In recent years, with the development of big data application technology, the real-world data and the corresponding generated real-world evidence have attracted the attention of healthcare regulatory authorities around the world. Regulators recognize that real-world research with specific purposes using real-world data can provide important evidence for regulatory decisions. A total of 90 instances of publicly released on the application of real-world evidence to support regulatory decisions of U. S. Food and Drug Administration are explored, and the positioning and value of real-world evidence in U. S. Food and Drug Administration regulatory decisions are summarized and analyzed, providing references for the use of real-world data and real-world evidence to promote medical devices whole cycle regulation in China.
United States ; United States Food and Drug Administration ; Equipment and Supplies ; Device Approval ; China

As the most abundant and essential structural protein in the human body, collagen is ubiquitously present in the interstitium of nearly all solid organs, playing a crucial role in maintaining the structural integrity and functional stability of human tissues and organs. Disorders associated with collagen structure and metabolisms impose a significant burden on society and healthcare systems. Post-translational modifications (PTMs) are essential steps in collagen metabolism, and recent studies have indicated that aberrant regulation of PTMs plays a pivotal role in the pathogenesis and progress of collagen-related disorders, including liver, kidney, heart, lung, and skin fibrosis, as well as keloid. This review provides a comprehensive summary of the regulatory mechanisms of both traditional and novel PTMs in collagen metabolism and collagen-related diseases. Furthermore, we summarize the drugs that modulate PTMs and their effects, with the aim of elucidating the pathophysiology of collagen-related diseases and provide new insights for their diagnosis, prevention, and treatment.

Colorectal tumorigenesis generally progresses from adenoma to adenocarcinoma, accompanied by dynamic changes in the tumor microenvironment (TME). A randomized controlled trial has confirmed the efficacy and safety of Shen-Bai-Jie-Du decoction (SBJDD) in preventing colorectal tumorigenesis. However, the mechanism remains unclear. In this study, we employed single-cell RNA sequencing (scRNA-seq) to investigate the dynamic evolution of the TME and validated cell infiltration with multiplex immunohistochemistry and flow cytometry. Bulk RNA sequencing was utilized to assess the underlying mechanisms. Our results constructed the mutually verifiable single-cell transcriptomic atlases in Apc ^Min/+ mice and clinical patients. There was a marked accumulation of CCL22⁺ dendritic cells (DCs) and an enhanced immunosuppressive action, which SBJDD and berberine reversed. Combined treatment with cholesterol and lipopolysaccharide induced characteristic gene expression of CCL22⁺ DCs, which may represent "exhausted DCs". Intraperitoneal injection of these DCs after SBJDD treatment eliminated its therapeutic effects. TMEM131 derived CCL22⁺ DCs generation by TNF signaling pathway and may be a potential target of berberine in retarding colorectal tumorigenesis. These findings emphasize the role of exhausted DCs and the regulatory mechanisms of SBJDD and berberine in colorectal cancer (CRC), suggesting that the multi-component properties of SBJDD may help restore TME homeostasis and offer novel cancer therapy.

The interest in covalent drugs has resurged in recent decades, spurring the development of numerous specialized computational docking tools to facilitate covalent ligand design and screening. Herein, we present CarsiDock-Cov, a new paradigm distinguishing itself as the first deep learning (DL)-guided approach for covalent docking. CarsiDock-Cov retains the core components of its non-covalent predecessor, leveraging a DL model pretrained on millions of docking complexes to predict protein-ligand distance matrices, along with a dedicated-designed geometric optimization procedure to convert these distances into refined binding poses. Additionally, it incorporates several key enhancements specifically tailored to optimize the protocol for covalent docking applications. Our approach has been extensively validated on multiple public datasets regarding the docking and screening of covalent ligands, and the results indicate that our approach not only achieves comparably improved applicability compared to its non-covalent predecessor, but also exhibits competitive performance against various state-of-the-art covalent docking tools. Collectively, our approach represents a significant advance in covalent docking methodology, offering an automated and efficient solution that shows considerable promise for accelerating covalent drug discovery and design.

