JerMa88/BMC_Gastroenterology_Peer_Reviews huggingface dataset:
Review for 10.1186/s12876-025-03642-3 (2025)

Title: Cardiometabolic Index as a Predictor of Gallstone Incidence in U.S. Adults: Insights from
NHANES 2017-2020
Version: 1 Date: 09 Jan 2025
Reviewer:  Amira A A Othman
Reviewer's report:
I want to extend my congratulations to all those involved in this work. All the required
amendments have already been made carefully and satisfactorily. I hope that the research will
be presented to science.
Review for 10.1186/s12876-025-03632-5 (2025)

Title: Neuregulin1 ameliorates metabolic dysfunction-associated fatty liver disease via the
ERK/SIRT1 signaling pathways
Version: 2 Date: 15 Sep 2024
Reviewer's report:
Reviewers' comments
Title:Neuregulin1 ameliorates nonalcoholic fatty liver disease via the ERK/SIRT1 signaling
pathways
Comments:
Neuregulin (NRG) family is involved in energy metabolism, among which NRG1 is a
neuregulin has been proved to upregulate the phosphorylation of ErbB3 in NAFLD cells.
This study aimed to investigate the role of NRG1 in the pathogenesis of hepatic steatosis
and steatohepatitis.HepG2 cells were exposed to oleic acid and palmitic acid to establish a
cellular model of NAFLD. NAFLD animal model was established by feeding C57BL/6J mice
with high-fat diet. H&E staining, oil red staining, and biochemical tests were used to evaluate
the models. The results  showed that #The expressions of NRG1 in NAFLD cell and animal
models were significantly lower than the control group. The intervention of NRG1 increased
its expressions. After the intervention of ERK inhibitor PD98059, no significant change was
observed in vivo, while its expression decreased significantly in vitro. #NRG1 ameliorates
hepatic steatosis, enhances cell viability, reduces cell apoptosis, and attenuates liver injury both
in vitro and in vivo. #After NRG1 intervention, the expressions of ERBB2, ERRBB3, p-ERK1/2,
SIRT1 and p-FOXO1 in NAFLD cells and liver tissues of NAFLD mice were significantly
increased. Furthermore, the LC3II/I ratio was increased, while the expression of SREBP1c was
decreased. The data above suggest  that  NRG1 might play a protective role in the pathogenesis
of NAFLD by activating the downstream ERK1/2 through the ErbB2-ErbB3, which promotes
the expression of SIRT1 and autophagy.
It is a topic of interest to the researchers in the related areas #but the paper needs large
improvements before acceptance for publication.My detailed comments are as follows:
1.the introduction ,materials and methods  in the paper work  well ,Cell culture
and treatments,nimal models,Oil Red O staining, Cell viability assay,Apoptosis analysis,
Intracellular ROS,Measurement of serum inflammatory factors,and  Western blotting.
2. Results are good and the resolutions of the figures are high, but the results got in the
experiments should be described objectively,not conclusions were made;In addition,the part of
dicussion is not well discussed combined with results and references and should make some
modifications.
3.The language is not fluent ,suggesting that it should be edited by an english native editor.
4.There are 19.4%  references which are not up-to-date,references of the last 10 years should be
cited,please cite last 10 years references ,especially references for the last 5 years.
Pelase make large revisions, espically in the part of results,discussion references  and languge-
editing. After making large  revisions,the paper may be considered for publication.
Review for 10.1186/s12876-025-03632-5 (2025)

Title: Neuregulin1 ameliorates metabolic dysfunction-associated fatty liver disease via the
ERK/SIRT1 signaling pathways
Version: 3 Date: 21 Oct 2024
Reviewer:  Panagiotis Tsibouris
Reviewer's report:
Abstract Background Known and unknown data should be defined If NRG1 is related with
MAFLD what should be clarified? Methods should define connection with NRG1 Numerical
values, when available, should be provided in results section Methods Measurement categories
should be defined Flow cytometry should be described Autophagy measurements should be
described In general it should be in parallel presentation in methods and results section Results
Significant number should be presented in the text
Review for 10.1186/s12876-025-03632-5 (2025)

