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Abstract The prognosis of extensive-stage small cell lung cancer is usually poor. In this study, a combined model based on pre-treatment CT radiomics and clinical features was constructed to predict the OS of extensive-stage small cell lung cancer after chemotherapy with immunotherapy.Clinical data of 111 patients with extensive stage small-cell lung cancer who received first-line immunotherapy combined with chemotherapy in our hospital from December 2019 to December 2021 were retrospectively collected. Finally, 93 patients were selected for inclusion in the study, and CT images were obtained through PACS system before treatment. All patients were randomly divided into a training set (n = 66) and a validation set (n = 27). Images were imported into ITK-SNAP to outline areas of interest, and Python software was used to extract radiomics features. A total of 1781 radiomics features were extracted from each patient’s images. The feature dimensions were reduced by MRMR and LASSO methods, and the radiomics features with the greatest predictive value were screened. The weight coefficient of radiomics features was calculated, and the linear combination of the feature parameters and the weight coefficient was used to calculate Radscore. Univariate cox regression analysis was used to screen out the factors significantly associated with prognosis from the radiomics and clinical features, and multivariate cox regression analysis was performed to establish the prognosis prediction model of extensive stage small cell lung cancer. The degree of metastases was selected as a significant clinical prognostic factor by univariate cox regression analysis. Seven radiomics features with significance were selected by LASSO-COX regression analysis, and the Radscore was calculated according to the coefficient of the radiomics features. An alignment diagram survival prediction model was constructed by combining Radscore with the number of metastatic lesions. The study population was stratified into those who survived less than 11 months, and those with a greater than 11 month survival. The C-index was 0.722 (se = 0.044) and 0.68(se = 0.074) in the training and the validation sets, respectively. The Log_rank test results of the combination model were as follows: training set: p

Abstract Background Dachsous cadherin related 1 (DCHS1) is one of calcium-dependent adhesion membrane proteins and is mainly involved in the development of mammalian tissues. There is a lack of more detailed research on the biological function of DCHS1 in pan-cancer. Materials and methods We evaluated the expression, the prognostic value, the diagnostic value and genomic alterations of DCHS1 by using the databases, including TCGA, UALCAN, HPA, GEPIA2.0 and GSCA. We employed the databases of UCSC, TIMER2.0, TISIDB, GSCA to analyze the association between DCHS1 expression and the immune microenvironment, stemness, TMB, MSI and anticancer drug sensitivity. BioGRID, STRING and GEPIA2.0 were used to perform protein interaction and functional enrichment analysis. Real-time quantitative PCR, CCK8, Transwell assay and Western blot were performed to determine the function of DCHS1 in UCEC. Results DCHS1 is differentially expressed in many cancers and its expression is significantly associated with tumor prognosis and diagnosis. DCHS1 expression was significantly correlated with the infiltration of cancer-associated fibroblasts (CAFs), Endothelial cell (ECs), and Hematopoietic stem cell in most cancers. In addition, DCHS1 was significantly associated with sensitivity to many antitumor drugs. Functional enrichment analysis revealed that DCHS1-related proteins were involved in Focal adhesion, Endometrial cancer and Wnt signaling pathway. GSEA results showed that DCHS1 was related to epithelial-mesenchymal transition (EMT) in many cancers. In vitro experiments in UCEC showed that DCHS1 regulated cell proliferation, migration and EMT. Conclusions Our findings indicated that DCHS1 might be a novel prognostic and diagnostic biomarker and immunotherapy target, and plays an important role in the proliferation, migration and EMT in UCEC.

The current design of member foundation only considers horizontal forces (H) and ignores the effect of torque (T), which may lead to torsional failure of the foundation. To analyze the bearing characteristics of rigid rectangular foundation subjected to horizontal force and torque (H-T), according to the stress characteristics of the foundation, the corresponding simplified calculation model is established, and the theoretical solutions of the stress and deformation analysis of the foundation under the two bearing modes of torque (T), horizontal force (H) - eccentric bending moment (M) are derived; numerical simulation analysis is carried out to obtain the failure envelope of rigid rectangular foundations under push torsion H-T load. And then the rationality of the theoretical calculation method is verified by the indoor model test. Finally, the influences of torsion ratio and foundation resistance ratio coefficient m on the stress and deformation of foundation are analyzed. The results show that the failure envelope of rigid rectangular foundation under push torsion H-T load is approximately parabolic. With the increase of torsion-thrust ratio, the horizontal bearing capacity of the foundation decreases, and its failure mode changes from horizontal deformation failure to torsional deformation failure. The increase of the proportional coefficient m can reduce the horizontal displacement and rotation angle at the foundation ground effectively. To ensure the safety and stability of the rigid rectangular foundation, the nature and compaction of the overlying backfill should satisfy the design requirements. This study can provide basic information for the design of multi-rod unified rod foundations.

Introduction: Despite radiotherapy being one of the major treatments for triple-negative breast cancer (TNBC), new molecular targets for its treatment are still required due to radioresistance. CDK2 plays a critical role in TNBC. However, the mechanism by which CDK2 promotes TNBC radioresistance remains to be clearly elucidated. Objectives: We aimed to elucidate the relationship between CDK2 and TRIM32 and the regulation mechanism in TNBC. Methods: We performed immunohistochemical staining to detect nuclear TRIM32, CDK2 and STAT3 on TNBC tissues. Western blot assays and PCR were used to detect the protein and mRNA level changes. CRISPR/Cas9 used to knock out CDK2. shRNA-knockdown and transfection assays also used to knock out target genes. GST pull-down analysis, immunoprecipitation (IP) assay and in vitro isomerization analysis also used. Tumorigenesis studies also used to verify the results in vitro. Results: Herein, tripartite motif-containing protein 32 (TRIM32) is revealed as a substrate of CDK2. Radiotherapy promotes the binding of CDK2 and TRIM32, thus leading to increased CDK2-dependent phosphorylation of TRIM32 at serines 328 and 339. This causes the recruitment of PIN1, involved in cis–trans isomerization of TRIM32, resulting in importin α3 binding to TRIM32 and contributing to its nuclear translocation. Nuclear TRIM32 inhibits TC45-dephosphorylated STAT3, Leading to increased transcription of STAT3 and radioresistance in TNBC. These results were validated by clinical prognosis confirmed by the correlative expressions of the critical components of the CDK2/TRIM32/STAT3 signaling pathway. Conclusions: Our findings demonstrate that regulating the CDK2/TRIM32/STAT3 pathway is a promising strategy for reducing radioresistance in TNBC.

Abstract Introduction Interleukin-17A (IL-17A) plays a crucial role in the pathogenesis of ankylosing spondylitis (AS), although not all patients respond to traditional IL-17A antibody treatments. QX002N injection, as a new monoclonal antibody targeting IL-17A, has shown potential in treating AS, offering a new treatment option for patients who do not respond well to existing therapies. Methods A randomized, open, parallel, single-center, phase I study was conducted to assess the pharmacokinetics, safety, and immunogenicity of single doses of QX002N injection administered intravenously (IV) or subcutaneously (SC) to healthy Chinese volunteers. Blood samples were collected at specified time intervals, and then serum concentrations of QX002N were analyzed by enzyme-linked immunosorbent assay. Results Pharmacokinetic analysis of the drug concentration–time data showed that the mean maximum observed serum QX002N concentration (C max) was 110 and 33.9 µg/ml, respectively. The average area under the drug concentration–time curves from 0 to the time of the last quantifiable concentration (AUClast) were 52,656 and 36,269 µg·h/ml, respectively and the average area under the drug concentration–time curves from 0 to infinity (AUCinf) were 54,867 and 38,194 µg·h/ml, respectively. The absolute bioavailability of QX002N after SC injection was 69.6%. Conclusions Immunogenicity was assessed and all the subjects in this study were Anti-drug antibody (ADA)-negative, which means no subjects appeared to develop immunogenicity to QX002N. All the results testify to the safety of QX002N injection, which is satisfactory after IV or SC dosing in healthy subjects. Trial Registration www.chinadrugtirals.org.cn , CTR20220430.

Introduction We conducted analyses of the association between smoking and osteoporosis and osteoporotic fractures using a secondary dataset analysis of the National Health and Nutrition Examination Survey (NHANES) database and the two-sample Mendelian randomization (MR) method. Methods The associations between smoking and osteoporosis or osteoporotic fractures were analyzed using weighted logistic regression models for both univariate and multivariable analyses using pooled 1999–2018 NHANES data. The summary-level data of genome-wide association studies (GWAS) of smoking and osteoporosis were extracted from the IEU Open GWAS project. The inverse variance weighted method was used as the main method for the two-sample MR analysis. Results We obtained the following main findings based on the NHANES data: smoking was associated with osteoporosis according to the analyses of 30856 participants (OR=1.21; 95% CI: 1.06–1.39, p=0.004); smoking was associated with hip osteoporotic fracture according to the analyses of 30928 participants (OR=1.47; 95% CI: 1.14–1.90, p=0.004); smoking was associated with wrist osteoporotic fracture according to the analyses of 30923 participants (OR=1.33; 95% CI: 1.18–1.49, p

Microalgae are a promising sustainable food source with high nutritional value and environmental benefits. This study investigated the presence of toxic metals and rare earth elements (REEs) in 68 microalgal-based food products and conducted a probabilistic risk assessment to evaluate potential health risks. The findings revealed high detection rates of REEs (80.96% to 100%) and heavy metals (83.82% to 100%), with REE concentrations ranging from 0.0055 to 0.5207 mg/kg. Heavy metals were detected at the following average concentrations: As (2.80 mg/kg) > Cr (1.27 mg/kg) > Pb (0.30 mg/kg) > Cd (0.20 mg/kg) > Hg (0.01 mg/kg). Carcinogenic risk analysis for Cd (3.004 × 10−3), Cr (1.484 × 10−3), and As (1.1283 × 10−2) indicated that 95th percentile values exceeded established safety thresholds (10−4). These findings highlight the critical need for stringent monitoring and the establishment of comprehensive regulatory frameworks for the safety of novel microalgae foods.

