ObjectiveTo analyze the research status and development trends of non-pharmacological therapies for post-stroke spasticity (PSS) over the past two decades. MethodsRelevant literatures on non-pharmacological rehabilitation of PSS published from January, 2004 to June, 2024 were retrieved from Web of Science Core Collection. CiteSpace 6.3.R6 and VOSviewer 1.6.18 were used for visualization analysis. ResultsA total of 780 publications were included. The annual number of publications showed an overall upward trend. China, the USA, and Italy contributed the highest number of publications. The Hong Kong Polytechnic University and researcher Noureddin Nakhostin Ansari were identified as the most influential institution and author, respectively. High-frequency keywords and cluster labels included electric stimulation, transcranial magnetic stimulation, robot and acupuncture. ConclusionOver the past 20 years, researches on non-pharmacological therapies for PSS have remained active, with hotspots focusing on diverse interventions such as electrical stimulation, magnetic stimulation and robot-assisted therapy.

Objective: To explore the association of vegetables and fruits intake with depressive symptoms among multi ethnic first year junior high school students in Yunnan Province, so as to provide data support for preventing and reducing depressive symptoms among first year junior high school students. Methods: From October to December 2022, a cluster random sampling method was used to select 8 500 first year junior high school students from 11 ethnic minority areas in Yunnan Province (Fugong County, Longling County, Longyang District, Luchun County, Mojiang County, Nanjian County, Qiaojia County, Shuangjiang County, Tengchong City, Yuanmou County, Zhenyuan County), to investigate with a questionnaire. The Dietary Frequency Questionnaire was used to collect dietary behavior datas, and the Chinese version of Depression Anxiety Stress Scale-21 (DASS-21) was used to assess depressive symptoms. The generalized linear model was used to analyze the association of vegetable and fruit intake with depressive symptoms in students, and stratified analysis was performed according to ethnicity. Results: The detection rate of depressive symptoms among first year junior high school students in Yunnan Province was 29.5%. The detection rates of depressive symptoms in Han and minority first year junior high school students were 26.9% and 31.6%. After controlling for demographic variables such as gender, age, family residence and other confounding factors, the generalized linear model analysis results showed that the intake of leafy vegetables ( β= -0.07 , 95%CI =-0.12 to -0.01), flat fruits ( β=-0.06, 95%CI =-0.12 to -0.00) and hot natured fruits ( β=0.11, 95%CI = 0.04- 0.17) were associated with depressive symptoms in Han first year junior high school students (all P <0.05). The intake of melon and fruit vegetables ( β=-0.06, 95%CI =-0.11 to -0.01) and hot natured fruits ( β=0.06, 95%CI =0.01-0.12) were associated with depressive symptoms in ethnic minority first year junior high school students (both P <0.05). Conclusions The intake of vegetables and fruits among multi ethnic first year junior high school students in Yunnan Province is related to the risk of depressive symptoms. It is suggested to strengthen the consumption guidance and education of vegetables and fruits to prevent depressive symptoms among first year junior high school students.

ObjectiveTo evaluate the efficacy and safety of Janus kinase （JAK） inhibitors combined with Chinese herbal medicine （CHM） in treating rheumatoid arthritis （RA）. MethodsClinical data from 169 RA patients were retrospectively collected. Among them， 71 cases received JAK inhibitors as the control group， while 98 cases received JAK inhibitors plus CHM as the observation group， both treated for 24 weeks. The rheumatoid factor （RF）， cyclic citic peptide antibody （anti-CCP）， erythrocyte sedimentation rate （ESR）， C-reactive protein （CRP）， and white blood cell count （WBC） were recorded before and after treatment. Databases including CNKI， Wanfang， VIP， PubMed and Web of Science were searched from inception till August 31st， 2025 for randomized controlled trials （RCTs） on the combined use of JAK inhibitors and CHM for RA. The methodological quality of the included studies was evaluated using the risk of bias assessment tool. Meta-analyses were performed for RF， anti-CCP， ESR， CRP， 28-joint disease activity score （DAS28）， overall clinical effective rate， and incidence of adverse events. Sensitivity analysis were also performed. ResultsThe retrospective study demonstrated that after treatment， ESR， CRP， and anti-CCP levels decreased in the observation group， while ESR and CRP levels decreased in the control group （P＜0.05）. Moreover， ESR and RF levels in the observation group were lower than those in the control group （P＜0.05）. A total of 9 RCTs involving 770 patients were included in the meta-analysis. The results indicated that the JAK inhibitors plus CHM group was superior to the JAK inhibitors group in reducing RF （MD=-8.97， 95%CI -15.01 to -2.94， P=0.004）， CRP （MD=-3.34， 95%CI -3.82 to -2.86， P＜0.001）， ESR （MD=-5.33， 95%CI -7.98 to -2.69， P＜0.001）， and DAS28 score （MD=-0.54， 95%CI -0.74 to -0.34， P＜0.001）， as well as in improving the overall clinical effective rate （OR=4.53， 95%CI 2.55 to 8.03， P＜0.001）. No statistically significant differences were observed between groups in anti-CCP levels （SMD=-2.08， 95%CI -4.41 to 0.24， P=0.080） or incidence of adverse events （OR=0.93， 95%CI 0.55 to 1.57， P=0.790）. ConclusionThe combination of JAK inhibitors and CHM demonstrates remarkable efficacy in treating RA， contributing to improved disease activity and reduced inflammatory markers with a favorable safety profile.

