OBJECTIVE: To investigate the current status of clinical genetics specialization development and the diagnostic and therapeutic capabilities for hereditary diseases across medical institutions in Shanghai, and to assess the necessity and feasibility of establishing training bases for clinical genetics specialists. METHODS: By employing a cross-sectional survey design, the Clinical Genetics Committee of Shanghai Medical Association has conducted questionnaire surveys from March to April 2025 across 54 healthcare institutions in Shanghai (including 33 tertiary hospitals and 21 secondary hospitals). The survey involved administrative departments and medical personnel from 15 clinical specialties. The survey has covered current genetic disease diagnosis and treatment practices, relevant and specialised disease types, genetic department establishment, testing capabilities, personnel teams, and training requirements. RESULTS: The results revealed that 78.0% of clinical departments surveyed had treated patients with hereditary disorders. Shanghai possesses diagnostic and therapeutic expertise for over 95% of hereditary diseases listed in its rare disease catalogue, reflecting both the practical clinical demand for such conditions and the city's overall diagnostic and therapeutic strengths in this field. Nevertheless, significant disparities exist in the development of genetics departments across different tiers of healthcare institutions. Resources for genetic testing capabilities (including molecular, cellular, and biochemical testing) are also unevenly distributed across different tiers of hospitals. The survey further revealed that only 26.0% of departments believe that their current physician structure fully meets the diagnostic and treatment demands. Over 90% of departments consider standard training for clinical genetic specialists necessary, with 74.0% expressing willingness to participate in establishing training bases. Based on above findings and thorough deliberation, the Clinical Genetics Committee of the Shanghai Medical Association proposes advancing specialist training and discipline development through establishing a standard training system. The committee has drafted a three-year training protocol featuring a "joint training"-centered model, recommending a pilot-first, dynamically optimized strategy for steadily advancing training base development. CONCLUSION Shanghai faces substantial demand for genetic disease diagnosis and treatment, yet exhibits shortcomings in clinical genetics specialization development, resource allocation, and talent pipeline cultivation. To establish a standard training system holds significant practical importance and is underpinned by a broad demand.
Humans ; China ; Surveys and Questionnaires ; Genetic Diseases, Inborn/genetics* ; Cross-Sectional Studies ; Genetics, Medical/education* ; Genetic Testing

Neurocritical care involves complex pathophysiological mechanisms, and its incidence is higher, injuries are more severe, and treatment is more challenging in high-altitude environments. This consensus, based on the latest domestic and international evidence-based medical data, establishes a standardized, goal-oriented framework for neurocritical care management applicable in high-altitude regions and nationwide. The consensus was developed following international standards for evidence quality assessment and underwent two rounds of Delphi expert consultation, resulting in 32 recommendation statements covering three parts: management systems, monitoring and assessment, and core strategies. Key updates include: advocating for the establishment of independent neurocritical care units and implementing precise tiered diagnosis and treatment based on the "Five Differences in Critical Care" concept; constructing a "trinity" multimodal brain monitoring system centered on cerebral blood flow, cerebral oxygenation, and brain function, emphasizing routine bedside transcranial Doppler ultrasound, cerebral oximetry, and continuous electroencephalography monitoring; shifting management strategies from mild hypothermia therapy to targeted temperature management, and defining the "446" target management pathway for the supercritical stage; emphasizing the assessment of static and dynamic cerebrovascular autoregulation functions through multimodal methods to achieve individualized optimal mean arterial pressure management; elevating cerebrospinal fluid management goals to the level of "glymphatic system" function maintenance; implementing a multidisciplinary collaborative, whole-process management model focusing on patients' long-term neurological functional outcomes; de-escalation criteria include multidimensional indicators such as recovery of brain structure, restoration of cerebrovascular autoregulation, improvement in cerebrospinal fluid dynamics, and reduction in biomarker levels; and integrating cutting-edge technologies like artificial intelligence into post-critical care management and rehabilitation planning. This consensus systematically integrates the entire process of neurocritical care management, reflecting the modern connotation of goal-oriented, dynamic, and multimodal integration in neurocritical care medicine. It aims to adapt to new trends such as deepening understanding of pathophysiological mechanisms, the integration of medicine and engineering, and the empowerment of artificial intelligence, thereby further advancing the discipline of critical care medicine.

