Aims: Patellar luxation can cause abnormal mechanical loading and is a leading cause of patellofemoral joint damage, however its contribution to femoral-tibial joint damage is poorly elucidated. In this study, we sought to investigate the role of patellar luxation in the femoral-tibial joint in both mice and humans. Methods: In this study, we generated a patellar luxation mouse model based on the standard operating procedure of destabilization of the medial meniscus (DMM) surgery which mimics osteoarthritis (OA). Then phenotypes including gait analysis, osteophyte formation, aberrant subchondral bone remodelling, cartilage degeneration, and synovitis of femoral-tibial joint were evaluated in vivo at eight weeks after surgery. Additionally, we also performed a retrospective study to investigate femoral-tibial joint characteristics in 18 patients with post-traumatic OA or recurrent patellar luxation. Results: We found that patellar luxation caused abnormal gait and augmented osteophyte outgrowth around the tibial plateau and patella. Furthermore, micro-CT analysis showed that mice treated with patellar luxation operation exhibited aberrant subchondral bone remodelling. Intriguingly, according to Safranin-O/Fast Green staining, mice with patellar luxation showed better articular cartilage integrity and less cartilage proteoglycan damage in the medial compartment of the femoral-tibial joint. Moreover, either patellar luxation operation or DMM surgery promoted the expression of TNF-α and F4/80 in synovium tissue. However, mice subjected to patellar luxation exhibited aggressive cartilage erosion in the lateral compartment of the knee joint. In addition, the clinical study showed that patellar luxation was associated with lateral cartilage degeneration of the femoral-tibial joint. Conclusion: This study confirmed that lateral patellar luxation induced subchondral bone osteopenia, promoted osteophyte formation as well as synovial inflammation, and caused lateral cartilage rather than medial cartilage degeneration in the femoral-tibial joint. Cite this article: Bone Joint Res 2026;15(4):363–374.

BACKGROUND:Gastric cancer (GC), one of the most prevalent malignancies worldwide, is characterized by complex etiological and pathological mechanisms. Emerging evidence on the dysregulation of circadian clock genes has revealed promising opportunities for improving the diagnosis, treatment, and prognosis of patients with GC. METHODS:This study utilized a multifaceted approach combining machine learning algorithms, gene set enrichment analysis, immune infiltration profiling, survival prognosis analysis, drug sensitivity testing, and in vitro experiments to investigate the functional roles of core clock genes in GC. RESULTS:By integrating data from The Cancer Genome Atlas, Gene Expression Omnibus datasets, and the National Center for Biotechnology Information database, we identified 29 differentially expressed clock genes in GC. Among these, the application of four distinct machine learning algorithms highlighted TIMELESS (TIM) and BHLHE41 as pivotal genes, with TIM demonstrating notable diagnostic performance (area under the receiver operating characteristic curve = 0.802). Elevated TIM expression was strongly associated with poor clinical prognosis and increased infiltration of immune cells in tumor tissues. Notably, a specific interaction was identified between TIM and the pyroptosis-associated molecule CASP8, indicating a potential synergistic role in GC pathogenesis. Additionally, bortezomib emerged as a potential targeted therapeutic agent capable of modulating TIM activity in GC. CONCLUSION:TIM is identified as a promising diagnostic biomarker and therapeutic target in GC, offering valuable implications for improving patient prognosis and guiding personalized treatment strategies.

