Objective To investigate the clinical features and genetic characteristics of patients with late-onset Pompe disease(LOPD).Methods A total of 13 patients diagnosed with LOPD in the First Affilia-ted Hospital of Zhejiang University School of Medicine from September 2020 to December 2023 were selected,and all patients were subjected to clinical investigation,GAA activity detection and GAA gene testing.Results Among the 13 patients,7 were males and 6 were females;5 were family patients and 8 were sporadic patients;and the median age of onset was 17 years(8-52 years),the median age of presentation was 24 years(10-52 years),and the median age of diagnosis was 31 years(14-58 years).In terms of the first symptoms,10 pa-tients presented with limb weakness and 3 patients presented with dyspnea.The average serum creatine kinase level was 552 U/L(55-1084 U/L),and the serum creatine kinase level was normal in one patient.All pa-tients had scoliosis and different degrees of restrictive ventilatory dysfunction.Neuroelectrophysiological exami-nations of 9 patients showed myogenic damage,and 8 of them had muscle tonic discharge.The mean value of GAA activity was 0.3 μmol/(L·h)[0.17-0.5 μmol/(L·h)].A total of 13 mutations were detected in GAA gene,and the most common mutation was c.2238G＞C(p.W746C).There were five new variant sites:c.543del(p.F181Lfs*40),c.839_840insCC(p.R281Pfs*34),c.1800_1823del(p.S601_R608del),c.2296T＞C(p.Y766H)and c.995C＞A(p.S332*).Conclusions LOPD is a rare disease that tends to delay diagnosis.Proximal limb weakness,decreased respiratory function,mild-to-moderate elevation of creatine kinase,scoliosis,and clinical inferior tonic discharge on electromyography are high-risk images of LOPD.c.2238G＞C(p.W746C)is a hotspot mutation,and the discovery of five new mutations enriches the GAA gene mutations lineage.

Objective:To explore the impact of treatment duration with human urinary kallidinogenase (HUK) on the efficacy and safety of acute ischemic stroke (AIS).Methods:In this subgroup analysis of RESK study, a total of 990 AIS patients recruited from 65 centers in China between August 2015 and June 2020 were included and divided into short medication group (HUK for 8 days, n=185) or long medication group (HUK for 15 days or 21 days, n=805). The proportions of patients with modified Rankin Scale (mRS) score of 0, 0-1, 0-2 at 90 days, National Institutes of Health Stroke Scale (NIHSS) score change from baseline to 22 days, the proportions of patients with Barthel index (BI)≥95 at 90 days, and the incidences of adverse events were analyzed. Comparisons between groups were conducted using chi-square test, single factor and multivariate Logistic regression analysis, etc. Results:Multivariate regression analysis showed that the proportions of patients with 90-day mRS score of 0-2 [74.1% (137/185) vs 75.0% (604/805); OR=1.047, 95% CI 0.676-1.620, P=0.838] and 22-day NIHSS score change from baseline (4.60±2.00 vs 4.26±2.80; OR=-0.390, 95% CI -1.125-0.344, P=0.297) showed no statistically significant difference between the short medication and long medication groups; the proportions of patients with 90-day mRS score of 0-1 [48.1% (89/185) vs 59.1% (476/805); OR=0.674, 95%CI 0.463-0.983, P=0.041] and 90-day BI≥95 [43.6% (79/181) vs 55.1% (442/802); OR=0.614, 95%CI 0.420-0.897, P=0.012] were significantly lower in the short medication group than in the long medication group. There was no statistically significant difference in the incidences of adverse events between these 2 groups. Conclusions:In AIS patients, consecutive 8-day dosing of HUK improved immediate (22-day NIHSS score) and long-term outcome (90-day mRS score 0-2) and was safely tolerated. When applicable, extended duration of HUK could improve long-term disability-free rate (90-day mRS score 0-1) and quality of life (90-day BI) without increasing the risk of adverse events.