OBJECTIVE To investigate the apoptosis-inducing effect of esculetin （Esc） on acute myeloid leukemia （AML） HL-60 cells by regulating the protein kinase B （AKT）/S-phase kinase-associated protein 2 （SKP2）/MutT homolog 1 （MTH1） pathway. METHODS AML HL-60 cells were randomly divided into control group （routine culture）， Esc low-concentration group （L-Esc group， 25 μmol/L Esc）， Esc medium-concentration group （M-Esc group， 50 μmol/L Esc）， Esc high-concentration group （H-Esc group， 100 μmol/L Esc）， and high-concentration of Esc+ SC79 （AKT agonist） group （100 μmol/L Esc+5 μmol/L SC79）. Cell proliferation in each group was detected by MTT assay and colony formation assay. The level of reactive oxygen species （ROS） in cells was measured by using the CM-H2DCFDA fluorescent probe. Cell apoptosis was analyzed by flow cytometry. Western blot assay was performed to detect the expression levels of apoptosis-related proteins [B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， cleaved caspase-3]， AKT/SKP2/MTH1 pathway-related proteins （p-AKT， AKT， SKP2， MTH1）， along with the upstream and downstream proteins of AKT phosphatidylinositol 3-kinase （PI3K）， cyclin-dependent kinase inhibitor 1 （P21） and cyclin-dependent kinase inhibitor 1B （P27）. RESULTS Compared with control group， the cell viability， colony number， and the phosphorylation levels of AKT and PI3K proteins as well as protein expressions of SKP2， MTH1 and Bcl-2 were significantly decreased （P＜0.05）， while ROS level， apoptosis rate， and the expression levels of Bax， cleaved caspase-3， P21 and P27 proteins were significantly increased （P＜0.05）. Moreover， the effects of Esc exhibited concentration-dependence （P＜0.05）. Compared with H-Esc group， above indexes of high-concentration of Esc+ SC79 group were reversed significantly （P＜0.05）. CONCLUSIONS Esc may promote massive ROS production and induce activation of apoptosis in HL-60 cells by inhibiting the AKT/SKP2/MTH1 pathway， thus inhibiting the proliferation of HL-60 cells.

Objective To study the photodynamic performance and the killing effect of photodynamic therapy on lung cancer of novel chlorin compounds 2-（4-（5,15,20-triphenyl-7H,8H-porphyrin-10-yl） phenoxy） acetic acid（D1）and 4-（4-（5,15,20-triphenyl-7H,8H-porphyrin-10-yl） phenoxy） butanoic acid （D2）. Methods The ultraviolet visible absorption spectrum and fluorescence spectrum of D1 and D2 were determined. The singlet oxygen generation capacity of D1 and D2 was measured by using DPBF as singlet oxygen capture agent. Fluorescence assay was used to detect the cellular phagocytosis rate of the compounds in A549 cells, and MTT assay was used to detect their dark toxicity and phototoxicity. A nude mouse model of lung cancer was established to investigate the antitumor activity of the compounds mediated photodynamic action in vivo, and the blood concentration of D2 in nude mice, its distribution in tumor tissue and skin tissue were further detected. Results D1 and D2 had strong absorption at 652 nm with the best excitation wavelength at 429 nm and 427 nm, and the optimal emission wavelength was at about 659 nm. They also had a higher singlet oxygen generation rate than the control drug m-THPC. D1 and D2 had no dark toxicity at concentrations below 10 μmol/L, and could be ingested by A549 cells, basically reaching saturation in 18~24 hours. After laser irradiation at 650 nm wavelength, D1 and D2 showed significant antitumor activity in vivo and in vitro （P<0.01）. However, D2 could selectively accumulate in tumor tissues after administration, and the optimal treatment time was less than 30 min after administration. Conclusion D2 had excellent photodynamic antitumor activity and could selectively aggregate in tumor tissues, which had the potential to be a candidate drug for photosensitizer and treatment of lung cancer with independent intellectual property rights, and was worth further research.