The integration of self-healing properties into waterborne polyurethane (WPU) represents a significant advancement in materials chemistry. However, the practical application of self-healing WPU is often hindered by its compromised toughness, flexibility, and water resistance, as well as the challenges accompanied by complex production processes and high manufacturing costs. In this study, we propose a novel network optimization strategy that leverages the synergistic effects of multiple lateral hydrogen bonds from amide (A)-urea (U) motifs, hydrophobic aggregation of non-crystalline flexible alkyl segments, branched topology, and intrinsic intermolecular interactions within WPU. This strategy is implemented through a straightforward, stepwise chain extension synthesis of WPU, incorporating a biomass-derived chain extender (CA) designed from the condensation of cost-effective dimer acid and pentylenediamine. Remarkably, the optimized WPU exhibited bio-elastic tissue-like properties, including self-healing capability, high strength, toughness, ductility, low modulus and minimal water absorption. The self-healed material, derived from recycled film fragments, achieves an ultimate tensile strength of 41.4 MPa and an elongation at break of 1040%, with no significant stiffening or loss of elasticity. Additionally, the material demonstrated excellent interfacial adhesion, conductivity and strain sensitivity, making it suitable for use as a conductive elastomer. Furthermore, when plasticized with electrolytes, the material exhibited room-temperature self-healing within the conductive network, providing broad potential for applications in flexible electronics and related fields.

Inflammation and pyroptosis are key characteristic features of Atherosclerosis (AS), a complex, multifaceted chronic vascular disease. Although microRNAs (miRNAs) have been substantially implicated, as pivotal post-transcriptional regulators, in molecular mechanisms underlying atherosclerotic development, the precise role of miR-9-3p in atherosclerotic progression remains unclear. Herein, we aimed to elucidate the regulatory function of miR-9-3p in Endothelial Cell pyroptosis and AS via integrated bioinformatics analysis, as well as in vitro and in vivo assays. We focused on identifying signaling pathways miR-9-3p modulated and assessing its potential to mitigate atherosclerotic plaque formation. According to the results, miR-9-3p promoted AKT phosphorylation by directly targeting the 3'-Untranslated Region (3'-UTR) of PTEN mRNA, suppressing EC pyroptosis. Notably, the AKT signaling pathway, which was significantly enriched in our analyses, functions upstream of the NLRP3 inflammasome, a principal mediator of pyroptosis. We also identified the SP1 Transcription Factor (TF) binding sites within the promoter region of MIR9-1HG, implying a regulatory mechanism in which SP1 modulates miR-9-3p expression and function. Given the reversibility of epigenetic modifications, the potential of restoring miR-9-3p expression presents a novel therapeutic strategy for AS. Overall, in addition to advancing the understanding of atherosclerotic treatment mechanisms, this study positions miR-9-3p as a potential therapeutic target.

Background: Cholangiocarcinoma (CHOL) is a malignant epithelial carcinoma of the digestive system with poor prognosis and high mortality. WNK lysine deficient protein kinase 1 (WNK1) is known to be associated with tumorigenesis in various cancers. However, the relationship between WNK1 and CHOL development, as well as the potential mechanisms involved, remains poorly understood. Methods: Microarray datasets of CHOL (GSE22633 and GSE32879) were retrieved from the Gene Expression Omnibus (GEO) database. Functional enrichment and immunoinfiltration analyses were performed for genes coexpressed with WNK1. GraphPad Prism 9 was utilized for statistical data analysis and the construction of receiver operating characteristic (ROC) curves. The impact of WNK1 on the CHOL tumor microenvironment was analyzed using Tumor Immune Estimation Resource (TIMER), Venn diagrams, STRING, and TISIDB database for information on WNK1-related chemokines and chemokine receptors. Protein-protein interaction (PPI) networks were used to predict transcription factors and microRNAs interacting with WNK1 and the associated hub genes. Results: Differential expression of WNK1 was observed between CHOL and normal samples, suggesting its diagnostic value. Functional analysis showed that WNK1 and its associated genes were primarily enriched in pathways such as leukocyte transendothelial migration and chemokine signaling. Neutrophils were the only type of infiltrating immune cells associated with WNK1 in the CHOL tumor microenvironment (TME). VEGFA and ALB were identified as hub genes, and X-C motif chemokine receptor 1 (XCR1) and C-X-C motif chemokine ligand 5 (CXCL5) were identified as core chemokines and chemokine receptors related to WNK1 and neutrophil infiltration in CHOL. Conclusions: Based on network analysis and the summary of previous studies, it was proposed that CHOL tumor cells secrete CXCL5, leading to neutrophil recruitment to the tumor microenvironment. Vascular endothelial growth factor A (VEGFA) released by the infiltrating neutrophils is suggested to promote overexpression of WNK1 by tumor cells, activating the VEGFA downstream pathway to promote angiogenesis and tumor progression.

