The inflammatory microenvironment is closely associated with the initiation and progression of osteoarthritis （OA）， specifically manifesting as macrophage activation， dysregulation of inflammatory cytokines， and redox imbalance. Following an overview of the pathological characteristics of the OA inflammatory microenvironment， this paper reviews the research progress on the mechanism of traditional Chinese medicine （TCM） intervening in OA by modulating the inflammatory microenvironment. It has been found that TCM monomers/active ingredients （such as total alkaloids from Strychnos nux-vomica ， quercetin， triptolide， etc.）， herb pairs （e.g. Angelica pubescens - Gentiana macrophylla ， Carthami Flos-Lycopodii Herba）， and TCM formulas （such as Zhuanggu jianxi formula， Duhuo jisheng decoction and Rongjin niantong formula， etc.） can inhibit macrophage activation， reduce the release of proinflammatory cytokines and the generation of reactive oxygen species by inhibiting multiple signaling pathways， including nuclear factor-κB， Wnt/ β -catenin， and mitogen-activated protein kinase， thereby alleviating the articular inflammatory microenvironment， restoring local joint homeostasis， and slowing the progression of OA.

ObjectiveTo explore the process and guidelines for ethical review in decentralized drug clinical trials， promote clinical trial progress， and ensure drug development progress. MethodsThe key points of the ethical review were summarized by studying the relevant laws and regulations on decentralized drug clinical trials， analyzing the advantages and challenges of decentralized drug clinical trials， and combining the experience of the ethics committee of the institution in reviewing decentralized drug clinical trials. ResultsRelevant laws and regulations were the basis for the ethical review， and the ethics committee should adopt appropriate review methods based on regulations and hospital ethical standard operating procedures. The ethics committee should focus on the feasibility， applicability， and rationality， the adequacy of informed consent， the protection of rights and interests and privacy of subjects， as well as the qualification and standard operating procedures of electronic platforms for conducting decentralized drug clinical trials. ConclusionDecentralized drug clinical trials are in their early stages and urgently require guidance from relevant laws and regulations. Ethical review is also constantly being refined through exploration. It is necessary to supervise the implementation of responsibilities by all parties， pay attention to the rights and interests of subjects， and gradually promote the implementation of decentralized drug clinical trials.

ObjectiveMicrotube associated protein-2 （MAP-2）， alpha-tubulin （α-tubulin）， and synaptophysin （SYP） are important proteins in neuronal signal communication. This paper observed the effects of modified Zhigancao Tang on the expression of serum α-Synuclein （α-Syn） and its oligomers， MAP-2， α-tubulin， and SYP of patients with liver and kidney deficiency of Parkinson's disease （PD）， analyzed their correlation， and evaluated the therapeutic effect of modified Zhigancao Tang in patients with liver and kidney deficiency of PD based on α-Syn transmission pathway mediated by neuronal communication in vivo. MethodsA total of 60 patients with PD who met the inclusion criteria were randomly divided into a treatment group （30 cases） and a control group （30 cases）. Both groups were treated on the basis of PD medicine， and the treatment group was treated with modified Zhigancao Tang. Both groups were treated for 12 weeks. The changes in UPDRS score， TCM syndrome score， and expression of serum α-Syn and its oligomers， MAP-2， α-tubulin， and SYP were observed before and after 12 weeks of treatment in each group. The correlation between the above-mentioned serum biological indexes and the levels of serum α-Syn and its oligomers was analyzed. ResultsAfter treatment， the TCM syndrome score， UPDRS score， UPDRS-Ⅱ score， and UPDRS-Ⅲ score of the treatment group were significantly decreased （P<0.05， P<0.01）. The UPDRS score， UPDRS-Ⅱ score， and UPDRS-Ⅲ scores in the treatment group were significantly decreased compared with those in the control group after treatment （P<0.05）. After treatment， the total effective rate of the control group was 63.3% （19/30）， and that of the treatment group was 86.7% （26/30）. The clinical effect of the observation group was better than the control group （Z=-2.03， P<0.05）. The total effective rate of the observation group was better than that of the control group， and the difference was statistically significant （χ²=5.136， P<0.05）. After treatment， the oligomer level of serum α-Syn and MAP-2 level in the treatment group were significantly decreased （P<0.05， P<0.01）. The levels of serum α-Syn and its oligomers， as well as α-tubulin in the treatment group， were significantly decreased compared with those in the control group after treatment （P<0.05， P<0.01）. Serum α-Syn was correlated with serum MAP-2 and α-Syn oligomer in patients with PD （P<0.05， P<0.01） but not correlated with serum SYP . Serum α-Syn oligomers of patients with PD were correlated with serum MAP-2 and α-tubulin （P<0.05， P<0.01） but not correlated with serum SYP level. Serum SYP of patients with PD was correlated with serum MAP-2 （P<0.05）. ConclusionModified Zhigancao Tang has a therapeutic effect on patients with liver and kidney deficiency of PD by inhibiting the production of α-Syn oligomers and intervening α-Syn microtubule transport pathway in vivo.