Abstract The Orthopoxvirus genus, especially variola virus (VARV), monkeypox virus (MPXV), remains a significant public health threat worldwide. The development of therapeutic antibodies against orthopoxviruses is largely hampered by the high cost of antibody engineering and manufacturing processes. mRNA-encoded antibodies have emerged as a powerful and universal platform for rapid antibody production. Herein, by using the established lipid nanoparticle (LNP)-encapsulated mRNA platform, we constructed four mRNA combinations that encode monoclonal antibodies with broad neutralization activities against orthopoxviruses. In vivo characterization demonstrated that a single intravenous injection of each LNP-encapsulated mRNA antibody in mice resulted in the rapid production of neutralizing antibodies. More importantly, mRNA antibody treatments showed significant protection from weight loss and mortality in the vaccinia virus (VACV) lethal challenge mouse model, and a unique mRNA antibody cocktail, Mix2a, exhibited superior in vivo protection by targeting both intracellular mature virus (IMV)-form and extracellular enveloped virus (EEV)-form viruses. In summary, our results demonstrate the proof-of-concept production of orthopoxvirus antibodies via the LNP-mRNA platform, highlighting the great potential of tailored mRNA antibody combinations as a universal strategy to combat orthopoxvirus as well as other emerging viruses.

Abstract Background Manual therapy (MT) is frequently used in combination with management of osteoarthritis of the knee, but there is no consensus on the exact efficacy of this treatment strategy. The purpose of this systematic review and meta-analysis was to evaluate the pain relief and safety of MT for treatment of knee osteoarthritis (KOA). Methods Randomized controlled trials evaluating MT in patients with KOA in major English and Chinese journals were searched in the following databases: Wanfang, China Science and Technology Journal Database (VIP database), China National Knowledge Infrastructure (CNKI), PubMed, Embase, Web of Science, and the Cochrane Library databases through June 2023. The methodological quality and quality of evidence of the included studies were assessed using Cochrane’s risk-of-bias 2 (ROB 2) tool and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool. Data analysis was performed using Stata version 15.0 software. After use of Galbraith plots to exclude studies that could lead to heterogeneity, random effects models were used to analyze the remaining data and test the consistency of the findings. We used meta-regression to assess the effect of treatment period, patient age, and sex ratio on outcomes. Funnel plots and Egger’s test were used to evaluate publication bias. Sensitivity analyses were used to determine the reliability of the results. Results A total of 25 studies, with 2376 participants, were included in this review. The overall methodological quality of the included studies was limited. Our findings suggest that MT has a positive impact on pain relief outcomes in KOA patients. The meta-analysis showed that MT was superior to usual care (SMD = 2.04, 95% CI 0.94, 3.14, I 2 = 96.3%; low evidence quality) and exercise (SMD = 1.56, 95% CI 0.41, 2.71, I 2 = 96.3%; low evidence quality) for reducing pain. In terms of improvement in visual analogue scale (VAS) scores, MT treatment beyond 4 weeks (SMD = 1.56, 95% CI 0.41, 2.71, I 2 = 96.3%) may be superior to treatments less than or equal to 4 weeks (SMD = 1.24, 95% CI 0.56, 1.95, I 2 = 94.7%). No serious adverse events associated with MT were reported. Conclusions MT may be effective at reducing pain in patients with KOA and may be more effective after a 4-week treatment period. Compared with usual care and exercise therapy, MT may be superior at reducing KOA pain in the short term (9 weeks), but its long-term efficacy requires careful consideration of evidence-based outcomes. MT appears to be safe for KOA patients, though clinicians should inform patients of the potential risk of MT-related adverse events.

Abstract The maturation process of natural killer (NK) cells, which is regulated by multiple transcription factors, determines their functionality, but few checkpoints specifically targeting this process have been thoroughly studied. Here we show that NK-specific deficiency of glucose-regulated protein 94 (gp96) leads to decreased maturation of NK cells in mice. These gp96-deficient NK cells exhibit undermined activation, cytotoxicity and IFN-γ production upon stimulation, as well as weakened responses to IL-15 for NK cell maturation, in vitro. In vivo, NK-specific gp96-deficient mice show increased tumor growth. Mechanistically, we identify Eomes as the downstream transcription factor, with gp96 binding to Trim28 to prevent Trim28-mediated ubiquitination and degradation of Eomes. Our study thus suggests the gp96-Trim28-Eomes axis to be an important regulator for NK cell maturation and cancer surveillance in mice.

The Orthopoxvirus (OPXV) genus of the Poxviridae includes human pathogens variola virus (VARV), monkeypox virus (MPXV), vaccinia virus (VACV), and a number of zoonotic viruses. A number of Bcl-2-like proteins of VACV are involved in escaping the host innate immunity. However, little work has been devoted to the evolution and function of their orthologues in other OPXVs. Here, we found that MPXV protein P2, encoded by the P2L gene, and P2 orthologues from other OPXVs, such as VACV protein N2, localize to the nucleus and antagonize interferon (IFN) production. Exceptions to this were the truncated P2 orthologues in camelpox virus (CMLV) and taterapox virus (TATV) that lacked the nuclear localization signal (NLS). Mechanistically, the NLS of MPXV P2 interacted with karyopherin α-2 (KPNA2) to facilitate P2 nuclear translocation, and competitively inhibited KPNA2-mediated IRF3 nuclear translocation and downstream IFN production. Deletion of the NLS in P2 or orthologues significantly enhanced IRF3 nuclear translocation and innate immune responses, thereby reducing viral replication. Moreover, deletion of NLS from N2 in VACV attenuated viral replication and virulence in mice. These data demonstrate that the NLS-mediated translocation of P2 is critical for P2-induced inhibition of innate immunity. Our findings contribute to an in-depth understanding of the mechanisms of OPXV P2 orthologue in innate immune evasion.

Glycyrrhizin (GL) has immunoregulatory effects on various inflammatory diseases including hepatitis and nephritis. However, the mechanisms underlying the anti-inflammatory effect of GL on renal inflammation are not fully understood. Hepatorenal syndrome (HRS) is a functional acute renal impairment that occurs in severe liver disease, and we found that kidney injury also occurs in Con A-induced experimental hepatitis in mice. We previously found that GL can alleviate Con A-induced hepatitis by regulating the expression of IL-25 in the liver. We wanted to investigate whether GL can alleviate Con A-induced nephritis by regulating IL-25. IL-25 regulates inflammation by modulating type 2 immune responses, but the mechanism by which IL-25 affects kidney disease remains unclear. In this study, we found that the administration of GL enhanced the expression of IL-25 in renal tissues; the latter promoted the generation of type 2 macrophages (M2), which inhibited inflammation in the kidney caused by Con A challenge. IL-25 promoted the secretion of the inhibitory cytokine IL-10 by macrophages but inhibited the expression of the inflammatory cytokine IL-1β by macrophages. Moreover, IL-25 downregulated the Con A-mediated expression of Toll-like receptor (TLR) 4 on macrophages. By comparing the roles of TLR2 and TLR4, we found that TLR4 is required for the immunoregulatory effect of IL-25 on macrophages. Our data revealed that GL has anti-inflammatory effects on Con A-induced kidney injury and that the GL/IL-25/M2 axis participates in the anti-inflammatory process. This study suggested that GL is a potential therapeutic for protecting against acute kidney injury.

Introduction Knee osteoarthritis (KOA) is one of the most common osteoarthritis, imposing substantial economic and medical burdens on both individuals and society. In China, Tuina has been selected as a complementary and alternative therapy to relieve knee pain and dysfunction symptoms. However, the current evidence is insufficient to support the efficacy of Tuina therapy in addressing knee pain and improving physical function. The trial aims to compare the effectiveness of Tuina with celecoxib, which is considered as the standard treatment, and to assess its potential as an alternative therapy through changes in outcome measures.Methods and analysis A total of 360 KOA patients aged between 40 and 70 years and classified as Kellgren and Lawrence grades I–II will be recruited from eight subcentral hospitals. The participants will be randomly assigned to either the treatment group (Tuina, Biw) or the control group (celecoxib, Qd), with both groups undergoing a 4-week intervention phase followed by an 8-week follow-up phase. The primary outcome is the change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale at week 4 compared with baseline. Secondary outcomes including WOMAC stiffness and function subscales, WOMAC total score, 36-item Short-Form Health Survey, Timed Up and Go test, Short Physical Performance Battery, gait analysis parameters and pain medication records will be assessed at weeks 4, 8 and 12. Any adverse events that occur during the trial will be promptly recorded.Ethics and dissemination This study has been approved by the Ethics Committee of Shanghai Municipal Hospital of Traditional Chinese Medicine (2023SHL-KY-16-01, 2023SHL-KY-16-02). Written informed consent will be obtained from all participants. Study results will be disseminated through peer-reviewed journals and conference presentations.Trial registration number ChiCTR2300069416.