Objective To investigate the impact of hemoglobin(Hb)level on the risk of all-cause mortality in elderly patients with stable coronary artery disease(SCAD)treated by percutaneous coronary intervention(PCI).Methods A retrospective cohort study was conducted on 195 elderly SCAD patients treated by PCI in our hospital from June 2016 to December 2017,a total of 180 case were followed up.They were divided into four groups based on quartiles of Hb levels:Q1 group[≤122(108.28±12.53)g/L,n=47],Q2 group[122＜Hb≤137(130.07±4.33)g/L,n=43],Q3 group[137＜Hb≤148(142.67±3.10)g/L,n=46],and Q4 group[＞148(158.36±8.50)g/L,n=44].Their clinical data were collected and compared among the groups.All patients were followed up,with all-cause mortality as endpoint.Cox regression analysis was used to evaluate the impact of Hb level on all-cause mortality in elderly SCAD patients treated by PCI.Results For the 180 patients with complete follow-up,the median follow-up time was 703(415,1121)d,and the incidence of all-cause mortality was 10.00％(totally 18 deaths).And the incidence was 25.50％(12 deaths),7.00％(3 death),4.30％(2 deaths)and 2.30％(1 death)in Q1,Q2,Q3,and Q4 groups,respectively,with statistically significant differences(P＜0.01).Univariate Cox regression analysis showed age was a risk factor for all-cause death(P＜0.01),while Hb level,BMI,smoking history,dyslipidemia,and aspirin use were a risk facotr for all-cause death(P＜0.05,P＜0.01).Further multivariate Cox regression analysis revealed Hb level was a risk facotr for all-cause death(HR=0.96,95％CI:0.93-0.99,P＜0.01).The risk of all-cause mortality was 3.68 times higher in the Q1 group than the Q2 group(HR=3.68,95％CI:1.01-13.45,P＜0.05),and there was no correlation in the incidence between the Q3 and Q4 groups(P＞0.05).Conclusion Low Hb level is an independent predictor for all-cause mortality in elderly SCAD pa-tients after PCI.

Objective:To preliminarily explore the role of silent information regulator 3 (SIRT3) in ferroptosis induced by high glucose in renal tubular epithelial cells, and to provide a new theoretical basis and treatment ideas for renal tubular injury in diabetic kidney disease patients.Methods:The single-cell transcriptomic analysis from "Tabula-muris" database was used to evaluate the expression of SIRT3 gene in different cellular subtypes of kidney tissues. HK-2 cells, a human immortalized proximal tubule epithelial cell line, were cultured in vitro and divided into following groups: (1) control group, mannitol group and high glucose group; (2) control group, negative control group, SIRT3 overexpression group, high glucose group and SIRT3 overexpression + high glucose group; (3) control group, negative control group, SIRT3 knockdown group, high glucose group and SIRT3 knockdown + high glucose group; (4) control group, Erastin intervention group and SIRT3 overexpression + Erastin intervention group. Normal glucose was 5.5 mmol/L, high glucose was 30 mmol/L, mannitol was 24.5 mmol/L, Erastin was 10 μmol/L, and the intervention time was 48 h. Cell counting kit-8 proliferation and cytotoxicity assay was used to determine cell viability. Real-time quantitative PCR and Western blotting were performed to assess the expression of SIRT3, kidney injury molecule-1 (KIM-1), and ferroptosis-related proteins acyl-CoA synthetase long chain family member 4 (ACSL4) and glutathione peroxidase 4 (GPX4) at the mRNA and protein levels. The malondialdehyde, glutathione, and iron levels were measured to evaluate the degree of cellular ferroptosis. DCFH-DA was used to analyze the intracellular reactive oxygen species level, while the JC-1 staining method was employed to evaluate alterations of mitochondrial membrane potential in HK-2 cells. Results:(1) The results of single-cell transcriptomic database analysis demonstrated that SIRT3 gene was expressed at the highest level in the subtypes of proximal tubule epithelial cells of kidney tissues. (2) Compared with the control group, the expression levels of KIM-1 and ACSL4 were higher, and the expression levels of SIRT3 and GPX4 and cell viability were lower in the high glucose group (all P<0.05), while there was no statistically significant difference of the aforementioned indicators between the mannitol group and the control group (all P>0.05). (3) Compared with the high glucose group, HK-2 cell vitality, GPX4 expression and intracellular glutathione were higher, ACSL4 expression, intracellular iron, malondialdehyde and reactive oxygen species were lower, mitochondrial membrane potential partially recovered in SIRT3 overexpression + high glucose group (all P<0.05). Compared with the high glucose group, HK-2 cell vitality and GPX4 expression were lower, ACSL4 expression was higher in SIRT3 knockdown + high glucose group (all P<0.05), and there were no statistically significant differences in intracellular iron, malondialdehyde and glutathione (all P>0.05). (4) Compared with the control group, Erastin intervention group had upregulated ACSL4 expression and downregulated GPX4 expression in HK-2 cells (all P<0.05). Compared with the Erastin intervention group, SIRT3 overexpression + Erastin intervention group had upregulated GPX4 expression and downregulated ACSL4 expression (all P<0.05). Conclusions:High glucose can decrease SIRT3 expression and mitochondrial membrane potential, and increase oxidative stress and ferroptosis in HK-2 cells. Overexpression of SIRT3 may reduce oxidative stress and alleviate mitochondrial dysfunction, thereby mitigating glucose-induced ferroptosis in HK-2 cells.

