OBJECTIVE: To explore the significance of thrombus biomarkers in evaluating the progression of immunoglobulin A vasculitis (IgAV) in children. METHODS: A total of 193 children who were diagnosed as IgAV from September 2021 to June 2023 in the Children's Hospital of Soochow University were enrolled. The levels of plasma thrombomodulin (TM), thrombin-antithrombin complex (TAT), plasmin-α2-plasmin inhibitor complex (PIC), tissue plasminogen activator-plasminogen activator inhibitor-1 complex (t-PAIC) and D-dimer (D-D) were analyzed retrospectively. And, 140 healthy children were selected as controls during the same period. The receiver operating characteristic (ROC) curves were drawn to analyze the role of thrombus parameters in estimating the progression of IgAV in children. Univariate and multivariate logistic regression analysis were used to assess the independent risk factors influencing the progression of pediatric IgAV in acute phase. RESULTS: The levels of D-D, TAT, PIC and t-PAIC in plasma of IgAV group were higher than those in control group (all P <0.001). The levels of D-D, TAT and PIC in acute phase children were significantly higher than those in non acute phase children (all P <0.001), while the levels of kidney injury related indicators such as 24h-UTP, urine albumin/creatinine ratio, positive urinary blood on dipstick, serum creatinine and cystatin C were lower (all P <0.05). ROC analysis showed that the area under curve (AUC) of PIC was 0.743 when the cut-off value was 0.93 μg/ml with 71.8% sensitivity and 78.3% specificity, while the AUC of D-D was 0.756 when the cut-off value was 550.0 μg/L with 81.3% sensitivity and 73.4% specificity. Univariate and multivariate logistic regression analysis showed that PIC≥0.93 μg/ml (OR =4.64, P =0.012) and D-D≥550.0 μg/L (OR =3.60, P =0.035) were the independent risk factors for the progression of IgAV in acute phase. CONCLUSION The pediatric patients with IgAV have shown hyperfibrinolysis in the acute stage. Furthermore, the levels of PIC and D-D should be of diagnostic value for evaluating the progression of IgAV in the acute phase.
Humans ; Biomarkers/blood* ; Child ; Fibrin Fibrinogen Degradation Products ; Retrospective Studies ; Thrombosis ; Female ; Male ; Disease Progression ; Thrombomodulin/blood* ; ROC Curve ; Vasculitis/blood* ; Antithrombin III ; Plasminogen Activator Inhibitor 1/blood* ; IgA Vasculitis/blood* ; alpha-2-Antiplasmin ; Adolescent ; Child, Preschool ; Fibrinolysin

Liposomes serve as critical carriers for drugs and vaccines, with their biological effects influenced by their size. The microfluidic method, renowned for its precise control, reproducibility, and scalability, has been widely employed for liposome preparation. Although some studies have explored factors affecting liposomal size in microfluidic processes, most focus on small-sized liposomes, predominantly through experimental data analysis. However, the production of larger liposomes, which are equally significant, remains underexplored. In this work, we thoroughly investigate multiple variables influencing liposome size during microfluidic preparation and develop a machine learning (ML) model capable of accurately predicting liposomal size. Experimental validation was conducted using a staggered herringbone micromixer (SHM) chip. Our findings reveal that most investigated variables significantly influence liposomal size, often interrelating in complex ways. We evaluated the predictive performance of several widely-used ML algorithms, including ensemble methods, through cross-validation (CV) for both liposome size and polydispersity index (PDI). A standalone dataset was experimentally validated to assess the accuracy of the ML predictions, with results indicating that ensemble algorithms provided the most reliable predictions. Specifically, gradient boosting was selected for size prediction, while random forest was employed for PDI prediction. We successfully produced uniform large (600 nm) and small (100 nm) liposomes using the optimised experimental conditions derived from the ML models. In conclusion, this study presents a robust methodology that enables precise control over liposome size distribution, offering valuable insights for medicinal research applications.

Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Practice Guidelines as Topic ; Drugs, Chinese Herbal/therapeutic use*

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective To investigate the imaging features of intestinal schwannoma(IS)in order to improve the diagnostic ability of the disease.Methods The clinical and imaging data of 14 patients with surgically and pathologically confirmed IS were retrospectively analyzed,including the location,size,morphology,nature,growth pattern,CT density,MRI signal,PET/CT metabolism and other characteristics of the tumors.Results Of the 14 IS cases,the lesions of 3 cases were located in the duodenum,2 cases in the cecum,8 cases in the colon and 1 case in the rectum.The lesions were all round or oval,with an average maximum diameter of(2.4±1.1)cm.The lesions were solid in 13 cases,extraluminal growth in 10 cases,cystic degeneration in 1 case and myxoid degeneration in 1 case.Chronic inflammatory lymph nodes were seen around the diseased intestines in 9 cases,and the short diameter of lymph nodes was greater than 5 mm in 6 cases.All 14 cases of IS showed low attenuation on plain CT scan,and progressive enhancement after contrast injection,including 1 case of mild enhancement,2 cases of moderate enhancement,and 11 cases of obvious enhancement.Two cases of IS showed low signal intensity on T1WI,slightly high signal intensity on T2WI,significantly high signal intensity on DWI,and obvious progressive enhancement after contrast injection on MRI.Two cases of IS showed high metabolism on 18F-FDG-PET/CT,and the SUVmax was 9.4 and 8.8,respectively.Conclusion The imaging findings of IS were characteristic to a certain extent.They mainly manifested as solid nodules or masses derived from the intestinal submucosa,with uniform attenuation or signal intensity,obvious progressive enhancement after contrast injection,obvious hypermetabolism on 18F-FDG-PET/CT,and slightly larger homogeneous lymph nodes were common around the lesions.

Objective To explore the carrier rate of thalassemia in Laibin city,Guangxi Province,and provide a theoretical basis for the prevention and control of thalassemia.Methods From January 2020 to December 2021,88 152 patients were screened for thalassemia in the outpatient department of the Women's and Children's Hospital of 4 counties,1 city and 1 district in Laibin by blood cell detection and hemoglobin electrophoresis.The common and rare genes in initially screened positive individuals were detected by gap polymerase chain reaction(Gap-PCR)and reverse dot blot(RBD),and the results were conducted by statistical analysis.Results ① There were 22 553 positive cases in the preliminary screening and 8 327 positive cases received the diagnosis of thalassemia gene.A total of 4 944 thalassemia carriers of thalassemia genes were detected,deducing that the total thalassemia carrier rate in the population of childbearing age in this region was 15.19%,including 3 200 cases of α-thalassemia carriers(64.73%),1 424 cases of β-thalassemia carriers(28.80%),and 320 cases of were carriers α-thalassemia combined with β-thalassemia(6.47%).② There were 3 168 cases of common thalassemia(99.00%)and 32 cases of rare thalassemia(1.00%)among α-thalassemia gene carriers.A total of 13 mutant genes and 34 genotypes were detected,and genotype SEA/αα was the comes first.③ Among the β-thalassemia gene carriers,there were 1 411 cases of(99.09%)common thalassemia and 13 cases(0.91%)of rare thalassemia.A total of 19 mutant genes and 25 genotypes were detected,with CD41-42(-CTTT)being the most common.④ A total of 53 different genotypes were detected in the carriers of α-thalassemia combined with β-thalassemia,and the top genotype was--SEA/αα βCD41-42M/βN.⑤ The carrier rates of Yao and Han nationality were comparable,and the differences were not significant(χ2=0.300,P=0.584).The differences in carrying rates between Zhuang and Yao(χ2=23.66,P＜0.001),and between Zhuang and Han(χ2=116.98,P＜0.001)were significant.⑥ The carrier rate in Xiangzhou County was the highest(20.04%),while the carrier rate in Heshan City was the lowest(12.38%).⑦ The carrier rate of females was higher than that of males,and the difference was significant(χ2=182.03,P＜0.001).Conclusion The variants genotypes of thalassemia in Laibin were complex.This study was the first to investigate the carrier rate and gene mutation spectrum of thalassemia in Laibin Area,which provides valuable baseline data for genetic counseling and prenatal diagnosis.

