Objective:To investigate the effect of toxifolin(TAX)on the malignant biological behaviors of human bladder cancer T24 cells through the Rac1/NF-κB/AKT signaling pathway.Methods:Bladder cancer T24 cells were routinely cultured and divided into:Ctrl group(untreated),TAX-L group(5 μmol/L TAX),TAX-M group(10 μmol/L TAX),TAX-H group(20 μmol/L TAX),and TAX-H+Rac1 activator group(20 μmol/L TAX+50 nmol/L ML-097).CCK-8 method,clone formation assay,scratch healing assay,Transwell chamber assay,and flow cytometry were used to evaluate the effects of different concentrations of TAX on the proliferation,migration,invasion,and apoptosis of T24 cells.WB method was used to examine the expression of apoptosis-related proteins,epithelial-mesenchymal transition(EMT)-related proteins,and Rac1/NF-κB/AKT axis related proteins in T24 cells;A nude mice xenograft model was used to assess the effect of TAX on tumor growth.Results:TAX dose-dependently inhibited the proliferation,migration,and invasion of T24 cells and promoted apoptosis(all P<0.05).TAX also increased the expression of apoptosis proteins BAX and E-cadherin,while decreasing the expression of Bcl-2,N-cadherin,and Rac1/NF-κB/AKT signaling pathway-related proteins(all P<0.05).Furthermore,TAX inhibited tumor growth in the xenograft model(P<0.05).ML-097 partially reversed these effects(all P<0.05).Conclusion:TAX inhibits the malignant biological behaviors of bladder cancer T24 cells and promotes their apoptosis by inhibiting Rac1/NF-κB/AKT signaling pathway.

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 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 value of ultrasonic biomicroscopy(UBM)imaging for diagnosing chestnut thorn foreign bodies in anterior segment.Methods A total of 70 patients who underwent UBM examination due to chestnut thorn injury or residue of chestnut thorn after removal and then operation were retrospectively enrolled.The distance of chestnut thorn foreign bodies from corneal limbus,and the subconjunctival depth and length of them were measured based on UBM imaging.The efficacy of UBM for diagnosing chestnut thorn foreign bodies in anterior segment was evaluated according to surgical findings,and the correlation of quantitative parameters of foreign bodies were analyzed.Results Among 70 cases of chestnut thorn foreign bodies in anterior segment,single ocular tissue(5/70,7.14％)involvement was detected in 5 cases,while multiple ocular tissues involvement(65/70,92.86％)were noticed in 65 cases according to UBM.Totally 109 foreign bodies were detected by UBM,among which 98 were consistent with surgical findings,with the diagnostic accuracy of 89.91％(98/109),while 11 foreign bodies were not found during operation,with the false positive rate of 10.09％(11/109).Meanwhile,4 foreign bodies found and removed with operation were not displayed with UBM,and the false negative rate of UBM was 3.92％(4/102).Among 98 chestnut thorn foreign bodies correctly diagnosed with UBM,10 located in stromal layer of cornea(10/98,10.20％)and 88 located in ocular wall(88/98,89.80％),including 43 subconjunctival(43/88,48.86％)and 45 sclerotic(45/88,51.14％)foreign bodies,with the median length of 0.200 mm.The distance of 88 foreign bodies in ocular wall from corneal limbus was(2.963±1.504)mm,and the subconjunctival depth was(0.785±0.388)mm.The distance of foreign bodies from corneal limbus were positively correlated with their subconjunctival depth(r,=0.361,P＜0.010),while their lengths were not correlated with their distance from corneal limbus and subconjunctival depth(both P＞0.05).Conclusion UBM imaging was valuable for clinical diagnosis and localization of chestnut thorn foreign bodies in anterior segment.

Objective To observe the value of ultrasonic biomicroscopy(UBM)imaging for diagnosing chestnut thorn foreign bodies in anterior segment.Methods A total of 70 patients who underwent UBM examination due to chestnut thorn injury or residue of chestnut thorn after removal and then operation were retrospectively enrolled.The distance of chestnut thorn foreign bodies from corneal limbus,and the subconjunctival depth and length of them were measured based on UBM imaging.The efficacy of UBM for diagnosing chestnut thorn foreign bodies in anterior segment was evaluated according to surgical findings,and the correlation of quantitative parameters of foreign bodies were analyzed.Results Among 70 cases of chestnut thorn foreign bodies in anterior segment,single ocular tissue(5/70,7.14％)involvement was detected in 5 cases,while multiple ocular tissues involvement(65/70,92.86％)were noticed in 65 cases according to UBM.Totally 109 foreign bodies were detected by UBM,among which 98 were consistent with surgical findings,with the diagnostic accuracy of 89.91％(98/109),while 11 foreign bodies were not found during operation,with the false positive rate of 10.09％(11/109).Meanwhile,4 foreign bodies found and removed with operation were not displayed with UBM,and the false negative rate of UBM was 3.92％(4/102).Among 98 chestnut thorn foreign bodies correctly diagnosed with UBM,10 located in stromal layer of cornea(10/98,10.20％)and 88 located in ocular wall(88/98,89.80％),including 43 subconjunctival(43/88,48.86％)and 45 sclerotic(45/88,51.14％)foreign bodies,with the median length of 0.200 mm.The distance of 88 foreign bodies in ocular wall from corneal limbus was(2.963±1.504)mm,and the subconjunctival depth was(0.785±0.388)mm.The distance of foreign bodies from corneal limbus were positively correlated with their subconjunctival depth(r,=0.361,P＜0.010),while their lengths were not correlated with their distance from corneal limbus and subconjunctival depth(both P＞0.05).Conclusion UBM imaging was valuable for clinical diagnosis and localization of chestnut thorn foreign bodies in anterior segment.