Title: Neuregulin1 ameliorates metabolic dysfunction-associated fatty liver disease via the
ERK/SIRT1 signaling pathways
Version: 3 Date: 24 Oct 2024
Reviewer's report:
Reviewers' comments
Title:Neuregulin1 ameliorates metabolic dysfunction-associated fatty liver disease via the ERK/
SIRT1 signaling pathways
Comments:
Neuregulin (NRG) family is involved in energy metabolism, among which NRG1 is a neuregulin
proved to upregulate the phosphorylation of ErbB3 in MAFLD cells. This study aimed to
investigate the role of NRG1 in the pathogenesis of MAFLD.HepG2 cells were exposed to oleic
acid and palmitic acid to establish a cellular model of MAFLD. MAFLD animal model was
established by feeding C57BL/6J mice with high-fat diet. H&E staining, oil red staining, and
biochemical tests were used to evaluate the models. The results showed that the expressions
of NRG1 in MAFLD cell and animal models were significantly lower than that in the control
group. After the intervention of ERK inhibitor PD98059, the expression of NRG1 decreased
significantly in vivo, but no significant change was observed in vitro. Moreover, NRG1
ameliorated hepatic steatosis, enhanced cell viability, reduced cell apoptosis, and attenuated liver
injury both in vitro and in vivo. After NRG1 intervention, the expressions of ERBB2, ERBB3,
p-ERK1/2, SIRT1 and p-FOXO1 as well as the LC3II/I ratio in MAFLD cells and liver tissues
of MAFLD mice were significantly increased, while the expression of SREBP1c was decreased.
The aforementioned therapeutic effect of NRG1 was lost after the intervention of PD98059.The
data above suggest that  NRG1 might play a protective role in the pathogenesis of MAFLD
by activating the downstream ERK1/2 through ErbB2-ErbB3, which promotes the expression
of SIRT1 and autophagy markers. This study might indicate a new therapeutic strategy for
MAFLD.
It is a topic of interest to the researchers in the related areas #but the paper needs minor
improvements before acceptance for publication.My detailed comments are as follows:
1.the introduction ,materials and methods  in the paper work  well ,especially  Animal
experiments,Histological analysis,Tunel staining,Western blotting analysis
, Cell culture and treatments,Cell viability assay, Enzyme-linked immunosorbent assay, and
Intracellular ROS.
2. Results are good and the resolutions of the figures are high,  the part of dicussion has been
well discussed combined with results and references .
3.there are still the few of  the references which are not up-to-date,references of the last 10 years
should be cited,please cite last 10 years references ,especially references for the last 5 years.
Pelase make minor revisions, espically in the part of rererences . After making minor
revisions,the paper may be considered for publication.
Review for 10.1186/s12876-025-03632-5 (2025)

Title: Neuregulin1 ameliorates metabolic dysfunction-associated fatty liver disease via the
ERK/SIRT1 signaling pathways
Version: 5 Date: 12 Nov 2024
Reviewer:  Panagiotis Tsibouris
Reviewer's report:
Abstract Numerical values should be presented in the results section The same is valid for the
results section where qualitative measures should be tranformed ito quantitative and results for
comparisons should be presented in conjuction with p-values
Review for 10.1186/s12876-025-03632-5 (2025)

Title: Neuregulin1 ameliorates metabolic dysfunction-associated fatty liver disease via the
ERK/SIRT1 signaling pathways
Version: 5 Date: 24 Nov 2024
Reviewer's report:
Reviewers' comments
Title:Neuregulin1 ameliorates metabolic dysfunction-associated fatty liver disease via the ERK/
SIRT1 signaling pathways
Comments:
Neuregulin (NRG) family is involved in energy metabolism, among which NRG1 is a neuregulin
proved to upregulate the phosphorylation of ErbB3 in MAFLD cells. This study aimed to
investigate the role of NRG1 in the pathogenesis of MAFLD.HepG2 cells were exposed to oleic
acid and palmitic acid to establish a cellular model of MAFLD. MAFLD animal model was
established by feeding C57BL/6J mice with high-fat diet. H&E staining, oil red staining, and
biochemical tests were used to evaluate the models. The results showed that the expressions
of NRG1 in MAFLD cell and animal models were significantly lower than that in the control
group. After the intervention of ERK inhibitor PD98059, the expression of NRG1 decreased
significantly in vivo, but no significant change was observed in vitro. Moreover, NRG1
ameliorated hepatic steatosis, enhanced cell viability, reduced cell apoptosis, and attenuated liver
injury both in vitro and in vivo. After NRG1 intervention, the expressions of ERBB2, ERBB3,
p-ERK1/2, SIRT1 and p-FOXO1 as well as the LC3II/I ratio in MAFLD cells and liver tissues
of MAFLD mice were significantly increased, while the expression of SREBP1c was decreased.
The aforementioned therapeutic effect of NRG1 was lost after the intervention of PD98059.The
data above suggest that  NRG1 might play a protective role in the pathogenesis of MAFLD
by activating the downstream ERK1/2 through ErbB2-ErbB3, which promotes the expression
of SIRT1 and autophagy markers. This study might indicate a new therapeutic strategy for
MAFLD.
It is a topic of interest to the researchers in the related areas .Because the authors have revised all
problem I raised, I think the paper should  be considered for publicatio.My detailed comments
are as follows:
1.the introduction ,materials and methods  in the paper work  well ,especially  Animal
experiments,Histological analysis,Tunel staining,Western blotting analysis
, Cell culture and treatments,Cell viability assay, Enzyme-linked immunosorbent assay, and
Intracellular ROS.
2. Results are good and the resolutions of the figures are high,  the part of dicussion has been
well discussed combined with results and references .
3. the references  are  up-to-date now#
Because the authors have revised all problem I raised, I think the paper should  be considered
for publication.
Review for 10.1186/s12876-025-03625-4 (2025)

Title: Associations between Systemic Inflammatory Biomarkers and Metabolic Dysfunction
Associated Steatotic Liver Disease: A cross-sectional study of NHANES 2017-2020
Version: 3 Date: 08 Jan 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
The responses are satisfactory.
Review for 10.1186/s12876-025-03625-4 (2025)

Title: Associations between Systemic Inflammatory Biomarkers and Metabolic Dysfunction
Associated Steatotic Liver Disease: A cross-sectional study of NHANES 2017-2020
Version: 3 Date: 11 Jan 2025
Reviewer:  Amira A A Othman
Reviewer's report:
I want to extend my congratulations to all those involved in this work. All the required
amendments have already been made carefully and satisfactorily. I hope that the research will
be presented to science.
Review for 10.1186/s12876-025-03649-w (2025)