Background Our objective is to develop a predictive model utilizing the ferritin and transferrin ratio (FTR) and clinical factors to forecast overall survival (OS) in breast cancer (BC) patients. Methods We conducted a retrospective analysis of clinical data from 2858 BC patients diagnosed between 2013 and 2021. Subsequently, the cohort of 2858 BC patients underwent random assignment into distinct subsets: a training cohort comprising 2002 patients and a validation cohort comprising 856 patients, maintaining a proportional ratio of 7:3. Employing multivariable Cox regression analysis within the training cohort, we derived a prognostic nomogram. The predictive performance was assessed using calibration curves, C-index, and decision curve analysis. Results The final prognostic model included the TNM stage, subtype, hemoglobin levels, and the ferritin-transferrin ratio. The nomogram achieved a C-index of .794 (95% CI: .777-.810). The nomogram demonstrated superior predictive accuracy for OS at 3, 5, and 7 years for BC, with area under the time-dependent curves of .812, .782, and .773, respectively. These values notably outperformed those of the conventional TNM stage. Decision curve analysis reaffirmed the greater net benefit of our nomogram compared to the TNM stage. These findings were subsequently validated in the independent validation cohort. Conclusion The FTR-based prognostic model may predict a patient’s OS better than the TNM stage in a clinical setting. The nomogram can provide an early, affordable, and reliable tool for survival prediction, as well as aid clinicians in treatment option-making and prognosis evaluation. However, further multi-center prospective trials are required to confirm the reliability of the existing nomogram.

For higher vocational students, the college stage is an important period in their career development, and the college experience plays an important role in the relationship between their proactive personality and career adaptability, which in turn has a significant impact on their future career development. From the perspective of social cognitive career theory and taking 476 vocational students as samples, this paper explores the mediating role of college experience between proactive personality and career adaptability of vocational college students. The college experience scale is revised for higher vocational students, and it is verified to have good reliability and validity. SPSS and Amos were used to conduct correlation analysis，and the PROCESS macro was used for mediating effect analysis. The results show that the college experience of vocational students plays a partial mediating role in the effect of proactive personality on career adaptability. This work innovatively uses social cognitive career theory to explore the role of college experience in the relationship between proactive personality and career adaptability among vocational students. The theoretical models are established and empirical verification is conducted, confirming that higher vocational students’ college experience can affect their career adaptability. These results provide empirical evidence for vocational colleges to improve the career guidance of college students, and intervention measures are proposed to enhance students’ career adaptability during school years, thus promoting their sustainable development.

Abstract Background and Purpose To identify anatomic prognostic factors and their potential roles in refining M1 classification for de novo metastatic nasopharyngeal carcinoma (M1‐NPC). Materials and Methods All M1‐NPC treated with chemotherapy and/or radiotherapy between 2010 and 2019 from two centers (training and validation cohort) were included. The prognostic value of metastatic disease extent and involved organs for overall survival (OS) were assessed by several multivariable analyses (MVA) models. A new M1 classification was proposed and validated in a separate cohort who received immuno‐chemotherapy. Results A total of 197 M1‐NPC in the training and 307 in the validation cohorts were included for M1 subdivision study with median follow‐up of 46 and 57 months. MVA model with “≤2 organs/≤5 lesions” as the definition of oligometastasis had the highest C‐index (0.623) versus others (0.606–0.621). Patients with oligometastasis had better OS versus polymetastasis (hazard ratio [HR] 0.47/0.63) while liver metastases carried worse OS (HR 1.57/1.45) in MVA in the training/validation cohorts, respectively. We proposed to divide M1‐NPC into M1a (oligometastasis without liver metastases) and M1b (liver metastases or polymetastasis) with 3‐year OS of 66.5%/31.7% and 64.9%/35.0% in the training/validation cohorts, respectively. M1a subset had a better median progress‐free survival (not reach vs. 17 months, p

Introduction Non-pharmacological interventions play a crucial role in the management of non-specific chronic low back pain (NSCLBP). One prime example is Tuina, a traditional Chinese manual therapy that incorporates pressing, kneading and rubbing techniques to alleviate physical discomfort and enhance overall well-being. It serves as a widely used technique in China and other East Asian countries. However, the effectiveness and safety of Tuina for managing NSCLBP have not been substantiated through rigorous clinical research. We sought to carry out a randomised controlled trial with an open-label design, blinded assessors and parallel arms to assess the effectiveness and safety of Tuina as a treatment for NSCLBP. The trial aims to provide high-quality evidence regarding the efficacy and safety of Tuina in improving outcomes for patients with NSCLBP.Methods and analysis A total of 150 patients aged 18–60 years with NSCLBP will be recruited. Participants will be randomly assigned to one of the two groups. Both groups will receive standard health education. In addition, the treatment group will receive Tuina therapy, while the control group will participate in core stability exercises. Each group will undergo a total of 18 interventions over 6 weeks, with the interventions administered three times per week. The primary outcome measure is the patient’s pain intensity, assessed using the Numerical Rating Scale, at week 6 following randomisation. Secondary outcomes encompass disability (measured by the Roland-Morris Disability Questionnaire), quality of life (assessed using the EuroQoL-5 dimensions questionnaire), adverse emotions (evaluated with the Pain Catastrophizing Scale, Tampa Scale of Kinesiophobia and Depression Anxiety Stress Scale), biomechanical outcomes, socioeconomic indicators (medication use, healthcare utilisation and absenteeism), patient satisfaction, treatment adherence and other relevant factors.The statistical analysis will follow the intention-to-treat principle. Two-way repeated measures analysis of variance will be used to compare the clinical data across different time points within both groups.Ethics and dissemination The study protocol has received approval from the Ethics Committee of Shuguang Hospital, Shanghai University of Traditional Chinese Medicine (2023-1366-133-01). All study participants will be required to give written informed consent. The findings of the study will be submitted to a peer-reviewed journal for publication and presented at scientific conferences. Additionally, the participants will receive copies of the results.Trial registration number ChiCTR2300076257.

Similar clinical features make the differential diagnosis difficult, particularly between lung cancer and pulmonary tuberculosis (TB), without pathological evidence for patients with concomitant TB infection. Our study aimed to build a nomogram to predict malignant pulmonary lesions applicable to clinical practice. We retrospectively analyzed clinical characteristics, imaging features, and laboratory indicators of TB infection patients diagnosed with lung cancer or active pulmonary TB at Xiangya Hospital of Central South University. A total of 158 cases from January 1, 2018 to May 30, 2019 were included in the training cohort. Predictive factors for lung cancer were screened by a multiple-stepwise logistic regression analysis. A nomogram model was established, and the discrimination, stability, and prediction performance of the model were analyzed. A total of 79 cases from June 1, 2019, to December 30, 2019, were used as the validation cohort to verify the predictive value of the model. Eight predictor variables, including age, pleural effusion, mediastinal lymph node, the number of positive tumor markers, the T cell spot test for TB, pulmonary lesion morphology, location, and distribution, were selected to construct the model. The corrected C-statistics and the Brier scores were 0.854 and 0.130 in the training cohort, and 0.823 and 0.163 in the validation cohort. Calibration plots showed good performance, and decision curve analysis indicated a high net benefit. In conclusion, the nomogram model provides an effective method to calculate the probability of lung cancer in TB infection patients, and it has excellent discrimination, stability, and prediction performance in detecting a malignant diagnosis of undiagnosed pulmonary lesions.

BackgroundBreast cancer (BC) is the most common and prominent deadly disease among women. Predicting BC survival mainly relies on TNM staging, molecular profiling and imaging, hampered by subjectivity and expenses. This study aimed to establish an economical and reliable model using the most common preoperative routine blood tests (RT) data for survival and surveillance strategy management.MethodsWe examined 2863 BC patients, dividing them into training and validation cohorts (7:3). We collected demographic features, pathomics characteristics and preoperative 24-item RT data. BC risk factors were identified through Cox regression, and a predictive nomogram was established. Its performance was assessed using C-index, area under curves (AUC), calibration curve and decision curve analysis. Kaplan-Meier curves stratified patients into different risk groups. We further compared the STAR model (utilizing HE and RT methodologies) with alternative nomograms grounded in molecular profiling (employing second-generation short-read sequencing methodologies) and imaging (utilizing PET-CT methodologies).ResultsThe STAR nomogram, incorporating subtype, TNM stage, age and preoperative RT data (LYM, LYM%, EOSO%, RDW-SD, P-LCR), achieved a C-index of 0.828 in the training cohort and impressive AUCs (0.847, 0.823 and 0.780) for 3-, 5- and 7-year OS rates, outperforming other nomograms. The validation cohort showed similar impressive results. The nomogram calculates a patient’s total score by assigning values to each risk factor, higher scores indicating a poor prognosis. STAR promises potential cost savings by enabling less intensive surveillance in around 90% of BC patients. Compared to nomograms based on molecular profiling and imaging, STAR presents a more cost-effective, with potential savings of approximately $700-800 per breast cancer patient.ConclusionCombining appropriate RT parameters, STAR nomogram could help in the detection of patient anemia, coagulation function, inflammation and immune status. Practical implementation of the STAR nomogram in a clinical setting is feasible, and its potential clinical impact lies in its ability to provide an early, economical and reliable tool for survival prediction and surveillance strategy management. However, our model still has limitations and requires external data validation. In subsequent studies, we plan to mitigate the potential impact on model robustness by further updating and adjusting the data and model.

