ObjectiveTo investigate the effect of bone morphogenetic protein 3 （BMP3） on the expression of inflammatory factors and joint damage in adjuvant arthritis （AA） induced by Freund′s complete adjuvant （FCA） in rats. MethodsThe AIA model was established in SD rats by intradermal injection of FCA into the toes of the left hind limb， and BMP3 overexpressing adenovirus （Ad-BMP3） or control adenovirus （Ad-NC） was injected in situ into the knee joint cavity on day 8 after modeling. Subsequently， HE staining was used to observe the histopathological changes in the synovium， immunohistochemistry was used to detect the expression of BMP3 in the synovium， and ELISA was used to analyze the expression levels of IL-6， IL-1β and TNF-α in the serum. Primary fibroblast-like synoviocytes （FLS） were isolated from AIA rats， the expression of BMP3 in FLS was knocked down or overexpressed， and Western blot and qRT-PCR were used to detect the expression levels of BMP3 and inflammatory factors in FLS. ResultsHE staining confirmed the successful establishment of the AIA model. Compared with normal rats， AIA rats showed decreased BMP3 expression in synovial tissue. Knockdown of BMP3 promoted the protein expression of inflammatory factors （IL-6， IL-1β， IL-17A， TNF-α） and the mRNA expression of chemokines ［C-C motif chemokine ligand 2 （CCL2）， C-C motif chemokine ligand 3 （CCL3）， Vascular Cell Adhesion Molecule-1 （VCAM-1）］ in FLS. In contrast， overexpression of BMP3 suppressed the expression of these inflammatory factors and chemokines. Intra-articular injection of BMP3-overexpressing adenovirus in AIA rats upregulated BMP3 expression in synovial tissue and inhibited synovial inflammation and bone erosion. ConclusionBMP3 suppresses the production of inflammatory factors and chemokines in FLS， thereby alleviating synovial hyperplasia and bone erosion in arthritis.

Vaccine immunization is the most effective and cost-efficient method for infectious disease prevention and control.Since the outbreak of novel coronavirus pneumonia(caused by the novel coronavirus,COVID-19)at the end of 2019,third generation mRNA nucleic acid vaccines has been applied to stop viral spread.mRNA vaccines,rather than relying on the immune activation mode of traditional vaccines,are an innovative breakthrough using the body's own cells to produce antigens,thereby activating double specific immunity,forming immune memory,and providing more lasting specific immunity.Com-pared with the traditional first-generation(inactivated)and second-generation(genetically engineered)vaccines,mRNA vac-cines,because of the advantages provided by this platform,play important roles in the prevention and control of major sudden infectious diseases.Consequently,mRNA vaccines were the world's first COVID-19 vaccines to be applied clinically,thus ser-ving as a barometer in the field of vaccine research and development.Herein,the molecular design and presentation of mRNA vaccines,and the molecular mechanisms of their activation of the immune response are reviewed,to provide a theoretical basis for future application of novel mRNA vaccines in the prevention and control of animal infectious diseases.

