bluuebunny/crossref_metadata_2025 huggingface dataset:
Epidemiological analysis of Group A streptococcus infection diseases among children in Beijing, China under COVID-19 pandemic
Authors: Li Hongxin , Zhou Lin , Zhao Yong , Ma Lijuan , Zhang Haihua , Liu Yan , Liu Xiaoyan , Hu Jin
Published: February 2023

Background

Group A streptococcus is human-restricted gram-positive pathogen, responsible for various clinical presentations from mild epidermis infections to life threatened invasive diseases. Under COVID-19 pandemic,. the characteristics of the epidemic strains of GAS could be different.

Purpose

To investigate epidemiological and molecular features of isolates from GAS infections among children in Beijing, China between January 2020 and December 2021. Antimicrobial susceptibility profiling was performed based on Cinical Laboratory Sandards Institute. Distribution of macrolide-resistance genes, emm types, and superantigens was examined by polymerase chain reaction.

Results

114 GAS isolates were collected which were frequent resistance against erythromycin (94.74%), followed by clindamycin (92.98%), tetracycline (87.72%). Emm12 (46.49%), emm1 (25.44%) were dominant emm types. Distribution of ermB, ermA, and mefA gene was 93.85%, 2.63%, and 14.04%, respectively. Frequent superantigenes identified were smeZ (97.39%), speG (95.65%), and speC (92.17%). Emm1 strains possessed smeZ, ssa, and speC, while emm12 possessed smeZ, ssa, speG, and speC. Erythromycin resistance was predominantly mediated by ermB. Scarlet fever strains harbored smeZ (98.81%), speC (94.05%). Impetigo strains harbored smeZ (88.98%), ssa (88.89%), and speC (88.89%). Psoriasis strains harbored smeZ (100%).

Conclusions

Under COVID-19 pandemic, our collections of GAS infection cutaneous diseases decreased dramatically. Epidemiological analysis of GAS infections among children during COVID-19 pandemic was not significantly different from our previous study. There was a correlation among emm, superantigen gene and disease manifestations. Long-term surveillance and investigation of emm types and superantigens of GAS prevalence are imperative.
Preferences for an eHealth tool to support physical activity and exercise training in COPD: a qualitative study from the viewpoint of prospective users
Authors: Sönnerfors Pernilla , Skavberg Roaldsen Kirsti , Lundell Sara , Toots Annika , Wadell Karin , Halvarsson Alexandra
Published: February 2023

Background

Despite well-known positive effects of pulmonary rehabilitation, access is limited. New strategies to improve access are advocated, including the use of eHealth tools.

Objectives

The aim of this study was to explore prospective users’ preferences for an eHealth tool to support the self-management of physical activity and exercise training in COPD.

Methods

A qualitative research design was applied. Data was collected in six, audio recorded, digital co-creation workshops, which were guided by a participatory and appreciative action and reflection approach. A total of 17 prospective users took part in the process, including people with COPD (n = 10), relatives (n = 2), health care givers (n = 4) and a patient organization representative (n = 1). During the workshops, pre-selected relevant topics to exploring end-users’ preferences for eHealth support in self-management in COPD were discussed. The workshops were recorded and transcribed. Data was analysed using inductive qualitative content analysis.

Results

The overarching theme “fusing with, rather than replacing existing support structures” was uncovered when the two-sided relationship between positive expectations towards digital solutions and the fear of losing access to established rehabilitation systems, emerged in the discussions. Three categories were identified, focused on wishes for an evidence-based support platform of information about COPD, a well-designed eHealth tool including functionalities to motivate in the self-management of physical activity and exercise training, and requirements of various forms of support. Co-creators believed that there were clear benefits in combining the best of digital and existing support systems.

Conclusions

Co-creators viewed an eHealth tool including support for physical activity and exercise training as a valuable digital complement to the now existing rehabilitation services. A future eHealth tool needs to focus on user-friendliness and prospective users’s requests.
Comparative analysis of pathogen distribution in patients with fracture-related infection and periprosthetic joint infection: a retrospective study
Authors: Ma Tiancong , Lyu Jinyang , Ma Jingchun , Huang Xin , Chen Kangming , Wang Siqun , Wei Yibing , Shi Jingsheng , Xia Jun , Zhao Guanglei , Huang Gangyong
Published: February 2023

Background

The purpose of this study is to investigate the microbial patterns of periprosthetic joint infection (PJI) and fracture-related infection (FRI), and guide for the formulation of more accurate empirical antimicrobial regimens based on the differences in pathogen distribution.

Methods

A comparative analysis of pathogen distribution was conducted between 153 patients (76 with PJI and 77 with FRI). Predicted analyses against isolated pathogens from two cohorts were conducted to evaluate the best expected efficacy of empirical antimicrobial regimens (﻿imipenem + vancomycin, ciprofloxacin + vancomycin, and piperacillin/tazobactam + vancomycin).

Results

Our study found significant differences in pathogen distribution between the PJI and FRI cohorts. Staphylococci (61.3% vs. 31.9%, p = 0.001) and Gram-negative bacilli (GNB, 26.7% vs. 56.4%, p < 0.001) were responsible for the majority of infections both in the PJI and FRI cohorts, and their distribution in the two cohorts showed a significant difference (p < 0.001). Multi-drug resistant organisms (MDRO) were more frequently detected in the FRI cohort (29.3% vs. 44.7%, p = 0.041), while methicillin-resistant coagulase-negative Staphylococci (MRCoNS, 26.7% vs. 8.5%, p = 0.002) and Canidia albicans (8.0% vs. 1.1%, p = 0.045) were more frequently detected in the PJI cohort. Enterobacter spp. and Acinetobacter baumannii were detected only in the FRI cohort (11.7% and 8.5%, respectively).