Objective:To observe the effects of Maxing Loushi decoction on the inflammatory response and inflammatory indicators in mice with chronic obstructive pulmonary disease (COPD) models.Methods:Thirty-six BALB/C mice were randomly divided into 4 groups by random number table method: 10 mice in the COPD model group (referred to as the model group), 10 mice in the Maxing Loushi decoction group (referred to as the traditional Chinese medicine group), 10 mice in the programmed death receptor-1 (PD-1) inhibitor group (referred to as the control group), and 6 mice in the normal group. The COPD models of mice in the model group, the traditional Chinese medicine group and the control group were prepared by cigarette smoking combined with lipopolysaccharide (LPS) induction method. During the modeling process, the model group and the traditional Chinese medicine group were respectively given normal saline and Maxing Loushi decoction by gavage. The control group was given intraperitoneal injection of PD-1 inhibitor, while the normal group was given intragastric administration of normal saline. Pathological changes of lung tissues in each group of mice were detected by HE staining. The levels of inflammatory factors [monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α)] in the plasma and alveolar lavage fluid (BALF) of mice in each group were determined by enzyme-linked immunosorbent assay (ELISA). The effects of Maxing Loushi decoction intervention on inflammatory responses and inflammatory factors were evaluated.Results:The lung tissue structure in the normal group was basically normal. There was no thickening of the alveolar walls, no infiltration of neutrophils in the tissues, and no obvious inflammatory infiltration. In the model group, the lung tissue structure was slightly abnormal. A small amount of alveolar atrophy could be observed, the alveolar walls were slightly thickened, and inflammatory infiltration could be seen. In the traditional Chinese medicine group, the lung tissue structure was slightly abnormal. A small amount of alveolar atrophy and collapse could be observed, the alveolar walls were not thickened, and individual neutrophil infiltration could be seen in the tissue. In the control group, the lung tissue structure was slightly abnormal, some alveoli atrophied, and a small amount of neutrophil infiltration could be seen in the tissue. The levels of MCP-1 and MIP-1α in plasma and lavage fluid of the model group were significantly higher than those of the normal group (all P<0.05), while the levels of MCP-1 and MIP-1α in plasma and lavage fluid of the traditional Chinese medicine group and the control group were significantly lower than those of the model group (all P<0.05). Moreover, the levels of plasma MCP-1 and MIP-1α in the traditional Chinese medicine group were significantly lower than those in the control group (all P<0.05), while there was no statistically significant difference in the levels of MCP-1 and MIP-1α in alveolar lavage fluid between the traditional Chinese medicine group and the control group (all P>0.05). The levels of IL-6 and TNF-α in plasma and alveolar lavage fluid of the model group were significantly higher than those of the normal group (all P<0.05), while the levels of IL-6 and TNF-α in plasma and alveolar lavage fluid of the traditional Chinese medicine group and the control group were significantly lower than those of the model group (all P<0.05). Moreover, the levels of IL-6 and TNF-α in plasma and alveolar lavage fluid of the traditional Chinese medicine group were significantly lower than those of the control group (all P<0.05). Conclusions:The intervention of Maxing Loushi decoction has a significant improvement effect on the inflammatory response of COPD model mice. Inflammatory factors such as MCP-1, MIP-1α, IL-6, and TNF-α can be used as indicators to determine the degree of COPD inflammation.

Objective To explore the effect of the teaching model based on"Academic-Industrial-Education Integration"in the clinical probation and practice teaching of rehabilitation.Methods 57 rehabilitation students were divided into control group(n=28)and experimental group(n=29)according to their volunteers.The control group took the traditional teaching method,and the experimental group took the teaching method of"Academic-Industrial-Education Integration".The two groups of students were compared in the assessment results of scientific research related courses,the participation rate of students in scien-tific research and innovation related projects,the satisfaction results of teaching effect,learning effect,self-theoretical ability and self-practical ability.The data of teachers' teaching results were collected.Results The scores of students in the experimental group were better than those in the control group in terms of scientific research-related courses and participation rate of scientific research,innovation and entrepreneurship projects(P＜0.05).There was no statistical difference in the satisfaction of teaching effect and theoretical ability improvement.Students' self-learning effect satisfaction and practical ability improvement satisfaction in the experimental group were higher than those in the control group(P＜0.05).The teaching achievements of teachers are in-creased,and the teaching level is promoted.Conclusion The application of"Academic-Industrial-Education Integration"teaching mode in clinical teaching of rehabilitation is helpful to improve students' participation rate in scientific research courses and innova-tive projects,improve the satisfaction of learning effect and practical ability,and promote the improvement of teaching level.