Title: Amarogentin suppresses cell proliferation and EMT process through inducing ferroptosis
in colorectal cancer
Version: 2 Date: 19 Dec 2024
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-"Colorectal cancer (CRC) is one swart tumor in human" – The term "swart" is unclear and
should likely be replaced with "serious" or "common."
-"The characteristics of CRC contain strong concealment" – This phrasing is awkward; it should
be reworded as "CRC is characterized by its ability to remain asymptomatic" or similar.
-While the manuscript suggests that AG induces ferroptosis in CRC cells, it lacks a detailed
mechanistic explanation. The molecular pathways or specific interactions through which AG
modulates ferroptosis (e.g., the involvement of key ferroptosis regulators like GPX4, ACSL4,
or FSP1) are not sufficiently discussed.
-The authors mention the suppression of Nrf2/HO-1/GPX4 activation by AG, but further
explanation of how AG interferes with these pathways is needed. For example, does AG directly
affect gene expression, protein stability, or post-translational modifications of these key players?
-The in vivo study is not described in sufficient detail. While the tumor volume and weight
reduction are mentioned, the specific data (e.g., percentage of tumor growth inhibition, statistical
significance) should be presented to better demonstrate AG’s efficacy in vivo.
-While the Nrf2/HO-1/GPX4 axis is mentioned, there is still limited discussion on how AG
specifically affects these pathways. For example, how does AG modulate Nrf2 activation? Is
AG directly influencing the transcriptional activity of Nrf2, or is it altering upstream signaling
events? It would be helpful to provide a more detailed mechanistic explanation or suggest
potential experiments to elucidate these aspects further.
-While the PTC model is mentioned, the discussion does not delve into how AG might interact
with various components of the tumor microenvironment (e.g., immune cells, stromal cells) that
are present in the PTC model. Exploring whether AG also affects immune cells or fibroblasts
in the tumor microenvironment could provide a more comprehensive understanding of its
therapeutic potential.
Review for 10.1186/s12876-025-03649-w (2025)

Title: Amarogentin suppresses cell proliferation and EMT process through inducing ferroptosis
in colorectal cancer
Version: 2 Date: 23 Dec 2024
Reviewer:  Mohamed H. Zidan
Reviewer's report:
Dear Authors,
Re: "Amarogentin suppresses cell proliferation and EMT process through inducing ferroptosis
in colorectal cancer"
Thank you for the opportunity to review your manuscript. Your study provides valuable insights
into the role of amarogentin (AG) in suppressing colorectal cancer (CRC) progression by
inducing ferroptosis and inhibiting epithelial-mesenchymal transition (EMT). The manuscript is
well-organized and employs robust methodologies, including in vitro and in vivo experiments,
to support your findings. However, several aspects require refinement to enhance clarity, rigor,
and accessibility.
The figures, particularly the blots and imaging data, were not fully assessable in their current
format (e.g., TIF). I recommend converting these images to a more universally accessible format
such as JPEG, ensuring adequate resolution for proper evaluation. Additionally, all blots should
include molecular weight markers and less cropping to avoid obscuring relevant data. Detailed
unprocessed images should be provided as supplementary materials, along with an explicit
statement in the methods if the blots were cut before hybridization with antibodies.
The methodology section is generally clear but could benefit from additional details to improve
reproducibility. For example, specify the AG concentration and dosing regimen for the in vivo
studies directly in the results section for clarity. Statistical analysis is thorough, but greater
emphasis on the biological relevance of key findings, such as the therapeutic implications of
IC50 values, would strengthen the manuscript. While the discussion effectively ties the results
to the Nrf2/HO-1/GPX4 pathway, comparisons with other ferroptosis-inducing agents in CRC
would add depth. For instance, Fu et al. (2023) demonstrated that targeting the Nrf2/HO-1/
GPX4 axis could enhance the efficacy of platinum-based therapies for CRC, emphasizing the
potential for combination approaches to overcome therapeutic resistance (Science Progress,
DOI:10.1177/00368504221147173).
The use of patient-derived tumor-like cell clusters (PTCs) is a commendable inclusion that
enhances the clinical relevance of your findings. However, a brief acknowledgment of potential
limitations regarding their ability to mimic the heterogeneity of CRC tumors would provide a
more balanced view. Language throughout the manuscript could be further polished, as certain
phrases (e.g., "AG has been verified to own regulatory roles") detract from the scientific tone
and clarity.
Overall, your work highlights the potential of AG as a therapeutic agent for CRC. By addressing
the aforementioned points, particularly the figure formatting and discussion of translational
implications, the manuscript will be significantly improved.
Kind regards,
Review for 10.1186/s12876-025-03649-w (2025)

