Background/Aims: The pathophysiology of refractory gastroesophageal reflux disease (RGERD), which differs from proton pump inhibitor dependent gastroesophageal reflux disease (DGERD), remains incompletely elucidated. This study aims to compare esophageal motility patterns, transdiaphragmatic pressure gradients (TPG), and reflux profiles between RGERD and DGERD patients, and to delineate dynamic pressure gradient-esophagogastric junction (EGJ) interactions in these patients. Methods: In this retrospective study, 274 patients who underwent 24-hour impedance-pH monitoring and high-resolution manometry, along with an assessment of proton pump inhibitor responsiveness, were classified as RGERD (32.5%), DGERD (54.4%), or non-GERD (13.1%). Clinical characteristics, TPG, esophageal motility, and reflux metrics were compared between RGERD and DGERD patients. Subgroup analysis excluding hiatal hernia (HH) was conducted to investigate the pathophysiology of RGERD. Results: The RGERD group exhibited a significantly higher proportion of chest pain compared to the DGERD group. Regarding reflux profiles, RGERD patients without HH (RGERDHH- group) experienced increased weakly acidic reflux (P < 0.001) and prolonged bolus exposure (P = 0.006) compared to their counterparts (DGERDHH- group). Mechanistically, the RGERDHH- group showed reduced lower esophageal sphincter basal pressure (P = 0.010) and EGJ contractile integral (P = 0.005). Notably, following a wet-swallow, the RGERDHH- group experienced the significant elevation in gastric pressure and TPG. Correlation analyses revealed weakly acidic reflux and bolus exposure were positively correlated with gastric pressure variation, and inversely correlated with lower esophageal sphincter basal pressure. Conclusions Transient gastric pressure elevation and compromised EGJ barrier function drive weakly acidic reflux and esophageal bolus exposure. This pressure gradient-barrier mismatch underpins the refractoriness of RGERD.

As a major challenge in the global field of critical care medicine, sepsis is associated with high morbidity and mortality, driving intensive research into the development of precise risk prediction models. Among these, machine learning and deep learning-based predictive models have garnered particular attention. This article systematically reviews the evolution of sepsis risk prediction models and the challenges associated with their clinical translation, with a focus on their clinical applicability in common septic complications, including acute kidney injury, encephalopathy, and coagulation disorders. Current evidence indicates that machine learning models, by integrating multidimensional dynamic data from electronic health records, significantly enhance early warning capabilities and individualized predictive performance. However, major bottlenecks limiting clinical translation include insufficient data standardization, lack of model interpretability, and inadequate external validation. Future research should prioritize multicenter collaboration, time-series modeling strategies, and explainable artificial intelligence frameworks to optimize clinical translation pathways and facilitate the paradigm shift from traditional empirical approaches to data-driven precision strategies in sepsis risk stratification.

Puerariae Lobatae Radix and Puerariae Thomsonii Radix are the dried roots of Pueraria lobata and Pueraria thomsonii of the Leguminosae family， respectively. Since their separate inclusion in the 2005 edition of Pharmacopoeia of the People's Republic of China， the two herbs have been individually recorded. Although they share the same functions and indications， the required content of puerarin differs by a factor of up to eightfold between them. The current quality standard relies solely on a single indicator， puerarin， which fails to reflect the correlation between chemical constituents and core therapeutic effects. This has resulted in prominent issues of mixed use in clinical practice and production， thereby constraining the high-quality development of the industry. Modern research has demonstrated that Puerariae Lobatae Radix contains a comprehensive range and higher content of isoflavonoid constituents， while Puerariae Thomsonii Radix is rich in starch and polysaccharides. Puerariae Lobatae Radix exhibits stronger effects in antipyresis， cardiovascular and cerebrovascular protection， and central analgesia， while Puerariae Thomsonii Radix demonstrates greater advantages in anti-inflammation， hypoglycemia， and peripheral analgesia. Based on this， the chemical material bases of Puerariae Lobatae Radix and Puerariae Thomsonii Radix at both the macromolecule and micromolecule levels were systematically reviewed and compared. The pharmacodynamic material bases and mechanisms of action underlying their three core therapeutic effects， namely "relieving exterior syndrome and clearing heat"， "promoting fluid production to quench thirst"， and "dredging channels and activating collaterals"， were summarized. The most highly correlated common metabolic pathway shared by both herbs for these three therapeutic effects is the arachidonic acid metabolic pathway， and their common core target is prostaglandin-endoperoxide synthase 2 （PTGS2）. This review provided clinical application recommendations based on the therapeutic differences between the two herbs， elucidated the scientific connotation of their "same origin but different effects"， and， grounded in the quality marker （Q-Marker）， proposed the concept of efficacy-related Q-Marker based on "substance-efficacy-syndrome" association， as well as a novel strategy for efficacy-oriented quality evaluation. Preliminary screening of quality markers associated with different therapeutic effects was also conducted. This study aims to provide critical scientific evidence for the precise clinical application of Puerariae Lobatae Radix and Puerariae Thomsonii Radix， the improvement of quality standards， and the high-quality development of the industry.

