Polycystic kidney disease (PKD) is a group of inherited disorders characterized by cystic lesions in the kidneys and multiple organs, primarily including autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD). ADPKD is mainly caused by variations in the PKD1 and PKD2 genes. Its clinical manifestations include progressive renal cyst growth, hypertension, and multi-system complications. ARPKD, on the other hand, is primarily caused by mutations in the PKHD1 gene. It commonly occurs in infants and young children, with hepatorenal cystic fibrosis being a key feature. Although there is currently no cure for PKD, the integration of multi-omics and precision medicine strategies holds promise for optimizing patient management and improving outcomes in the future. This review summarizes the genetic basis, pathogenic mechanisms, diagnostic techniques, and therapeutic advances in PKD, providing a reference for clinical practice and research.
Humans ; Polycystic Kidney Diseases/genetics* ; TRPP Cation Channels/genetics* ; Mutation ; Polycystic Kidney, Autosomal Dominant/therapy* ; Receptors, Cell Surface

ObjectiveTo sort out the pre-ethical review status of drug clinical trials in a tertiary A hospital， summarize practical experience， and provide references for pre-ethical review. MethodA retrospective analysis was conducted on the ethical review of pre-ethical projects in a tertiary A hospital from 2018 to 2023. ResultsFrom 2018 to 2023， a total of 285 pre-ethical projects were reviewed in this tertiary hospital， including 79 projects where it served as the leading unit. Among these， 279 clinical trials ultimately received approval of the ethical review committee， while 6 projects were not approved due to sponsors’ refusal to modify study protocols. In terms of trial phases， phase III clinical trials constituted the largest proportion， and the oncology center was the department with the highest number of projects. In 2023， the average time for pre-ethical review projects from submission to approval was 43 calendar days， 3 days longer than for other project types. In 2023， this hospital reviewed 75 pre-ethical review projects， including 58 where it served as a participating unit. Among these， 42 projects received approval later than the leading unit， while 9 projects were approved earlier than the leading unit’s ethical approval date. Among the pre-ethical review projects applied in 2023， 70 projects obtained drug clinical trial notifications from the National Medical Products Administration， while 5 projects had unknown notification status due to the lack of ethical approval or discontinuation. Of the projects receiving approval notifications， 16 were annotated with matters requiring enhanced attention during clinical trials， and 7 necessitated protocol improvements. ConclusionThis tertiary A hospital has implemented multiple measures to optimize the management of pre-ethical review. This ethical review model does not compromise the quality of ethical review and contributes to accelerating the initiation of clinical trials. Notably， it is crucial to construct a patient-centered drug development system. Clinical trials guided by this concept align with ethical values， laying the foundation for the smooth conduct of clinical trials， assisting in the drug development process， and safeguarding patients’ medication needs.

This study aimed to design and synthesize a series of novel photocaged compounds based on the precise binding mode of cyclin-dependent kinase 2 (CDK2) inhibitor AT7519 with its target, to achieve precise optical control over molecular activity. Using AT7519 as the structural foundation, different types of photoremovable protecting groups were introduced at its key interaction sites (the NH of the pyrazole ring and the NH of the piperidine ring), resulting in the synthesis of eight dual-photocaged compounds. Their structures were confirmed by NMR and mass spectrometry, and their photochemical properties—including photolysis wavelength, photolysis time, and photolysis efficiency—were systematically evaluated. The optically controlled inhibitory effects of the compounds on HCT116 cell proliferation were assessed using MTT assay. The photoresponsive characteristics of the photocaged compounds were significantly influenced by the type of photoremovable protecting group and its introduction site. Among them, compounds 1a, 1b, and 2d exhibited excellent photolysis efficiency, each achieving a rate exceeding 90%. Particularly, compounds 1b and 2d demonstrated excellent optically controlled activity: under dark conditions, their half maximal inhibitory concentration (IC50) values were both greater than 150 µmol/L, indicating negligible cell proliferation inhibitory activity; however, upon irradiation, their cell proliferation inhibitory activity significantly increased, with IC50 values comparable to those of the positive control AT7519. The obtained compounds 1b and 2d possess excellent optically controlled properties, and can be further investigated as potential candidates for optically controlled CDK2 inhibitors.

Liver cirrhosis is the end-stage of various chronic liver diseases， and hepatic fibrosis caused by persistent inflammation is the core mechanism of the development and progression of liver cirrhosis. With the evolution of disease spectrum and a deeper understanding of the reversal of hepatic fibrosis， dual antiviral-antifibrotic therapy initially applied in the treatment of hepatitis B cirrhosis has gradually evolved into a broad-sense dual therapy for liver cirrhosis， which integrates etiological treatment with antifibrotic and/or anti-inflammatory interventions. This article systematically reviews the conceptual evolution of dual therapy for liver cirrhosis and related research advances.