Title: Amarogentin suppresses cell proliferation and EMT process through inducing ferroptosis
in colorectal cancer
Version: 3 Date: 13 Jan 2025
Reviewer:  Mohamed H. Zidan
Reviewer's report:
Dear Authors,
Re: The manuscript titled "Amarogentin Suppresses Cell Proliferation and EMT Process
Through Inducing Ferroptosis in Colorectal Cancer"
The study's statistical methods and data analysis, particularly for IC50 determination and
significance testing (Figures 1A and 5A), are appropriately conducted, though some biological
interpretations (e.g., clinical implications of IC50 values) lack depth. The manuscript addresses
this gap by emphasizing IC50's importance in drug efficacy but could further compare AG's
potency with established CRC therapeutics.
While the results strongly indicate pathway modulation, the mechanistic insights remain
speculative. For example, the study does not elucidate whether AG directly affects
transcriptional activity or post-translational stability of these proteins. This limitation,
acknowledged by the authors, is a critical area for future exploration.
The use of patient-derived tumor-like cell clusters (PTCs) enhances the translational relevance
of findings. However, as noted by reviewers, the study does not sufficiently discuss the
heterogeneity of CRC tumors and how well PTCs mimic the tumor microenvironment,
particularly interactions with immune and stromal cells. This oversight limits the broader
applicability of the findings to clinical settings.
The in vivo experiments effectively demonstrate AG's tumor-suppressive effects, supported
by reductions in tumor volume and weight. However, the description of dosing regimens
and therapeutic efficacy, while improved in the revision, remains succinct. Greater detail in
presenting tumor growth inhibition percentages and statistical analyses would enhance the rigor
of this section.
The manuscript's writing quality, while improved, still suffers from occasional lapses in
scientific tone and grammatical clarity (e.g., "AG has been verified to own ameliorative
properties"). These issues, highlighted by reviewers, appear to have been addressed partially but
require additional polishing for academic rigor.
Kind regards
Review for 10.1186/s12876-025-03630-7 (2025)

Title: CT Features with Histopathological Correlation in Inflammatory Versus Benign &
Malignant Neoplastic Appendiceal Mucoceles: A Retrospective Cross-Sectional Study
Version: 1 Date: 27 Oct 2024
Reviewer's report:
Appendiceal mucoceles are rare entities and research data are correspondingly rare. Therefore,
this manuscripts provides an excellent overview and new insights, relevant for the clinical
practice.
However, I would recommend adding further data and images to the manuscript to increase its
clinical relevance:
- Please add additional images of different types of mucoceles to facilitate the diagnosis
- A very relevant limitation of the study is mentioned in the discussion - the authors did not
compare mucoceles with cases of acute appendicitis. Given that almost 1/3 of the patients
with mucoleceles present with signs of acute appendicitis, it is the most relevant differential
diagnosis. The authors should compare exsisiting research data with their imaging findings to
guide readers through this issue.
Review for 10.1186/s12876-025-03630-7 (2025)

Title: CT Features with Histopathological Correlation in Inflammatory Versus Benign &
Malignant Neoplastic Appendiceal Mucoceles: A Retrospective Cross-Sectional Study
Version: 1 Date: 31 Oct 2024
Reviewer's report:
Thank you for submitting this paper. Differentiation of benign vs malignant lesions is important
as it alters the operative approach. Some specific comments about your paper are:
1. you only used a single search phrase of "appendiceal mucocele". If you use other phrases,
you might find more cases.
2.in the introduction, the first sentence contradicts the second.
3.Introduction: do you have a better figure for incidence? % in excised lesions is largely
meaningless.
4. You talk about 3 groups; benign, low grade/hyperplasia and malignant.  I think that this
should be simplified based upon what operation you would ideally get. Who gets a simple
appendicectomy, vs caecectomy, versus hemicolectomy? This is the clinical question that needs
to be answered, so the paper should be set up that way.
5. Under CT findings you state "Soft-tissue thickening was seen in 15%"Soft-tissue thickening
was seen in 15%,". This represents 4.65 patients. How is that possible?
6. Table 4 is inflammatory vs benign. This needs to address malignant to be clinically relevant.
7. did you consider doing a multivariate analysis?
Review for 10.1186/s12876-025-03630-7 (2025)

Title: CT Features with Histopathological Correlation in Inflammatory Versus Benign &
Malignant Neoplastic Appendiceal Mucoceles: A Retrospective Cross-Sectional Study
Version: 3 Date: 16 Dec 2024
Reviewer's report:
Thank you for the revisions.
Review for 10.1186/s12876-025-03630-7 (2025)

Title: CT Features with Histopathological Correlation in Inflammatory Versus Benign &
Malignant Neoplastic Appendiceal Mucoceles: A Retrospective Cross-Sectional Study
Version: 3 Date: 31 Dec 2024
Reviewer's report:
Thank you for adding more imaging data to the manuscript to enhance clinical utility.
Review for 10.1186/s12876-025-03598-4 (2025)

Title: Establishing of a risk prediction model for metabolic dysfunction associated steatotic liver
disease: a retrospective cohort study
Version: 1 Date: 25 Sep 2024
Reviewer's report:
I thank the editor for inviting me to review this manuscript and I have several comments.
1. In Figure 1, the exclusion criterion (Excluding previous history of other serious illnesses
(n=289)) appears twice. Please verify this.
2. What methods are used for collinearity diagnosis? What indicators are adopted? How is
the judgment made? If collinearity exists, how is it handled? These should be clarified in the
statistical analysis section.
3. Line 153, is the word 'occucation' spelled incorrectly?
4. On what principles were the clinical characteristics chosen in this study?
5. What are the p-value thresholds for variables entering and exiting the model in the stepwise
regression analysis?
6. The participants in this study are all from the Chinese population, which has its own diagnostic
criteria for MASLD. These criteria seem to differ somewhat from those used by the authors in the
article. Did the authors compare the differences between the two sets of criteria? Additionally,
have they considered whether using the Chinese population's own MASLD diagnostic criteria
would be more reasonable?
Review for 10.1186/s12876-025-03598-4 (2025)