Objective:To explore the different metabolites in the follicular fluids (FFs) of polycystic ovary syndrome (PCOS) patients and non-PCOS patients and their effects on the maturation of mouse oocytes and the developmental potential of in vitro fertilization (IVF) embryos. Methods:The clinical data were collected for the retrospective cohort study. Animal experiments were conducted in a randomized controlled trial. This study included PCOS ( n=71) and non-PCOS ( n=70) patients who underwent the first IVF or intracytoplasmic sperm injection (ICSI) cycle in Shanghai JIAI Genetics & IVF institute from June 2019 to June 2020. The patients' FFs were collected and the clinical data from these patients were analyzed. Raman spectroscopy analysis technology was used to detect differences in the metabolic spectra of FFs between the two groups. Mouse GV phase oocytes were placed in FFs from PCOS patients and non-PCOS patients for in vitro maturation (IVM) culture respectively, then the matured mouse oocytes were collected for IVF. The effects of differential metabolites in FFs on mouse oocyte maturation and embryonic development were further explored. The Raman spectrum was also applied to identify the differences of the IVM spent culture media. Results:The MⅡ rate [82.19% (886/1 078)] and day 3 available embryo rate [51.30% (553/1 078)] from PCOS group were significantly lower than those of the non-PCOS group [85.85% (625/728), P=0.038; 53.30% (388/728), P=0.042]. However, there were no significant differences between the two groups in the cumulative clinical pregnancy rate and the cumulative live birth rate (all P>0.05). Raman was capable of distinguishing PCOS from non-PCOS FFs. The characteristic Raman displacement difference between the two groups is mainly concentrated in the 600-1 000 cm -1, as well as 1 168 cm -1, 1 344 cm -1, 1 440 cm -1, 1 504 cm -1, 1 632 cm -1 and 1 664 cm -1. The Raman characteristic shift database showed that the different metabolites of the two sets of FFs samples were mainly concentrated in protein, lipids, free nucleic acis, glucose, cholesterol, carotenoids, and amino acids. Mouse oocyte IVM results showed that the PCOS-FF group had a lower MⅡ rate [49.04% (77/157)] than that of non-PCOS group [65.07% (95/146), P=0.005). IVF results showed the PCOS-FF group had a significantly lower cleavage rate [46.75% (36/77)] than that of non-PCOS group [63.16% (60/95), P=0.031], but there was no significant difference in the blastocyst rate between the two groups ( P>0.05). Conclusion:Differential metabolites detected by Raman spectrum in the PCOS FFs may cause defected maturation of the oocytes, leading to infertility, and Raman spectroscopy is an effective approach towards PCOS diagnosis and the identification of metabolomics differences.

Objective:To explore the different metabolites in the follicular fluids (FFs) of polycystic ovary syndrome (PCOS) patients and non-PCOS patients and their effects on the maturation of mouse oocytes and the developmental potential of in vitro fertilization (IVF) embryos. Methods:The clinical data were collected for the retrospective cohort study. Animal experiments were conducted in a randomized controlled trial. This study included PCOS ( n=71) and non-PCOS ( n=70) patients who underwent the first IVF or intracytoplasmic sperm injection (ICSI) cycle in Shanghai JIAI Genetics & IVF institute from June 2019 to June 2020. The patients' FFs were collected and the clinical data from these patients were analyzed. Raman spectroscopy analysis technology was used to detect differences in the metabolic spectra of FFs between the two groups. Mouse GV phase oocytes were placed in FFs from PCOS patients and non-PCOS patients for in vitro maturation (IVM) culture respectively, then the matured mouse oocytes were collected for IVF. The effects of differential metabolites in FFs on mouse oocyte maturation and embryonic development were further explored. The Raman spectrum was also applied to identify the differences of the IVM spent culture media. Results:The MⅡ rate [82.19% (886/1 078)] and day 3 available embryo rate [51.30% (553/1 078)] from PCOS group were significantly lower than those of the non-PCOS group [85.85% (625/728), P=0.038; 53.30% (388/728), P=0.042]. However, there were no significant differences between the two groups in the cumulative clinical pregnancy rate and the cumulative live birth rate (all P>0.05). Raman was capable of distinguishing PCOS from non-PCOS FFs. The characteristic Raman displacement difference between the two groups is mainly concentrated in the 600-1 000 cm -1, as well as 1 168 cm -1, 1 344 cm -1, 1 440 cm -1, 1 504 cm -1, 1 632 cm -1 and 1 664 cm -1. The Raman characteristic shift database showed that the different metabolites of the two sets of FFs samples were mainly concentrated in protein, lipids, free nucleic acis, glucose, cholesterol, carotenoids, and amino acids. Mouse oocyte IVM results showed that the PCOS-FF group had a lower MⅡ rate [49.04% (77/157)] than that of non-PCOS group [65.07% (95/146), P=0.005). IVF results showed the PCOS-FF group had a significantly lower cleavage rate [46.75% (36/77)] than that of non-PCOS group [63.16% (60/95), P=0.031], but there was no significant difference in the blastocyst rate between the two groups ( P>0.05). Conclusion:Differential metabolites detected by Raman spectrum in the PCOS FFs may cause defected maturation of the oocytes, leading to infertility, and Raman spectroscopy is an effective approach towards PCOS diagnosis and the identification of metabolomics differences.