Objective : To explore the role of lysophosphatidylcholine acyltransferase 3(LPCAT3) in Erastin-induced ferroptosis of acute myeloid leukemia(AML) cells and its related molecular regulatory mechanisms. Methods : Tetrazolium salt(MTS) method was used to detect the sensitivity of different AML cells to the classic ferroptosis inducer Erastin, real time quantitative polymerase chain reaction(qPCR) was used to detect the basal expression level ofLPCAT3mRNA, and the correlation between them was analyzed. Lentivirus-mediatedLPCAT3overexpression AML cell lines(OE group) and negative control lines(NC group) were constructed. After Erastin intervention, MTS, flow cytometry, and micromethods were used to detect cell viability, lipid reactive oxygen species(ROS), and Malondialdehyde(MDA), respectively. qPCR and Western blot were used to detect unfolded protein response(UPR) classic pathway signaling molecules(PERK, ATF4, GRP78, etc.) expression levels. The above ferroptosis-related indicators were detected after combined intervention with the UPR inhibitor 4-phenylbutyric acid(4-PBA), and the regulatory relationship was analyzed. Results : Four different types of AML cells had different sensitivities to ferroptosis, among which K562 cells were relatively insensitive. The IC50of the four types of AML cells to Erastin was negatively correlated with the expression level ofLPCAT3(r=-0.919,P<0.001). After Erastin intervention, the cell viability of K562 cells in the OE group was significantly inhibited by Erastin compared with the NC group(P<0.001), and the levels of lipid ROS and MDA increased(P<0.001). The results of qPCR and Western blot showed that, compared with the NC group, the mRNA and protein expression of UPR classic pathway moleculesPERK,ATF4, andGRP78mRNA and protein increased in the OE group(P<0.01). After inhibiting the UPR pathway by 4-PBA, the viability of K562 cells decreased(P<0.01), and lipid ROS and MDA levels increased(P<0.01) compared with the uninhibited state. Conclusion Overexpression ofLPCAT3can promote ferroptosis in K562 cells, and this process is negatively regulated by the classical UPR pathway PERK/ATF.

Objective To understand the impact of bed-making manipulation on the air surrounding bed units in hemodialysis room,evaluate the effectiveness of routine terminal disinfection,and provide scientific basis for optimi-zing infection control measures.Methods Air specimens(pre-bed-making group)and environmental object surface specimens(pre-terminal disinfection group)around bed units were collected when hemodialysis was about to be fi-nished.Air specimens after bed-making(bed-making group)and environmental object surface specimens after ter-minal disinfection(terminal disinfection group)were also collected.Bacterial colonies were counted and identified.Results A total of 714 air specimens were collected from 238 bed units of 45 hemodialysis units before and during bed-making.The average bacterial colony count during bed-making was higher than that before bed-making([2.72±3.43]CFU/plate vs[0.69±1.50]CFU/plate,P＜0.05).The qualified rate of microbial colony count before bed-making was higher than that during bed-making(96.64％vs 64.71％,P＜0.05).A total of 450 environmental ob-ject surface specimens from 90 bed units of 45 hemodialysis units were collected before and after terminal disinfec-tion.The average bacterial colony count before terminal disinfection was higher than that after terminal disinfection([8.18±20.6]CFU/cm2 vs[1.49±3.44]CFU/cm2.P＜0.05).The qualified rate of microbial colony count after terminal disinfection was higher than that before terminal disinfection(98.22％vs 92.44％,P＜0.05).The micro-organisms in the air and environment were mainly coagulase negative Staphylococcus.Conclusion Bed-making has a certain impact on the air microorganisms around the bed units,and terminal disinfection can reduce the bacterial co-lony count of the environment.It is necessary to pay attention to the cleaning and disinfection of the environment for medical treatment,and carry out bed-making manipulation under clear condition to minimize the risk of infection.