Conclusions

Staphylococci and GNB were responsible for the majority of infections in both PJI and FRI. Empirical antimicrobial therapy should focus on the coverage of Staphylococci in PJI and GNB in FRI, and infections caused by MDROs should be more vigilant in FRI, while the high incidence of MRCoNS in PJI should be noted, which could guide for the formulation of more accurate empirical antimicrobial regimens. Targeted therapy for FRI caused by A. baumannii and PJI caused by C. albicans needs to be further investigated. Our study reports significant differences in pathogen distribution between the two infections and provides clinical evidence for studies on the mechanism of implant-associated infection.
Clinic follow-up of orthopaedic trauma patients during and after the post-surgical global period: a retrospective cohort study
Authors: Bhashyam Abhiram R. , Challa Sravya T. , Thomas Hannah , Rodriguez Edward K. , Weaver Michael J.
Published: February 2023

Background

Insurance status is important as medical expenses may decrease the likelihood of follow-up after musculoskeletal trauma, especially for low-income populations. However, it is unknown what insurance factors are associated with follow-up care. In this study, we assessed the association between insurance plan benefits, the end of the post-surgical global period, and follow-up after musculoskeletal injury.

Methods

This is a retrospective cohort study of 394 patients with isolated extremity fractures who were treated at three level-I trauma centers over four months in 2018. Paired t-tests were utilized to assess the likelihood of follow-up in relation to the 90-day post-surgical global period. Regression analysis was used to assess factors associated with the likelihood of follow-up. Supervised machine learning algorithms were used to develop predictive models of follow-up after the post-surgical global period.

Results

Our final analysis included 328 patients. Likelihood of follow-up did not significantly change while within the post-surgical global period. When comparing follow-up within and outside of the post-surgical global period, there was a 20.1% decrease in follow-up between the 6-weeks and 6-month time points (68.3% versus 48.2%, respectively;p < 0.0001). Medicaid insurance compared to Medicare (OR 0.27, 95% confidence interval (CI) = [0.09, 0.84],p = 0.02) was a predictor of decreased likelihood of follow-up at 6-months post-operatively.

Conclusions

Our study demonstrates a statistically significant decrease in follow-up for orthopaedic trauma patients after the post-surgical global period, particularly for patients with Medicaid or Private insurance.
Is it feasible to treat unstable traumatic spondylolisthesis of the axis via posterior fixation without fusion?
Authors: Zhang Jian , Li Guangzhou , Wang Qing
Published: February 2023

Background

Few studies reported treatment of unstable traumatic spondylolisthesis of the axis using posterior fixation without fusion. The aim of this study was to evaluate the results and feasibility of posterior fixation without fusion in treating unstable traumatic spondylolisthesis of the axis.

Methods

Eleven patients with traumatic spondylolisthesis of the axis were included in this study, and posterior fixation without fusion using screw-rod system was performed for them. The clinical outcomes were assessed using the Visual Analog Scale (VAS), the Neck Disability Index (NDI), and the Odom’s grading system. Plain radiography was used to measure the displacement and angulation of C2-C3, and cervical lordosis. Plain radiography and computed tomography were also used to observe the bony fusions of fracture lines and postoperative spontaneous fusion of C2-C3.

Results

The mean follow up time was 24.6 months (range, 12–72 months). The VAS and NDI scores were significantly improved at the final follow-up compared with those before operation (P < 0.05), and according to Odom’s criteria, 90.9% (10/11) of patients rated their level of satisfaction as excellent or good. The angulation and displacement of C2-C3, and cervical lordosis were significantly improved after operation compared with those before operation (P < 0.05), and at the final follow-up, and these radiological parameters were maintained. All patients achieved solid bony fusions of fracture lines. No operative segment instability was found in all patients during the follow-up period. Spontaneous fusion at bilateral C2-C3 facet joints was found in 11 cases, and anterior and/or posterior bony bridge of intervertebral bodies at C2-C3 was found in 9 cases.

Conclusions

Posterior fixation without fusion may be a feasible and effective option for unstable traumatic spondylolisthesis of the axis.
Establishment of an overactive bladder model in mice
Authors: Lv Tengfei , Zhong Shan , Guo Xiao
Published: February 2023

Background

Overactive bladder (OAB) is a syndrome characterized by symptoms of urinary urgency, often accompanied by frequent urination and nocturia or urge incontinence.

Methods

Twenty female ICR mice were randomly divided into pBOO (partial bladder outlet obstruction) and control groups. The mouse OAB model was constructed by ligating the bladder outlet. Eight weeks after the operation, the methods of voiding spot on paper (VSOP), isolated detrusor muscle, and HE staining were used for analysis and research.