Title: Establishing of a risk prediction model for metabolic dysfunction associated steatotic liver
disease: a retrospective cohort study
Version: 1 Date: 07 Oct 2024
Reviewer's report:
The study uses a cohort over a roughly four year period with a  training a a validation cohort.  The
model includes mostly variables that are used in the diagnosis of MAFLD (as the authors point
on in the paper).    The model AUC is somewhat underwhelming (approx 0.75-0.79).  There
were a few issues I thought could use clarification
1. the authors discuss the incidence of MAFLD.  However, it seems from the methods that only
one ultrasound was done during a time period.  Is this an incidence study, or was this a cross
sectional study of prevalence?  It is not clear from the methods
2. the diagnosis of MAFLD required the presence of one metabolic risk factors and then the
authors found that the presence of these risk factors were associated with MAFLD.  Perhaps it
would make the most sense to focus on imaging evidence of steatosis?
3. I am still confused on the time dependent incidence.  Did the participants have more than
one ultrasound?
4.  Looking at figure 4, WC, blood glucose and HDL have a large influence on the diagnosis of
fatty liver.  This has been well described already.  The weight of these seems enough that this
is accounting for the majority of the model to discriminate fatty liver cases
Review for 10.1186/s12876-025-03598-4 (2025)

Title: Establishing of a risk prediction model for metabolic dysfunction associated steatotic liver
disease: a retrospective cohort study
Version: 1 Date: 08 Oct 2024
Reviewer:  Maria Eugenia Icaza-Chávez
Reviewer's report:
I find this study very important. The current parameters accepted now a days for selecting wich
patients should be submited to further study to detect those at risk of advanced liver fibrosis are
not ideal (like FIB-4 and NAFLD score).
I have some comments:
A)   What kind of hormone use was an exclusion criteria? Levothyroxine, estradiol?
B) So during a maximum of 4 years follow up, almost 20% of individuals developed MASLD?
The prevalence of MASLD in general population has been described to be 30 to 40%, so it seems
quite high that a check up population develops this condition in  4 years. Just asking.
C) Before stating that  the model effectively assist clinical physicians in predicting and
evaluating the probability of MASLD incidence, they have to be tested in other populations
Review for 10.1186/s12876-025-03598-4 (2025)

Title: Establishing of a risk prediction model for metabolic dysfunction associated steatotic liver
disease: a retrospective cohort study
Version: 2 Date: 04 Nov 2024
Reviewer's report:
The auhors present an interesting article suggesting a risk prediciton model for the development
of MASLD in a cohort of non-MASLD patients. The idea is overall well execute, however there
are a few things that need improvement before final publication.
1. English language must be re-checked throughout the manuscript. Examples are: line 49: 'it can
also', 'it' should be substituted with MASLD; line 50: 'along with their incidence and motality'
should be deleted as it is not needed'; line 70: 'those who are 18 years of age or older' should
be sustituted  with age of at least 18 years, etc
2. The results of MASLD in endothelial function leading to inflammation and subsequent
atherosclerosis and CVD should be highlighted in the introduction (ref: doi: 10.1007/
s00018-023-04966-7; doi: 10.3390/cells11162511)
3. In both introduction and discussion, the authors present details about nomograms. This is
unnecessary and the discussion part should be deleted
4. The authors should evaluate their risk prediction model in subgroups of interst, like patiens
with hypertension,  hyperlipidemia and diabetes and note possible differences
5.  Finally, the retrospective status of the study should be added as study limitation
Review for 10.1186/s12876-025-03598-4 (2025)

Title: Establishing of a risk prediction model for metabolic dysfunction associated steatotic liver
disease: a retrospective cohort study
Version: 2 Date: 05 Nov 2024
Reviewer's report:
The authors have mainly addressed critiques.  It would be useful to have clarification on one
issue
the authors state
We appreciate the Reviewer’s comments. All subjects underwent abdominal
ultrasound examinations at baseline and during each follow-up. Additionally, all relevant
indicators involved in the MASLD diagnostic criteria are
complete
It  would be useful to define this better in the methods.  I assume at baseline there was no steatosis
and participants developed steatosis over a 4 year follow up period?
a table showing the development of fatty liver at each annual US would be helpful as well
Review for 10.1186/s12876-025-03615-6 (2025)

Title: Effect of KRAS mutation status on clinicopathological characteristics and overall survival
in patients with rectal cancer
Version: 0 Date: 29 Oct 2024
Reviewer's report:
This is an interesting study where  authors aimed to compare wKRAS and mKRAS, as well
as kodon 12 and 13 in rectal  cancer patients with managed with surgical resection. However,
there’s some points which authors should  be care.
First of all, article should be check for typos and grammar, and should be refrase  by the native
english. There a lot of typos, for example “differeniated” should be written “differentiation”
and etc.
Although, authors pointed on limitation that there is no information about NCRT, but I think
it should provided in this study (chemotherapy  drugs, type of radiotherapy -short/long course;
waiting time before the surgery). Also, information about the adj#vant therapy are also essential
when evaluating the survival rates.  Moreover, there’s no information about the surgical
techniques (open, laparoscopic or robotic) which also have a significance effect on the survival.
I will be greatfull if authors  may provide abovementioned issues, and while doing it using the
regarding literature  about these  points.
Thank you!
Review for 10.1186/s12876-025-03604-9 (2025)