With the rapid development of sequencing technologies, the detection of alternative polyadenylation (APA) in mammals has become more precise. APA precisely regulates gene expression by altering the length and position of the poly(A) tail, and is involved in various biological processes such as disease occurrence and embryonic development. The research on APA in mammals mainly focuses on the following aspects:(1) identifying APA based on transcriptome data and elucidating their characteristics; (2) investigating the relationship between APA and gene expression regulation to reveal its important role in life regulation;(3) exploring the intrinsic connections between APA and disease occurrence, embryonic development, differentiation, and other life processes to provide new perspectives and methods for disease diagnosis and treatment, as well as uncovering embryonic development regulatory mechanisms. In this review, the classification, mechanisms and functions of APA were elaborated in detail and the methods for APA identifying and APA data resources based on various transcriptome data were systematically summarized. Moreover, we epitomized and provided an outlook on research on APA, emphasizing the role of sequencing technologies in driving studies on APA in mammals. In the future, with the further development of sequencing technology, the regulatory mechanisms of APA in mammals will become clearer.

ObjectiveTo observe the effect of Huayu Mingmu prescription on retinal angiogenesis and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR）-hypoxia inducible factor-1α/vascular endothelial growth factor A （HIF-1α/VEGFA） signaling pathway in diabetic retinopathy （DR） rats. MethodsSixty-four SPF-grade male SD rats were used in the study. Eleven rats were randomly selected as the normal group， while the remaining 53 rats were fed a high-sugar， high-fat diet combined with low-dose streptozotocin （STZ） intraperitoneal injection to establish a type 2 diabetes mellitus （T2DM） rat model. DR model evaluation was performed after 12 weeks of diabetes. The rats were then divided into model， low-dose， medium-dose， and high-dose groups of Huayu Mingmu prescription （9.29， 18.57， 37.14 g·kg^-1）， and a calcium dobesilate group （0.16 g·kg^-1）， with 10 rats in each group. The rats were orally administered the corresponding doses of Huayu Mingmu prescription and calcium dobesilate. The normal and model groups received equal volumes of physiological saline via gavage for 8 consecutive weeks. Retinal vascular changes were observed through fundus photography， and pathological changes in retinal tissue were evaluated using hematoxylin-eosin （HE） staining. Retinal microvascular pathological changes were examined through retinal vascular network preparation and periodic acid-Schiff （PAS） staining. Immunofluorescence （IF） was used to detect the expression of VEGFA and angiopoietin-2 （Ang-2） in retinal tissue. Western blot was employed to detect the protein expression of PI3K， Akt， mTOR， HIF-1α， VEGFA， and VEGFR2 in retinal tissue. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to assess the mRNA expression of PI3K， Akt， mTOR， HIF-1α， VEGFA， and VEGFR2 in retinal tissue. ResultsCompared with the normal group， the model group exhibited significant pathological changes in retinal tissue， including the appearance of acellular capillaries， as well as significant endothelial cell （E） proliferation and pericyte （P） loss （P<0.01）. The E/P was significantly elevated （P<0.01）. Protein and mRNA expression levels of PI3K， Akt， mTOR， HIF-1α， VEGFA， and VEGFR2 in retinal tissue were significantly increased （P<0.01）， and the expression of Ang-2 protein was significantly elevated （P<0.01）. In contrast， retinal tissue in the treatment groups showed alleviated pathological changes， with reduced endothelial cell proliferation and pericyte loss （P<0.05， P<0.01）. Among the treatment groups， the high-dose Huayu Mingmu prescription and the calcium dobesilate group exhibited a decreased E/P （P<0.01）. Protein and mRNA expression levels of PI3K， Akt， mTOR， HIF-1α， VEGFA， and VEGFR2 in retinal tissue were significantly reduced （P<0.05， P<0.01）， and the expression of Ang-2 protein was significantly decreased （P<0.01）. ConclusionHuayu Mingmu prescription can intervene in retinal neovascularization in DR rats， delay the progression of DR， and its mechanism may be related to antagonizing the PI3K/Akt/mTOR-HIF-1α/VEGFA signaling pathway.

GBA1 gene mutation is an important genetic risk factor for Parkinson’s disease (PD). This paper reports a case of a 43-year-old male PD patient carrying a rare heterozygous Thr408Met mutation in the GBA1 gene identified through whole-exome sequencing, leading to a diagnosis of GBA1-associated PD. The patient’s motor symptoms were primarily characterized by bradykinesia and rigidity, without significant cognitive decline. Treatment with low-dose levodopa combined with a dopamine agonist resulted in significant symptomatic improvement.