Introduction Knee osteoarthritis (KOA) is still a challenging degenerative joint disease with high morbidity and disease burden. Early-stage KOA, the focus of this study, could present a Window of Opportunity to arrest the disease process and reduce the disease burden. Yijinjing exercise is an important part of physical and psychological therapies in Traditional Chinese Exercise and may be an effective treatment. However, there is no clinical efficacy assessment of Yijinjing exercise for patients with early-stage KOA. Therefore, we designed a randomised controlled trial to evaluate the effectiveness of Yijinjing exercise on patients with early-stage KOA.Methods and analysis This is a parallel-design, two-arm, analyst assessor-blinded, randomised controlled trial. In total, 60 patients with early-stage KOA will be recruited and randomly assigned to the Yijinjing exercise group (n=30) and health education group (n=30) at a ratio of 1:1, receiving 12 weeks of Yijinjing exercise or health education accordingly. The primary outcome will be measured with the Western Ontario and McMaster Universities Osteoarthritis Index, and the secondary outcomes will include the Visual Analogue Scale, Short-Form 36 Item Health Survey Questionnaire, Beck Depression Inventory, Perceived Stress Scale, Berg Balance Scale, and Gait Analysis for a comprehensive assessment. Outcome measures are collected at baseline, at 12 week ending intervention and at the 12 week, 24 week and 48 week ending follow-up. The primay time point will be 12 weeks postintervention. Adverse events will be recorded for safety assessment.Ethics and dissemination This study has been approved by the ethical application of the Shanghai Municipal Hospital of Traditional Chinese Medicine Ethics Committee (2021SHL-KY-78).Trial registration number ChiCTR2200065178

Background: Acute respiratory tract infections (ARTIs) are the most common cause of morbidity and mortality worldwide, with most people experiencing at least one episode per year. Current treatment options are mainly symptomatic therapy. Antivirals, antibiotics, and glucocorticoids are of limited benefit for most infections. Traditional Chinese medicine has shown potential benefits in the treatment of ARTIs.Objective: The objective of this study was to determine the efficacy, effectiveness, and safety of Phragmites communis Trin. (P. communis, a synonym of Phragmites australis (Cav.) Trin. ex Steud) as monotherapy or as part of an herb mixture for ARTIs.Method: Eight databases and two clinical trial registries were searched from inception to 8 February 2023 for randomized controlled trials (RCTs) evaluating any preparation involving P. communis without language restrictions. The Risk of Bias Tool 2.0 was used to assess the risk of bias of the included trials. RevMan 5.3 software was used for data analyses with effects estimated as risk ratios (RRs), mean differences (MDs), or standardized mean differences (SMDs) with 95% confidence intervals (CIs). The online GRADEpro tool was used to assess the certainty of the evidence, if available.Results: Forty-two RCTs involving 6,879 patients with ARTIs were included, with all trials investigating P. communis as part of an herbal mixture. Of the included trials, the majority (38/42) were considered high risk. Compared to the placebo, P. communis preparations improved the cure rate [RR = 1.60, 95% CI (1.13, 2.26)] and fever clearance time [MD = −2.73 h, 95% CI (−4.85, −0.61)]. Compared to usual care alone, P. communis preparations also significantly improved the cure rate [RR = 1.57, 95% CI (1.36, 1.81)] and fever clearance time [SMD = −1.24, 95% CI (−2.37, −0.11)]. P. communis preparations plus usual care compared to usual care alone increased the cure rate [RR = 1.55, 95% CI (1.35, 1.78)], shortened the fever clearance time [MD = −19.31 h, 95% CI (−33.35, −5.27)], and improved FEV1 [ MD = 0.19 L, 95% CI (0.13, 0.26)] and FVC [ MD = 0.16 L, 95% CI (0.03, 0.28)].Conclusion: Low- or very low-certainty evidence suggests that P. communis preparations may improve the cure rate of ARTIs, shorten the fever clearance time in febrile patients, and improve the pulmonary function of patients with acute exacerbation of chronic obstructive pulmonary disease or chronic bronchitis. However, these findings are inconclusive and need to be confirmed in rigorously designed trials.Systematic review registration: PROSPERO, identifier CRD42021239936

ABSTRACTIt is urgently needed to evaluate the necessity and benefits of booster vaccination against the coronavirus 2 of the severe acute respiratory syndrome (SARS-CoV-2) Omicron to facilitate clinical decision-making for 2019 coronavirus disease (COVID-19) convalescents. We conducted a multicenter, prospective clinical trial (registration number: ChiCTR2100045810) in the first patients with COVID-19 from 28 January 2020 to 20 February 2020 to assess the long-term durability of neutralizing antibodies against live Omicron BA.5 and further assess the efficiency and safety of CoronaVac in the convalescent group. A total of 96 COVID-19 convalescents were enrolled in this study. Neutralizing antibody titers in convalescents were significantly reduced in 9–10 months. A dose-refreshing vaccination in 28 convalescents with an antibody titer below 96 significantly induced neutralizing antibodies against live Omicron by 4.84-fold. Meanwhile, the abundance of naive T cells increased dramatically, and TEMRA and TEM cells gradually decreased after vaccination. Activation-induced cell death and apoptosis-related genes were significantly elevated after vaccination in all T-cell subtypes. One-dose booster vaccination was effective in inducing a robust antibody response against SARS-CoV-2 Omicron in COVID-19 convalescents with low antibody titers. However, vaccine-mediated T-cell consumption and regeneration patterns may be detrimental to the antiviral response.IMPORTANCEThe globally dominant coronavirus 2 of the severe acute respiratory syndrome (SARS-CoV-2) Omicron variant raises the possibility of repeat infections among 2019 coronavirus disease (COVID-19) convalescents with low neutralizing antibody titers. The importance of this multicenter study lies in its evaluation of the long-term durability of neutralizing antibodies in COVID-19 convalescents and the efficacy of a booster vaccination against the live Omicron. The findings suggest that a one-dose booster vaccination is effective in inducing a robust antibody response against SARS-CoV-2 Omicron in convalescents with low antibody titers. However, the study also highlights the potential detrimental effects on the antiviral response due to vaccine-mediated T-cell consumption and regeneration patterns. These results are crucial for facilitating clinical decision-making for COVID-19 convalescents and informing public health policies regarding booster vaccinations.

Abstract Using amino silica modified with fluorescein isothiocyanate (FITC), a quick fluorescence analysis technique is used for the detection of 3-monochloropropane-1,2-diol (3-MCPD). At 100 °C and pH 8.5, FITC-modified amino silica exhibits the lowest fluorescence intensity in the presence of 3-MCPD. This can predominantly be explained mostly explained by 3-MCPD’s capacity to occupy the amino group that FITC normally binds to. The fluorescence intensity of FITC-modified amino silica was greatly quenched by 3-MCPD’s reaction with the amino group under alkaline conditions, and the fluorescence intensity is different at different reaction times, reaction pH, and reaction temperature. The effects of various 3-MCPD concentrations on the optical characteristics of FITC-modified amino silica were also investigated. Fluorescence analysis is used to obtain a linear range from 0.025 to 1.0 mg/L for 3-MCPD detection under optimal experimental conditions, with a detection limit of 0.025 mg/L and a correlation coefficient of 0.9915. The quantity of 3-MCPD in soy sauce was measured under ideal conditions. Using the optimized conditions, the contents of 3-MCPD in soy sauce were determined. These results suggest that this method is sensitive to 3-MCPD and may have a substantial application in the rapid detection of food contaminants particularly, where the quality and safety of food products are of paramount concern.

Aflatoxin B1 (AFB1), a widespread contaminant in food and feeds, poses a threat to the health of animals and humans. Consequently, it is significant to develop a rapid, precise and highly sensitive analytical method for the detection of AFB1. Herein, we developed an immunochromatographic strip (ICS) based on a tetrahedral DNA (TDN) immunoprobe for AFB1 determination in rice bran oil. Three sizes of TDN immunoprobes (AuNP-TDN13bp-mAb, AuNP-TDN17bp-mAb, AuNP-TDN26bp-mAb) were constructed, and the performance of these three immunoprobes, including the effective antibody labeling density and immunoaffinity, was measured and compared with that of the immunoprobe (AuNP-mAb) developed using the physical adsorption method. Subsequently, the optimal TDN immunoprobe, namely AuNP-TDN13bp-mAb, was selected to prepare the immunochromatographic strip (ICS) for the qualitative and quantitative detection of AFB1 in rice bran oil. The visual limits of detection (vLODs) of the ICS based on AuNP-TDN13bp-mAb and AuNP-mAb were 0.2 ng/mL and 2 ng/mL, with scanning quantitative limits (sLOQs) of 0.13 ng/mL and 1.4 ng/mL, respectively. The ICS demonstrated a wide linear range from 0.02 ng/mL to 0.5 ng/mL, with good specificity, accuracy, precision, repeatability, and stability. Moreover, a high consistency was observed between the constructed ICS and ultra-high-performance liquid chromatography (UPLC) in the quantification of AFB1. The results indicated that the introduction of TDN was beneficial for promoting efficient antibody labeling, protecting the bioactivity of immunoprobes, and increasing the sensitivity of detection, which would provide new perspectives for the achievement of the highly sensitive detection of mycotoxins.

Deoxynivalenol (DON), 3-acetyldeoxynivalenol (3-ADON) and 15-acetyldeoxynivalenol (15-ADON) belong to type B trichothecenes that are widely detected in agricultural products as one of the most common classes of mycotoxins. In the present study, we aimed to characterize the alteration of lipid metabolism in normal human hepatocytes by poisoning with DON and its acetylated derivatives. After verifying the hepatotoxicity of the three toxins, DON, 15-ADON, and 3-ADON, the mRNA expression was determined by transcriptomics, and the results showed that DON and 15-ADON had a significant regulatory effect on the transcriptome, in which glycerophospholipid metabolism pathway and phospholipase D signaling pathways have not been reported in studies of DON and its acetylated derivatives. For further validation, we explored lipid metabolism in depth and found that PC (15:0/16:0), PC (16:1/18:3), PC (18:1/22:6), PC (16:0/16:0), PC (16:0/16:1), PC (16:1/18:1), PC (14:0/18:2), PE (14:0/16:0) and PE (18:1/18:3) were downregulated for all nine lipids. Combined with the transcriptome results, we found that hepatic steatosis induced by the three toxins, DON, 15-ADON and 3-ADON, was associated with altered expression of genes related to lipid oxidation, lipogenesis and lipolysis, and their effects on lipid metabolism in L-02 cells were mainly realized through the PC-PE cycle.