Results

After the operation, two mice in the experimental and one in control died, and one in the control groups had an abnormal bladder size, so it was excluded from the statistical analysis. Eight weeks after the operation, there was an insignificant difference (P = 0.15) in the body weight of mice in the pBOO (26.54 ± 2.62 g) and the control group (24.84 ± 1.76 g). The number of urinations in 12 h was significantly higher (P < 0.001) in the pBOO (7.63 ± 1.19) than in the control group (4.13 ± 0.99). Also, the 12-h urine volume of pBOO (1491.23 ± 94.72 μL) was significantly greater (P = 0.006) than that of the control group (1344.86 ± 88.17 μL). The isolated bladder of the pBOO mice was significantly heavier than that in the control group (53.16 ± 1.79 mg vs. 24.54 ± 1.80 mg, P < 0.001), the horizontal and vertical length of the bladder in pBOO group were larger than those in the control group (P < 0.001). The detrusor thickness of pBOO group (357.50 ± 11.88 µm) was significantly thicker than that of control group (258.52 ± 17.22 µm, P < 0.001), and the isolated muscle strip was more sensitive to carbachol stimulation. According to HE staining, the bladder wall of the pBOO mice was significantly thickened.

Conclusions

A pBOO-mediated mouse OAB model was successfully established by ligating the bladder outlet.
Nomograms for predicting survival in patients with micropapillary bladder cancer: a real-world analysis based on the surveillance, epidemiology, and end results database and external validation in a tertiary center
Authors: Liu Peng , Xu Lei , Chen Guanghao , Shi Benkang , Zhang Qiujie , Chen Shouzhen
Published: February 2023

Background

The present study aimed to construct and validate nomograms that can be used to predict cancer-specific survival (CSS) and overall survival (OS) in patients with micropapillary bladder cancer.

Methods

The data of 627 patients diagnosed with micropapillary bladder cancer between 2000 and 2018 were obtained from the surveillance, epidemiology, and end results database. Patients were randomly divided into the training and internal validation sets (7:3). The Cox proportional hazards regression model was applied to evaluate the association between variables and survival and then nomograms were constructed to predict the survival of an individual patient. The performance of nomograms was validated by using calibration curves, concordance index, receiver operating characteristic curves with the calculated area under the curve and decision curve analysis in the training and internal validation set. Data from 41 micropapillary bladder cancer patients at Qilu Hospital of Shandong University from 2000 to 2022 were collected for external validation.

Results

Several independent risk factors were taken into the two nomograms (CSS and OS), including age, marital status, AJCC TMN stage, surgical approach, lymph node ratio, and tumor size while the OS nomogram additionally contained race. The concordance index of the training set, internal validation set, and external verification set were all over 0.7. The calibration curve indicated good consistence between the nomogram prediction and actual survival. Area under the curve and decision curve analysis results indicated great clinical usefulness of nomograms.

Conclusions

The nomograms predicting the survival outcome of patients with micropapillary bladder cancer would provide a valuable tool to help clinicians to evaluate the risk of patients and make individual treatment strategies.
Role of breast cancer screening in the overdiagnosis of thyroid cancer: results from a cross-sectional nationwide survey
Authors: Lee Eunhye , Jeong Sung Hoon , Nam Chung Mo , Jun Jae Kwan , Park Eun-Cheol
Published: February 2023

Background

South Korea has the highest incidence of thyroid cancer worldwide, raising questions regarding the possibility of overdiagnosis. Examining the factors affecting thyroid cancer screening is crucial in elucidating the reasons for this unusually high incidence of thyroid cancer. Therefore, in the present study, we investigated the association between breast cancer screening and thyroid cancer screening to determine the potential role of breast cancer screening in the overdiagnosis of thyroid cancer in South Korea.

Methods

We analyzed the data of women aged > 30 years who were enrolled in the 2014 Korean National Cancer Screening Survey. Self-reported breast cancer screening behavior was categorized as follows: no screening, mammography only, ultrasonography only, and both ultrasonography and mammography. Thyroid cancer screening behavior was categorized as follows: those who had or had not undergone ultrasonography screening. Logistic regression analysis was used to examine the associations between breast and thyroid cancer screening behaviors.

Results

Of the 2270 participants, a total of 569 (25.1%) were screened for thyroid cancer. Those who underwent only mammography, only ultrasonography, or both mammography and ultrasonography were more likely to be screened for thyroid cancer than those who did not undergo breast cancer screening (odds ratio [OR]: 1.47, 95% confidence interval [CI] 1.06–2.04; OR 2.71, 95% CI 1.83–4.02; OR 2.75, 95% CI 1.99–3.80, respectively).

Conclusions

Our findings indicate that thyroid cancer screening in Korea is likely to be performed on an opportunistic basis. Therefore, a nationwide public health and medical initiative is needed to curb the unnecessary use of thyroid screening in the asymptomatic general population.
Team effectiveness: epidemiologists’ perception of collective performance during emergency response
Authors: Parry Amy Elizabeth , Richardson Alice , Kirk Martyn D. , Colquhoun Samantha M. , Durrheim David N. , Housen Tambri
Published: February 2023

Background

To describe epidemiologists’ experience of team dynamics and leadership during emergency response, and explore the utility of the Team Emergency Assessment Measure (TEAM) tool during future public health emergency responses. The TEAM tool included categories for leadership, teamwork, and task management.

Methods

We conducted a cross-sectional survey between October 2019 and February 2020 with the global applied field epidemiology workforce. To validate the TEAM tool for our context, we used exploratory and confirmatory factor analysis.

Results

We analysed 166 completed surveys. Respondents included national and international emergency responders with representation of all WHO regions. We were unable to validate the TEAM tool for use with epidemiology teams involved in emergency response, however descriptive analysis provided insight into epidemiology emergency response team performance. We found female responders were less satisfied with response leadership than male counterparts, and national responders were more satisfied across all survey categories compared to international responders.