Objective The aim is to utilize CRISPR/Cas9 gene editing technology to construct Dmd gene mutant mice with a point mutation in exon 23 of the Dmd gene. Subsequently, the phenotypic changes of the mice in muscles and immune systems are analyzed and verified, providing an evaluation model for Duchenne muscular dystrophy and other related diseases.MethodsBased on the sequence characteristics of exon 23 of the Dmd gene, small guide RNA (sgRNA) was designed and synthesized. Cas9 mRNA, sgRNA fragments, and oligo donor DNA were microinjected into fertilized eggs of C57BL/6J mice. After transferring the fertilized eggs to surrogate mice, F0 generation mice were born. After mating with F0 generation mice, offspring mice were obtained, and Dmd gene positive mutant (Dmd^Mu/+) mice were obtained after genotype identification. Male hemizygous Dmd^Mu/+(Dmd^Mu/Y) mice were selected for phenotype validation. The body weight of live 3- and 9-month-old mice were recorded. Muscle tension was evaluated through the grid test. Hearts and semitendinosus muscles were collected, and the histopathological changes were observed using HE staining. Further, the expression of Dmd protein in muscle tissue of 9-month-old mice was analyzed by Western blotting.An acute inflammation model was established in Dmd^Mu/Y mice using lipopolysaccharide induction. Peripheral blood from the submandibular vein was collected, and the changes in the proportion of neutrophils and monocytes were detected by flow cytometry.Results The results of genome sequencing and Western blotting confirmed the successful construction of Dmd gene point mutant mice (Dmd^Mu/+ mice). Dmd protein expression was not detected in skeletal muscle and myocardium of Dmd^Mu/+ mice, and it was significantly reduced compared to wild-type C57BL/6J mice (P<0.05). Compared with wild-type mice of the same background, Dmd^Mu/Y mice at 3 and 9 months of age showed significant weight loss (P<0.01) and decreased muscle tension (P<0.05). 9-month-old Dmd^Mu/Y mice exhibited significant pathological changes in skeletal muscle and myocardium, including widening of intermuscular space. Under normal condition, compared with wild-type mice, the proportion of neutrophils and monocytes in the peripheral blood of 3-month-old Dmd^Mu/Y mice was significantly lower than that of wild-type mice (P<0.01). After lipopolysaccharide stimulation, the proportion of neutrophils in peripheral blood of 3-month-old Dmd^Mu/Y mice remained significantly lower compared to that of wild-type mice (P<0.01). The proportion of neutrophils in peripheral blood of 9-month-old Dmd^Mu/Y mice significantly decreased after lipopolysaccharide induction (P<0.01), with a trend of change observed in monocytes between groups.Conclusion The successful construction of the Dmd gene mutant mouse model has confirmed the vital function of Dmd gene in maintaining normal muscle tissue morphology and muscle tone. It preliminarily indicated that Dmd gene deletion could significantly reduce the proportion of neutrophils in peripheral blood, offering a new perspective for the study of immune system alterations in Duchenne muscular dystrophy patients.