Recurrent joint bleeding in hemophilia patients frequently causes hemophilic arthropathy (HA). Drastic degradation of cartilage is a major characteristic of HA, but its pathological mechanisms has not yet been clarified. In HA cartilages, we found server matrix degradation and increased expression of DNA methyltransferase proteins. We thus performed genome-wide DNA methylation analysis on human HA (N=5) and osteoarthritis (OA) (N=5) articular cartilages, and identified 1228 differentially methylated regions (DMRs) associated with HA. Functional enrichment analyses revealed the association between DMR genes (DMGs) and extracellular matrix (ECM) organization. Among these DMGs, Tenascin XB (TNXB) expression was down-regulated in human and mouse HA cartilages. The loss of Tnxb in F8-/- mouse cartilage provided a disease-promoting role in HA by augmenting cartilage degeneration and subchondral bone loss. Tnxb knockdown also promoted chondrocyte apoptosis and inhibited phosphorylation of AKT. Importantly, AKT agonist showed chondroprotective effects following Tnxb knockdown. Together, our findings indicate that exposure of cartilage to blood leads to alterations in DNA methylation, which is functionally related to ECM homeostasis, and further demonstrate a critical role of TNXB in HA cartilage degeneration by activating AKT signaling. These mechanistic insights allow development of potentially new strategies for HA cartilage protection.

Background:Intervertebral disc degeneration (IDD) is a major cause of lower back pain (LBP), in which inflammatory is frequently involved. Amygdalin (AMD) is a naturally occurring compound that exerts anti-fibrotic, anti-inflammatory, analgesic, and immunomodulatory effects in various diseases. The purpose of this study was to investigate the therapeutic effects and molecular mechanisms of AMD on Lumbar spine instability (LSI)-induced IDD in mice.Methods:In this study, we first explored the effects of AMD in vivo, and then further explored the mechanism of its effects both in vivo and in vitro. Ten-week-old male C57BL/6J mice were administrated with AMD. At 10 weeks after LSI, spinal were collected for tissue analyses, including histology, micro-CT, and immunohistochemistry for Col2, Mmp-13, TNF-α, and p-P65. Additionally, we also evaluated the mRNA and protein expression level of p-P65 and p-IKBα after being treated with AMD in vitro.Results:Histological staining, micro-CT and immunohistochemical analysis showed that AMD treatment significantly inhibited the expression of TNF-α and Mmp-13, increased the expression of Col2 as well as attenuated the calcification of cartilage endplates, eventually to delayed the progression of IDD. Meanwhile, in vivo and in vitro fluorescence imaging revealed that AMD markedly inhibited the AMD significantly inhibited the LSI-induced increase in TNF-α expression and P65and IKBα phosphorylation.Discussion:Our findings suggest that AMD partly inhibits the activation of NF-κB signaling pathway to reduce the release of inflammatory mediators and delay the degeneration of cartilage endplate in IDD model mice. Therefore, AMD may be a potential candidate for the treatment of IDD.

