Objective:To analyze the efficacy of enzyme replacement therapy and anti-drug antibody production in children with Fabry disease.Methods:The clinical data of 7 children with Fabry disease treated with enzyme replacement therapy for more than 1 year at Children′s Hospital of Zhejiang University School of Medicine from July 2021 to June 2024 were retrospectively analyzed. The basic information and the changes of related clinical indicators before and after treatment were collected. Paired sample t test was used to compare renal function, left heart mass index, pain score and other related indexes before and after treatment. The anti-drug antibodies were detected by enzyme-linked immunosorbent assay. Results:A total of 6 boys and 1 girl were included. The age of diagnosis was (12.2±1.8) years. After 1 year of enzyme replacement therapy, the abnormal substrate globotriaosylsphingosine and brief pain inventory scores of all children were significantly lower than those before treatment ((16±11) vs. (63±42) μg/L, 22±19 vs. 45±29, t=3.88, 3.43, both P<0.05). There were no significant differences in glomerular filtration rate, urinary microalbumin to creatinine and left heart mass index before and after treatment ((124±35) vs. (136±26) ml/(min·1.73 m 2), (9.3±8.3) vs. (3.8±2.5) mg/g, (38±9) vs. (33±6) g/m 2.7, t=1.33, 1.74, 1.19, all P>0.05). Patients 4, 5 and 6 developed anti-drug antibodies at 1 month, 4 months and 1 month after medication, respectively. Patient 4 had persistently high anti-drug antibody titers (absorbance 3.65-3.73) accompanied by urticaria, elevated globotriaosylsphingosine and worsening clinical symptoms. Conclusions:The enzyme replacement therapy can effectively improve the clinical symptoms and reduce the level of globotriaosylsphingosine in children with Fabry disease. The anti-drug antibody is common in patients after long-term enzyme replacement therapy and may diminish the efficacy, which needs dynamic monitoring.

Objective: To investigate the epidemic situation of notifiable infectious diseases in Zhejiang Province in 2024, so as to summarize the epidemic characteristics. Methods: Data of notifiable infectious diseases cases in Zhejiang Province from January 1 to December 31, 2024 were collected from the Infectious Disease Surveillance System of Chinese Disease Prevention and Control Information System. The epidemiological characteristics were analyzed according to the classification and transmission routes using the descriptive epidemiological method. Results: A total of 32 types of notifiable infectious diseases with 1 858 695 cases and 392 deaths were reported in Zhejiang Province in 2024, with a reported incidence of 2 804.73/105 and a reported mortality of 0.591 5/100 000. A total of 238 infectious disease public health emergencies were reported, of which 218 (91.60%) occurred in schools and kindergartens. There were 22 types of class A and B notifiable infectious diseases reported, with incidence of 470.62/100 000 and mortality of 0.591 5/100 000. Totally 10 types of class C notifiable infectious diseases, with a reported incidence of 2 334.11/105, and no deaths were reported. Classified by transmission route, respiratory infectious diseases had the highest reported incidence of 2 423.87/100 000, among which influenza exhibited the highest reported incidence of 2 024.22/100 000. The reported incidence of intestinal infectious diseases was 312.94/105, among which the incidence of other infectious diarrhea and hand-foot-mouth disease (HFMD) were high, with reported incidences of 169.52/100 000 and 136.18/100 000, respectively. Blood-borne and sexually transmitted infectious diseases accounted for the largest number of reported deaths, among which AIDS had the highest mortality of 0.424 0/100 000. Natural and insect-borne infectious diseases exhibited a low reported incidence of 1.37/105. The reported incidence of dengue fever was 0.40/100 000, and 95.08% of the cases were imported. Conclusions The reported incidence of respiratory and intestinal infectious diseases and the reported mortality of AIDS were high in Zhejiang Province in 2024. It is recommended to strengthen the prevention and control of infectious diseases such as influenza, other infectious diarrhea, and HMFD in schools and kindergartens.