Cranial bone defect repair remains a significant challenge in craniomaxillofacial surgery， particularly when defects exceed the critical size defect （CSD） threshold， rendering them incapable of spontaneous healing without external intervention. Mechanical forces—including compression， tension， and shear stress—play a pivotal role in cranial development and regeneration. These forces regulate osteoblast differentiation and bone regeneration by activating key mechanotransduction pathways， such as the Wnt/β-catenin signaling pathway， the piezoelectric mechanosensitive ion channel Piezo1， and the transcriptional co-activators Yes-associated protein （Yes-Associated Protein，YAP） and Transcriptional co-activator with PDZ-binding motif （Transcriptional co-activator with PDZ-binding motif，TAZ）. Distinct types of mechanical forces exert specific effects on cellular behavior and the microenvironment. Clinically， applications such as Negative Pressure Wound Therapy （NPWT） have demonstrated efficacy in promoting angiogenesis-osteogenesis coupling， while tensile forces stimulate the dura mater to secrete osteogenic factors. Preliminary studies using artificial periosteum and other biomaterials have further validated that appropriate mechanical stimulation enhances bone repair. This review summarizes the effects of various mechanical forces and their associated signaling pathways on osteoblasts and their microenvironment， alongside an overview of current technological applications in this field.

Objective: To investigate the characteristics of malignant tumor incidence and mortality in cancer registration areas of Zhejiang Province in 2021. Methods: Based on the 2021 cancer registration data from 22 national cancer registries in Zhejiang Province, the crude incidence, crude mortality, and cumulative rate for 0 to 74 years were calculated. Age standardized was performed using the age composition of the standard population from the Fifth National Population Census in 2000 and Segi's world standard population. The incidence and mortality characteristics of malignant tumor in different genders, urban/rural areas and ages were described. The order of crude incidence and mortality of malignant tumor were analyzed. Results: In 2021, there were 116 639 new malignant tumor cases in Zhejiang Province. The crude, Chinese population standardized, and world population-standardized incidences were 530.93/100 000, 304.83/100 000, and 288.20/100 000, respectively. The cumulative incidence for 0 to 74 years was 31.92%. There were 40 475 death cases. The crude, Chinese population-standardized, and world population-standardized mortalities were 184.24/100 000, 79.40/100 000, and 78.97/100 000, respectively. The cumulative mortality for 0 to 74 years was 8.37%. The Chinese population-standardized incidence for males and females were 286.34/100 000 and 323.45/100 000, respectively, and the Chinese population-standardized mortality were 106.25/100 000 and 54.17/100 000, respectively. The Chinese population-standardized incidence for urban and rural were 316.85/100 000 and 285.11/100 000, respectively, and the Chinese population-standardized mortality were 75.59/100 000 and 85.48/100 000, respectively. The crude incidence and crude mortality of malignant tumor both increased with age, peaking in the groups aged 80-<80 and ≥85 years at 1 845.06/100 000 and 1 656.88/100 000, respectively. The top ten malignant tumors with the highest crude incidence were, in descending order: lung cancer, thyroid cancer, breast cancer, prostate cancer, colorectal cancer, gastric cancer, liver cancer, cervical cancer, lymphoma, and brain tumors. These accounted for 80.34% of all new malignant tumor cases. The top ten malignant tumors with the highest crude mortality were, in descending order: lung cancer, liver cancer, colorectal cancer, gastric cancer, pancreatic cancer, prostate cancer, breast cancer, esophageal cancer, lymphoma, and gallbladder cancer. These accounted for 82.26% of all malignant tumor deaths. Conclusions In 2021, the cancer registration areas of Zhejiang Province were characterized by a relatively high malignant tumor incidence and a comparatively low mortality compared to national data. Males and the elderly emerged as key populations for targeted prevention and control. It is recommended to enhance screening, early diagnosis, and early treatment for lung cancer, thyroid cancer, prostate cancer, breast cancer, and gastric cancer malignancies.