Conclusion

Functional teams are a core attribute of effective public health emergency response. Our findings have shown a need for a greater focus on team performance. We recommend development of a fit-for-purpose performance management tool for teams responding to public health emergencies. The importance of building and supporting the development of the national workforce is another important finding of this study.
The effect of COVID-19 pandemic on diabetes care indices in Southern Iran: an interrupted time series analysis
Authors: Mirahmadizadeh Alireza , Sharifi Mohammad Hossein , Hassanzadeh Jafar , Heiran Alireza , Ardekani Fariba Moradi , Hadizadeh Neda , Sharafi Mehdi , Abnavi Mohammad Mohammadi
Published: February 2023

Background

Type 2 diabetes mellitus (T2DM) requires a continues bulk of cares. It is very probable COVID-19 pandemic is affected its healthcare coverage.

Methods

The interrupted time series analysis is used to model the trend of diabetes healthcare indices, such as the health worker visits, physician visits, body mass index (MBI), fasting blood sugar (FBS), and hemoglobin A1c (HbA1c), before and after the start of COVID-19 pandemic. The reference of data was the totals of all T2DM patients living in Fars Province, Southern Iran, areas covered by Shiraz University of Medical Science (SUMS), from 2019 to 2020.

Results

A significant decrease for visits by the health workers, and physicians was observed by starting COVID-19 pandemic (β2 = -0.808, P < 0.001, β2 = -0.560, P < 0.001); Nevertheless, the coverage of these services statistically increased by next months (β3 = 0.112, P < 0.001, β3 = 0.053, P < 0.001). A same pattern was observed for the number of BMI, FBS and HbA1c assessments, and number of refer to hospital emergency wards (β3 = 0.105, P < 0.001; β3 = 0.076, P < 0.001; β3 = 0.022, P < 0.001; β3 = 0.106, P < 0.001). The proportion of T2DM patients with HbA1C < 7%, and controlled hypertension during study period was statistically unchanged.

Conclusions

When the COVID-19 pandemic was announced, T2DM healthcare coverage drastically decreased, but it quickly began to rebound. The health monitoring system could not have any noticeable effects on diabetes outcomes.
Epigenome-wide analysis of aging effects on liver regeneration
Authors: Wang Junying , Zhang Wen , Liu Xiaoqin , Kim Minjee , Zhang Ke , Tsai Robert Y. L.
Published: February 2023

Background

Aging is known to exert an effect on liver regeneration, with the ability of liver to regenerate displaying a significant decline over time. Liver physiological parameters such as liver volume, blood flow, and metabolism, as well as the ability to regenerate after injury have all been shown to decrease at old age in humans and model systems, with a number of molecular mechanisms proposed to be involved, including DNA methylation-dependent genome remodeling. To address how changes in DNA methylation mediate the adverse aging effect on liver regeneration, we searched for differentially methylated genomic regions (DMRs) in mouse livers co-regulated by aging and regeneration and determined their associated genes and enriched pathways.

Results

DMRs were identified using whole-genome bisulfite sequencing (WGBS). Pathway analysis of aging DMR-mapped genes revealed two distinct phases of aging, 2-to-8 and 8-to-16 months old (m/o). Regenerative DMR-mapped differentially expressed genes (DEGs) were enriched in pathways controlling cell proliferation and differentiation. Most DMRs shared by both aging and regeneration changed in the same methylation direction between 2 and 8 m/o but in the opposite direction between 8 and 16 m/o. Regenerative DMRs inversely affected by aging during 8-to-16 m/o were found in the promoter/gene regions of 12 genes. Four regenerative DEGs were synchronously regulated by early aging and inversely regulated by mid-to-late aging DMRs. Lead DMR-mapped genes were validated by their expression profiles in liver aging and regeneration.

Conclusions

Our study has uncovered new DMRs and gene targets inversely affected by liver aging and regeneration to explain the adverse aging effect on liver regeneration. These findings will be of fundamental importance to understand the epigenomic changes underlying the biology of aging on liver regeneration.
Comparison of 2 anesthetic protocols and surgical timing during cesarean section on neonatal vitality and umbilical cord blood parameters
Authors: Antończyk Agnieszka , Kiełbowicz Zdzisław , Niżański Wojciech , Ochota Małgorzata
Published: February 2023

Background

The objective of this study was to evaluate the relationship between the mode of anesthesia, the time form the induction to the extraction of a puppy and the immediate postnatal vitality and umbilical cord blood gases parameters in cesarean section derived-puppies. Two different anesthetic protocols were used: inhalation using isoflurane (ISO) and combined—inhalation and epidural (EPI) with propofol being the induction agent.

Results

Significant differences were found in ISO group in pH values, pCO2 levels and Apgar scores between puppies at different extraction times (< 30 vs. ≥ 30 min). In ISO group puppies extracted later were more acidic (7.16 vs. 7.22), had higher levels of pCO2 (69 vs. 57 mmHg) and lower Apgar scores at birth (1.2 vs. 2.5). On the contrary, in EPI group no differences were observed between the delivery time, umbilical blood gas parameters and puppies’ vitality. Furthermore, the dams from the EPI group required lower concentrations of isoflurane (MAC 1.11 ± 0.19 vs.1.37 ± 0.16, p < 0.001).