Allergic rhinitis (AR), a chronic airway inflammation, has witnessed a rising prevalence in recent decades. Recent research indicates that various EVs are released into plasma in allergic airway inflammation, correlating with impaired airway function and severe inflammation. However, the contribution of plasma EVs to AR pathogenesis remains incompletely understood. We isolated plasma EVs using differential ultracentrifugation or size exclusion chromatography (SEC) and obtained differential microRNA (miRNA) expression profiles through miRNA sequencing. Peripheral blood mononuclear cells (PBMCs) were exposed to plasma EVs and miRNA mimics and inhibitors to assess the effect of plasma EVs and the underlying mechanisms. We found that EVs from HC and AR patients exhibited comparable characteristics in terms of concentration, structure, and EV marker expression. AR-EVs significantly enhanced Th2 cell levels and promoted ILC2 differentiation and IL-13+ ILC2 levels compared to HC-EVs. Both HC-EVs and AR-EVs were efficiently internalized by CD4+ T cells and ILCs. miRNA sequencing of AR-EVs revealed unique miRNA signatures implicated in diverse biological processes, among which miR-150-5p, miR-144-3p, miR-10a-5p, and miR-10b-5p were identified as pivotal contributors to AR-EVs' effects on CD4+ T cells and ILC2s. MiR-150-5p exhibited the most pronounced impact on cell differentiation and was confirmed to be upregulated in AR-EVs by PCR. In total, our study demonstrated that plasma EVs from patients with AR exhibited a pronounced capacity to significantly enhance the differentiation of Th2 cells and ILC2, which was correlated with an elevated expression of miR-150-5p within AR-EVs. These findings contribute to the advancement of our comprehension of EVs in the pathogenesis of AR and hold the potential to unveil novel therapeutic targets for the treatment of AR.

Knee osteoarthritis (KOA), a major health and economic problem facing older adults worldwide, is a degenerative joint disease. Glycyrrhiza uralensis Fisch. (GC) plays an integral role in many classic Chinese medicine prescriptions for treating knee osteoarthritis. Still, the role of GC in treating KOA is unclear. To explore the pharmacological mechanism of GC against KOA, UPLC-Q-TOF/MS was conducted to detect the main compounds in GC. The therapeutic effect of GC on DMM-induced osteoarthritic mice was assessed by histomorphology, μCT, behavioural tests, and immunohistochemical staining. Network pharmacology and molecular docking were used to predict the potential targets of GC against KOA. The predicted results were verified by immunohistochemical staining Animal experiments showed that GC had a protective effect on DMM-induced KOA, mainly in the improvement of movement disorders, subchondral bone sclerosis and cartilage damage. A variety of flavonoids and triterpenoids were detected in GC via UPLC-Q-TOF/MS, such as Naringenin. Seven core targets (JUN, MAPK3, MAPK1, AKT1, TP53, RELA and STAT3) and three main pathways (IL-17, NF-κB and TNF signalling pathways) were discovered through network pharmacology analysis that closely related to inflammatory response. Interestingly, molecular docking results showed that the active ingredient Naringenin had a good binding effect on anti-inflammatory-related proteins. In the verification experiment, after the intervention of GC, the expression levels of pp65 and F4/80 inflammatory indicators in the knee joint of KOA model mice were significantly downregulated. GC could improve the inflammatory environment in DMM-induced osteoarthritic mice thus alleviating the physiological structure and dysfunction of the knee joint. GC might play an important role in the treatment of knee osteoarthritis.

筋属中医五体之一,其内涵丰富,分布遍及全身.筋在狭义上指具有连接骨节、协助运动功能的肌腱、韧带、筋膜等,广义上又可包括关节囊、腱鞘、椎间盘、关节软骨、神经、肌肉等组织.筋虽为肝所主,但与多脏腑在生理和病理上密切相关.除了外力损伤,多脏腑功能异常可以导致筋病,筋病亦可影响人体气血运行,引起内伤脏腑疾病.筋病治疗可采用中药、推拿、针灸、针刀、内热针、手术等多种疗法,临床可根据病情灵活选用.筋病的外治法注重整体平衡调节,除了医者以手法、器械等施治,引导患者自行运动配合治疗也十分重要;在内服汤药方面,尤其需要注重从肝论治筋病,辨别病之在气在血、寒热虚实,合理运用清肝、柔肝、泻肝、疏肝、镇肝、敛肝、补肝等法,以期提高临床疗效.