L-citrulline is a nonprotein amino acid that plays an important role in human health and has great market demand. Although microbial cell factories have been widely used for biosynthesis, there are still challenges such as genetic instability and low efficiency in the biosynthesis of L-citrulline. In this study, an efficient, plasmid-free, non-inducible L-citrulline-producing strain of Escherichia coli BL21(DE3) was engineered by combined strategies. Firstly, a chassis strain capable of synthesizing L-citrulline was constructed by block of L-citrulline degradation and removal of feedback inhibition, with the L-citrulline titer of 0.43 g/L. Secondly, a push-pull-restrain strategy was employed to enhance the L-citrulline biosynthesis, which realized the L-citrulline titer of 6.0 g/L. Thirdly, the NADPH synthesis and L-citrulline transport were strengthened to promote the synthesis efficiency, which achieved the L-citrulline titer of 11.6 g/L. Finally, fed-batch fermentation was performed with the engineered strain in a 3 L fermenter, in which the L-citrulline titer reached 44.9 g/L. This study lays the foundation for the industrial production of L-citrulline and provides insights for the modification of other amino acid metabolic networks.
Citrulline/biosynthesis* ; Escherichia coli/genetics* ; Metabolic Engineering/methods* ; Fermentation ; NADP/biosynthesis*

Objective To analyze the usage of pediatric drugs in 17 pediatric specialty hospitals from 2016 to 2020, and provide reference and guidance for the development of the essential medicine list （EML） for children and the improvement of the National Reimbursement Drug List （NRDL） in China. Methods Based on the pediatric medication monitoring data from 17 children's specialized hospitals reported to the Chinese Medical Economic Information Network (CMEI) of the Chinese Pharmaceutical Association between 2016 and 2020, this study analyzes the overall situation of the sample hospitals and the clinical use of pediatric drugs according to the major categories of the Anatomical Therapeutic Chemical Classification System （ATC）. Results In the various ATC categories, the trend of systemic use of anti-infective drugs decreasing was significant in the average hospital expenditure, while the trend of respiratory and digestive system and metabolic drugs decreasing was significant in the average hospital DDDS. In 2020, the average number of hospital grade standards for essential drugs （2018 version） accounted for 15.82% of the total number of drug use standards, while the average number of hospital grade standards for medical insurance （2019 version） accounted for 8.23% of the total number of drug use standards. Conclusion The use of pediatric medication in sample hospitals from 2016 to 2020 was generally reasonable, and there would still a certain gap between the actual clinical usage habits with the existing EML and NRDL，which still need to be adjusted.

Objective:To analyze the current status and trends of lung cancer incidence and mortality in China and selected global regions, providing evidence for lung cancer prevention strategies in China.Methods:We extracted data from the GLOBOCAN 2022 database. Age-standardized Incidence rate (ASIR) and Age-standardized Mortality rate (ASMR) were calculated using Segi's world standard population. Epidemiological patterns were analyzed by region, age, sex, and human development index (HDI). Simple linear regression and Spearman's rank correlation coefficient were used to examine associations between HDI and ASIR/ASMR.Results:In 2022, global lung cancer incidence and mortality reached 2.48 million and 1.82 million cases respectively, with age-standardized rates of 23.6 per 100 000 (ASIR) and 16.8 per 100 000 (ASMR). Gender disparities were prominent, with male ASIR and ASMR being 2.0-fold and 2.5-fold higher than females. Elderly populations showed 11.6-fold higher ASIR and 14.4-fold higher ASMR compared to working-age adults. HDI demonstrated strong positive correlations with both ASIR ( r=0.79, P＜0.001) and ASMR ( r=0.74, P＜0.001). China accounted for 1.06 million new cases and 0.73 million deaths, with ASIR (40.8 per 100 000) and ASMR (26.7 per 100 000) exceeding global averages by 1.7-fold and 1.6-fold respectively. Chinese males showed 1.7-fold higher ASIR and 2.7-fold higher ASMR than females. Trend analysis revealed persistently high male incidence in China whereas rapidly increasing female rates, narrowing gender disparities. Projections estimate 1.80 million incident cases and 1.41 million deaths by 2050, representing 69.3% and 92.0% increases from 2022 levels. Conclusions:Significant heterogeneity exists in lung cancer burden across demographics and development levels, with strong HDI correlations. China bears disproportionate disease burden, necessitating intensified prevention efforts. These findings underscore the urgency of targeted interventions in high-risk populations.