Objective: To explore the association between greenness surrounding school and aggression among primary school students, and to explore the potential mediating roles of social support, loneliness, particulate matter (PM2.5) and Nitrogen Dioxide (NO2) in this association, in order to provide a scientific reference for preventing and ameliorating aggressive behaviors of primary school students. Methods: The data was used from a survey of children and adolescents conducted in 2015. The Chinese version of the Buss-Warren Aggression Questionnaire was used to assess total and subtypes of aggression, and the mean values of normalized difference vegetation index (NDVI) of 100 m, 500 m, 1 000 m circular buffers surrounding school were used to indicate the participants greenness exposure. PM2.5 and NO2 datas were obtained from the China High Air Pollutants Dataset.Generalized Linear Mixed Models were used to assess the associations of greenness surrounding school with total and subtypes of aggression. Results: Per IQR increment of NDVI-500 m [OR(95%CI)=1.09(1.03-1.15)] and NDVI-1 000 m[OR(95%CI)=1.07(1.02-1.13)] were positively correlated with physical aggression among primary school children, and per IQR increment of NDVI-100 m [OR(95%CI)=0.94(0.90-0.99)], NDVI-500 m [OR(95%CI)=0.93(0.89-0.98)] and NDVI-1 000 m [OR(95%CI)=0.95(0.91-1.00)] were negatively associated with verbal aggression (P<0.05). Mediation analyses revealed that social support partially mediated the association between the NDVI-500 m and physical aggression (mediation ratio:18.0%) and verbal aggression (mediation ratio:-8.3%) among primary school students, and loneliness partially mediated the association between the NDVI-500 m and physical aggression and verbal aggression among elementary school students effects, with proportion mediated ratios of -10.0% and 21.0%, respectively (P<0.05). Conclusions Exposure to school surrounding greenness is likely to associated with physical aggression and verbal aggression in primary school students, and social support and loneliness may partially mediate these associations.

With persistent breakthrough and maturity of surgical procedures and postoperative immunosuppressive therapy, the survival rate of liver transplant recipients and grafts has been significantly increased. The shortage of donor liver has become the main obstacle for clinical development of liver transplantation. How to expand the source of donor liver has become an urgent issue. Groundbreaking progresses have been made in the use of common marginal donor livers in clinical liver transplantation, such as elderly donor liver, steatosis donor liver, viral hepatitis donor liver and liver from donation after cardiac death. Nevertheless, multiple restrictions still exist regarding the use of marginal donor liver. Consequently, the definition of marginal donor liver and research progress in the application of common marginal donor livers were reviewed, and the opportunities and challenges of mariginal donoor liver were illustrated, aiming to provide reference for expanding the donor pool for clinical liver transplantation and bringing benefits to more patients with end-stage liver disease.

Objective: To investigate epidemiological characteristics of notifiable infectious diseases in Zhejiang Province in 2023, so as to provide the evidence for strengthening prevention and control of infectious diseases. Methods: Data pertaining to notifiable infectious diseases reported in Zhejiang Province in 2023 were retrieved from the Infectious Disease Surveillance System of Chinese Disease Prevention and Control Information System. The incidence and mortality were analyzed according to the classification of notifiable infectious diseases and transmission routes, and epidemiological characteristics of infectious diseases were descriptively analyzed. Results: Thirty types of notifiable infectious diseases with 2 955 699 cases and 427 deaths were reported in Zhejiang Province in 2023, with a reported incidence rate of 4 493.93/105 and a reported mortality rate of 0.649 2/105. A total of 679 notifiable infectious disease emergencies were reported, with 26 514 cases and 1 case death (rabies). The emergencies mainly occurred in schools and preschool institutions, with 621 cases accounting for 91.46%. There were 1 case of cholera reported in class A notifiable infectious diseases and no death, 22 types of class B notifiable infectious diseases, with a reported incidence rate of 552.46/105 and a reported mortality rate of 0.644 7/105, and 8 types of class C notifiable infectious diseases, with a reported incidence rate of 3 941.48/105 and a reported mortality rate of 0.004 6/105. The incidence rates of respiratory, intestinal, blood-borne and sexually transmitted, natural and insect-borne infectious diseases were 4 028.67/105, 381.59/105, 81.15/105 and 1.35/105, respectively, according to transmission routes. Influenza (3 561.78/105) and COVID-19 (423.77/105) reported the highest incidence, and AIDS (0.477 4/105) and tuberculosis (0.130 8/105) reported the highest mortality. Conclusion The incidence rates of respiratory and intestinal infectious diseases were high in Zhejiang Province in 2023, and schools and preschool institutions were the main places of diseases occurred.