Objective To verify the clinical efficacy of Zhang’s Xibi formula (ZSXBF) and explain the mechanism underlying its therapeutic effect. Methods Preliminary elucidation of the clinical efficacy of ZSXBF in treating KOA in self-control studies, exploration of its mechanism of action with network pharmacology methods, and validation in animal experiments. Results In clinical studies, ZSXBF administration effectively improved patient quality of life and reduce pain. Network pharmacology was used to explore the possible mechanisms underlying its treatment effect, and after verification in clinical experience and animal experiments, it was found that ZSXBF regulated the expression of immune-related proteins such as IL-17, ERK1, and TP53 in mouse knee joints. Conclusion ZSXBF, which is a traditional Chinese medicine compound that is used to clear heat and detoxify, can effectively improve the clinical symptoms of KOA patients, and its underlying mechanism includes the regulation of human immune-related proteins.

OBJECTIVE:The study aims to investigate and visualize the hotspots of acupuncture for Allergic rhinitis (AR) over the past two decades and pinpoint future trends in this field.METHOD:We conducted a systematic search of English-language articles or reviews on acupuncture for AR in the Web of Science Core Collection from 2002 to 2022. Using Citespace, VOSviewer, and Bibliometrix, we analyzed and visualized the publications, countries, institutions, authors, journals, and keywords from various angles.RESULT:The study identified 197 documents, 80 journals, 458 keywords, and 928 authors associated with acupuncture for AR. Although article publication fluctuated over the past 20 years, an overall upward trend emerged, with rapid growth during the second decade. China contributed the most to acupuncture research on AR and had the closest collaborations with the United States and Germany. China Medical University was the most prolific institution, and Benno Brinkhaus was the most productive and influential author. The most published journal was Medicine, while the Journal of Allergy and Clinical Immunology was the most frequently cited journal. The highest frequency keywords included acupuncture, allergic rhinitis, and asthma. Randomized controlled trials and alternative & complementary medicine remained significant research hotspots, while rhinoconjunctivitis is expected to be the emerging focus of future investigations.CONCLUSION:acupuncture has experienced robust development for the treatment of allergic rhinitis over the last two decades, with rhinoconjunctivitis and clinical research being the anticipated trends and frontiers of future research.

Background Knee osteoarthritis (KOA) is the primary prevalent disabling joint disorder among osteoarthritis (OA), and there is no particularly effective treatment at the clinic. Traditional Chinese medicine (TCM) herbs, such as Eucommia ulmoides Oliv. and Glycyrrhiza uralensis Fisch. (E.G.) couplet medicines, have been reported to exhibit beneficial health effects on KOA, exact mechanism of E.G. nevertheless is not fully elucidated. Purpose We assess the therapeutic effects of E.G. on KOA and explore its underlying molecular mechanism. Methods UPLC-Q-TOF/MS technique was used to analyze the active chemical constituents of E.G. The destabilization of the medial meniscus model (DMM) was employed to evaluate the chondroprotective action of E.G. in KOA mice using histomorphometry, μCT, behavioral testing and immunohistochemical staining. Additionally, network pharmacology and molecular docking were used to predict potential targets for anti-KOA activities of E.G., which was further verified through in vitro experiments. Results In vivo studies have shown that E.G. could significantly ameliorate DMM-induced KOA phenotypes including subchondral bone sclerosis, cartilage degradation, gait abnormality and thermal pain reaction sensibility. E.G. treatment could also promote extracellular matrix synthesis to protect articular chondrocytes, which was indicated by Col2 and Aggrecan expressions, as well as reducing matrix degradation by inhibiting MMP13 expression. Interestingly, network pharmacologic analysis showed that PPARG might be a therapeutic center. Further study proved that E.G.-containing serum (EGS) could up-regulate PPARG mRNA level in IL-1β-induced chondrocytes. Notably, significant effects of EGS on the increment of anabolic gene expressions (Col2, Aggrecan) and the decrement of catabolic gene expressions (MMP13, Adamts5) in KOA chondrocytes were abolished due to the silence of PPARG. Conclusion E.G. played a chondroprotective role in anti-KOA by inhibiting extracellular matrix degradation, which might be related to PPARG.