Objective:To investigate the change trend of hepatectomy for hepatocellular carcinoma and efficacy of fluorescent laparoscopic hepatectomy in a single center from 2014?2023.Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 17 232 patients of hepatocellular carcinoma who were admitted to Zhongshan Hospital of Fudan University from January 2014 to December 2023 were collected. There were 14 404 males and 2 828 females, aged 58(range, 11?94)years. Observation indicators: (1) change trend of hepatectomy for hepatocellular carcinoma and application of fluorescent laparoscopy in 2014?2023; (2) propensity score matching between patients undergoing fluorescent and conventional laparoscopic hepatectomy; (3) intraoperative and postoperative conditions of patients in the fluorescent laparoscopy group and the conventional laparoscopy group after propensity score matching. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test. Comparison of ordinal data between groups was conducted using the nonparametic rank sum test. Propensity score matching was performed using the 1∶3 nearest neighbor matching method, with the caliper value of 0.01. Results:(1) Change trend of hepatectomy for hepatocellular carcinoma and application of fluorescent laparoscopy in 2014-2023. Among 17 232 patients of hepatocellular carcinoma, 4 074 cases underwent laparoscopic surgery, and 13 158 cases underwent open surgery or conversion from laparoscopic to open surgery. From 2014 to 2023, the proportions of laparos-copic surgery in hepatectomy were 8.993%(117/1 301), 6.804%(99/1 455), 9.379%(145/1 546), 17.511%(287/1 639), 23.828%(427/1 792), 24.572%(459/1 868), 29.662%(544/1 834), 31.568%(584/1 850), 38.080%(599/1 573), and 34.246%(813/2 374), respectively. The proportions of Grade Ⅲ surgery in laparoscopic hepatectomy were 11.966%(14/117), 7.071%(7/99), 12.414%(18/145), 21.254%(61/287), 28.337%(121/427), 27.887%(128/459), 34.375%(187/544), 34.644%(214/584), 35.726%(214/599), and 42.681%(347/813), respectively. From 2016 to 2023, the proportions of the application of fluorescent laparoscopy in laparoscopic hepatectomy were 2.069%(3/145), 5.923%(17/287), 8.431%(36/427), 10.022%(46/459), 17.647%(96/544), 24.829%(145/584), 9.182%(55/599), and 12.915%(105/813), respectively. (2) Propensity score matching between patients undergoing fluorescent and conventional laparoscopic hepatectomy. Among the 4 074 patients who underwent laparoscopic liver resection, 503 cases using fluorescent laparoscopy were assigned to the fluorescent laparoscopy group, 3 571 cases using conventional laparoscopy were assigned to the conventional laparoscopy group. A total of 1 794 patients were successfully matched, with 483 cases in the fluorescent laparoscopy group and 1 311 cases in the conventional laparoscopy group. After propensity score matching, the confounding biases of the maximum tumor diameter and the year of surgery were eliminated, and the two groups were comparable. (3) Intraoperative and postoperative conditions of patients in the fluorescent laparoscopy group and the conventional laparoscopy group after propensity score matching. After propensity score matching, there was no perioperative death in either the fluorescent laparoscopy group or the conventional laparoscopy group.The operation time of patients in the fluorescent laparoscopy group was 240(150,328)minutes, the portal triad clamping time was 30(15,45)minutes, the volume of intraoperative blood loss was 50(30,100)mL, the number of patients with complication 72, respectively. For patients in the conventional laparoscopy group, the above indicators were 180(131,240)minutes, 23(15,30)minutes, 55(50,100)mL, and 248, respectively. There were significant differences in the above indicators between the two groups ( Z=?7.593, ?7.372, ?4.941, χ2=3.873, P<0.05). Conclusion:The proportion and difficulty level of laparoscopic hepatectomy for hepatocellular carcinoma in Zhongshan Hospital of Fudan University have shown an upward trend during 2014?2023. Compared with conventional laparoscopy, patients undergoing fluorescent laparoscopic hepatectomy have longer operation time and portal triad clamping time, but less intraoperative blood loss and lower iproportion of complications.