Objective: To investigate the characteristics of public health emergencies in Zhejiang Province in 2023, so as to provide the reference for public health risk management. Methods: Data of public health emergencies and related information in Zhejiang Province from January 1 to December 31, 2023 was collected through Emergency Public Reporting System of Chinese Disease Prevention and Control Information System. Attack rates, disease types, distribution of time and places, and responses were descriptively analyzed. Results: A total of 718 public health emergencies were reported in 2023 in Zhejiang Province, and all were infectious disease events. There were 27 128 reported cases and 3 deaths, with an attack rate of 3.22%. The top five infectious diseases with the highest number of reported events were influenza, norovirus infection, monkeypox, varicella and hand, foot and mouth disease, accounting for 95.54% of total reported events. There were 355 public health emergencies with less than 30 cases each, accounting for 49.44%. The reported emergencies peaked from February to March (186 events, 25.91%) and from November to December (327 events, 45.54%), and mainly occurred in schools and preschool institutions (651 events, 90.67%). The median responding time, reporting time and duration of emergencies were 6.50 (interquartile range, 10.84) h, 0.53 (interquartile range, 0.63) h and 7.24 (interquartile range, 11.71) d, respectively. Conclusion Public health emergencies in Zhejiang Province in 2023 were mainly caused by influenza and norovirus infection, with February, March, November and December being the peak reporting periods, and schools and preschool institutions being the main places where these events occurred.

Objective To observe the effect of electroacupuncture on corneal Toll-like receptor 4(TLR4)-mediated inflammatory signaling pathway in diabetic dry eye rats and to explore the mechanism of electroacupuncture in the treat-ment of diabetic dry eye.Methods A type 2 diabetic rat model was established in 32 healthy male Sprague-Dawley(SD)rats by intraperitoneal injection of streptozotocin(30 mg·kg-1)for 12 weeks after feeding with high-sugar and high-fat di-et for 4 weeks.Twenty-five successfully modeled diabetic dry eye rats were randomly divided into the model group(non-in-tervention),electroacupuncture group(the"Jingming","Cuanzhu","Sizhukong","Taiyang"and"Tongziliao"acupoints were treated with acupuncture,and then"Cuanzhu"and"Tongzilao"acupoints were treated with electroacupuncture,15 min for each time,once a day),sham acupuncture group(blunt-tip needle pricking was performed at the same acupoints as the electroacupuncture group),and fluorometholone group(1 g·L-1fluorometholone eye drops were used in both eyes at 8 o'clock,13 o'clock,and 18 o'clock,1 drop each time),with 6 rats in each group,lasting for 2 weeks.Another 6 healthy male SD rats were selected as a blank group.Random blood glucose,tear film breakup time(BUT),tear secre-tion,corneal fluorescein staining(FL)score,and corneal touch threshold(CTT)of rats in each group were detected be-fore modeling,after modeling,and after the intervention.Hematoxylin and Eosin(HE)staining was performed to observe the corneal morphologic changes in each group.Immunofluorescence histochemical staining was adopted to detect the cor-neal TLR4-positive expression in each group.The TLR4,phosphorylated nuclear factor-kappa P65(P-NF-KB P65),inter-leukin(IL)-1β,and IL-18 expression levels in the cornea were detected by Western blot.Results After modeling,com-pared with the blank group,BUT,tear secretion and CTT decreased and FL increased in all experimental groups,and the differences were statistically significant(all P＜0.01).After the intervention,compared with the model group,FL de-creased,and BUT,tear secretion and CTT increased in the electroacupuncture group,and the differences were statistically significant(all P＜0.05).Corneal HE staining showed that after the intervention,the corneal surface of rats in the model group and sham acupuncture group was not smooth,and the corneal epithelial cells were thickened and disorganized;the corneal surface of rats in the electroacupuncture group and fluorometholone group was smooth,and the corneal epithelial cells were arranged neatly.After the intervention,compared with the blank group,the corneal TLR4 expression of rats in all other groups was elevated,and the differences were statistically significant(all P＜0.05);compared with the model group,the corneal TLR4 expression of rats in the electroacupuncture group and fluorometholone group was reduced(both P＜0.01).Compared with the blank group,corneal TLR4,P-NF-κBP65,IL-1β and IL-18 protein expressions increased in the model group and sham acupuncture group(all P＜0.05);compared with the model group,these expressions decreased in the electroacupuncture group and the fluorometholone group(all P＜0.05).Conclusion Electroacupuncture can im-prove the ocular surface signs and inhibit the expressions of TLR4,P-NF-κB P65,IL-1 β,and IL-18 in the cornea of type 2 diabetic dry eye rats,and its mechanism of action may be related to the regulation of TLR4-mediated inflammatory signaling pathway,which inhibits ocular surface inflammation in diabetic dry eye rats.