Objective:To analyze the role of psychological detachment(PD) and career calling(CC) in the relationship between hospital workplace violence(HV) and turnover intention(TI), so as to provide references for developing effective intervention measures for medical personnel who have suffered from HV.Methods:From October and November 2022, convenient sampling was used to select medical staff from public hospitals in 16 provinces of China, and a questionnaire survey was conducted on HV, TI, PD, and CC. Pearson′s test was used for correlation analysis, and mediation effect analysis and moderated mediation effect analysis were used to explore the role of PD and CC in the relationship between HV and TI.Results:A total of 1 090 medical personnel were included in this survey, of whom 600(55.0%) had been subjected to HV. The findings showed that HV was positively correlated with TI( r = 0.27, P<0.05). From the analysis of mediation effect, HV had a negative predictive effect on PD( β =-0.82, P<0.05). PD had a negative predictive effect on TI( β =-0.31, P<0.05). PD partially mediated the association between HV and TI, with a mediation effect value of 0.25(17.39%). From the analysis of moderated mediation effect, interaction between HV and CC( β =-0.41, P<0.05) and the interaction between PD and TI( β = 0.17, P<0.05) had a moderating effect on the level of TI of medical personnel. Conclusions:HV was an important factor in predicting the TI of medical personnel, with PD partially mediating between HV and TI. The sense of CC played a moderating role between HV and TI, as well as between PD and TI.

Objective:To investigate the prognostic significance of anemia in elderly patients with stable coronary artery disease treated by percutaneous coronary intervention(PCI).Methods:In this retrospective cohort study, 180 patients with stable coronary artery disease aged ≥60 years undergone percutaneous coronary intervention and with complete clinical data, admitted to Nanjing Meishan Hospital between June 2016 and December 2017, were selected.Baseline clinical data of the patients were collected, including hemoglobin, C-reactive protein, lipids, fasting glucose, glycated hemoglobin, blood creatinine, and left ventricular ejection fraction on cardiac color ultrasound.The endpoints of the follow-up included major adverse cardiac events(MACE), such as all-cause death, non-fatal myocardial infarction, and non-fatal stroke.According to the hemoglobin level, participants were divided into an anemia group(n=32)and a non-anemia group(n=148). Clinical data of the two groups were compared, and the Kaplan-Meier method and multivariate analysis with the Cox regression method were used to evaluate the effect of anemia on the occurrence of MACE in elderly patients with stable coronary artery disease treated by PCI.Results:The median duration of the follow-up of the 180 patients was 702.5 days and MACE occurred in 27(15.0%). Compared with the non-anemia group, the anemia group had a higher age, C-reactive protein level and MACE ratio, lower levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol and the glomerular filtration rate, and higher proportions of patients with smoking history and patients with dyslipidemia( P<0.05). Kaplan-Meier curves suggested that the incidence of MACE in the anemia group was higher than that in the non-anemia group[37.5%(12/32) vs.10.1%(15/148), P<0.05]. Multivariate analysis with the Cox regression method showed that the risk of MACE in the anemia group was 2.91 times higher than that in the non-anemia group( HR=2.91, 95% CI: 1.13-7.48, P<0.05). Conclusions:Anemia is an independent predictor of MACE in elderly patients with stable coronary artery disease after PCI.

Closed-loop hospital management can effectivly cope with the COVID-19 pandemic. In order to ensure the continuity of treatments for hemodialysis patients under closed-loop management and minimize possible medical and infection risks, Huashan Hospital affiliated to Fudan University and 9 hospitals in Shanghai established a hemodialysis alliance in January 2021.The alliance optimized hemodialysis resources within the region through overall planning by preparing sites, materials and personnel shifts in advance, and establishing management systems and work processes to ensure that patients could be quickly and orderly diverted to other blood dialysis centers for uninterrupted high-quality hemodialysis services, in case that some hemodialysis centers in the alliance under closed-loop management.From November 2021 to April 2022, 317 of 1 459 hemodialysis patients in the alliance were diverted to other centers for treatment, accumulating 1 215 times/cases of treatments without obvious adverse reactions. The practice could provide a reference for medical institutions to quickly establish mutual support mode under major public health events.