Objective: To establish a prediction model of herpangina epidemic trend based on Baidu index and hand, foot and mouth disease, so as to provide insights into analyses of communicable disease epidemics with limited or missing surveillance data. Methods: The incidence of hand, foot and mouth disease in Zhejiang Province during the period from the first week of 2015 through the 39th week of 2021 was retrieved from the China Information System for Disease Control and Prevention, and the Baidu index of hand, foot and mouth disease and herpangina was collected via the Baidu search engine during the same period. The correlation between the Baidu index and time series of hand, foot and mouth disease was examined using wavelet analysis. In addition, a random forest training model was created based on the Baidu index and incidence of hand, foot and mouth disease, and the fitting effectiveness was evaluated using the mean percentage error, while the Baidu index of herpangina was included in the model to predict the epidemic trend of herpangina during the study period. Results: The Baidu index of herpangina and hand, foot and mouth disease, and the Baidu index and incidence of hand, foot and mouth disease all appeared two peaks at the 26th and 52th week. The phase difference was less than 0.1 week between the Baidu index and time series of hand, foot and mouth disease, and the mean percentage error of the training model was 13.07%, with high concordance between the predicted number and actual report number of cases with hand, foot and mouth disease. The numbers of herpangina cases were predicted to be 28 822, 27 341, 28 422, 51 782, 52 457 and 5 691 from 2015 to 2020, and there were totally 48 702 herpangina cases reported until the 39th week of 2021. Like hand, foot and mouth disease, the incidence of herpangina peaked between May and July. Conclusion The random forest training model based on the Baidu index and incidence of hand, foot and mouth disease is feasible to predict the epidemic trend of herpangina.

Objective: To investigate the epidemiological features of notifiable infectious diseases in Zhejiang Province in 2021, so as to provide the evidence for formulating infectious disease control measures. Methods: The data pertaining to notifiable infectious diseases reported in Zhejiang Province in 2021 were retrieved from the Infectious Disease Surveillance System of China Information System for Disease Control and Prevention. The incidence and mortality of notifiable infectious diseases in Zhejiang Province in 2021 were descriptively analyzed. Results: Totally 29 types of notifiable infectious diseases with 396 623 cases and 391 deaths were reported in Zhejiang Province in 2021, with a reported incidence of 614.28/105 and a reported mortality of 0.605 6/105, respectively. There were 93 204 cases with class B notifiable infectious diseases, with a reported incidence rate of 144.35/105 and 303 419 cases with class C notifiable infectious diseases, with a reported incidence rate of 469.92/105; while no cases with class A notifiable infectious diseases were reported. Syphilis (39.45/105), tuberculosis (37.12/105), viral hepatitis (31.90/105) and gonorrhea (26.34/105) were the four most common class B notifiable infectious diseases, and AIDS (0.477 0/105) and pulmonary tuberculosis (0.116 2/105) were the two most deadly class B notifiable infectious diseases, while hand, foot and mouth disease (192.00/105), other infectious diarrhea (184.24/105) and influenza (86.45/105) were the three most common class C notifiable infectious diseases. According to the transmission route, intestinal and respiratory infectious diseases were the two most common infectious diseases, with reported incidence rates of 384.10/105 and 133.73/105, respectively; and according to the reported region, the highest incidence of class B notifiable infectious diseases was reported in Zhoushan and Ningbo cities, and the highest incidence of class C notifiable infectious diseases was reported in Ningbo City. Totally 1 101 COVID-19 cases were reported in Zhejiang Province in 2021, including 712 confirmed cases and 389 asymptomatic cases, and no deaths occurred. Conclusions The reported incidence of notifiable infectious diseases declined in Zhejiang Province in 2021 as compared to that prior to COVID-19 epidemics, with remarkable reductions in the incidence of respiratory and intestinal infectious diseases. The management of pulmonary tuberculosis, viral hepatitis and AIDS requires to be reinforced during the containment of COVID-19, to prevent the seasonable epidemic of influenza, hand, foot and mouth disease and other infectious diarrhea in Zhejiang Province.