Objective To reveal the potential mechanism of electroacupuncture regulating the neuroinflammatory signaling pathway mediated by triggering receptor expressed on myeloid cells 2(TREM2)in trigeminal ganglion(TG)and caudate nucleus of spinal trigeminal nucleus(SpVc)of rats with type 2 diabetes and dry eyes and alleviating ocular surface sensory abnormalities.Methods Healthy male Sprague-Dawley(SD)rats were induced by intraperitoneal injection of 10 g·L-1 streptozotocin to establish a type 2 diabetes dry eye rat model after 4 weeks of high-glucose and high-fat diets.In the 12th week of the experiment,successfully modeled rats were randomly divided into the model group,electroacupunc-ture group,sham-acupuncture group and fluorometholone group,and healthy male SD rats fed with normal diets were se-lected as the blank group.Rats in all groups were intervened for 2 weeks.The corneal fluorescein sodium staining(FL),tear secretion[detected by phenol red thread(PRT)test],tear film break-up time(BUT),and corneal touch threshold(CTT)in each group were measured before,after modeling,and after the intervention.The changes in tissue morphology of TG and SpVc and TREM2 positive expression sites in each group were observed.The messenger ribonucleic acid(mR-NA)expression of TREM2,interleukin-18(IL-18)and interleukin-1β(IL-1β)of TG and Sp Vc in each group were detec-ted.Results After modeling,compared with the blank group,the FL scores of rats significantly increased and PRT,BUT and CTT significantly decreased in other groups(all P＜0.01).After the intervention,compared with the model group,the electroacupuncture group and fluorometholone group showed significant reductions in FL scores and significant increases in PRT,BUT and CTT(all P＜0.01);there was no statistically significant difference in these indicators in the sham-acupuncture group(all P＞0.05).Compared with the electroacupuncture group,the PRT and CTT of rats in the flu-orometholone group and sham-acupuncture group were significantly reduced,the FL score significantly increased and BUT significantly decreased in the sham-acupuncture group(all P＜0.01),and there was no statistically significant difference in FL score and BUT of rats in the fluorometholone group(both P＞0.05).Compared with the sham-acupuncture group,the fluorometholone group showed a decrease in FL score and an increase in PRT,BUT and CTT in rats,with statistically dif-ferent significances(all P＜0.05).The immunofluorescence double-labeling assay showed a positive expression of TREM2 in activated microglia of TG and SpVc in the model group.The reverse transcription-polymerase chain reaction of TG and SpVc showed that compared with the blank group,the TREM2 mRNA expression in the TG and SpVc of the model group,electroacupuncture group,fluorometholone group and sham-acupuncture group decreased,the IL-18 and IL-1β mRNA in TG and SpVc of the model group,IL-18 and IL-1β mRNA in TG and IL-1β mRNA in SpVc of the sham-acupuncture group increased(all P＜0.05);compared with the model group,the TREM2 mRNA expression increased and IL-18 and IL-1β mR-NA expression decreased in the TG and SpVc of the electroacupuncture group and fluorometholone group(all P＜0.05).Compared with the electroacupuncture group,the TREM2 mRNA expression decreased and IL-18,IL-1β mRNA expression increased in TG and SpVc of the sham-acupuncture group(all P＜0.05),and no significant difference was found in TREM2,IL-18 and IL-1β mRNA expression in TG and SpVc of the fluorometholone group(all P＞0.05).Compared with the sham-acupuncture group,the TREM2 mRNA expression in TG and SpVc increased in the fluorometholone group,while the IL-18 mRNA expression in SpVc decreased(all P＜0.05);the IL-1β mRNA in TG and SpVc and the IL-18 mRNA in TG of the fluorometholone group showed no statistically significant difference(all P＞0.05).Conclusion Electroacupunc-ture can effectively alleviate the ocular surface sensory abnormalities of rats with type 2 diabetes and dry eyes by regulating the inflammatory signaling pathway mediated by TREM2 in TG and SpVc.