Objective To construct a classification model for surgical patients and apply it in the allocation of nursing human resources,providing a reference for nursing human resource management.Methods A convenience sampling method was used to retrospectively select 5,431 hospitalized surgical patients admitted to 6 surgical nursing units of a tertiary general hospital in Suzhou from July to November 2022 as the subjects of this study.The nursing hours were measured,and related influencing factors were analyzed.A decision tree classification method was used to establish a classification model for surgical patients.From August to October 2022,1,527 hospitalized surgical patients admitted to 3 nursing units of the same hospital were conveniently selected.The minimum number of nurses required daily was calculated using the surgical patient classification model,actual nursing hours measurement method,nurse-to-bed ratio method,and 8-hour continuous shift scheduling method.The application effect of the surgical patient classification model in nursing human resource allocation was evaluated with the actual nursing hours measurement method as the standard.Results The surgical patient classification model includes 7 classification indicators:length of hospital stay,diagnosis-related group weight,presence or absence of secondary care orders,surgical grade,anesthesia method,age,and presence or absence of critical illness orders.Patients were divided into 14 groups,and the model explained 90.5％of the total variance in nursing workload.The minimum number of nurses required in surgical nursing units calculated based on this model was closest to the result of the actual nursing hours measurement method and was superior to the results of the nurse-to-bed ratio method and the 8-hour continuous shift scheduling method.Conclusion The surgical patient classification model can accurately reflect the nursing workload of such patients.The classification indicators are simple and easy to obtain,and can guide the allocation of human resources in surgical nursing units.

Objective Tetanus is a serious infectious diseases with high mortality,which is an important global public health issue.This study aims to analyze the epidemiological burden and changing trends of tetanus in China from 1990 to 2021,providing a basis for disease prevention and control.Methods Epidemiological indicators and global socio-demographic index(SDI)related to tetanus in China were retrieved and collected from the 2021 Global Burden of Disease database(GBD 2021).The trend analysis of the incidence rate,mortality rate and disability-ad-justed life years(DALYs)rate of tetanus in China from 1990 to 2021 was conducted by Joinpoint 5.3 software.Results From 1990 to 2021,the age-standardized incidence rate(ASIR),age-standardized mortality rate(ASMR),and age-standardized disability-adjusted life years(DALYs)rate of tetanus in China decreased significantly(average annual percent change[AAPC]＜0,P＜0.001),with males being significantly higher than females.The crude incidence rate,crude mortality rate,and crude DALYs rate for all age groups showed overall declining trends,with the lar-gest decline in the 0-14 years age group.In 2021,the crude incidence rate,crude mortality rate,and crude DALYs rate of tetanus in the population aged 70-years were higher than those in the population aged 0-14,15-49,and 50-69 years groups.The ASIR,ASMR,and age-standardized DALYs rate of tetanus in China in 2021 were lower than the global level,only higher than those in the high SDI regions.Conclusion From 1990 to 2021,the disease burden of tetanus in China varied with gender and age,with an overall declining trend over time.It is necessary to strengthen tetanus health education for males and the ≥70 years population,and to improve the overall level of pri-mary prevention measures for tetanus.

Objective To explore the value of dual factor combined detection using tuberculosis(TB)specific cy-tokines interferon-γ(IFN-γ)and interleukin-2(IL-2)in TB diagnosis in patients with human immunodeficiency vi-rus(HIV)infection,and the influencing factors for underdiagnosis.Methods HIV-infected patients admitted to and underwent TB-related examination in the Department of Infectious Diseases in Hezhou People's Hospital from July 2022 to September 2024 were collected.According to the clinical diagnosis criteria,patients were divided into the HIV infection with TB group(HIV/TB group)and the HIV infection without TB group(control group).Diag-nostic efficacy of dual factor combined detection was evaluated.HIV/TB group was further divided into a true-posi-tive group and a false-negative group based on the detection results.The independent influencing factors for underdia-gnosis was analyzed using multivariate logistic regression.Results A total of 306 patients were included in the analysis,with an average age of(55.69±14.02)years.There were 105 patients in the HIV/TB group and 201 in the control group.The sensitivity and specificity of dual factor combined detection for TB in all HIV-infected pa-tients were 72.4％(76/105)and 87.1％(175/201),respectively.There was a statistically significant difference in sensitivity(x2=9.488,P=0.009)and no statistically significant difference in specificity(x2=5.846,P=0.054)among the three CD4+T lymphocyte count gradients in the dual factor detection.Among them,patients with CD4+T cell count＜100 cells/μL had lower sensitivity(58.8％)in dual factor detection than patients with CD4+T cell count ≥200 cells/μL(88.9％)and 100-199 cells/μL(81.5％),differences were both statistically significant(both P＜0.05).In HIV/TB co-infected patients with CD4+T lymphocyte count ≥100 cells/μL,the general sensi-tivity and the specificity of dual factor combined detection were 85.2％(46/54)and 82.0％(91/111),respectively.Multivariate analysis showed that CD4+T lymphocyte count was an independent influencing factor for the underdia-gnosis in HIV/TB patients conducting dual factor combined detection(P＜0.05),while age,gender,pathogen re-sults,and the presence or absence of TB had no statistically significant impact on the results of dual factor combined detection(all P＞0.05).Conclusion Dual factor combined detection using tuberculosis-specific cytokines IFN-γand IL-2 has a high diagnostic value in the diagnosis of TB in HIV-infected patients,especially in those with CD4+T lymphocyte count ≥100/μL,which can provide auxiliary diagnostic value for the clinical diagnosis of HIV infection combined with TB.