Objective:To analyze the application effect of integrated medical and nursing management model based on intelligent medical system in preventing postoperative breast cancer lymphedema.Methods:A total of 180 patients undergoing axillary lymph node dissection for breast cancer were selected in the Affiliated Hospital of Nantong University from July 2018 to August 2019. According to the random number table method, they were divided into treatment group and control group for 90 cases in each group, and finally completed the study: 86 cases in treatment group and 82 cases in control group. The control group was given routine health management, and the treatment group was given an integrated management model based on intelligent medical systems. After 6 months of follow-up, the two groups of patients were compared for their cognition of lymphedema, prevention behavior, incidence of lymphedema, and patient satisfaction.Results:The incidence, clinical manifestations, risk factors, prevention methods, and overall awareness rates of lymphedema in the treatment group were 82.56%(71/ 86), 84.88%(73/86), 83.72%(72/86), 83.72%(72/86), 83.72%(72/86), and the control group were 67.07%(55/82), 70.73%(58/82), 68.29%(56/82), 69.51%(57/82), 70.73%(58/82), the differences were statistically significant ( χ2 values were 4.046-5.508, P<0.05). The total scores of skin care, lifestyle, avoidance of upper limb compression, and prevention of lymphedema in the treatment group were (9.54±1.04), (30.45±2.45), (9.35±1.08), (58.92±8.20) points, and the control group were (8.12±1.32), (8.12±1.32), (8.74±1.14), (53.45±7.64) points, the differences were statistically significant ( t values were 3.561-7.764, P<0.01). The incidence of lymphedema in the treatment group was 9.30%(8/86), and that in the control group was 23.17%(19/82), the difference was statistically significant ( χ2 value was 5.985, P<0.05). Satisfaction was 95.35%(82/86) in the treatment group and 82.93%(68/82) in the control group, the difference was statistically significant ( χ2 value was 6.771, P<0.01). Conclusions:The integrated management of medical care and patients based on intelligent medical system can help improve the level of lymphedema cognition in patients with breast cancer surgery, promote the development of lymphedema prevention behavior, reduce the incidence of postoperative lymphedema, and improve patient satisfaction.

Objective:To deliver understanding of the latest research progress on clinical trials and approval of dermatological drugs in China in 2020.Methods:A registration and information disclosure platform for drug clinical studies and a query system for domestic and imported drugs in the National Medical Products Administration of China were searched for registered clinical trials and approved dermatological drugs, respectively. The number and stages of clinical trials, indications and classification of involved products, and listed dermatological drugs in 2020 were summarized and depicted.Results:There were 157 dermatological drug trials registered in China in 2020, accounting for 6.16% of all the 2 548 clinical drug trials, including 127 (80.9%) initiated by Chinese pharmaceutical enterprises and 25 (15.9%) international multicenter trials. Among the 127 drug trials initiated by Chinese pharmaceutical enterprises, bioequivalence trials were mostly common, accounting for 55.9% (71/127) . Compared with global pharmaceutical enterprises, domestic pharmaceutical companies initiated significantly decreased proportions of international multicenter trials (1.9% [3/157] vs. 14.0% [22/157], P < 0.001) , but significantly increased proportions of phaseⅠclinical trials and bioequivalence trials (24.4% [31/127] vs. 10.0% [3/30], 55.9% [71/127] vs. 0, respectively, both P < 0.001) . Totally, 90 kinds of dermatological drug were involved in all the trials, psoriasis, atopic dermatitis and melanoma were the most common indications, and innovative drugs accounted for 53.3% (48/90) ; the proportion of innovative drugs was significantly lower in domestic pharmaceutical companies than in global pharmaceutical companies (43.2% [32/74] vs. 16/16, P < 0.001) . In addition, 28 dermatological drugs developed by 22 pharmaceutical companies were approved in China in 2020, of which 21 drugs were developed by domestic pharmaceutical companies. Conclusion:Clinical drug trials carried out by domestic pharmaceutical companies mostly focus on generic drugs, and it is still necessary for domestic pharmaceutical companies to further improve the innovation ability.

Objective:To construct a multi-stage dynamic prevention and control model, establish a system of intervention points and prevention and control measures for the prevention and control of workplace violence in hospitals, so as to provide guidance for hospitals and medical staffs to effectively prevent and respond to such incidents.Methods:Based on the crisis management theory, a model for the prevention and control of workplace violence in hospitals was constructed, the intervention points and prevention and control measures were screened by the Delphi method.Results:A multi-stage dynamic prevention and control model of workplace violence in hospitals was constructed, and a system of intervention points and prevention and control measures for workplace violence in hospitals were established according to the model. The system was divided into three stages: the pre-event stage contained 10 intervention points and 48 countermeasures, the in-event stage contained 6 intervention points and 17 countermeasures, and the post-event stage contained 3 intervention points and 12 countermeasures.Conclusions:It is an effective way to avoid violence and reduce the damage degree of violent incidents by selecting different countermeasures for different intervention points and carrying out multi-stage dynamic prevention and control of workplace violence in hospitals.