Conclusions

Multiple pregnancies frequent in dogs lead to significant differences in extraction times between the first and the last puppy during cesarean section. Obtained results showed that the mode of anesthesia and the surgical time would influence the neonatal outcome during cesarean section in dogs. The higher concentration of isoflurane with the longer time of exposure had a negative effect on the initial newborn vitality as well as the umbilical cord blood gas parameters. Therefore, when performing CS in giant dog breeds or expecting many puppies in the litter, it is worth considering epidural component that allow for lower concentrations of inhalant agents, which may contribute to a better clinical condition of newborns.
Prevalence of prediabetes and undiagnosed diabetes in a large urban middle-aged population: the CARVAR 92 cohort
Authors: Hauguel-Moreau Marie , Hergault Hélène , Cazabat Laure , Pépin Marion , Beauchet Alain , Aïdan Vincent , Ouadahi Mounir , Josseran Loïc , Hage Mirella , Rodon Christophe , Dubourg Olivier , Massy Ziad , Mansencal Nicolas
Published: February 2023

Background

The aim of this study was to assess the prevalence of prediabetes and unknown diabetes and its long-term change in a large middle-aged urban population.

Methods

We conducted a screening campaign between 2007 and 2018 for cardiovascular risk factors in the western suburbs of Paris including subjects aged 40–70 (CARVAR 92). Among subjects who reported no previous diabetes, prediabetes and undiagnosed diabetes were defined as follows: fasting plasma glucose (FPG) ≥ 6.1 mmol/l (110 mg/dl) and < 7 mmol/l (126 mg/dl) for prediabetes according to WHO criteria (FPG between 5.6 and 6.9 mmol/l according to ADA criteria) and FPG ≥ 7.0 mmol/l for undiagnosed diabetes.

Results

Of the 32,721 subjects in the CARVAR 92 cohort, 32,675 were included in this analysis. The median age of the patients was 56 years [30, 94], 45.4% were male, 5.9% had known diabetes, 36.4% were overweight and 18.7% obese. Among patients without previously known diabetes (n = 30,759), 8.1% had prediabetes according to WHO criteria (27.2% according to ADA criteria) and 2.3% had diabetes. Subjects with prediabetes and unknown diabetes were more likely to be male, older, and overweight or obese than non-diabetic subjects. From 2007 to 2018, the prevalence of prediabetes, unknown diabetes, and known diabetes decreased, except for prediabetes which remained stable for people aged 55–64.

Conclusion

The prevalence of prediabetes and unknown diabetes remains high but decreased during a 12-year period. About one-quarter of diabetes cases remain undiagnosed. Our results highlight that there is still a room for screening and cardiovascular prevention campaigns.

Trial registration: IRB00012437.
Low intensity ultrasound-mediated drug-loaded nanoparticles intravaginal drug delivery: an effective synergistic therapy scheme for treatment of vulvovaginal candidiasis
Authors: Yang Min , Cao Yuchao , Zhang Zhifei , Guo Jiajun , Hu Can , Wang Zhibiao , Du Yonghong
Published: February 2023

Purpose

Vulvovaginal candidiasis (VVC) is a mucosal infection of the female lower genital tract for which treatment using conventional antifungal drugs shows limited effectiveness. Herein, amphotericin B-loaded poly(lactic-co-glycolic acid)-polyethylene glycol (PLGA-PEG) nanoparticles (AmB-NPs) were fabricated and combined with low intensity ultrasound (US) to mediate AmB-NPs intravaginal drug delivery to achieve productive synergistic antifungal activity in a rabbit model of VVC.

Methods

Polymeric AmB-NPs were fabricated by a double emulsion method and the physical characteristics and biosafety of nanoparticles were analyzed. The distribution and tissue permeability of nanoparticles after intravaginal ultrasound irradiation (1.0 MHz, 1.0 W/cm2, 5 min, 50% duty ratio) were observed in the vagina. The synergistic therapeutic activity of US-mediated AmB-NPs treatment was evaluated using an experimental rabbit model of VVC. Vaginal C. albicans colony counts, the pathological structure of the vagina epithelium, and Th1/Th2/Th17-type cytokine and oxidative stress levels were analyzed to investigate the therapeutic effect in vivo.

Results

The prepared AmB-NPs showed an obvious shell and core structure with uniform size and good dispersion and displayed high biosafety and US-sensitive slow drug release. Ultrasound significantly enhanced nanoparticle transport through the mucus and promoted permeability in the vaginal tissue. US-mediated AmB-NPs treatment effectively increased drug sensitivity, even in the presence of the vaginal mucus barrier in vitro. On the seventh day after treatment in vivo, the combination treatment of AmB-NPs and US significantly reduced the fungal load in the vagina, achieving over 95% clearance rates, and also improved the pathological epithelium structural damage and glycogen secretion function. The expression of Th1 (IFN-γ, IL-2) and Th17 (IL-17) cytokines were significantly increased and Th2 (IL-6, IL-10) cytokines significantly decreased in the US + AmB-NP group. Furthermore, US-mediated AmB-NPs treatment effectively increased C. albicans intracellular reactive oxygen species (ROS) levels and promoted vaginal oxidation and antioxidants to normal levels.

Conclusion

US-mediated drug-loaded nanoparticles with intravaginal drug delivery exhibited a productive synergistic antifungal effect, which may provide a new non-invasive, safe, and effective therapy for acute or recurrent fungal vaginitis.