Title: Effect of probiotics combined with immune checkpoint suppressors and chemotherapeutic
agents on digestive system function, intestinal immunity and prognosis in patients with
metastatic colorectal carcinoma: a quasi-experimental study
Version: 0 Date: 20 Dec 2024
Reviewer's report:
1.Whether this manuscript is a retrospective or prospective study, we failed to find out in the
manuscript. For a retrospective study, how many cases were collected, how many cases met the
inclusion criteria, and how many cases were excluded, and 96 cases remained. They were then
divided into control and study groups as treated, and this process is described in a Fig. If it is
a prospective study,  the selected size of the sample , the method of grouping, etc.should be
describe . Please explain it.
2.In the Methods section, please describe the time of each treatment cycle.
3.The names of the two groups are inconsistent in the text: study group or research group or R
group; control group or C group, please modified.
4.In the chart, the marker for statistical results are inconsistent, A should be changed to a
5.In the observation index, the observation point of each index should be indicated as 4 treatment
cycles, which are not specified in the stool culture and quality of life.
6.In the discussion, this sentence:‘Our findings indicated that the levels of D-LA and DAO were
elevated, the and the increase in the study group was smaller after treatment’ should be placed
in the upper paragraph.
7.In the graphical representation of survival groups, six weeks, 12 weeks and two years were
inconsistent. Please modify.
8.This sentence ‘Immune checkpoint suppressor-based and chemotherapy in combination with
probiotic administration did not influence the prognosis of the patients’Inconsistent with the
result, please modify it
9‘Note: the control group before and after treatment, aP < 0.05; Comparison of the study
group before and after treatment, bP < 0.05.’may be#Compare with Before treament, a:P <
 0.05;Compare with control group,b:P < 0.05.Please checkout and revise it.
Review for 10.1186/s12876-025-03604-9 (2025)

Title: Effect of probiotics combined with immune checkpoint suppressors and chemotherapeutic
agents on digestive system function, intestinal immunity and prognosis in patients with
metastatic colorectal carcinoma: a quasi-experimental study
Version: 0 Date: 21 Dec 2024
Reviewer's report:
This study presents a significant investigation into the potential benefits of combining
probiotics with immune checkpoint inhibitors and chemotherapeutic agents for patients with
metastatic colorectal carcinoma. By examining outcomes such as survival rates, immune
function, intestinal flora balance, and quality of life, the authors provide valuable insights
into the therapeutic potential of this combination strategy. However, some points merit further
consideration:
1. The study emphasizes the benefits of probiotics in reducing chemotherapy-associated
toxicities and improving immune parameters. Could additional data on the therapeutic effects
and potential toxicities of these treatments, beyond the initial two-year follow-up period, provide
a more comprehensive understanding of long-term outcomes?
2. The reliance on a single hospital cohort may limit the generalizability of the findings.
Would including additional cases from diverse demographic and geographic settings enhance
the robustness and applicability of the conclusions?
3. While the results highlight a significant improvement in intestinal flora and immune
markers, the mechanisms underlying these changes remain insufficiently explored. Could further
molecular analyses, such as metagenomic sequencing or cytokine profiling, clarify the causal
pathways and strengthen the study's conclusions?
4. The quality-of-life data demonstrate noticeable improvement in the study group, yet the
underlying factors driving these enhancements are not fully dissected. Would including patient-
reported outcomes and detailed psychological assessments provide a deeper understanding of
these observations?
5. The study mentions that probiotics may regulate immune function via T-cell modulation.
Could additional experiments or analyses, such as ex vivo immune cell studies or cytokine
quantifications, validate these findings and provide mechanistic insights?
6. The paper acknowledges limitations related to sample size and study scope. A more detailed
discussion of potential confounding factors, such as dietary patterns or concurrent medications,
would provide clarity on how these variables might influence the observed results.
7. The chosen probiotic formulation includes multiple bacterial strains. Could a breakdown
of the individual contributions of each strain to the observed effects help refine therapeutic
strategies?
Review for 10.1186/s12876-025-03604-9 (2025)

Title: Effect of probiotics combined with immune checkpoint suppressors and chemotherapeutic
agents on digestive system function, intestinal immunity and prognosis in patients with
metastatic colorectal carcinoma: a quasi-experimental study
Version: 1 Date: 10 Jan 2025
Reviewer's report:
The reviewer's question was answered and the manuscript has be revised according to the
suggestion of the reviewer by the author and can be receive now.
Review for 10.1186/s12876-025-03604-9 (2025)

Title: Effect of probiotics combined with immune checkpoint suppressors and chemotherapeutic
agents on digestive system function, intestinal immunity and prognosis in patients with
metastatic colorectal carcinoma: a quasi-experimental study
Version: 1 Date: 10 Jan 2025
Reviewer's report:
Thank you for submitting the revised manuscript and for your detailed responses to the
reviewers' comments. The revisions have addressed the key concerns effectively, including
clarifying the study's prospective design, standardizing group labels, and improving statistical
clarity. The authors have also adequately acknowledged limitations, such as the single-center
cohort and the need for further mechanistic exploration through additional molecular analyses.
The discussion now more clearly reflects the study's results, aligning conclusions with the
presented data. Overall, the manuscript is substantially improved, and I recommend it for
acceptance in its current form.
Review for 10.1186/s12876-025-03624-5 (2025)