Abstract Background IL-33 is a multifunctional cytokine with dual functions. However, the clinicopathological and prognostic significance of IL-33 in cancer patients, especially in patients with hepatocellular carcinoma (HCC), remains controversial. Therefore, we conducted a study of 565 patients with HCC and 561 healthy controls and performed a meta-analysis to quantitatively evaluate the above problems. Methods We collected blood from 565 patients with HCC and 561 healthy controls. ELISA was used to detect the concentrations of IL-33 and ST2 in the serum, and RT‒PCR was used to detect the levels of IL-33 and ST2 mRNA. Meanwhile, we collected comprehensive literature on IL-33 and the clinical characteristics of cancer patients retrieved from the PubMed, Web of Science and CNKI databases as of December 2022. An odds ratio (OR) with a 95% confidence interval (CI) was used to estimate the impact through overall and stratified analyses. Results Compared with the healthy control group, the levels of ST2 mRNA and serum in the peripheral blood of HCC patients increased (p 0.05). In the meta-analysis section, at the tissue level, the overall analysis showed that the expression of IL-33 was positively correlated with tumor stage, histological grade, distant metastasis, and tumor size. Compared with patients with low IL-33 expression, the 3-year overall survival (OS) rate (OR = 3.467, p

Abstract Background Knee osteoarthritis (KOA) is a common public health problem and a leading cause of long-term pain, decreased muscle strength, and even disability. Tai Chi has been proved effective and highly recommended for KOA management worldwide. However, little is known about its benefits on quadriceps strength which is closely associated with relieving knee pain. This trial is designed to evaluate the efficacy and safety of Tai Chi on knee pain and muscle strength in middle-aged and older adults with KOA. Methods A total of 100 participants will be randomly divided into a Tai Chi group (TC group) (1x/week for 12 weeks) and a control group with a health education and stretching program (1x/week for 12 weeks) with a follow-up period of 6 weeks. The primary outcome is the change of Western Ontario and McMaster Universities (WOMAC) pain subscale at week 12 compared with baseline. Secondary outcomes include WOMAC stiffness and function subscales, data from isokinetic dynamometry, gait analysis with electromyography (EMG), and a 36-item short form health survey (SF-36). The daily dose of pain-relieving medication will also be recorded. All adverse effects will be assessed by the Treatment Emergent Symptom Scale (TESS). Discussion We expect this randomized trial to evaluate the effectiveness of Tai Chi on relieving pain and increasing quadriceps strength in KOA patients. This protocol, if proven effective, will contribute to providing a promising alternative intervention for middle-aged and older adults with KOA. Trials registration number This trial has been registered in the China Clinical Trials Registry (registration number: ChiCTR2300069339).

Abstract Background The close relationship between pain and mental health problems is well-known, and psychological intervention can provide an effective alternative to medication-based pain relief. However, previous studies on the connection between pain and psychological problems, the findings thus far have been inconclusive, limiting the potential for translating psychological interventions into clinical practice. To complement the gap, this study utilized genetic data and Mendelian randomization (MR) to examine the potential relationship between pain in different parts and common mental disorders. Methods Based on the instrumental variables selected from the Genome-wide association study summary statistics of localized pain and mental disorders, we conducted bidirectional two-sample MR analyses to infer bidirectional causal associations between pain and mental disorders. The inverse-variance weighted MR method and MR-Egger were used as the primary statistical method according to the horizontal pleiotropy and heterogeneity level. We reported the odds ratio to infer the causal effect between pain and mental disorders. F statistic was calculated to measure the statistical efficacy of the analyses. Results Insomnia is causally related to the genetic susceptibility of multisite pain including head (OR = 1.09, 95% CI: 1.06–1.12), neck/shoulder (OR = 1.12, 95% CI: 1.07–1.16), back (OR = 1.12, 95% CI: 1.07–1.18) and hip (OR = 1.08, 95% CI: 1.05–1.10). Reversely, headache (OR = 1.14, 95% CI: 1.05–1.24), neck/shoulder pain (OR = 1.95, 95% CI: 1.03–3.68), back pain (OR = 1.40, 95% CI: 1.22–1.60), and hip pain (OR = 2.29, 95% CI: 1.18–4.45) promote the genetic liability of insomnia. Depression is strongly associated with the predisposition of multisite pain including headache (OR = 1.28, 95% CI: 1.08–1.52), neck/shoulder pain (OR = 1.32, 95% CI: 1.16–1.50), back pain (OR = 1.35, 95% CI: 1.10–1.66) and stomach/abdominal pain (OR = 1.14, 95% CI: 1.05–1.25), while headache (OR = 1.06, 95% CI: 1.03–1.08), neck/shoulder (OR = 1.09, 95% CI: 1.01–1.17), back (OR = 1.08, 95% CI: 1.03–1.14), and stomach/abdominal pain (OR = 1.19, 95% CI: 1.11–1.26) are predisposing factors for depression. Additionally, insomnia is associated with the predisposition of facial, stomach/abdominal, and knee pain, anxiety was associated with the predisposition of neck/shoulder and back pain, while the susceptibilities of hip and facial pain are influenced by depression, but these associations were unidirectional. Conclusions Our results enhance the understanding of the complex interplay between pain and mental health and highlight the importance of a holistic approach to pain management that addresses both physical and psychological factors.

Abstract Background Nasopharyngeal carcinoma (NPC) is a type of head and neck cancer with high incidence in China. The molecular mechanisms of vasculogenic mimicry (VM) and angiogenesis are not fully elucidated in NPC. More specially, it has seldomly been reported that Epstein–Barr virus‐encoded miRNA can regulate VM and angiogenesis in NPC. The aim of this study was to investigate the function and molecular mechanism of a targeting exosome system (iRGD‐exo‐antagomiR) against VM and angiogenesis in NPC, and to provide new approaches for improving the comprehensive treatment of NPC. Methods Exosomes were isolated by differential ultracentrifugation. Dynamic light scattering, transmission electron microscopy and western blotting were performed to characterize the exosomes. The 3D‐Culture assay, tube formation assay, chicken chorioallantoic membrane assay, Matrigel plug assay, mouse xenograft tumor modeling and immunohistochemical staining were applied to evaluate the anti‐VM and anti‐angiogenic effects of the targeting exosome system in vitro and in vivo. Western blot was performed to detect the changes of downstream regulated networks following interference and recovery of the target gene. Results In vitro or in vivo treatment with iRGD‐tagged exosome containing antagomiR‐BART1‐5p specifically suppressed VM and angiogenesis in NPC. EBV‐miR‐BART1‐5p promoted VM and angiogenesis in vitro and in vivo by regulating VEGF, PI3K, Akt, mTOR and HIF1‐α in a Spry2‐dependent manner. Conclusions Our findings demonstrated that targeting exosomes enveloped EBV‐miR‐BART1‐5p‐antagomiRs in a Spry2‐dependent manner for NPC therapy through both anti‐VM and anti‐angiogenesis in vitro and in vivo.

Natural polysaccharides extracted from plants have received increasing attention due to their rich bioactivity. In our study, peach gum polysaccharides (PGPs) were extracted by water extraction-alcohol precipitation method. PGPs are typical pyranose polysaccharides with a mean molecular weight of 3.68 × 106 g/mol. The antioxidant activity and hepatoprotective capacity of PGPs were studied. In vitro, assays showed that PGPs scavenged DPPH, OH, and O2– in a dose-dependent manner. PGPs exhibited antioxidative properties against alcohol-induced HL7702 cells, as evidenced by the normalization of MDA, SOD, ROS, and GSH levels. To further elucidate the hepatoprotective mechanism of PGPs, we carried out in vivo experiments in male mice. PGPs exerted hepatoprotective effects in alcohol liver disease (ALD) mice by exerting antioxidant effects, decreasing the inflammatory response and modulating lipid metabolism. In addition, metabolomic analysis indicated that PGPs mainly regulate D-glutamine and D-glutamate metabolism, alanine, aspartate and glutamate metabolism, and arginine biosynthesis to promote hepatic metabolism and maintain body functions. Overall, this study revealed that the hepatoprotective mechanism of PGPs against ALD might be associated with the regulation of oxidative stress and lipid metabolism.