Osteoarthritis (OA) is an entire joint disease with pathological alteration in both articular cartilage and subchondral bone. It has been recognized recently the association between metabolic syndrome and OA, particularly glucose metabolism in regulation of articular cartilage homeostasis and joint integrity. Whereas the role of glucose metabolism in subchondral bone sclerosis remains largely unknown during pathogenesis of OA. Consistent with common OA features, we observed subchondral bone sclerosis and abnormal bone remodeling in human OA joints and murine OA joints as reflected by hyperactive bone resorption and overall bone formation which was measured via dynamic histomorphometry. Osx-CreER;tdTomato mice also displayed the similar overall bone formation under injury-induced OA condition. Immunohistochemistry further revealed increased IL-1β expression in human and murine OA subchondral bone. Given the inflammatory environment in joints under OA condition, we treated MC3T3-E1 cell, a pre-osteoblast cell line, with IL-1β in this study and demonstrated that IL-1β treatment could stimulate the cell osteogenic differentiation and meanwhile upregulate glycolysis and oxidative phosphorylation in cell cultures. More importantly, intraperitoneal injection of 2-deoxy-D-glucose (2-DG) and oligomycin (OGM), respectively, suppressed the subchondral bone glycolysis and oxidative phosphorylation in mice. Consequently, 2-DG and OGM treatment attenuated abnormal osteoblast differentiation and protected against aberrant bone formation in subchondral bone and articular cartilage degradation in wildtype mice following with joint injury. Collectively, these data strongly suggest glycolysis and oxidative may serve as important therapeutic targets for OA treatment.

目的 评价"小组化"助教指导模式在临床技能同质化培训中的应用效果.方法 以心肺复苏实训课程为试点,将上海中医药大学2018级中西医结合临床专业(五年制)32位学生作为研究对象,随机分为对照组及助教授课(teaching assistant,TA)组,各16人.对照组实施传统授课方法;TA组内再分为A小组、B小组、C小组、D小组,分别由4位研究生助教进行小组化授课.比较两组学生的满意度和考核成绩.采用SPSS 25.0进行t检验和方差分析.结果 与对照组相比,TA组在学生满意度调查结果中,增加实践机会、临床技能操作能力、学习效果、总体满意度均高于对照组,差异有统计学意义.课堂考核成绩,TA组[(85.19±2.93)分]和对照组[(82.75±4.52)分]比较差异无统计学意义,30 d后考核成绩比较,TA组(83.50±5.13)分优于对照组(74.68±3.87)分;且对照组30 d后成绩低于即刻成绩,前后对比有统计学意义(P＜0.001),TA组成绩前后比较差异无统计学意义.结论 "小组化"助教指导模式在临床技能同质化培训中效果较好,且有稳定的远期培训效果,学生满意度高.