Title: Capecitabine enhances sensitivity to oxaliplatin in advanced gastric cancer and the effects
on patients' FOXP1 and GGT levels
Version: 0 Date: 24 Nov 2024
Reviewer:  Panagiotis Tsibouris
Reviewer's report:
Abstract It should be defined whether they were consecutive patients Numerical values about
the study population would be better presented in the results What was the effect of treatment
reported in the first sentence of the results Was it complete and partial response or was stable
disease included as well? Quantitative measurements of FOXP1 would be better to accompany
p-values OS rates should be followed by p-values Significant factors determining OS should be
presented in one instead of two sentences and followed by OR and p-value Methods Numerical
values for the study population belong in the results It is stated that patients are diagnosed for
the first time but it is also stated that patients might have reoccure after surgery This point
needs futher definition It should be defined at what point an imbalance of various organ function
was acceptable since it mentioned that "is generaly normal " and also it is mentioned that
diabetes , heart, liver and kidney comorbidities were excluded  It should be stated whether
mixed neoplasms of the stomach were excluded Was the study FOLFOX vs capecitabine or
FOLFOX  vs FOLFOX+capecitabine? The latter is mentioned in the results but it is not clear
in methods section Quantitation of FOXP1 expression should be provided  At what time point
was efficacy  measured? Grading of adverse reactions should be described Statistics Power of
the study calculation should be provided Results Because FOXP1 was mentioned it is graded
between 0 and 3 , were any cases with grade higher than 1 Table 2 gives the impression that are
none Grading of adverse reactions should be provided Significant determinants of OS should
be icluded in the text followed by OR and p-value Corrected OR after multivariated analysis
should be presented I am not sure that pair presentation of OS in various subgroups is needed
Review for 10.1186/s12876-025-03624-5 (2025)

Title: Capecitabine enhances sensitivity to oxaliplatin in advanced gastric cancer and the effects
on patients' FOXP1 and GGT levels
Version: 0 Date: 25 Nov 2024
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors , please address the following points below:
-While the clinical outcomes and biomarker changes are reported, the study would benefit
from a deeper exploration of the mechanisms by which capecitabine specifically enhances
oxaliplatin sensitivity at the molecular level. Additional data on the molecular interactions or
signaling pathways—such as DNA repair mechanisms and apoptosis pathways—would improve
the understanding of the synergy between the two drugs.
-The statistical methods employed are generally sound; however, providing more information
on the corrections for multiple comparisons and potential confounders (such as patient age and
prior treatments) would be beneficial.
-Although the correlation between drug sensitivity and FOXP1/GGT levels is intriguing, there
is limited explanation regarding the underlying biology. How do changes in FOXP1 expression
affect drug metabolism or resistance pathways in gastric cancer cells? Additionally, does GGT
influence capecitabine metabolism or the cellular response to oxidative stress induced by
oxaliplatin?
-While FOXP1 and GGT levels were assessed, further validation in independent cohorts and
through different platforms, such as proteomics and gene expression profiling, would strengthen
their role as reliable biomarkers for predicting treatment outcomes.
-It would also be helpful to evaluate whether the relationship between FOXP1/GGT and
treatment response is consistent across various patient subgroups (e.g., age, gender, tumor
stage, prior therapies). This could help identify subpopulations more likely to benefit from the
combination therapy.
-The study does not examine other potential factors that could influence drug sensitivity, such
as genetic or epigenetic changes, tumor microenvironment factors, or variations in immune
response. Acknowledging these variables would strengthen the discussion and suggest ways
they could be integrated into future studies.
-The role of FOXP1 in cancer is complex; it can function as both a tumor suppressor and an
oncogene, depending on the context. Further clarification of FOXP1’s specific role in gastric
cancer and how it modulates drug response in this particular setting would enrich the discussion.
Review for 10.1186/s12876-025-03624-5 (2025)

Title: Capecitabine enhances sensitivity to oxaliplatin in advanced gastric cancer and the effects
on patients' FOXP1 and GGT levels
Version: 1 Date: 06 Jan 2025
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
The responses are satisfactory.
Review for 10.1186/s12876-025-03624-5 (2025)

Title: Capecitabine enhances sensitivity to oxaliplatin in advanced gastric cancer and the effects
on patients' FOXP1 and GGT levels
Version: 1 Date: 12 Jan 2025
Reviewer:  Mohamed H. Zidan
Reviewer's report:
Dear authors,
The manuscript is well-designed and the authors have clearly answered all the reviewer's
concerned. I fins no crirical points to raise further.
Kind regards
Review for 10.1186/s12876-025-03635-2 (2025)