Objective To explore the clinical value of three-dimensional(3D)fracture mapping in improving the consistency of Arbeitsgemeinschaft für Osteosynthesefragen(AO)/the Orthopaedic Trauma Association(OTA)classification and optimizing preoperative surgical planning for Pilon fractures.Methods This single-center retrospective cohort study included 60 Pilon fracture patients admitted to the Trauma Emergency Center of the Third Hospital of Hebei Medical University between January 2022 and December 2024.All patients underwent preoperative computed tomography(CT)scans.Image standardization and expert manual segmentation/annotation of fracture lines and fragments were performed with 3D Slicer software.3D fracture lines extracted from gold-standard models were registered to a unified standard tibial model.A 3D probability heatmap was constructed by counting spatial fracture frequency,with high-incidence zones analyzed via spatial clustering algorithms.Three orthopedic surgeons independently completed AO/OTA classification and preoperative planning with the assistance of conventional CT only and CT with 3D fracture mapping.Accuracy,time consumption,inter-observer consistency(Cohen's κ),planning time,plan modification frequency,and subjective scores were evaluated.Results The 3D fracture heatmap revealed that fracture lines predominantly concentrated in the anterolateral and posteromedial regions of the distal tibia,with an average of(4.2±1.1)hotspots,a coverage rate of(78.3±5.6)%,and(3.5±1.0)clustering areas.With 3D fracture mapping assistance,classification accuracy was improved to(88.0±5.0)%compared to(75.0±8.0)%with conventional CT(P=0.001);classification time reduced to(10.4±2.5)min from(15.2±3.1)min(P<0.001);and Cohen's κ increased from 0.68±0.05 to 0.82±0.03(P=0.002).For preoperative planning,the average planning time was(15.8±3.2)min in the 3D mapping-assisted group,which was significantly shorter than that of conventional CT group(22.5±4.3)min(P<0.001);the number of plan modifications was(1.5±0.7)times,lower than that of conventional CT group(3.2±1.1)times(P<0.001),and the subjective score was 8.9±0.9,higher than that of conventional CT group(6.8±1.2)(P<0.001).Conclusion The 3D fracture mapping accurately characterizes spatial distribution patterns of Pilon fractures,significantly improves classification accuracy,inter-observer consistency,and preoperative planning efficiency,and thus holds substantial clinical value.

Objective To analyze the MRI imaging characteristics of brain metastases in non-small cell lung cancer(NSCLC)with different epidermal growth factor receptor(EGFR)mutation types and programmed cell death-ligand 1(PD-L1)expression,and to provide imaging diagnostic support for patients who can't undergo genetic and immunohistochemical testing.Methods A retrospec-tive selection was performed in 88 patients diagnosed with brain metastases of NSCLC,all patients were divided into EGFR mutation group and wild group according to the results of genetic testing,and patients with EGFR mutation group were divided into EGFR mutation with PD-L1 expression positive group and EGFR mutation with PD-L1 expression negative group according to whether the expression of PD-L1 was≥1％.The clinical data and MR image characteristics of brain metastases were compared in EGFR mutation group and wild group,as well as in EGFR mutation with PD-L1 expression positive group and EGFR mutation with PD-L1 expres-sion negative group.Results There were statistically significant differences in smoking history and intracranial symptoms between EGFR mutation group and wild group(P＜0.05).The edema diameter,edema index and enhancement ratio of EGFR mutation group and wild group were(0.67±1.10)cm,0.39±0.54,0.32±0.17 and(1.57±2.04)cm,1.05±1.21,0.53±0.27,respectively,and the differences were statistically significant(P＜0.05).There were 43 cases and 23 cases in EGFR mutation group and wild group with ≥2 metastases,respectively,and the difference was statistically significant(P＜0.05).Compared with＞60 years old,there were 15 patients(75％)of EGFR mutation with PD-L1 expres-sion positive in≤60 years old(P＜0.05).Conclusion Compared with EGFR wild patients,patients with EGFR mutation have more brain metastases(≥2),milder enhancement,less peritumoral edema,and fewer intracranial symptoms at initial diagnosis,and patients with EGFR mutation aged≤60 years are more likely to have PD-L1 expression positive.