Objective To establish a dynamic prediction model of fatal massive hemorrhage in trauma based on the vital signs time series data and machine learning algorithms.Methods Retrospectively analyze the vital signs time series data of 7522 patients with trauma in the Medical Information Mart for Intensive Care-Ⅳ(MIMIC-Ⅳ)database from 2008 to 2019.According to the occurrence of posttraumatic fatal massive hemorrhage,the patients were divided into two groups:fatal massive hemorrhage group(n=283)and non-fatal massive hemorrhage group(n=7239).Six machine learning algorithms,including logistic regression(LR),support vector machine(SVM),random forests(RF),adaptive boosting(AdaBoost),gated recurrent unit(GRU),and GRU-D were used to develop a dynamic prediction models of fatal massive hemorrhage in trauma.The probability of fatal massive hemorrhage in the following 1,2,and 3 h was dynamically predicted.The performance of the models was evaluated by accuracy,sensitivity,specificity,positive predictive value,negative predictive value,Youden index,and area under receiver operating characteristic curve(AUC).The models were externally validated based on the trauma database of the Chinese PLA General Hospital.Results In the MIMIC-Ⅳ database,the set of dynamic prediction models based on the GRU-D algorithm was the best.The AUC for predicting fatal major bleeding in the next 1,2,and 3 h were 0.946±0.029,0.940±0.032,and 0.943±0.034,respectively,and there was no significant difference(P=0.905).In the trauma dataset,GRU-D model achieved the best external validation effect.The AUC for predicting fatal major bleeding in the next 1,2,and 3 h were 0.779±0.013,0.780±0.008,and 0.778±0.009,respectively,and there was no significant difference(P=0.181).This set of models was deployed in a public web calculator and hospital emergency department information system,which is convenient for the public and medical staff to use and validate the model.Conclusion A set of dynamic prediction models has been successfully developed and validated,which is greatly significant for the early diagnosis and dynamic prediction of fatal massive hemorrhage in trauma.

Objective To compare the effects of 20 mg qd and 10 mg bidadministration of iprrazole enteric-coated tablets on the control of gastric acid in healthy subjects.Methods A randomized,single-center,parallel controlled trial was designed to include 8 healthy subjects.Randomly divided into 2 groups,20 mg qd administration group:20 mg enteric-coated tablets of iprrazole in the morning;10 mg bid administration group:10 mg enteric-coated tablets of iprrazole in the morning and 10 mg in the evening.The pH values in the stomach of the subjects before and 24 h after administration were monitored by pH meter.The plasma concentration of iprazole after administration was determined by HPLC-MS/MS.The main pharmacokinetic parameters were calculated by Phoenix WinNonlin(V8.0)software.Results The PK parameters of iprrazole enteric-coated tablets and reference preparations in fasting group were as follows:The Cmax of 20 mg qd group and 10 mg bid group were(595.75±131.15)and(283.50±96.98)ng·mL-1;AUC0-t were(5 531.94±784.35)and(4 686.67±898.23)h·ng·mL-1;AUC0-∞ were(6 003.19±538.59)and(7 361.48±1 816.77)h·ng·mL-1,respectively.The mean time percentage of gastric pH＞3 after 20 mg qd and 10 mg bid were 82.64％and 61.92％,and the median gastric pH within 24 h were 6.25±1.49 and 3.53±2.05,respectively.The mean gastric pH values within 24 h were 5.71±1.36 and 4.23±1.45,respectively.The correlation analysis of pharmacokinetic/pharmacodynamics showed that there was no significant correlation between the peak concentration of drug in plasma and the inhibitory effect of acid.Conclusion Compared with the 20 mg qd group and the 10 mg bid group,the acid inhibition effect is better,the administration times are less,and the safety of the two administration regimes is good.

S100 calc-binding protein A8/A9(S100A8/A9)can induce the migration of primary tumor cells to distant target organs by binding multiple channel proteins,promote the formation of tumor metastasis microenvironment,and play an important role in the immune and inflammatory response of the body.It provides a new target and idea for the prevention and treatment of tumor metastasis and invasion.This paper mainly reviewed the expression and mechanism of S100A8/A9 on related channel proteins in a variety of high incidence tumors,in order to provide a new strategy for tumor prevention,diagnosis and treatment.