Objective:To integrate implicit templates with deep learning techniques, a novel neural network, the tooth-deformable deep implicit network (T-DDIN), was constructed to achieve high-precision shape completion of tooth defects in a personalized manner.Methods:A total of 550 intraoral scan models were collected from patients treated at the Department of Orthodontics and Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University (500 for training and 50 for testing), between March 2022 and March 2024. T-DDIN reconstructed defective tooth morphology using an implicit template and a latent encoding prediction network. During model evaluation, Class Ⅱ cavity defects and occlusal wear defects were simulated in the test set. Morphological restoration was performed using both traditional computer aided design (CAD) methods and the T-DDIN deep learning approach. The two methods were compared based on three-dimensional deviation, occlusal adjustment volumes, cusp angle deviation, and restoration time.Results:The T-DDIN group demonstrated significantly lower three-dimensional deviation for Class Ⅱ cavity defects and occlusal wear restoration [(0.14±0.05) and (0.16±0.09) mm], occlusal adjustment volumes [(0.44±0.03) and (0.49±0.03) mm 3], and difference value of the tooth cusp angles (5.69°±1.90° and 6.04°±0.53°) compared to the traditional CAD group (both P<0.001). No significant differences were observed within the T-DDIN group between the two defect types in terms of three-dimensional deviation ( P=0.098) or occlusal adjustment volume ( P=0.154) or difference value of the tooth cusp angles ( P=0.196). However, in the traditional CAD group, three-dimensional deviation, occlusal adjustment volume and difference value of the tooth cusp angles was significantly higher in occlusal wear restorations than in Class Ⅱ cavity defects restorations ( P<0.001). The T-DDIN group, which involved Class Ⅱ cavity defects and occlusal wear, demonstrated significantly less recovery time of morphology (37.2±7.7) and (39.4±6.2) s compared to the traditional CAD group ( P<0.001). Conclusions:T-DDIN demonstrated superior stability and accuracy in morphological reconstruction for various types of dental defects while significantly reducing restoration time.

Objective:To investigate the relationship of several adiposity-related anthropometric parameters, including BMI, waist circumference (WC), waist-to-hip ratio (WHR), body fat percentage (BFP) and indoles in plasma with the incidence of atherosclerotic cardiovascular disease (ASCVD) in adults in China.Methods:In China Kadoorie Biobank (CKB) study, blood samples were collected from 2 183 participants in the first resurvey in 2008 to detect indoles. Participants' body weight, body height, WC, hip circumference, and BFP were measured at baseline survey in 2004 and resurvey in 2008, the BMI and WHR were calculated with standardized methods. The long-term follow-up of all participants started from the completion of the resurvey in 2008 until the occurrence of incident ASCVD, death, loss to follow-up or until December 31, 2018. CKB ascertained outcome status (incident ASCVD) through death and disease registries and national health insurance databases, supplemented by active follow-up. Multivariate linear regression model was used to estimate the associations of anthropometric measurements at baseline survey and the first resurvey, and changes in these measurements with 3 indoles [indole, indole-3-acetic acid (IAA), and indole-3-propionic acid (IPA)]. Cox proportional hazard regression model was used to estimate the associations between indoles and the risk for ASCVD.Results:Anthropometric measurements at baseline survey or the first resurvey were negatively associated with plasma IPA level. The regression coefficient ( β) of baseline BMI (per 1.0 kg/m 2) with 0.1 standard deviation ( SD) IPA was -0.23 (95% CI: -0.36 - -0.10) (false discovery rate=0.004). After adjusting for baseline BMI, the β of baseline WC, WHR and BFP with 0.1 SD IPA were -0.09 (95% CI: -0.18 - -0.01), -0.12 (95% CI: -0.19 - -0.05), and -0.20 (95% CI: -0.32 - -0.08), respectively. The annual change in BMI (difference between BMI in 2008 and 2004 divided by the time interval) was associated with indole and IAA, with β of 1.40 (95% CI: 0.58 - 2.21) and -1.07 (95% CI: -1.91 - -0.23), respectively, at each 0.1 increase of SD. Over a median ( Q1, Q3) follow-up of 10.46 (10.36, 10.53) years after 2008 resurvey, 236 cases of ASCVD were recorded. IAA and IPA levels were negatively associated with the risk for ASCVD, with hazard ratios for one SD increase of IAA and IPA of 0.87 (95% CI: 0.76 - 0.99) and 0.84 (95% CI: 0.73 - 0.96), respectively. Conclusions:Our results suggested that anthropometric measurements and their changing trends affect the levels of plasma imicrobial tryptophan metabolite levels, decreased levels of IAA and IPA levels are associated with increased risk of ASCVD and indoles in plasma including IPA and IAA might be the mediating factors for adiposity-induced ASCVD.