Objective:To analyze the epidemiological characteristics and infection sources of cholera in China from 2005 to 2024.Methods:A total of 2 066 cholera cases were included in the study, which were obtained from the China Disease Control and Prevention Information System (CDPCIS) of China CDC. The information on cholera clusters was downloaded from the National Public Health Emergency Event Surveillance System (PHEESS) of China CDC. A total of 128 cholera clusters were included and analyzed in this study. The epidemiological characteristics and infection sources of cholera were analyzed. The Jointpoint model was applied to analyze the incidence trend, and annual percentage change (APC) was also quantified.Results:From 2005 to 2024, a total of 2 066 cholera cases were reported, with an average of 103 cases reported annually. Specifically, the incidence showed a marked downward trend from 2004 to 2015 ( APC=-26.78%, P=0.006). During 2015-2024, the disease remained at low endemic levels, with an average of 18 reported cases annually ( APC=-2.68%, P=0.807). Cholera peak season was from May to October. A total of 24 provinces reported cholera cases, which were mainly distributed in Zhejiang, Fujian, Beijing, Jiangsu, Anhui, Guangdong, and Hainan provinces, accounting for 78.03% of the total cases. Pathogen surveillance indicated an alternating prevalence of Vibrio cholerae serogroups O1 and O139 among laboratory-confirmed cases between 2005 and 2024. There was a disparity in the dominant serogroup of Vibrio cholerae by region. The results from 128 cholera clusters indicated that cholera outbreaks frequently occurred in rural banquets (64.84%), followed by regular restaurants (13.28%). Among these, 63 clusters (49.22%) with identified infection sources indicated that foodborne transmission (95.24%) was the primary mode of cholera transmission, which mainly through seafood and aquatic products, such as soft-shelled turtles, shrimp and shellfish. The characteristics of cholera clusters caused by Vibrio cholerae serogroups O1 and O139 showed statistically significant differences in scale, attack rate, place of residence, setting, and infection source ( P<0.05). Conclusion:Cholera incidence has remained consistently low since 2015 in China, mainly in sporadic cases. Rural gatherings (e.g., wedding banquets) are the main settings for cholera clusters. The main infection sources are predominantly caused by cross-contamination due to improper processing practices of aquatic products, such as soft-shelled turtles.

The extracellular matrix is an important component of articular cartilage,and in previous stud-ies it was more commonly recognized as a scaffolding structure supporting chondrocytes that provides protection from mechanical loading and elastic compression.As research continues to progress,a large body of literature sug-gests that the extracellular matrix is dynamic in nature.It degrades,deposits,and releases components in response to changes in its local microenvironment,which in turn dynamically regulates chondrocyte function and fate.There-fore,this review outlines the impact of matrix-chondrocyte interactions on chondrocyte behavior and joint homeosta-sis in osteoarthritis.It is hoped that the systematic elucidation of matrix-cell reciprocal relationships will provide new insights into the pathological mechanisms of osteoarthritis and the design and construction of cartilage tissue engineering.Specifically,we first summarize the typical molecular components that make up the extracellular matrix and the mechanical properties they confer in the matrix and the mechanotransduction functions they exert in chondrocytes.Next,we discuss the negative impact of chondrocytes on the synthesis and breakdown of matrix com-ponents during the osteoarthritic process in response to abnormal mechanical loading in the local microenvironment or disturbance by trauma.Finally,we focus on the impact of an abnormally remodeled extracellular matrix on chon-drocyte signaling and the pathological progression of osteoarthritis by mediating the generation of bioactive catabolic fragments,modulating cytokine release,and altering mechanical properties.