OBJECTIVES: To investigate the efficacy of Ag₂Se nanoparticles for eliminating intracellular Porphyromonas gingivalis (P. gingivalis) in esophageal cancer and examine the effect of P. gingivalis clearance on progression of esophageal cancer. METHODS: Ag₂Se nanoparticles were synthesized via a chemical synthesis method. The effects of Ag₂Se nanoparticles on P. gingivalis viability and colony-forming ability were assessed using fluorescence staining and colony formation assays. In a mouse model bearing subcutaneous murine esophageal cancer cell allograft with P. gingivalis infection, the effect of treatment with Ag₂Se nanoparticles on the abundance of P. gingivalis in the tumor tissues was quantified using RNAscope in situ hybridization and quantitative polymerase chain reaction (qPCR), and the changes in tumor volume were monitored. The biosafety of Ag₂Se nanoparticles was assessed by examining liver and kidney functions and pathological changes in the major organs of the mice. RESULTS: Transmission electron microscopy revealed that the synthesized Ag₂Se nanoparticles were uniformly dispersed spherical particles with a diameter around 50 nm. In vitro experiments demonstrated that exposure to Ag₂Se nanoparticles significantly reduced the viability and clonal proliferation capacity of P. gingivalis in a dose-dependent manner. In the tumor-bearing mice, treatment with Ag₂Se nanoparticles significantly reduced the abundance of P. gingivalis in tumor tissues and suppressed tumor cell proliferation. No significant damages to the liver and kidney functions or the major organs were observed in Ag₂Se nanoparticle-treated mice, demonstrating good biocompatibility of Ag₂Se nanoparticles. CONCLUSIONS Ag₂Se nanoparticles exhibit significant bactericidal and inhibitory effects against P. gingivalis, and can effectively eliminate intracellular P. gingivalis to suppress the growth of esophageal cancer allograft in mice, suggesting the potential of Ag₂Se nanoparticles in the treatment of esophageal cancer.
Animals ; Porphyromonas gingivalis/drug effects* ; Mice ; Esophageal Neoplasms/pathology* ; Nanoparticles ; Metal Nanoparticles ; Bacteroidaceae Infections ; Cell Line, Tumor

OBJECTIVES: To investigate the ethnic origin of Chuanqing people, one of the largest unidentified ethnic groups in Guizhou, China, and analyze its genetic relationships with surrounding populations. METHODS: Based on a self-developed microhaplotype system, we conducted genotyping and analyzed the genetic distribution of microhaplotype loci and their forensic applicability in Chuanqing population in Guizhou Province. Using the microhaplotype data from different intercontinental populations and previously reported data from Han population living in Guizhou Province, we systematically investigated the genetic background of Chuanqing people through population genetic approaches, including genetic distance estimation, principal component analysis, and phylogenetic tree construction. RESULTS: Among the studied population, the number of haplotype per microhaplotype ranged from 6 to 25. The average expected heterozygosity (He), observed heterozygosity (Ho), power of discrimination (PD), and probability of exclusion (PE) were 0.8291, 0.8301, 0.9387, and 0.6593, respectively. The cumulative power of discrimination (CPD) and cumulative probability of exclusion (CPE) for these 33 loci were 1-2.62×10^-41 and 1-7.64×10^-17, respectively. Population genetic analyses revealed that the Chuanqing population had close genetic relationships with the East Asian populations, especially the local Guizhou Han population, Beijing Han population and the Han populations living in southern China. CONCLUSIONS The 33 microhaplotypes exhibit high levels of genetic diversity in the Guizhou Chuanqing population, highlighting their potentials for both forensic identification and parentage testing. The Han populations might have contributed a significant amount of genetic material to the Chuanqing population during the formation and development of the latter.
Humans ; China/ethnology* ; Ethnicity/genetics* ; Forensic Genetics/methods* ; Genetics, Population ; Genotype ; Haplotypes ; Phylogeny ; East Asian People/genetics*

Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
Animals ; NFATC Transcription Factors/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Ovariectomy ; Osteoclasts/metabolism* ; Female ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; NF-kappa B/genetics* ; Osteoporosis/genetics* ; Signal Transduction/drug effects* ; Bone Resorption/genetics* ; Cell Differentiation/drug effects* ; Humans ; RANK Ligand/metabolism* ; Mitogen-Activated Protein Kinases/genetics* ; Transcription Factors

ObjectiveTo investigate the prevalence and associated factors of malocclusion among preschool children in Fengxian District, Shanghai, and to provide a scientific basis for local medical and public health departments to formulate targeted interventions. MethodsA cross-sectional study was conducted from September to December 2024. A total of 1 172 children aged 3‒5 years were recruited from 10 kindergartens across 5 townships in Fengxian District, using stratified cluster random sampling method. Clinical examinations were conducted to record occlusal parameters such as the relationship of the second deciduous molars, canine teeth relationship, anterior overbite and overjet, anterior and posterior crossbite, and crowded dentition. A questionnaire survey was performed to the parents to collect information on factors influencing malocclusion, including genetic predisposition, poor oral habits, dietary patterns, and sleep-related breathing conditions. Data were statistically analyzed using IBM SPSS Statistics 27 software, with chi-square test for categorical data and binary logistic regression analysis for influencing factors. ResultsThe overall prevalence of malocclusion among 3‒5-year-old children in Fengxian District of Shanghai was 70.73%, with no statistically significant differences between genders (P>0.05). Deep overbite accounted for the highest proportion (49.66%), followed by Angle Class Ⅱ malocclusion of the second deciduous molars (17.83% on the left, 19.11% on the right), midline deviation (13.23%), anterior crossbite (6.74%), and crowding of the maxillary and mandibular anterior teeth (16.38% for the maxillary dentition, 17.58% for the mandibular dentition). Multivariate analyses showed that habitual mouth breathing during the day (OR=0.509, P=0.009) and morning dry mouth upon waking (OR=1.455, P=0.023) were independent influencing factors for malocclusion. ConclusionThe prevalence of malocclusion is relatively high among preschool children in Fengxian District, Shanghai,with deep overbite being the dominant trait. Sleep-related breathing conditions (such as habitual mouth breathing during the day and morning dry mouth) is an important influencing factor for malocclusion. Public health authorities should strengthen oral health education and promote the correction of bad habits to reduce the prevalence of malocclusion and improve children’s oral health.

Objective:To examine the effects of an improved mindfulness-based intervention program(IMIP)on depression,anxiety,psychological resilience,and marital quality among perinatal women.Methods:We enrolled 120 perinatal women receiving care at the obstetrics departments of Pudong Hospital and Nanhui Maternity and Child Health Hospital from December 2022 to August 2024.They were randomly assigned to either routine care group or IMIP group.The routine care group received standard prenatal care,while the IMIP group received,in addition to routine care,an eight-week course of IMIP intervention,administered once a week.Outcome mea-sures included the Edinburgh Postnatal Depression Scale(EPDS),Hospital Anxiety and Depression Scale(HADS),Connor-Davidson Resilience Scale(CD-RISC),and ENRICH Marital Satisfaction Scale,assessed at six time points—before intervention,after interven-tion(at 35 weeks of gestation),and at 3 days,42 days,3 months,and 6 months postpartum.A repeated measures ANOVA was con-ducted,with the score changes(Δ values)at individual time points from baseline as the dependent variable.Results:The IMIP group showed significantly greater improvements than the routine care group in EPDS,HADS-anxiety,CD-RISC,and ENRICH scores,with the main effects of group and time and their interaction effect all being significant(all P<0.001).For HADS-depression,the group×time interaction was not significant,but the main effect of group was significant(P<0.001).CD-RISC and ENRICH scores in-creased with time in the IMIP group.Conclusion:IMIP effectively alleviates depressive and anxiety symptoms,enhances psychological resilience,and improves marital quality for perinatal women,showing strong potential for clinical application.