Objective To explore the clinical value of three-dimensional(3D)fracture mapping in improving the consistency of Arbeitsgemeinschaft für Osteosynthesefragen(AO)/the Orthopaedic Trauma Association(OTA)classification and optimizing preoperative surgical planning for Pilon fractures.Methods This single-center retrospective cohort study included 60 Pilon fracture patients admitted to the Trauma Emergency Center of the Third Hospital of Hebei Medical University between January 2022 and December 2024.All patients underwent preoperative computed tomography(CT)scans.Image standardization and expert manual segmentation/annotation of fracture lines and fragments were performed with 3D Slicer software.3D fracture lines extracted from gold-standard models were registered to a unified standard tibial model.A 3D probability heatmap was constructed by counting spatial fracture frequency,with high-incidence zones analyzed via spatial clustering algorithms.Three orthopedic surgeons independently completed AO/OTA classification and preoperative planning with the assistance of conventional CT only and CT with 3D fracture mapping.Accuracy,time consumption,inter-observer consistency(Cohen's κ),planning time,plan modification frequency,and subjective scores were evaluated.Results The 3D fracture heatmap revealed that fracture lines predominantly concentrated in the anterolateral and posteromedial regions of the distal tibia,with an average of(4.2±1.1)hotspots,a coverage rate of(78.3±5.6)%,and(3.5±1.0)clustering areas.With 3D fracture mapping assistance,classification accuracy was improved to(88.0±5.0)%compared to(75.0±8.0)%with conventional CT(P=0.001);classification time reduced to(10.4±2.5)min from(15.2±3.1)min(P<0.001);and Cohen's κ increased from 0.68±0.05 to 0.82±0.03(P=0.002).For preoperative planning,the average planning time was(15.8±3.2)min in the 3D mapping-assisted group,which was significantly shorter than that of conventional CT group(22.5±4.3)min(P<0.001);the number of plan modifications was(1.5±0.7)times,lower than that of conventional CT group(3.2±1.1)times(P<0.001),and the subjective score was 8.9±0.9,higher than that of conventional CT group(6.8±1.2)(P<0.001).Conclusion The 3D fracture mapping accurately characterizes spatial distribution patterns of Pilon fractures,significantly improves classification accuracy,inter-observer consistency,and preoperative planning efficiency,and thus holds substantial clinical value.

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.

Objective:The objective of this study was to understand the incidence, spatial and temporal distribution characteristics and trends of bacillary dysentery in China from 2005 to 2024 in order to identify the high-risk groups and reveal the potential risk factors and to provide a scientific basis for optimizing the allocation of preventive and control resources, formulating targeted intervention strategies and assessing the effectiveness of the measures.Methods:The nationally reported incidence data of bacillary dysentery was collected from 2005 to 2024 in the Chinese Center for Disease Control and Prevention National Notifiable Diseases Reporting Information System. Descriptive epidemiological methods were used to analyze the population characteristics of bacillary dysentery cases. A Joinpoint regression model was constructed to examine long-term trends in reported incidence rates and spatial dynamic window scanning statistics were applied to detect spatial clusters of bacillary dysentery cases.Results:Between 2005 and 2024, 3 520 247 cases of bacillary dysentery were reported across China, with an average incidence rate of 12.88 per 100 000 people, after which the rate of decline decreased. The incidence rate showed a general downward trend, featuring a significant inflection point in 2016. It exhibited marked seasonality, peaking from May to October (summer-autumn), which weakened over time. From 2005 to 2024, the most likely clusters were in Beijing and Tianjin. Males, infants, the elderly, farmers, and children not in daycare showed many cases.Conclusions:The results revealed that the peak incidence of bacillary dysentery in China from 2005 to 2024 was featured in the summer-autumn months. High-incidence areas were mainly Beijing and Tianjin. The key groups, including males, infants, the elderly, farmers and children not in daycare, were identified. Enhancing surveillance, targeted health education, and preventive measures, especially in these key populations and in regions where the disease shows a high incidence should be strengthened.