Graphical Abstract
Structure, signal transduction, activation, and inhibition of integrin αIIbβ3
Authors: Xin Honglei , Huang Jiansong , Song Zhiqun , Mao Jianhua , Xi Xiaodong , Shi Xiaofeng
Published: February 2023

Integrins are heterodimeric receptors comprising α and β subunits. They are expressed on the cell surface and play key roles in cell adhesion, migration, and growth. Several types of integrins are expressed on the platelets, including αvβ3, αIIbβ3, α2β1, α5β1, and α6β1. Among these, physically αIIbβ3 is exclusively expressed on the platelet surface and their precursor cells, megakaryocytes. αIIbβ3 adopts at least three conformations: i) bent-closed, ii) extended-closed, and iii) extended–open. The transition from conformation i) to iii) occurs when αIIbβ3 is activated by stimulants. Conformation iii) possesses a high ligand affinity, which triggers integrin clustering and platelet aggregation. Platelets are indispensable for maintaining vascular system integrity and preventing bleeding. However, excessive platelet activation can result in myocardial infarction (MI) and stroke. Therefore, finding a novel strategy to stop bleeding without accelerating the risk of thrombosis is important. Regulation of αIIbβ3 activation is vital for this strategy. There are a large number of molecules that facilitate or inhibit αIIbβ3 activation. The interference of these molecules can accurately control the balance between hemostasis and thrombosis. This review describes the structure and signal transduction of αIIbβ3, summarizes the molecules that directly or indirectly affect integrin αIIbβ3 activation, and discusses some novel antiαIIbβ3 drugs. This will advance our understanding of the activation of αIIbβ3 and its essential role in platelet function and tumor development.
Epstein‒Barr virus and human herpesvirus 6 infection in patients with systemic lupus erythematosus
Authors: Chen Xiaotong , Li Hui , Wu Chunling , Zhang Yan
Published: February 2023

Background

Systemic lupus erythematosus (SLE) is a complex autoimmune disease, and the etiology is still unclear. Some studies have indicated that viral infection might contribute to the development of SLE.

Methods

A total of 105 individuals with SLE and 110 matched healthy controls were tested for EBV-specific DNA fragments in peripheral blood monocytes by PCR-Southern blotting. The expression of EBV-encoded genes was determined by RT-PCR and Southern blotting in EBV-positive patients. Serum EBV-specific IgM antibody was determined by ELISA. HHV-6 DNA in peripheral blood monocytes of those SLE patients and normal controls was tested by nested PCR.

Results

Statistical analysis showed that the EBV-positive rate of SLE patients was significantly higher than that of the control group (χ2 = 87.329, P = 0), while the difference in the HHV-6-positive rate between the two groups was not significant (P > 0.05). An association of EBV and HHV-6 positivity in SLE patients was found (P = 0, r = 0.38). The EBV IgM level was significantly higher in SLE patients than in healthy controls (χ2 = 25.184, P = 0). Forty-two of the 75 EBV DNA-positive specimens were positive for EBNA2 mRNA, and an association between EBV EBNA2 mRNA and anti-Sm antibody positivity was found (P = 0, r = 0.409). LMP1 mRNA was positive in 2 SLE patients with active phase, and no LMP2A mRNA expression was detected in EBV DNA-positive specimens. EBV early gene BARF1 mRNA was detected in 2 cases of EBV-positive SLE patients, and these 2 patients were also HHV-6 DNA positive. Thirty-eight patients were BcLF1 mRNA positive, and 33 of them were HHV-6 positive as well. These factors were associated (χ2 = 15.734, P = 0). The expression of the EBV immediate early gene BZLF1 was negative in all 75 EBV-positive SLE patients.

Conclusions

The results suggest that EBV infection might be related to the occurrence of SLE. Although there is no direct evidence that HHV-6 infection is associated with the development of SLE, EBV and HHV-6 infection may have a coacceleration effect in SLE patients. This study provides a new theoretical and experimental basis for the study of viral etiology and the prevention and treatment of SLE.
Clinical outcomes and survival following lung transplantation for work-related lung disease: a single-center retrospective cohort study
Authors: Ju Chunrong , Yang Yalan , Lian Qiaoyan , Wang Lulin , Wang Xiaohua , Wei Bing , Huang Danxia , Xu Xin , He Jianxing
Published: February 2023

Background

Patients with work-related lung disease (WRLD) are at increased risk of death caused by severe lung tissue damage and fibrosis. This study aimed to assess the clinical outcomes of lung transplantation (LTx) for WRLD and compare the results of LTx between WRLD and idiopathic pulmonary fibrosis (IPF).

Methods

This single-center retrospective cohort study reviewed the clinical data of patients who underwent LTx for WRLD or IPF at our hospital between January 2015 and December 2021. Cumulative survival rates after LTx were estimated using the Kaplan-Meier method.

Results

The final analysis included 33 cases of WRLD and 91 cases of IPF. The 33 WRLD patients consisted of 19 (57.6%) cases of silicosis, 8 (24.2%) cases of coal workers’ pneumoconiosis, 3 (9.09%) cases of asbestosis, and 3 (9.09%) cases of other WRLD. Pneumothorax as an indication for LTx was significantly more common in the WRLD group than in the IPF group (51.5% vs. 2.2%, P < 0.001). There was no significant difference in the 5-year cumulative survival rate between the WRLD patients and the IPF patients (66.6% vs. 56.7%, P = 0.67). There was no significant difference in the best performance of exercise capacity and lung function between the two groups at 1 year post-transplant.

Conclusions

LTx had similar survival outcomes and lung function for WRLD and IPF patients. Pneumothorax was the primary indication for lung transplantation in WRLD.
A novel digital arthrometer to measure anterior tibial translation
Authors: Wu Danni , Wang Donghai , Han Yongjie , Guo Luqi , Wang Shaobai
Published: February 2023

Background

Measurement of knee laxity after anterior cruciate ligament (ACL) injury is crucial for appropriate treatment and rehabilitation decision-making. This study examined the potential of a new digital arthrometer (Ligs, Innomotion, Shanghai, China) to quantify anterior tibial translation (ATT) in patients with ACL injuries and in healthy subjects.