Pancreatic portal hypertension （PPH） is a type of regional portal hypertension secondary to pancreatic diseases and their complications. Unlike portal hypertension caused by liver cirrhosis， PPH is confined to the splenic venous system， and most patients tend to have normal liver function. Splenic vein obstruction and impaired blood return are the core mechanisms underlying the development of PPH， and isolated gastric fundal varices represent a characteristic manifestation of PPH. For patients with pancreatic diseases， it is necessary to establish early warning and risk stratification strategies， and high-quality studies are needed to further confirm the safety and efficacy of anticoagulation， surgical approaches， and interventional therapies in patients with PPH. This article systematically reviews the pathogenesis， etiological classification， clinical features， and key diagnostic points of PPH and discusses the current status of PPH treatment and existing challenges.

The endochondral ossification of the growth plate is crucial for the longitudinal growth of long bones. Mechanical loading plays an important regulatory role in endochondral ossification. Absence or improper mechanical loading can inhibit growth plate development, while moderate mechanical stimuli promote chondrocyte proliferation and differentiation, thereby facilitating long bone growth. Mechanosensitive structures, such as primary cilia, mechanosensitive ion channels, integrins, and the cytoskeleton, play key roles in the regulation of mechanical loading. This review summarizes how mechanical loading influences growth plate endochondral ossification and discusses potential underlying mechanisms, offering theoretical insights for the management and research of bone development disorders in children and adolescents.

BackgroundWith the rapid development of the networking technologies， internet addiction has increasingly become a serious mental health issue. Previous studies have revealed the link between childhood trauma and internet addiction， while the mediating role of perceived stress in this link is not yet clear. ObjectiveTo investigate the role of medical students' perceived stress in the relationship between childhood trauma and internet addiction， so as to provide references for the intervention of internet addiction. MethodsFrom February to March 2023， a random sampling technique was used to select 1 232 undergraduate students from the School of Clinical Medical Sciences of Southwest Medical University as research subjects. The Childhood Trauma Questionnaire-Short Form （CTQ-SF）， Perceived Stress Scale （PSS）， Internet Gaming Disorder Scale （IGDS）， and Bergen Social Media Addiction Scale （BSMAS） were used for assessment. Pearson's correlation coefficients were calculated. The mediation effect of perceived stress in the relationship between childhood trauma and internet addiction was tested using Model 4 in the SPSS Process 4.1， and Bootstrapping procedure involving 5 000 replicates was employed to confirm the statistical significance. ResultsA total of 1 016 （82.47%） valid completed questionnaires were gathered. The CTQ-SF scores of medical students were positively correlated with PSS scores， IGD scores， and BSMAS scores （r=0.583， 0.474， 0.465， P<0.01）. PSS scores were positively correlated with IGD scores and BSMAS scores （r=0.369， 0.479， P<0.01）. Childhood trauma in medical students was found to positively predict perceived stress （β=0.191， P<0.01）， social media addiction （β=0.160， P<0.01）， and internet gaming disorder （β=0.106， P<0.01）. Perceived stress played a significant mediating role in the relationship between childhood trauma and internet gaming disorder， indirect effect value was 0.018 （95% CI： 0.009~0.027）， accounting for 16.98%. Perceived stress also exhibited a significant mediating role in the relationship between childhood trauma and social media addiction， indirect effect value was 0.063 （95% CI： 0.048~0.079）， accounting for 39.38%. ConclusionChildhood trauma in medical students may affect internet gaming disorder and social media addiction through perceived stress. ［Funded by 2022 Annual Research Project of Sichuan Applied Psychology Research Center，（number，CSXL-22102）］

It is proposed that the essence of the half-interior half-exterior theory of the membrane-source lies in the concept of the interstitial space being half-interior half-exterior. Through analysis of classical medical texts and commentaries by renowned physicians， the relationship between the membrane-source interstitial layer and the Governor Vessel （督脉） is explored. It is argued that the Governor Vessel traverses beyond the membrane-source interstitial half-interior half-exterior layer， and that this layer is related to， but distinct from， the shaoyang channel's half-interior half-exterior characteristic. By examining both historical and modern clinical approaches， further evidence is provided to support the view that the Governor Vessel passes outside this interstitial layer. Based on this relationship， treatment principles and prescriptions for Governor Vessel-related disorders are referenced to formulate strategies for membrane-source disorders， offering new perspectives for addressing complex and difficult clinical conditions.

With the rapid advancement of vaccines, the research and application of vaccine adjuvants have garnered significant attention. Despite the development of numerous vaccine adjuvants, their applications in human vaccines remain limited due to either insufficient efficacy or severe side effects. Consequently, there is growing interest in developing bioactive compounds derived from traditional Chinese medicines (TCMs) as vaccine adjuvants, owing to their natural biocompatibility, diversity, and safety. Here, we systematically review the current application status and potential value of TCM-based bioactive compounds in vaccine adjuvants. Firstly, we elaborate on the types and characteristics of active ingredients, such as polysaccharides, saponins, flavonoids, acids, and alkaloids. The mechanisms by which these compounds function as vaccine adjuvants are then discussed, including their roles in enhancing humoral immunity, cellular immunity, and relieving the immune suppression in the microenvironment. Additionally, we summarize the current strategies for structural modification and platform optimization to adapt to different application scenarios. Finally, we offer insights into the future development directions for these potential adjuvants, highlighting research priorities, technical approaches, and application prospects. In conclusion, natural vaccine adjuvants derived from TCMs present broad application prospects and hold promise for future vaccine development.