This article introduces an overview of management system for conflict of interest of the European Pharmacopoeia Commission (EPC) and the United States Pharmacopoeia Convention (USP). The EPC and USP have standardized the management system for conflict of interest in drug standard work in multiple management documents, such as the Guide for the Work, Code of Practice for the Work, Form for Declaration of Interests and Confidentiality Undertaking of the EPC, bylaws, Rules and Procedures of the Council of Experts, Code of Ethics, Standards of Conduct of the USP, in order to ensure the transparency and fairness of drug standard development, improve the credibility and rigor of drug standards. This article introduces the management system for conflict of interest of the EPC and USP, providing reference for the improvement of relevant management systems of the Chinese Pharmacopoeia Commission.

Objective:To investigate the clinicopathological features, immunophenotype, molecular characteristics, and differential diagnosis of primary intracranial DICER1-mutant sarcoma in order to better understand this tumor type.Methods:A retrospective analysis was conducted on 7 cases of primary intracranial DICER1-mutant sarcoma diagnosed in the Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, China between 2021 and 2023 using next-generation sequencing. At the same time, 10 gliosarcomas, 4 intracranial FET::CREB fusion-positive mesenchymal tumors, 4 malignant meningiomas, 3 malignant solitary fibrous tumors, 3 malignant peripheral nerve sheath tumors, 3 synovial sarcomas and 3 rhabdomyosarcomas (total 30 cases) were selected as control.Results:Among the 7 patients with primary intracranial DICER1-mutant sarcoma, 6 were male and 1 was female, aged 10-32 years (median, 23 years). The tissue morphology was predominantly spindle or pleomorphic sarcoma-like, with 6 cases exhibiting eosinophilic globules, and 3 cases showing rhabdomyoblastic or rhabdomyosarcoma-like cell differentiation. Immunohistochemistry revealed focal desmin expression in 3 cases (3/7), ATRX loss in 3 cases (3/7), and p53 mutant pattern in 4 cases (4/7). Additionally, 4 cases (4/7) showed focal or diffuse SALL4 expression, whereas the control cases (30 cases) did not exhibit SALL4 protein expression, suggesting that SALL4 may possess certain auxiliary diagnostic value. Next-generation sequencing confirmed that all 7 cases of primary intracranial DICER1-mutant sarcoma harbored mutations in the DICER1 gene, with 5 cases having the mutation site at p.E1813D. Until May 2024, all 7 patients were alive.Conclusions:Primary intracranial DICER1-mutant sarcoma is a rare tumor. Understanding its morphological characteristics, immunohistochemical and molecular markers and differential diagnosis is crucial to avoid misdiagnosis and to improve diagnostic accuracy of this tumor.