BackgroundExtensive evidence links Clonorchis sinensis (C. sinensis) to cholangiocarcinoma; however, its association with hepatocellular carcinoma (HCC) is less acknowledged, and the underlying mechanism remains unclear. This study was designed to investigate the association between C. sinensis infection and HCC and reveal the relationship between C. sinensis infection and cancer stemness.MethodsA comprehensive analysis of 839 HCC patients categorized into C. sinensis (-) HCC and C. sinensis (+) HCC groups was conducted. Chi-square and Mann-Whitney U tests were used to assess the association between C. sinensis infection and clinical factors. Kaplan-Meier and Cox regression analyses were used to evaluate survival outcomes. Immunohistochemistry was used to determine CK19 and EpCAM expression in HCC specimens.ResultsCompared to C. sinensis (-) HCC patients, C. sinensis (+) HCC patients exhibited advanced Barcelona Clinic Liver Cancer (BCLC) stage, higher male prevalence and more liver cirrhosis as well as elevated alpha-fetoprotein (AFP), carbohydrate antigen 19-9 (CA19-9), eosinophil, complement 3 (C3), and complement 4 (C4) values. C. sinensis infection correlated with shorter overall survival (OS) (p < 0.05) and recurrence-free survival (RFS) (p < 0.05). Furthermore, Cox multivariate analysis revealed that C. sinensis infection was an independent prognostic factor for OS in HCC patients. Importantly, C. sinensis infection upregulated the expression of HCC cancer stem cell markers CK19 and EpCAM.ConclusionHCC patients with C. sinensis infection exhibit a poor prognosis following hepatectomy. Moreover, C. sinensis infection promotes the acquisition of cancer stem cell-like characteristics, consequently accelerating the malignant progression of HCC.Author summaryClonorchis sinensis (C. sinensis) is a prominent food-borne parasite prevalent in regions such as China, particularly in Guangxi. C. sinensis has been associated with various hepatobiliary system injuries, encompassing inflammation, periductal fibrosis, cholangiocarcinoma and even hepatocellular carcinoma (HCC). A substantial body of evidence links C. sinensis to cholangiocarcinoma, However, the connection between C. sinensis and HCC and the intricate mechanisms underlying its contribution to HCC development remain incompletely elucidated. Our study demonstrates clear clinicopathological associations between C. sinensis and HCC, such as gender, BCLC stage, liver cirrhosis, MVI, AFP, CA19-9, circulating eosinophils and complements. Furthermore, we found that the co-occurrence of C. sinensis exhibited a significant association with shorter OS and RFS in patients diagnosed with HCC. A major finding was that C. sinensis infection promotes the acquisition of cancer stem cell-like characteristics, consequently accelerating the malignant progression of HCC. Our results provide a more comprehensive comprehension of the interplay between C. sinensis and HCC, shedding fresh light on the carcinogenic potential of C. sinensis.

Summary: Ubiquitination modification is an important post-translational modification that regulates the stability and function of proteins. Here, we present a protocol to detect the K27-linked polyubiquitination of exogenous and endogenous mitochondrial antiviral signaling protein. We describe steps for detecting ubiquitination of exogenous protein, transfecting the encoding plasmid of the protein, and immunoprecipitating the target protein with an antibody. We then detail procedures for detecting ubiquitin of the target protein by western blot. This protocol applies to other proteins of interest.For complete details on the use and execution of this protocol, please refer to Jiang et al. (2023).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

ABSTRACTCurrent unprecedented mpox outbreaks in non-endemic regions represent a global public health concern. Although two live-attenuated vaccinia virus (VACV)-based vaccines have been urgently approved for people at high risk for mpox, a safer and more effective vaccine that can be available for the general public is desperately needed. By utilizing a simplified manufacturing strategy of mixing DNA plasmids before transcription, we developed two multi-antigen mRNA vaccine candidates, which encode four (M1, A29, B6, A35, termed as Rmix4) or six (M1, H3, A29, E8, B6, A35, termed as Rmix6) mpox virus antigens. We demonstrated that those mpox multi-antigen mRNA vaccine candidates elicited similar potent cross-neutralizing immune responses against VACV, and compared to Rmix4, Rmix6 elicited significantly stronger cellular immune responses. Moreover, immunization with both vaccine candidates protected mice from the lethal VACV challenge. Investigation of B-cell receptor (BCR) repertoire elicited by mpox individual antigen demonstrated that the M1 antigen efficiently induced neutralizing antibody responses, and all neutralizing antibodies among the top 20 frequent antibodies appeared to target the same conformational epitope as 7D11, revealing potential vulnerability to viral immune evasion. Our findings suggest that Rmix4 and Rmix6 from a simplified manufacturing process are promising candidates to combat mpox.

BackgroundCOVID-19 has the potential to greatly impact an individual mental well-being. However, an individual’s psychological resilience, combined with support from their community and government disaster relief efforts can aid individuals in confronting crises with a positive mindset. The purpose of this study is to investigate how individuals, across three dimensions of individual resilience perception, community resilience perception, and government trust perception, mitigate individual anxiety during COVID-19.MethodsThis study employed an online survey method that was not restricted by geographical location. Data collection took place from January 2022 to June 2022, and the valid questionnaires covered all 31 provinces, autonomous regions, and municipalities in China. The assessment of community resilience was conducted employing the Conjoint Community Resilience Assessment Measure-10 (CCRAM-10). Structural Equation Modeling (SEM) was also used to examine the relationship between community resilience, government trust, individual psychological resilience, and anxiety.ResultsThe SEM results reveal that individual psychological resilience is significantly negatively correlated with anxiety (b = −0.099, p

The incidence of hyperuricemia is on the rise in China, primarily due to dietary habits. However, limited data exists regarding dietary purine intake in the country. This study aimed to estimate the daily dietary purine intake among Chinese residents from 2014 to 2021 and evaluate the temporal trend using joinpoint regression analysis. The analysis revealed an annual percentage change (APC) of 0.8% (95% CI: 0.1–1.5%) in dietary purine intake prior to the joinpoint (2014–2019). Following the joinpoint (2019–2021), the APC significantly increased to 6.5% (95% CI: 3.3–9.8%), indicating a noteworthy upward trend (p = 0.045). Furthermore, the average daily purine intake varied significantly among different regions of China, with the southern region showing the highest dietary intake of purines. Considering the diverse contributions of various food sources to dietary purine intake, it was observed that meat consumption had the greatest impact, accounting for 36.2% of purine intake, followed by cereals consumption (25.3%) and vegetables and edible fungi (24.2%). These findings hold significance for dietary intervention and management strategies aimed at reducing purine intake among the population.

Abstract Background During the COVID-19 pandemic, it is vital for individuals to comply with the government’s prevention and control measures. This study aims to explore determinants of college students’ compliance behaviour during the COVID-19 pandemic. Methods This study conducted an online survey among 3,122 individuals aged 18 and above from March to November 2022 in China. Individuals’ compliance behaviour was divided into protective behaviour (that includes wearing a mask, maintaining a physical distance, and getting vaccinated) and restrictive behaviour (that includes offering health codes and a nucleic acid test certificate). Individuals’ compliance motivation was divided into calculated motivation (including the fear of being infected, the fear of being published, and previous experience of pandemic prevention) and normative motivation (including the sense of social responsibility and trust in government). We defined young people aged between 18 and 24 with a college degree as young elites, and constructed ordinary least squares linear regression to compare their compliance behaviour with young people without a college degree (young non-elites), and non-young people with a college degree (non-young elites). Results Almost three years after the outbreak of the pandemic, Chinese individuals retained a high degree of compliance with COVID-19 prevention and control policies, particularly with respect to the provision of health codes. Young elites were more compliant with getting vaccinated, wearing a mask, providing health codes and testing results than their counterparts. The sense of social responsibility and trust in government were the major drivers of young elites’ compliance behaviour during the pandemic. Young elites who were male, had a rural “hukou”, and were not a member of the China Communist Party were more compliant with COVID-19 prevention and control measures. Conclusion This study found that young elites in China had high policy compliance during the COVID-19 pandemic. These young elites’ compliance behaviour was driven by their sense of social responsibility and trust in government rather than the fear of being infected and the fear of being punished as a result of violating the regulations. We suggest that in the context of managing health crises, in stead of introducing punitive measures to enforce citizens to comply with the management measures, promoting citizens’ sense of social responsibility and building a trusting relationship with citizens contrite to the enhancement of citizens’ policy compliance.

Abstract Thymic epithelial tumors (TETs) are a relatively rare type of thoracic tumor, accounting for less than 1% of all tumors. The incidence of TETs is about 3.93/10000 in China, slightly higher than that of European and American countries. For resectable TETs, complete surgical resection is recommended. Radiotherapy or chemotherapy may be used as postoperative adjuvant treatment. Treatment for advanced, unresectable TETs consist mainly of radiotherapy and chemotherapy, but there is a lack of standard first‐ and second‐line treatment regimens. Recently, targeted therapies and immune checkpoint inhibitors have shown promising outcomes in TETs. Based on the currently available clinical evidences and the opinions of the national experts, the Thymic Oncology Group of Yangtze River Delta Lung Cancer Cooperation Group (East China LUng caNcer Group, ECLUNG; Youth Committee) established this Chinese expert consensus on the clinical diagnosis and treatment of TETs, covering the epidemiology, diagnosis, treatment, prognosis and follow‐up of TETs.

Abstract Animal models play crucial roles in the rapid development of vaccines/drugs for the prevention and therapy of COVID-19, but current models have some deficits when studying the pathogenesis of SARS-CoV-2 on some special tissues or organs. Here, we generated a human ACE2 and SARS-CoV-2 NF/F knockin mouse line that constitutively expresses human ACE2 and specifically expresses SARS-CoV-2 N gene induced by Cre-recombinase. By crossing with Cre transgenic lines allowing for lung-specific and constitutive expression, we generated lung-specific (Sftpc-hACE2-NF/F) and constitutive SARS-CoV-2 N (EIIa-hACE2-NF/F) expressing mice. Upon intranasal infection with a SARS-CoV-2 GFP/ΔN strain which can only replicate in SARS-CoV-2 N expressed cells, we demonstrated that both the Sftpc-hACE2-NF/F and EIIa-hACE2-NF/F mice support viral replication. Consistent with our design, viral replication was limited to the lung tissues in Sftpc-hACE2-NF/F mice, while the EIIa-hACE2-NF/F mice developed infections in multiple tissues. Furthermore, our model supports different SARS-CoV-2 variants infection, and it can be successfully used to evaluate the effects of therapeutic monoclonal antibodies (Ab1F11) and antiviral drugs (Molnupiravir). Finally, to test the effect of SARS-CoV-2 infection on male reproduction, we generated Sertoli cell-specific SARS-CoV-2 N expressed mice by crossing with AMH-Cre transgenic line. We found that SARS-CoV-2 GFP/ΔN strain could infect Sertoli cells, led to spermatogenic defects due to the destruction of blood-testis barrier. Overall, combining with different tissue-specific Cre transgenic lines, the human ACE2 and SARS-CoV-2 NF/F line enables us to evaluate antivirals in vivo and study the pathogenesis of SARS-CoV-2 on some special tissues or organs.