BACKGROUND: Salvianolate is a compound mainly composed of salvia magnesium acetate, which is extracted from the Chinese herb Salvia miltiorrhiza . In recent years, salvianolate injection has been widely used in the treatment of cardiovascular diseases, but the mechanism of how it can alleviate cardiotoxicity remains unclear. METHODS: The cardiac injury model was constructed by treatment with doxorubicin (Dox) or azithromycin (Azi) in zebrafish larvae. Heart phenotype, heart rate, and cardiomyocyte apoptosis were observed in the study. RNA-sequencing (RNA-seq) analysis was used to explore the underlying mechanism of salvianolate treatment. Moreover, cardiomyocyte autophagy was assessed by in situ imaging. In addition, the miR-30a/becn1 axis regulation by salvianolate was further investigated. RESULTS: Salvianolate treatment reduced the proportion of pericardial edema, recovered heart rate, and inhibited cardiomyocyte apoptosis in Dox/Azi-administered zebrafish larvae. Mechanistically, salvianolate regulated the lysosomal pathway and promoted autophagic flux in zebrafish cardiomyocytes. The expression level of becn1 was increased in Dox-induced myocardial tissue injury after salvianolate administration; overexpression of becn1 in cardiomyocytes alleviated the Dox/Azi-induced cardiac injury and promoted autophagic flux in cardiomyocytes, while becn1 knockdown blocked the effects of salvianolate. In addition, miR-30a, negatively regulated by salvianolate, partially inhibited the cardiac amelioration of salvianolate by targeting becn1  directly. CONCLUSION This study has proved that salvianolate reduces cardiomyopathy by regulating autophagic flux through the miR-30a/becn1 axis in zebrafish and is a potential drug for adjunctive Dox/Azi therapy.
Animals ; Zebrafish ; MicroRNAs/genetics* ; Autophagy/drug effects* ; Myocytes, Cardiac/metabolism* ; Cardiomyopathies/metabolism* ; Beclin-1/genetics* ; Apoptosis/drug effects* ; Plant Extracts/therapeutic use* ; Doxorubicin

Objective: To explore the prospective association between multidimensional sleep indicators and the risk of newlyonset dental caries, providing a reference for childrens oral healthrelated sleep intervention. Methods: In October 2021, 1 417 students in grades 1 to 4 (aged 6 to 11) from two elementary schools in Bengbu, Anhui Province, were selected by cluster sampling method. Surveys and followup visits were conducted at baseline (T1), November 2022 (T2), May 2023 (T3), and November 2023 (T4), respectively, including parental questionnaires, oral health and physical examination. Bedtime, sleep duration, sleep midpoint, social jet lag, weekend catchup sleep, and sleep habits were collected and calculated. A multifactorial Cox proportional risk regression model was used to analyze the association between multidimensional sleep indicators and newlyonset caries in schoolaged children after 2 years. Results: The prevalence of dental caries in children was 65.1% at baseline, and the prevalence was 59.0% at the end of the 2year followup. Cox proportional risk regression model showed that for every 1point increase in the childrens bedtime resistance, nocturnal awakenings, parasomnias, and daytime sleepiness scores, the risk of newlyonset caries increased by 12% (HR=1.12, 95%CI=1.08-1.15), 22% (HR=1.22, 95%CI=1.15-1.29), 12% (HR=1.12, 95%CI=1.08-1.17), and 15% (HR=1.15, 95%CI=1.12-1.19), respectively; the risk of newlyonset caries increased by 23% for each 1 h increase in the length of weekend catchup sleep (HR=1.23, 95%CI=1.14 -1.33); compared with children who went to bed before 21:00 on school days, those who went to bed later than 22:00 had a 57% higher risk of newlyonset caries (HR=1.57, 95%CI=1.22-2.03). Compared to children who slept adequately (≥9 h/d), those with insufficient sleep had a 67% higher risk of new caries (HR=1.67, 95%CI=1.43-1.95) (P<0.01). Conclusions These findings suggest a significant association between sleep patterns/sleep disorders and the development of childhood dental caries. Incorporating sleep behavior optimization and sleep quality improvement into comprehensive caries prevention and oral health management protocols may represent a promising intervention strategy to enhance childrens oral health outcomes.

A 20-year-old male patient presented to the Department of Dermatology of Peking Union Medical College Hospital with complaints of an 8-year history of facial scarring, swelling of the lower limbs, and a 4-year history of scalp thickening. Physical examination showed thickening furrowing wrinkling of the skin on the face and behind the ears, ciliary body hirsutism, blepharoptosis, and cutis verticis gyrate. Both lower limbs were swollen, especially the knees and ankles. The skin of the palms and soles of the feet was keratinized and thickened. Laboratory examination using bone and joint X-ray showed periostosis of the proximal middle phalanges and metacarpals of both hands, distal ulna and radius, tibia and fibula, distal femurs, and metatarsals.Genetic testing revealed two variants in SLCO2A1, c.1658T > A and c.96+4A > C.Through multidisciplinary consultation, we confirmed the diagnosis of pachydermoperiostosis.