This study systematically reviewed the randomized controlled trial(RCT) of traditional Chinese medicine(TCM) treatment of post-stroke depression(PSD) and analyzed the clinical study characteristics and outcome indicators, aiming to optimize the design and establish the core outcome set in the future clinical trials of the TCM treatment of PSD. PubMed, Web of Science, Cochrane Library, EMbase, CNKI, VIP, Wanfang, and SinoMed were searched for the relevant RCT published in recent 3 years. The basic characteristics, intervention measures, and outcome indicators of the included RCT were extracted, and the descriptive analysis was carried out. A total of 76 RCTs were eventually included, with the sample size concentrated in 80-100 cases. The most frequent TCM syndromes were liver depression and Qi stagnation(15 times, 31.91%) and phlegm combined with stasis(5 times, 10.63%). The frequency of intervention methods followed a descending trend of TCM decoction(35 times, 46.05%) and TCM decoction + acupuncture(4 times, 5.26%), Chinese patent medicine(3 times, 3.94%), and the intervention mainly lasted for 1 to 3 months(43 times, 60.56%). The adverse reactions of patients were mainly digestive system reaction(150 patients, 39.37%) and nervous system reaction(112 patients, 29.39%). Most of the included studies had unclear risk of bias, involving 84 outcome indicators, which belonged to 8 indicator domains. The RCTs of TCM treatment of PSD showed a variety of problems, such as non-standard TCM syndrome differentiation, inconsistent names of TCM syndrome scores and measurement tools, low quality, unclear risk of bias, neglect of endpoint indicators, unreasonable selection of substitute indicators, lack of differentiation between primary and secondary outcome indicators, non-standard reporting of safety indicators, insufficient attention to economic indicators, and lack of long-term prognosis evaluation. It is suggested that the future research should improve the quality of methodology and build a standardized core outcome set to promote the development of high-quality clinical research in this field.
Humans ; Randomized Controlled Trials as Topic ; Drugs, Chinese Herbal/administration & dosage* ; Stroke/psychology* ; Depression/etiology* ; Treatment Outcome ; Medicine, Chinese Traditional

This study aims to evaluate the efficacy of Chinese medicine injections in treating transient ischemic attack(TIA) based on network Meta-analysis. Randomized controlled trial(RCT) about Chinese medicine injections in treating TIA were retrieved from PubMed, Web of Science, Cochrane Library, EMbase, CNKI, VIP, Wanfang, and SinoMed with the time interval from inception to March 1, 2024. The methodological quality of the included articles was assessed by ROB 2.0, and the GRADE system was employed to evaluate the quality of evidence. The gemtc package of R 4.1.2 was used to perform the network Meta-analysis. Finally, 63 RCTs with a total sample size of 5 750 cases were included, involving 11 Chinese medicine injections(Shuxuetong Injection, Danhong Injection, Shuxuening Injection, Ginkgo Damo Injection, Shenxiong Glucose Injection, Ligustrazine Injection, Salviae Miltiorrhizae and Ligustrazine Hydrochloride Injection, Salvianolic Acids for Injection, Dengzhan Xixin Injection, Guhong Injection, and Xueshuantong Injection). All patients received conventional western medicine treatment, and the experimental group was additionally treated with Chinese medicine injection. Network Meta-analysis yielded the following results.(1) In terms of improving the clinical total response rate, 11 Chinese medicine injections combined with conventional western medicine outperformed conventional western medicine alone, and Dengzhan Xixin Injection + conventional western medicine had the best effect.(2) In terms of reducing plasma viscosity, 7 Chinese medicine injections combined with conventional western medicine outperformed conventional western medicine alone, and Shenxiong Glucose Injection + conventional western medicine had the best effect.(3) In terms of reducing whole blood high shear viscosity, 6 Chinese medicine injections combined with conventional western medicine outperformed conventional western medicine alone, and Guhong Injection + conventional western medicine had the best effect.(4) In terms of reducing whole blood low shear viscosity, 6 Chinese medicine injections combined with conventional western medicine outperformed conventional western medicine alone, and Shuxuening Injection + conventional western medicine had the best effect.(5) In terms of reducing fibrinogen, 9 Chinese medicine injections combined with conventional western medicine outperformed conventional western medicine alone, and Ginkgo Damo Injection + conventional western medicine had the best effect.(6) In terms of increasing the average blood flow velocity, 3 Chinese medicine injections combined with conventional western medicine outperformed conventional western medicine alone, and Shuxuening Injection + conventional western medicine had the best effect. In summary, compared with conventional western medicine alone, Chinese medicine injections combined with conventional western medicine were effective in improving the clinical total response rate and the average blood flow velocity, as well as reducing plasma viscosity, whole blood high shear viscosity, whole blood low shear viscosity, and fibrinogen. However, due to the limited quality and quantity of the included articles, the above conclusions need to be verified by more high-quality, multi-center, and large-sample RCT.
Humans ; Drugs, Chinese Herbal/administration & dosage* ; Injections ; Ischemic Attack, Transient/drug therapy* ; Randomized Controlled Trials as Topic ; Treatment Outcome