Title: The Prognostic Value of Systemic Inflammation Response Index in Digestive System
Carcinomas: A Systematic Review and Meta-Analysis
Version: 2 Date: 01 Oct 2024
Reviewer's report:
The primary aim of this systematic review and meta-analysis is to investigate the prognostic
value of the Systemic Inflammation Response Index (SIRI) in patients with digestive system
carcinomas (DSC). The study evaluates the association between pre-treatment SIRI levels
and various clinical outcomes, such as overall survival (OS), progression-free survival (PFS),
disease-free survival (DFS), time to progression (TTP), and disease-specific survival (DSS).
The goal is to provide a comprehensive understanding of whether SIRI can be utilized as a
reliable and non-invasive biomarker to predict the prognosis of DSC patients, potentially aiding
in treatment planning and improving patient outcomes.
However, there exist some limitations:
Significant Heterogeneity: The meta-analysis for overall survival (OS) exhibited high
heterogeneity (I² = 76.5%), which may affect the reliability of the pooled results. Although the
meta-regression and subgroup analyses attempted to address this, heterogeneity remained in
some subgroups, particularly the non-metastatic subgroup.
Publication Bias: Egger's test indicated publication bias in the meta-analysis of OS, which
suggests that some negative results may have been underreported or unpublished. This could
skew the overall findings.
Language and Geographical Bias: The study only included English-language publications,
which may introduce a language bias. Additionally, the majority of the included studies
originated from China, limiting the generalizability of the findings to other populations.
Limited Data on Secondary Outcomes: Due to the small number of studies evaluating PFS, DFS,
TTP, and DSS, detailed subgroup analyses or sensitivity analyses could not be performed for
these outcomes.
Categorization of SIRI: The conversion of continuous SIRI values into categorical variables
based on an optimal cutoff may lead to loss of statistical power and residual confounding,
limiting the robustness of the results.
Proposed Improvement Methods:
Addressing Heterogeneity: Future studies should aim to standardize the cutoff values used for
SIRI to reduce heterogeneity. Additionally, individual patient data (IPD) meta-analysis could
be considered to adjust for patient-level factors and provide more accurate estimates.
Inclusion of Gray Literature: Incorporating gray literature and non-English publications may
reduce publication bias and provide a more comprehensive overview of SIRI’s prognostic value.
Expanding Geographical Representation: Conducting studies in diverse geographical settings
with varied population characteristics would enhance the generalizability of the findings.
Review for 10.1186/s12876-025-03635-2 (2025)

Title: The Prognostic Value of Systemic Inflammation Response Index in Digestive System
Carcinomas: A Systematic Review and Meta-Analysis
Version: 2 Date: 04 Oct 2024
Reviewer's report:
This study consists in a systematic review and meta-analysis on the role of systemic
inflammation (measured by the SIRI index) as a prognostic factor for gastrointestinal neoplasms.
Inflammation markers as prognostic tools is a hot topic in medical oncology literature, and
a systematic review of current evidence is welcome. However, the current paper has serious
methodological problems, and will require major revisions before publication.
The authors have established as inclusion criteria that the selected studies should have evaluated
SIRI as a prognostic tool for GI tumors, and that a lower SIRI group was compared to a higher
SIRI one. The first aspect of these criteria is absolutely appropriate given the goals of this
systematic review. The second aspect, however, introduces unnecessary heterogeneity, since
different studies compared different SIRI cutoffs, so the validity of pooling data from such
is studies is highly questionable, even using random effects model. Besides that, this second
inclusion criteria may exclude some interesting papers which have evaluated the prognostic
effect of SIRI, but didn’t establish any “high versus low” threshold, therefore limiting the data
collect in this systematic review with the sole porpoise of concluding it with a meta-analysis of
little clinical and scientific utility.
Given this very high heterogeneity, I don’t believe that pooled data from these studies should be
synthetized through a meta-analysis, therefore. Therefore, I do not believe that this paper should
published in its current form, since its main results (the meta-analyses) and conclusions are not
scientifically sound.
However, there is a reason why I suggest a major revision of this paper instead of rejection. A
systematic literature search on information about SIRI role in cancer prognostic is warranted.
Therefore, the first part of this trial’s results is actually quite interesting. Systematic reviews
do not necessarily have to end in meta-analyses: many times, exposing the current available
evidence in organized tables is of much more value. Table 1, for instance, gives us a good picture
of state-of-the-art research on SIRI. From there, instead of proceeding to perform meta-analyses,
the authors should expand the exposition of gathered information. More tables summarizing
the design of each study, as well as their main results, are warranted. No meta-analyses are
applicable on this type of literature.
Also, the inclusion criteria for the systematic review should be slightly expanded, for the reason
I’ve already hinted on my third paragraph. Any studies evaluating prognostic impact of SIRI
should be included, even if the said study did not perform a “high vs low” comparison.
Last but not least, English language usage should be improved throughout this paper. After the
technical revision is performed, a suggest a language revision by a native English speaker
Review for 10.1186/s12876-025-03635-2 (2025)

Title: The Prognostic Value of Systemic Inflammation Response Index in Digestive System
Carcinomas: A Systematic Review and Meta-Analysis
Version: 4 Date: 19 Dec 2024
Reviewer:  Anwar Ashraf Abouelnasr
Reviewer's report:
Dear Authors, please address the following points below
-A brief section on the mechanistic pathways through which inflammation contributes to cancer
progression, particularly in the context of DSC, would enhance the depth of the introduction.
This would also help to better justify the clinical relevance of SIRI.
-Acknowledging the limitation of restricting to English-language studies and discussing its
potential impact on the results would add transparency and allow readers to consider this factor
when interpreting the findings.
-While the discussion provides an overview of the roles of immune cells in cancer progression,
further exploration of the molecular mechanisms behind SIRI’s predictive value could provide
more clarity. For example, linking SIRI to specific inflammatory cytokines, immune pathways,
or tumor microenvironment changes would help strengthen the biological plausibility of the
findings.
-The authors should discuss how different cut-off values for SIRI might impact its prognostic
accuracy. What are the implications of using an "optimal" cut-off, and how does it vary across
different cancers or treatment regimens?
-While the potential clinical applications of SIRI are mentioned, the discussion could benefit
from specific examples of how SIRI could be integrated into clinical practice. For example,
could it be used as a screening tool for identifying high-risk DSC patients, or could it help guide
decisions regarding treatment intensification or de-escalation?
-The authors could expand on how publication bias might affect their findings, and discuss the
implications of this bias in more detail. Could alternative methods for addressing publication
bias (e.g., sensitivity analyses for negative studies or gray literature) further strengthen the
conclusions?