 1 Date: 09 Dec 2024
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-As with the earlier version of the study, the cross-sectional nature of the design limits the
ability to infer causal relationships. Although significant associations between hypertension
and gallstone disease are observed, the study cannot determine whether hypertension causes
gallstone formation or if the reverse is true.
-While several important confounders (e.g., age, gender, race, diabetes, hypercholesterolemia)
are controlled for, other factors such as obesity, diet, physical activity, and genetic
predispositions to gallstones may not be fully accounted for. These factors could influence both
hypertension and gallstone disease and should be considered in future analyses.
-While the study identifies a threshold effect for SBP at 170 mmHg, the explanation for this
threshold and its clinical significance could be expanded. The potential reasons behind this
threshold—whether it reflects a biological change or is merely a statistical artifact—are not fully
addressed.
-The authors mention that missing continuous variables were recoded as categorical, with
missing data being designated as "unclear." This approach, while common, may introduce bias,
as the reasons for missing data are not addressed. The method of handling missing values could
be discussed in more detail, including any potential impact on the results.
-The subgroup analysis shows variability in the association between hypertension and
cholecystectomy across different racial groups. In particular, the lack of significant associations
in Non-Hispanic Blacks and Mexican Americans raises concerns about potential bias or other
factors that may influence the results. It would be helpful to explore this further and consider
whether the observed disparities reflect true differences or other unmeasured confounders.
-The authors mention the potential for recall bias due to the reliance on self-reported data
for gallstone disease and cholecystectomy history. However, the discussion could further
elaborate on how this may affect the results. For example, individuals who have undergone
cholecystectomy may be more likely to remember and report their diagnosis, while others who
have gallstones but have not undergone surgery may be less likely to report it accurately.
Addressing this potential bias in more detail would help readers better understand the study's
limitations.
-While hypertension is the primary exposure variable in this study, it would be helpful for
the discussion to acknowledge the complexity of risk factors for gallstone disease. Other
factors, such as obesity, hypercholesterolemia, and diabetes, could also play important roles
in the development of gallstones, and a more balanced discussion of these factors alongside
hypertension would provide a more comprehensive view of the disease's etiology.
Review for 10.1186/s12876-025-03641-4 (2025)

Title: TITLE: The Association Between Blood Pressure and Gallstones and the Age of First
Cholecystectomy in U.S. Adults: Results from a Cross-Sectional Study
Version: 1 Date: 11 Dec 2024
Reviewer:  Yüksel Do#an
Reviewer's report:
The text is detailed and comprehensive, covering studies on hypertension and its association
with gallstones and cholecystectomy. However, clarity and readability could be improved.
I think that the practical implications of the findings should be succinctly emphasised... For
example, it is appropriate to state how these findings may influence public health strategies or
clinical guidelines...
A clearer transition from the global prevalence and risk factors of gallstones to the study's focus
on hypertension and gallbladder disease needs to be added.
It is appropriate to emphasise why the association between systolic blood pressure (SBP) and
age at first cholecystectomy is a new and important area of research ...
Kindly Consider breaking large tables into smaller, thematic tables for better readability.
Kindly Use simplified labels for figures and tables (e.g., ‘Figure 2: SBP and Age Correlation’).
Kindly Make sure figure captions are descriptive, e.g., the legend for Figure 3 could clarify how
the red line indicates threshold.
Kindly Address limitations such as the cross-sectional nature of the NHANES data or potential
confounders not accounted for.
Review for 10.1186/s12876-025-03641-4 (2025)

Title: TITLE: The Association Between Blood Pressure and Gallstones and the Age of First
Cholecystectomy in U.S. Adults: Results from a Cross-Sectional Study
Version: 1 Date: 15 Dec 2024
Reviewer:  Bahtiyar Muhammedo#lu
Reviewer's report:
The study found a correlation between blood pressure and gallstone prevalence in patients
and a positive association between age at first cholecystectomy. Although causality cannot be
confirmed, these findings may help identify early risk groups for GD and early cholecystectomy,
so I think this study has scientific value.
Review for 10.1186/s12876-025-03641-4 (2025)

Title: TITLE: The Association Between Blood Pressure and Gallstones and the Age of First
Cholecystectomy in U.S. Adults: Results from a Cross-Sectional Study
Version: 3 Date: 26 Dec 2024
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
The responses are satisfactory, can be accepted for publication
Review for 10.1186/s12876-025-03641-4 (2025)