Abstract Background Studies have not systematically compared the ability to verify performance of prognostic transcripts in paired bulk mononuclear cells versus viable CD34-expressing leukemic blasts from patients with acute myeloid leukemia. We hypothesized that examining the homogenous leukemic blasts will yield different biological information and may improve prognostic performance of expression biomarkers. Methods To assess the impact of cellular heterogeneity on expression biomarkers in acute myeloid leukemia, we systematically examined paired mononuclear cells and viable CD34-expressing leukemic blasts from SWOG diagnostic specimens. After enrichment, patients were assigned into discovery and validation cohorts based on availability of extracted RNA. Analyses of RNA sequencing data examined how enrichment impacted differentially expressed genes associated with pre-analytic variables, patient characteristics, and clinical outcomes. Results Blast enrichment yielded significantly different expression profiles and biological pathways associated with clinical characteristics (e.g., cytogenetics). Although numerous differentially expressed genes were associated with clinical outcomes, most lost their prognostic significance in the mononuclear cells and blasts after adjusting for age and ELN risk, with only 11 genes remaining significant for overall survival in both cell populations (CEP70, COMMD7, DNMT3B, ECE1, LNX2, NEGR1, PIK3C2B, SEMA4D, SMAD2, TAF8, ZNF444). To examine the impact of enrichment on biomarker verification, these 11 candidate biomarkers were examined by quantitative RT/PCR in the validation cohort. After adjusting for ELN risk and age, expression of 4 genes (CEP70, DNMT3B, ECE1, and PIK3CB) remained significantly associated with overall survival in the blasts, while none met statistical significance in mononuclear cells. Conclusions This study provides insights into biological information gained/lost by examining viable CD34-expressing leukemic blasts versus mononuclear cells from the same patient and shows an improved verification rate for expression biomarkers in blasts.

Pervious concrete is an innovative eco-friendly construction material. Through the application of mineral admixtures and microscopic analysis to optimize its performance and analyze its mechanisms, its traits as a sustainable building option may be further improved. This study primarily examines the impact of the optimal blend quantities of fly ash, silica fume, and reinforcing agent on the attributes, micro-morphology, and phase composition of porous concrete. The optimal admixture was chosen after analyzing the effects of various factors on the mix ratio and properties of permeable concrete. To understand the degree of impact, performance tests were conducted on the 28-day compressive strength, water permeability coefficient, and porosity. Furthermore, the micro-mechanisms of the admixtures and reinforcing agents on the properties of permeable concrete were analyzed from a microscopic point of view using scanning electron microscopy (SEM) and X-ray diffraction (XRD) analysis. This research found that the advantageous properties of permeable concrete were enhanced by the simultaneous integration of appropriate quantities of fly ash, silica fume, and reinforcing agent. This resulted in a 28-day compressive strength of 18.33 MPa and a permeability coefficient of 8.27 mm/s. Compared with the unadulterated mineral admixture, the optimal admixture of fly ash, silica fume, and reinforcing agent at the same time increased the 28-day compressive strength by about double; the permeability coefficient was reduced by 36%, but it was still at a high level; and the measured porosity did not differ much from the designed porosity. Through thorough microanalysis, the hydration reaction was significantly improved, which could enhance the microstructure and pore structure of the concrete. This was supported by a substantial increase in the macroscopic compressive strength and a decrease in the water permeability coefficient, which were consistent with the aforementioned enhancement found in the microanalysis.

Introduction Chronic low back pain (cLBP) is one of the largest and most frequent public health problems worldwide. Tuina is a physical therapy commonly used in China to treat musculoskeletal diseases. Compared with traction, there is little high-quality scientific evidence that can demonstrate the effectiveness of Tuina in the treatment of patients with cLBP. Therefore, the purpose of this clinical trial is to evaluate the effect of massage on cLBP patients compared with traction.Methods and analyses This is a single-centre, assessor-blinded and analyst-blinded prospective randomised controlled trial with two parallel arms. Ninety-four patients with cLBP will be recruited. Three treatments were given every week for a total of 4 weeks. In the Traction group, participants were given traction therapy in the Tuina group, participants will receive a four-step physiotherapy including kneading, rolling, plucking and oblique pulling. The outcomes will be measured at baseline, at the end of treatment, as well as 1 and 2 months after treatment. The primary outcome will be the Hamilton Anxiety Scale after 12 sessions of treatment. The secondary outcomes will be the Visual Analogue Scale, the medical outcomes study Short Form 36, Serum Quantitative Index and genetic testing after 12 sessions of treatment.Ethics and dissemination The study was approved by the Ethics Committee of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine affiliated with Shanghai University of Traditional Chinese Medicine.Trial registration number ChiCTR2200065448.

BTK inhibitors, Bcl-2 inhibitors, and other targeted therapies have significantly improved the outcomes of patients with chronic lymphocytic leukemia (CLL). With increased survivorship, monitoring disease and deciphering potential mechanisms of resistance to these agents are critical for devising effective treatment strategies. We used duplex sequencing, a technology that enables detection of mutations at ultra-low allelic frequencies, to identify mutations in five genes associated with drug resistance in CLL and followed their evolution in two patients who received multiple targeted therapies and ultimately developed disease progression on pirtobrutinib. In both patients we detected variants that expanded and reached significant cancer cell fractions (CCF). In patient R001, multiple known resistance mutations in both BTK and PLCG2 appeared following progression on zanubrutinib (BTK p.L528W, p.C481S; PLCG2 S707F, L845F, R665W, and D993H). In contrast, patient R002 developed multiple BTK mutations following acalabrutinib treatment, including known resistance mutations p.C481R, p.T474I and p.C481S. We found that pirtobrutinib was able to suppress, but not completely eradicate, BTK p.C481S mutations in both patients, but other resistance mutations such as mutations in PLCG2 and new BTK mutations increased while the patients were receiving pirtobrutinib. For example, BTK p.L528W in patient R001 increased in frequency more than 1,000-fold (from a CCF of 0.02% to 35%), and the CCF in p.T474I in patient R002 increased from 0.03% to 4.2% (more than 100-fold). Our data illuminate the evolutionary dynamics of resistant clones over the patients’ disease course and under selective pressure from different targeted treatments.

In this paper, the antihypertension effect of rice peptide (RP) was studied. With spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) as the research objects, RP disposable gastric and long-term gastric irrigation experiments were carried out and systolic blood pressure (SBP) was measured. At the end of the long-term gastric irrigation experiment, the content of nitric oxide (NO), angiotensin-converting enzyme (ACE), angiotensin II (Ang II) and renin in the plasma and the activity of ACE were determined. The results showed that RP could reduce systolic pressure of SHR and had time-dose dependence while high-dose RP significantly reduced systolic pressure by 24.6 and 17.2 mmHg, respectively after a single and long-term gastric irrigation test. RP also could inhibit the activity of ACE and increase the release of NO. These results suggested that the decompression mechanism of RP is likely to be related to the regulation of the renin-angiotensin system (RAS) and NO.

Abstract Background Since early 2022, patients with 2019 novel coronavirus (COVID-19) infection have increased rapidly in Shanghai, China. Nevertheless, there is no widely used unified rehabilitation treatment available for discharged patients with post-infection sequelae such as dyspnea, depression, and fatigue. To promote the rehabilitation of discharged patients, our team formulated Kangyi Qiangshen Gong exercise prescription on the basis of traditional Chinese medicine rehabilitation exercises (TCMRE). We designed a randomized controlled trial to evaluate the efficacy of rehabilitation and advantages of KQG for discharged patients with post-COVID-19 syndrome. Methods/design This is a parallel-design, two-arm, analyst assessor-blinded, randomized controlled trial. In total, 60 discharged patients with COVID-19 sequelae, aged from 20 to 80 years will be recruited and randomly assigned to the World Health Organization instructed breathing techniques (BT) group and the Kangyi Qiangshen Gong exercise prescription (KQG) group at a ratio of 1:1. The patients in the BT group will perform breathing techniques exercise, and the patients in the KQG group will perform KQG exercise. Both groups will perform exercises twice a day for 3 months. The primary outcome will be measured with the Modified Medical Research Council Dyspnea Scale, and the secondary outcomes will include the Modified Borg Scale, Fatigue Scale-14, Patient Health Questionnaire-9 Scale, Pittsburgh Sleep Quality Index, and the Respiratory Symptoms Scale. Clinical scales will be assessed at three points (pre-exercise, 3 months post-exercise, and 3 months follow-up). Adverse events will be recorded for safety assessment. Discussion This trial will serve high-quality evidence of the value of KQG for treating discharged patients with COVID-19 in rehabilitation period. Trial registration Chinese Clinical Trial Registry ChiCTR2200059504. Registered on 03 May 2022. Dissemination The results will be published in peer-reviewed journals and disseminated through the study’s website, and conferences.