Objective: To determine the clinical efficacy and mechanism of Piwei Peiyuan Pill (PPP) combined with moxibustion for treating patients with chronic atrophic gastritis (CAG) with spleen and stomach weakness syndrome. Methods: Ninety-six CAG patients with spleen and stomach weakness syndrome who met the inclusion and exclusion criteria were enrolled at the Department of Spleen and Stomach Diseases of the Second Affiliated Hospital of Anhui University of Chinese Medicine from June 2022 to December 2023. The patients were randomly divided into a control, a Chinese medicine, and a combined group using a random number table method, with 32 cases in each group (two cases per group were excluded). The control group was treated with rabeprazole combined with folic acid tablets (both thrice daily), the Chinese medicine group was treated with PPP (8 g, thrice daily), and the combined group was treated with moxa stick moxibustion (once daily) on the basis of the Chinese medicine group for 12 consecutive weeks. Gastric mucosa atrophy in the three groups was observed before and after treatment. The gastric mucosal pathological score was evaluated. The Patient Reported Outcome (PRO) scale was used to evaluate the patients′ physical and mental health status and quality of life.An enzyme-linked immunosorbent assay was used to detect serum tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-4, IL-10, IL-37, and transforming growth factor (TGF)-β levels in each group. Real-time fluorescence PCR was used to detect the relative expression levels of signal transducer and activator of transcription 3 (STAT3) and mammalian target of rapamycin (mTOR) mRNA in each group. Western blotting was used to detect the relative expression levels of proteins related to the STAT3/mTOR signaling pathway, and the adverse drug reactions and events were recorded and compared. Results: There was no statistical difference in age, gender, disease duration, family history of gastrointestinal tumors, alcohol consumption history, and body mass index among the three groups of patients.The total therapeutic efficacy rates of the control, Chinese medicine, and combined groups in treating gastric mucosal atrophy were 66.67% (20/30), 86.67% (26/30), and 90.00% (27/30), respectively (P<0.05). Compared to before treatment, the pathological and PRO scale scores of gastric mucosa in each group decreased after treatment, and TNF-α, IL-1β, IL-37, and TGF-β levels decreased. The relative STAT3 and mTOR mRNA expression levels, as well as the relative STAT3, p-STAT3, mTOR, and p-mTOR protein expression levels decreased (P<0.05), whereas the IL-4 and IL-10 levels increased (P<0.05). After treatment, compared to the control group, the pathological score of gastric mucosa, PRO scale score, TNF-α, IL-1β, IL-37, TGF-β content, relative STAT3 and mTOR mRNA expression levels, and relative STAT3, p-STAT3, mTOR, and p-mTOR protein expression levels in the Chinese medicine and combined groups after treatment were reduced (P<0.05), whereas the IL-4 and IL-10 levels increased (P<0.05). After treatment, compared to the Chinese medicine group, the combined group showed a decrease in relative STAT3, mTOR mRNA expression levels, and STAT3, p-STAT3, mTOR, and p-mTOR protein expression levels (P<0.05). Conclusion The combination of PPP and moxibustion may regulate the inflammatory mechanism of the body by inhibiting the abnormal activation of the STAT3/mTOR signaling pathway, upregulating related anti-inflammatory factor levels, downregulating pro-inflammatory factor expression, and increasing related repair factor expression, thereby promoting the recovery of atrophic gastric mucosa, reducing discomfort symptoms, and improving the physical and mental state of CAG patients with spleen and stomach weakness syndrome.