Title: TITLE: The Association Between Blood Pressure and Gallstones and the Age of First
Cholecystectomy in U.S. Adults: Results from a Cross-Sectional Study
Version: 3 Date: 01 Jan 2025
Reviewer:  Yüksel Do#an
Reviewer's report:
The revised manuscript is of good quality in terms of clarity, logic and adherence to scientific
rules. Significant improvements with respect to earlier drafts can be seen in the presentation of
the results and the strengthening of the statistical analysis. However, the primary focus appears
to be on extending the analysis and increasing the depth of the narrative, as no specific statements
were identified regarding the correction of previous data.
1.Consistency of abbreviations: The use of 'GD' (gallstone disease) has been standardised;
occasionally 'GDS' is used incorrectly.
2.Original: "Effective blood pressure control not only improves cardiovascular outcomes, but
also reduces the risk of GD or delays in gallbladder-related procedures."
Proposed: "Effective blood pressure control improves cardiovascular outcomes and reduces the
risk of GD or delays in gallbladder-related procedures."
3.For accuracy, replace "poses significant risks" with "carries significant risks" in the the
INTRODUCTION for accuracy.
4.Unnecessary statements: Eliminate redundancies such as "further investigation of the
underlying mechanisms" (already implied by "future longitudinal studies").
5.Correct "reduce complications" in DISCUSSION to "reduce complications".
These corrections will further improve the clarity and readability of the article.
‘’This study identified an association between modifiable risk factors, particularly BP, and GD
in individuals aged > 48 years, as well as the age at first cholecystectomy’’. EVEN IF THE
ARTICLE WAS WRITTEN CAREFULLY, I THINK THERE IS NOT ENOUGH DATA TO
REACH THE FINAL CONCLUSION. FUTURE STUDIES NEED TO SUPPORT THIS. .
Review for 10.1186/s12876-025-03608-5 (2025)

Title: A Foundation Systematic Review of Natural Language Processing Applied to
Gastroenterology & Hepatology
Version: 2 Date: 05 Dec 2024
Reviewer's report:
The authors have satisfied the requests of the editorial board.
Additional minor notes.
"Maximize" is spelled wrong in first paragraph of the article retrieval section of the Methods.
In "Study purpose and and primary findings" section gastroscopy is listed twice as a subject
matter. I believe the later mention with only 2 studies is meant to refer to gastrointestinal
bleeding.
Review for 10.1186/s12876-025-03608-5 (2025)

Title: A Foundation Systematic Review of Natural Language Processing Applied to
Gastroenterology & Hepatology
Version: 2 Date: 18 Dec 2024
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-The introduction briefly mentions applications such as adenoma detection from colonoscopy
reports, there is limited detail on the specific clinical tasks where NLP could be applied
in gastroenterology (e.g., diagnostic decision support, prediction of disease progression,
personalized treatment planning). Providing a broader overview of potential use cases within
gastroenterology would make the introduction more comprehensive.
-While the introduction addresses general challenges in NLP (e.g., morphology and syntax),
it would benefit from a discussion of unique challenges in gastroenterology. For instance,
gastroenterology-specific language (e.g., medical terminology, abbreviations, jargon) or the
need to process complex procedural data (e.g., colonoscopy and endoscopy reports) could be
explored in more detail.
-While the review adheres to numerous guidelines and checklists (e.g., PRISMA, AMSTAR,
TRIPOD, SWiM, ROBINS-I), the sheer number of frameworks mentioned may be
overwhelming for some readers. A more concise explanation or a focused discussion on the
most relevant guidelines for this specific review could improve clarity. For example, a summary
table or flowchart of the reporting and quality appraisal process might help readers navigate this
complexity.
-While using well-established checklists is a strength, it may also lead to a somewhat formulaic
approach. Given the rapidly evolving nature of NLP in healthcare, there could be value in
addressing emerging or specific concerns (e.g., model interpretability in clinical settings) that
are not fully captured by traditional checklists. Some form of flexibility in evaluating NLP
studies beyond these standardized frameworks might be beneficial for capturing the unique
characteristics of the field.
- The review mentions the heterogeneity of methodologies, it could benefit from a more detailed
examination of why certain methods are favored over others. For instance, why are rule-based
methods still widely used, and how do they compare to machine learning (ML) approaches
in terms of clinical efficacy? A deeper dive into the strengths and limitations of different
approaches would provide readers with a clearer understanding of their practical implications.
-While the review touches on data protection and patient privacy when discussing model sharing,
it could delve deeper into the ethical considerations surrounding NLP in gastroenterology. For
example, how might biases in data affect model predictions, particularly regarding race, sex,
and socioeconomic status? The article would benefit from a more robust ethical analysis of the
implications of NLP in clinical settings.