Abstract Background Local neuroinflammation secondary to spinal nerve compression in lumbar disk herniation (LDH) is a key driver contributing to neuropathic pain. Manual therapy (MT), a widely used nonsurgical therapy, can relieve LDH-mediated pain by reducing inflammation. MT has attracted extensive attention; however, its mechanism remains poorly understood. MicroRNAs (miRNAs) are important regulators of pain signaling transduction, but are rarely reported in the chronic compression of dorsal root ganglia (CCD) model, and further investigation is needed to decipher whether they mediate anti-inflammatory and analgesic effects of MT. Methods We used a combination of in vivo behavioral and molecular techniques to study MT intervention mechanisms. Neuropathic pain was induced in a CCD rat model and MT intervention was performed according to standard procedures. Enzyme-linked immunosorbent assay (ELISA) was used to detect inflammatory cytokine levels in dorsal root ganglia (DRG). Small RNA sequencing, immunofluorescence, Western blot, and qRT-PCR were performed to screen miRNAs and their target genes and determine core factors in the pathway possibly regulated by miRNA-mediated target gene in DRG of MT-treated CCD rats. Results Compared with naive rats, small RNA sequencing detected 22 differentially expressed miRNAs in DRG of CCD rats, and compared with CCD rats, MT-treated rats presented 19 differentially expressed miRNAs, which were functionally associated with nerve injury and inflammation. Among these, miR-547-3p was screened as a key miRNA mediating neuroinflammation and participating in neuropathic pain. We confirmed in vitro that its function is achieved by directly regulating its target gene Map4k4. Intrathecal injection of miR-547-3p agomir or MT intervention significantly reduced Map4k4 expression and the expression and phosphorylation of IκBα and p65 in the NF-κB pathway, thus reducing the inflammatory cytokine levels and exerting an analgesic effect, whereas intrathecal injection of miR-547-3p antagomir led to opposite effects. Conclusions In rats, CCD-induced neuropathic pain leads to variation in miRNA expression in DRG, and MT can intervene the transcription and translation of inflammation-related genes through miRNAs to improve neuroinflammation and alleviate neuropathic pain. MiR-547-3p may be a key target of MT for anti-inflammatory and analgesia effects, which is achieved by mediating the Map4k4/NF-κB pathway to regulate downstream inflammatory cytokines.

Abstract Background The chronic pain of patients with knee osteoarthritis (KOA) seriously affects their quality of life and leads to heavy social and economic burden. As a nondrug therapy in Traditional Chinese Medicine (TCM), Tuina is generally recognised as safe and effective for reducing the chronic pain of KOA. However, the underlying central mechanisms of Tuina for improving the pain of KOA are not fully understood. Methods/design This study will be a randomised controlled trial with a parallel-group design. A total of 60 eligible participants will be assigned to the Tuina group or healthcare education group (Education group) at 1:1 ratio using stratified randomisation with gender and age as factors. The interventions of both groups will last for 30 min per session and be conducted twice each week for 12 weeks. This study will primarily focus on pain evaluation assessed by detecting the changes in brain grey matter (GM) structure, white matter (WM) structure, and the cerebral functional connectivity (FC) elicited by Tuina treatment, e.g., thalamus, hippocampus, anterior cingulate gyrus, S1, insula, and periaqueductal grey subregions (PAG). The two groups of patients will be evaluated by clinical assessments and multimodal magnetic resonance imaging (MRI) to observe the alterations in the GM, WM, and FC of participants at the baseline and the end of 6 and 12 weeks’ treatment and still be evaluated by clinical assessments but not MRI for 48 weeks of follow-up. The visual analogue scale of current pain is the primary outcome. The Short-Form McGill Pain Questionnaire, Western Ontario and McMaster Universities Osteoarthritis Index, 36-Item Short Form Health Survey, Hamilton Depression Scale, and Hamilton Anxiety Scale will be used to evaluate the pain intensity, pain feeling, pain emotion, clinical symptoms, and quality of life, respectively. MRI assessments, clinical data evaluators, data managers, and statisticians will be blinded to the group allocation in the outcome evaluation procedure and data analysis to reduce the risk of bias. The repeated measures analysis of variance (2 groups × 6 time points ANOVA) will be used to analyse numerical variables of the clinical and neuroimaging data obtained in the study. P

IntroductionLumbar disc herniation, a chronic degenerative disease, is one of the major contributors to chronic low back pain and disability. Although many studies have been conducted in the past on brain function in chronic low back pain, most of these studies did not classify chronic low back pain (cLBP) patients according to their etiology. The lack of etiologic classification may lead to inconsistencies between findings, and the correlation between differences in brain activation and clinical symptoms in patients with cLBP was less studied in the past.MethodsIn this study, 36 lumbar disc herniation patients with chronic low back pain (LDHCP) and 36 healthy controls (HCs) were included to study brain activity abnormalities in LDHCP. Visual analogue scale (VAS), oswestry disability index (ODI), self-rating anxiety scale (SAS), self-rating depression scale (SDS) were used to assess clinical symptoms.ResultsThe results showed that LDHCP patients exhibited abnormally increased and diminished activation of brain regions compared to HCs. Correlation analysis showed that the amplitude of low frequency fluctuations (ALFF) in the left middle frontal gyrus is negatively correlated with SAS and VAS, while the right superior temporal gyrus is positively correlated with SAS and VAS, the dorsolateral left superior frontal gyrus and the right middle frontal gyrus are negatively correlated with VAS and SAS, respectively.ConclusionLDHCP patients have brain regions with abnormally increased and abnormally decreased activation compared to healthy controls. Furthermore, some of the abnormally activated brain regions were correlated with clinical pain or emotional symptoms.

Tuina, a method of traditional Chinese manual manipulation, is an effective alternative therapy for neuropathic pain (NP), but its analgesic mechanism remains unclear. In this study, we used resting-state functional magnetic resonance imaging (R-fMRI) to explore the analgesic mechanism of Tuina in an NP rat model. After undergoing surgery to induce chronic compression of the dorsal root ganglion (CCD), one group of rats underwent Tuina at the ipsilateral BL40 acupoint once a day for 10 min during the 25 days following surgery while another group did not. Behavioral tests were performed at baseline, on the third day following surgery, and once a week for the next 4 weeks. R-fMRI was performed at baseline and 7 days and 28 days following surgery. Behavioral testing revealed that the Tuina group presented a significant response improvement to mechanical and thermal nociception stimuli compared to the untreated group 2 weeks following CCD surgery. Interestingly, rats submitted to Tuina presented higher measures of spontaneous neuronal activity in basal forebrain region, primary somatosensory cortex barrel field, dentate gyrus, secondary somatosensory cortex, striatum, descending corticofugal pathways, and globus pallidum of the left hemisphere 4 weeks after the CCD surgery compared to rats having undergone CCD only. In addition, on the 28th day, the ALFF signals of the left dentate gyrus, left secondary somatosensory cortex, left striatum, and bilateral primary cingulate cortex were significantly increased while those in the right dentate gyrus and bilateral periaqueductal gray were significantly decreased compared to those on the 7th day. Correlation analysis showed that the ALFF values of the left descending corticofugal pathways and globus pallidum had a positive correlation with mechanical withdrawal threshold and paw withdrawal thermal latency tests. Altogether, these results indicate that NPP induced by CCD surgery affects the plasticity of the cerebral cortex, and that Tuina alleviate pain behavior by promoting cortical remodeling.

ObjectiveTo evaluate the efficacy of Traditional Chinese Exercises (TCEs) in treating knee osteoarthritis (KOA).MethodsFour databases without language or publication status restrictions were searched until April 1, 2022. Based on the principle of Population, Intervention, Comparison, Outcomes and Study design, the researchers searched for randomized controlled trials of TCEs in treating KOA. The Western Ontario and McMaster Universities Osteoarthritis (WOMAC) pain was defined as the primary outcome, whereas stiffness and physical function were the secondary outcomes. Subsequently, two researchers conducted the process independently, and the data were analyzed using the RevManV.5.3 software.ResultsOverall, 17 randomized trials involving 1174 participants met the inclusion criteria. The synthesized data of TCEs showed a significant improvement in WOMAC pain score [standardized mean difference (SMD) = −0.31; 95% confidence interval (CI): −0.52 to −0.10; p = 0.004], stiffness score (SMD = −0.63; 95% CI: −1.01 to −0.25; p = 0.001) and physical function score (SMD = −0.38; 95% CI: −0.61 to −0.15; p = 0.001) compared with the control group. Sensitivity analyses were performed to determine the combined results' stability, which was unstable after excluding articles with greater heterogeneity. A further subgroup analysis showed that it might be the reason for the heterogeneity of the different traditional exercise intervention methods. Additionally, it showed that the Taijiquan group improved pain (SMD = 0.74; 95% CI: −1.09 to 0.38; p < 0.0001; I2 = 50%), stiffness (SMD = −0.67; 95% CI −1.14 to 0.20; p = 0.005) and physical function score (SMD = −0.35; 95% CI: −0.54 to 0.16; p = 0.0003; I2 = 0%) better than the control group. The Baduanjin group improved stiffness (SMD = −1.30; 95% CI: −2.32 to 0.28; p = 0.01) and physical function (SMD = −0.52; 95% CI: −0.97 to 0.07; p = 0.02) better than the control group. However, the other interventions showed no difference compared with the control group.ConclusionThis systematic review provides partial evidence of the benefits of TCEs for knee pain and dysfunction. However, due to the heterogeneity of exercise, more high-quality clinical studies should be conducted to verify the efficacy.Systematic review registrationhttps://inplasy.com/inplasy-2022-4-0154/, identifier: International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY) [INPLSY202240154].