Methods

A total of 60 participants included 30 subjects with single-leg ACL injuries and 30 healthy subjects included as controls. The lower leg was immobilized. The thruster is positioned posterior to the lower leg and parallel to the tibial tuberosity in the sagittal plane. The load is applied vertically to the tibia under a dynamic load of 0–150 N, with continuous displacement recorded. The intrarater and interrater reliability will be examined. ATT and side-to-side differences (SSD) between the control and ACL injury groups were compared. Receiver operating characteristic (ROC) curves were analyzed, and the area under the curve (AUC) was calculated to determine the diagnostic accuracy of the Ligs.

Results

The interrater ICC was 0.909 and the intrarater ICC was 0.943. Significant differences in the SSD were observed between the control and ACL injury groups (for all P < 0.05), with the largest effect size (ES = 1.12) at 80 N. When comparing ATT at different loads between injured and healthy sides in the ACL injury group, displacement was statistically significant at different loads. At a load of 150 N, the AUC was the maximum (0.857) and the sensitivity and specificity were 0.87 and 0.73, respectively.

Conclusions

A digital arthrometer can be used as a quantitative instrument to quantify knee laxity. Quantitative measurement of ATT and SSD under controlled loading can be an objective and effective tool for clinical practice.
Assessing the importance of predictors of adherence to a digital self‑management intervention for osteoarthritis
Authors: Kiadaliri Ali , Dell’Isola Andrea , Lohmander L. Stefan , Hunter David J. , Dahlberg Leif E.
Published: February 2023

Objective

Treatment adherence is suggested to be associated with greater improvement in patient outcomes. Despite the growing use of digital therapeutics in osteoarthritis management, there is limited evidence of person-level factors influencing adherence to these interventions in real-world settings. We aimed to determine the relative importance of factors influencing adherence to a digital self-management intervention for hip/knee osteoarthritis.

Methods

We obtained data from people participating in a digital OA treatment, known as Joint Academy, between January 2019 and September 2021. We collected data on the participants’ adherence, defined as the percentage of completed activities (exercises, lessons, and quizzes), at 3 (n = 14,610)- and 12-month (n = 2682) follow-up. We used dominance and relative weight analyses to assess the relative importance of sociodemographic (age, sex, place of residence, education, year of enrolment), lifestyle (body mass index, physical activity), general health (comorbidity, overall health, activity impairment, anxiety/depression), and osteoarthritis-related (index joint, fear of moving, walking difficulties, pain, physical function, wish for surgery, Patient Acceptable Symptom State) factors, measured at baseline, in explaining variations in adherence. We used bootstrap (1000 replications) to compute 95% confidence intervals.

Results

Mean (SD) adherences at 3 and 12 months were 86.3% (16.1) and 84.1% (16.7), with 75.1% and 70.4% of participants reporting an adherence ≥ 80%, respectively. The predictors included in the study explained only 5.6% (95% CI 5.1, 6.6) and 8.1% (7.3, 11.6) of variations in 3- and 12-month adherences, respectively. Sociodemographic factors were the most important predictors explaining more variations than other factors altogether. Among single factors, age with a nonlinear relationship with adherence, was the most important predictor explaining 2.3% (95% CI 1.9, 2.8) and 3.7% (2.4, 5.3) of variations in 3- and 12-month adherences, respectively.

Conclusion

Person-level factors could only modestly explain the variations in adherence with sociodemographic characteristics, mainly age, accounting for the greatest portion of this explained variance.
A 9-year analysis of medical malpractice litigations in coronary artery bypass grafting in China
Authors: Chen Jie , Zhang Tianyi , Feng Dan , Liu Yuehui , Zhang Tao , Wang Jingtong , Liu Lihua
Published: February 2023

Background

The coronary artery bypass grafting (CABG) is one of the high-risk litigated medical specialties. Further elucidating the causes behind these malpractice claims can help physicians avoid patient injury. This study analyzed CABG litigations occurred in different level hospitals to outline the basic characteristics, as well as present a analysis on the medical malpractice that result in lawsuits.

Methods

This study utilized the “China Judgments Online” database to compile litigations from 2012 to 2021 across China. 109 cases related to the CABG were included in the study, and were analyzed for demographic, patient outcomes and verdict characteristics in different levels of hospitals.

Results

The median age of plaintiff patient was 62 years, the median length of stay was 25 days, and the median responsibility ratio of the litigation cases was 30%. The average proportion of responsibility of national, provincial and municipal hospitals were 29.6%, 28.4% and 39.5% respectively, and the median days after surgery to death of that were 15, 9 and 5 separately. The top 5 postoperative complications in dispute cases were: low cardiac output syndrome, postoperative hemorrhage, non-surgical site infections, surgical site infections and arrhythmia.