Gujian oral liquid (GJ), a traditional herbal formula in China, has been widely used to treat patients with osteoarthritis (OA). Nevertheless, the active component and potential mechanism of GJ are not fully elucidated. Thus, we investigate the effect of GJ and explore its underlying mechanism on OA through network pharmacology and experimental validation. First, a total of 175 bioactive compounds were identified, and 134 overlapping targets were acquired after comparing the targets of the GJ with those of OA. 8 hub targets, including IL6 and AKT1, were obtained in PPI network analysis. Then, we built up GJ-target-OA network and protein-protein interaction (PPI) network, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The results underlined inflammatory tumor necrosis factor (TNF) as a promising signaling pathway of GJ for OA treatment. Moreover, molecular docking also verified the top two active compounds had direct bindings with the top three target genes. Finally, we verified the effect of GJ on OA in vivo and in vitro. In vivo experiments validated that GJ not only significantly attenuated OA phenotypes including articular cartilage degeneration and subchondral bone sclerosis but also reduced the expressions of tumor necrosis factor-α (TNF-α) and p-p65 in articular chondrocytes. Besides, GJ serum also had a protective effect on chondrocytes against inflammation caused by TNF-α in vitro. Hence, our study predicted and verified that GJ could exert anti-inflammation and anticatabolism effects partially via regulating TNF-α/NF-kappa B (NF-κB) signaling.

Sepsis is a common and fatal disease with high mortality. Sepsis is a life-threatening organ dysfunction caused by abnormal host response to infection. Some patients also complicate with hypo-albuminemia, hypotension, oliguria, edema and other phenomena, namely capillary leakage syndrome (CLS). Sepsis with CLS is a complex disease urgently needs active treatment, but a successful treatment must be based on in-depth understanding of the pathogenesis and combined with clinical treatment experience.

Abnormal coagulation and increased risk of thrombosis are some of the symptoms associated with COVID-19 severity. Anti-phospholipid antibodies (aPLs) present in critically ill COVID-19 patients contribute to systemic thrombosis. The aim of this study was to identify key common genes to characterize genetic crosstalk between COVID-19 and antiphospholipid syndrome (APS) using bioinformatics analysis and explore novel mechanisms of immune-mediated thrombosis in critically ill COVID-19 patients. The transcriptome data of mononuclear cells from severe COVID-19 patients and APS patients were evaluated to obtain the common genes. The protein-protein interaction network and cytoHubba module analysis in Cytoscape software were used to find the associated hinge genes and hub genes. Among the common differentially expressed genes, TIMELESS depletion was identified only in patients with severe COVID-19 and not in patients with mild COVID-19, and it was validated with the GSE159678 dataset. Functional analyses using gene ontology terms and the Kyoto Encyclopedia of Genes and Genomes pathway suggested that TIMELESS might contribute to the production of antiphospholipid antibody and thrombosis in both COVID-19 and APS patients. The potential role of TIMELESS and autophagy genes in momonuclear cells were further investigated, and GSK3B was found to be associated with TIMELESS. Autophagy targeting agents have a therapeutic potential against COVID-19 and thrombogenesis in APS, which may be related to the role of autophagy genes in the modification of circadian clock proteins. Interference with TIMELESS and other genes associated with it to regulate autoantibody expression may be a potential strategy for immunotherapy against thrombogenesis in severe COVID-19 patients.

The aim of this study is to systematically evaluate existing evidence of the Chinese herbal formula, Zuogui pill (ZGP), for the treatment of osteoporosis. A systematic literature search was performed in six electronic databases. The authors independently extracted data in pairs and evaluated the risk of bias. A total of 221 articles were identified initially, of which 12 relevant studies were enrolled. The primary outcome was fracture incidence and bone mineral density (BMD) at different sites. Bone metabolism markers, clinical symptoms, quality of life, and adverse events or adverse drug reactions (ADRs) were secondary outcomes. The results showed that ZGP, combined with anti‐osteoporosis drugs, significantly increased BMD at the lumbar spine, Ward's area, and total hip. In terms of markers for improved bone metabolism, ZGP plus conventional drugs dramatically improved the levels of alkaline phosphatase, bone Gla protein, bone alkaline phosphatase, and tartrate‐resistant acid phosphatase. Gastrointestinal discomfort, dizziness, and fatigue were found in the combined therapy group. Although the results indicate that ZGP is a potential candidate for osteoporosis, evidence remains insufficient. Further rigorously designed and high‐quality trials with a larger sample size are warranted to verify the current conclusions.