Computational analysis can accurately detect drug-gene interactions(DGIs)cost-effectively.However,transductive learning models are the hotspot to reveal the promising performance for unknown DGIs(both drugs and genes are present in the training model),without special attention to the unseen DGIs(both drugs and genes are absent in the training model).In view of this,this study,for the first time,proposed an inductive learning-based model for the precise identification of unseen DGIs.In our study,by integrating disease nodes to avoid data sparsity,a multi-relational drug-disease-gene(DDG)graph was constructed to achieve effective fusion of data on DDG intro-relationships and inter-actions.Following the extraction of graph features by utilizing graph embedding algorithms,our next step was the retrieval of the attributes of individual gene and drug nodes.In this way,a hybrid feature charac-terization was represented by integrating graph features and node attributes.Machine learning(ML)models were built,enabling the fulfillment of transductive predictions of unknown DGIs.To realize inductive learning,this study generated an innovative idea of transforming known node vectors derived from the DDG graph into representations of unseen nodes using node similarities as weights,enabling inductive predictions for the unseen DGIs.Consequently,the final model was superior to existing models,with significant improvement in predicting both external unknown and unseen DGIs.The practical feasibility of our model was further confirmed through case study and molecular docking.In summary,this study establishes an efficient data-driven approach through the proposed modeling,suggesting its value as a promising tool for accelerating drug discovery and repurposing.

Transformer models have emerged as pivotal tools within the realm of drug discovery,distinguished by their unique architectural features and exceptional performance in managing intricate data landscapes.Leveraging the innate capabilities of transformer architectures to comprehend intricate hierarchical dependencies inherent in sequential data,these models showcase remarkable efficacy across various tasks,including new drug design and drug target identification.The adaptability of pre-trained trans-former-based models renders them indispensable assets for driving data-centric advancements in drug discovery,chemistry,and biology,furnishing a robust framework that expedites innovation and dis-covery within these domains.Beyond their technical prowess,the success of transformer-based models in drug discovery,chemistry,and biology extends to their interdisciplinary potential,seamlessly combining biological,physical,chemical,and pharmacological insights to bridge gaps across diverse disciplines.This integrative approach not only enhances the depth and breadth of research endeavors but also fosters synergistic collaborations and exchange of ideas among disparate fields.In our review,we elucidate the myriad applications of transformers in drug discovery,as well as chemistry and biology,spanning from protein design and protein engineering,to molecular dynamics(MD),drug target iden-tification,transformer-enabled drug virtual screening(VS),drug lead optimization,drug addiction,small data set challenges,chemical and biological image analysis,chemical language understanding,and single cell data.Finally,we conclude the survey by deliberating on promising trends in transformer models within the context of drug discovery and other sciences.

AIM To establish an HPLC-MS/MS method for the simultaneous content determination of gallic acid,protocatechuic acid,oxypaeoniflorin,catechin,epicatechin,albiflorin,paeoniflorin,rutin,calycosin-7-glucoside,syringaldehyde,ferulic acid,coumarin,ononin,calycosin,cinnamic alcohol,cinnamic acid,benzoylpaeoniflorin,cinnamaldehyde,astragaloside,astragaloside Ⅲ,6-gingerol in Huangqi Guizhi Wuwu Decoction.METHODS The analysis was performed on a 30 ℃ thermostatic Thermo Scientific Hypersil GOLD column(150 mmx4.6 mm,3 μm),with the mobile phase comprising of 0.015％formic acid-acetonitrile flowing at 0.4 mL/min in a gradient elution manner,and electrospray ionization source was adopted in positive and negative ion modes with multiple reaction monitoring.RESULTS Twenty-one constituents showed good linear relationships within their own ranges(r＞0.990 5),whose average recoveries were 93.99％-108.52％with the RSDs of 1.04％-5.97％.CONCLUSION This simple,feasible,stable and reliable method can be used for the quality control of Huangqi Guizhi Wuwu Decoction.