Conclusions

The diagnosis and treatment capabilities of coronary artery bypass grafting in different levels of hospitals in China were inconsistent, and the treatment capabilities in prefecture-level hospitals were lower than that in national hospitals. The procedural error, failure to properly monitor the patient and diagnostic errors were common in CABG litigations. Postoperative complications related to surgical injuries and insufficient basic postoperative management lead to a higher responsibility proportion.
Identification of histone acetyltransferase genes responsible for cannabinoid synthesis in hemp
Authors: Cheng Yufei , Ning Kang , Chen Yongzhong , Hou Cong , Yu Haibin , Yu Huatao , Chen Shilin , Guo Xiaotong , Dong Linlin
Published: February 2023

Background

Histone acetyltransferases (HATs) play an important role in plant growth and development, stress response, and regulation of secondary metabolite biosynthesis. Hemp (Cannabis sativa L.) is famous for its high industrial, nutritional, and medicinal value. It contains non-psychoactive cannabinoid cannabidiol (CBD) and cannabinol (CBG), which play important roles as anti-inflammatory and anti-anxiety. At present, the involvement of HATs in the regulation of cannabinoid CBD and CBG synthesis has not been clarified.

Methods

The members of HAT genes family in hemp were systematically analyzed by bioinformatics analysis. In addition, the expression level of HATs and the level of histone acetylation modification were analyzed based on transcriptome data and protein modification data. Real-time quantitative PCR was used to verify the changes in gene expression levels after inhibitor treatment. The changes of CBD and CBG contents after inhibitor treatment were verified by HPLC-MS analysis.

Results

Here, 11 HAT genes were identified in the hemp genome. Phylogenetic analysis showed that hemp HAT family genes can be divided into six groups. Cannabinoid synthesis genes exhibited spatiotemporal specificity, and histones were acetylated in different inflorescence developmental stages. The expression of cannabinoid synthesis genes was inhibited and the content of CBD and CBG declined by 10% to 55% in the samples treated by HAT inhibitor (PU139). Results indicated that CsHAT genes may regulate cannabinoid synthesis through altering histone acetylation.

Conclusions

Our study provides genetic information of HATs responsible for cannabinoid synthesis, and offers a new approach for increasing the content of cannabinoid in hemp.
Glucosylsphingosine (Lyso-Gb1) as a reliable biomarker in Gaucher disease: a narrative review
Authors: Giuffrida Gaetano , Markovic Uros , Condorelli Annalisa , Calafiore Valeria , Nicolosi Daniela , Calagna Marianna , Grasso Stephanie , Ragusa Marco Tindaro Valentino , Gentile Jennifer , Napolitano Mariasanta
Published: February 2023

Background

Gaucher disease (GD) is a rare, inherited, autosomal recessive disorder caused by a deficiency of the lysosomal enzyme, acid β-glucosidase. Its diagnosis is achieved via measurements of acid β-glucosidase activity in either fresh peripheral blood leukocytes or dried blood spots, and confirmed by identifying characteristic mutations in the GBA1 gene. Currently, several biomarkers are available for disease monitoring. Chitotriosidase has been used over the last 20 years to assess the severity of GD, but lacks specificity in GD patients. Conversely, the deacylated form of glucosylceramide, glucosylsphingosine (also known as lyso-Gb1), represents a more reliable biomarker characterized by its high sensitivity and specificity in GD.

Main text

Herein, we review the current literature on lyso-Gb1 and describe evidence supporting its usefulness as a biomarker for diagnosing and evaluating disease severity in GD and monitoring treatment efficacy.

Conclusion

Lyso-Gb1 is the most promising biomarker of GD, as demonstrated by its reliability in reflecting disease burden and monitoring treatment response. Furthermore, lyso-Gb1 may play an important role in the onset of monoclonal gammopathy of uncertain significance, multiple myeloma, and Parkinson’s disease in GD patients.
Lung morphology impacts the association between ventilatory variables and mortality in patients with acute respiratory distress syndrome
Authors: Chen Hui , Sun Qin , Chao Yali , Liu Yue , Yu Qian , Xie Jianfeng , Pan Chun , Liu Ling , Yang Yi , Qiu Haibo
Published: February 2023

Background

Acute respiratory distress syndrome (ARDS) patients with different lung morphology have distinct pulmonary mechanical dysfunction and outcomes. Whether lung morphology impacts the association between ventilatory variables and mortality remains unclear. Moreover, the impact of a novel combined ventilator variable [(4×DP) + RR] on morality in ARDS patients needs external validation.

Methods

We obtained data from the Chinese Database in Intensive Care (CDIC), which included adult ARDS patients who received invasive mechanical ventilation for at least 24 h. Patients were further classified into two groups based on lung morphology (focal and non-focal). Ventilatory variables were collected longitudinally within the first four days of ventilation. The primary outcome was 28-day mortality. Extended Cox regression models were employed to explore the interaction between lung morphology and longitudinal ventilatory variables on mortality.

Findings

We included 396 ARDS patients with different lung morphology (64.1% non-focal). The overall 28-day mortality was 34.4%. Patients with non-focal lung morphology have more severe and persistent pulmonary mechanical dysfunction and higher mortality than those with focal lung morphology. Time-varying driving pressure (DP) was more significantly associated with 28-day mortality in patients with non-focal lung morphology compared to focal lung morphology patients (P for interaction = 0.0039). The impact of DP on mortality was more significant than that of respiratory rate (RR) only in patients with non-focal lung morphology. The hazard ratio (HR) of mortality for [(4×DP) + RR] was significant in patients with non-focal lung morphology (HR 1.036, 95% CI 1.027–1.045), not in patients with focal lung morphology (HR 1.019, 95% CI 0.999–1.039).

Interpretation

The association between ventilator variables and mortality varied among patients with different lung morphology. [(4×DP) + RR] was only associated with mortality in patients with non-focal lung morphology. Further validation is needed.