ObjectiveTo investigate the optimal ratio of goat horn replacing antelope horn in Fufang Lingjiao Jiangya pills and the blood pressure-lowering mechanism of this medicine. MethodsThe blood pressure-lowering efficacy of Fufang Lingjiao Jiangya pills with varying proportions of goat horn replacing antelope horn was evaluated on spontaneous hypertensive rats （SHR）. In this experiment， 50 SHR rats were randomly grouped as follows： model （n=8）， captopril （0.01 g·kg^-1） （n=6）， low-dose blank Fufang Lingjiao Jiangya pills （0.342 g·kg^-1） （n=6）， high-dose blank Fufang Lingjiao Jiangya pills （0.684 g·kg^-1） （n=6）， low-dose antelope horn-containing Fufang Lingjiao Jiangya pills （0.378 g·kg^-1） （n=6）， high-dose antelope horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1） （n=6）， low-dose goat horn-containing Fufang Lingjiao Jiangya pills （0.378 g·kg^-1） （n=6）， and high-dose goat horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1） （n=6）. Additionally， 8 WKY rats were used as the normal group. Drugs were administered by gavage for 4 weeks while an equal volume of distilled water was administered for the normal and model groups. Blood pressure was measured before administration， 3 h post administration， and biweekly thereafter. In the experiment for Fufang Lingjiao Jiangya pills with goat horn replacing antelope horn in different proportions， 48 SHR rats were randomly grouped as follows： model， blank Fufang Lingjiao Jiangya pills （0.684 g·kg^-1）， antelope horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1）， 2× goat horn-containing Fufang Lingjiao Jiangya pills （0.824 g·kg^-1）， 4× goat horn Fufang Lingjiao Jiangya pills （0.969 g·kg^-1）， and 6× goat horn Fufang Lingjiao Jiangya pills （1.112 g·kg^-1）. The normal group included 8 WKY rats， and the normal group and model group received an equal volume of distilled water. The treatment lasted for 2 weeks， and blood pressure was recorded at various time points （pre-administration， 3 h post administration， and on days 4， 7， 10， and 14 of administration）. Serum levels of angiotensin-converting enzyme （ACE）， angiotensin Ⅱ（Ang Ⅱ）， renin， and interleukin-6 （IL-6） were measured by enzyme-linked immunosorbent assay. Histopathological changes in the heart， kidney， and thoracic aorta were observed by hematoxylin-eosin staining. The protein levels of ACE2， angiotensin Ⅱ type 1 receptor （AT1R）， and angiotensinogen （AGT） in the kidney tissue were determined by Western blot， while the expression of nuclear factor （NF）-κB p65 and Toll-like receptor 4 （TLR4） in the thoracic aorta tissue was assessed by immunohistochemistry. ResultsCompared with the model group， all treatment groups showed lowered blood pressure （P<0.05， P<0.01）， and the 6× goat horn-containing Fufang Lingjiao Jiangya pills group showed consistent blood pressure-lowering effect with the antelope horn-containing Fufang Lingjiao Jiangya pills group. Compared with the normal group， the model group showed elevated serum levels of ACE， Ang Ⅱ， renin， and IL-6， while the elevations were declined in the Fufang Lingjiao Jiangya pills groups （P<0.05， P<0.01）. Pathological changes in the heart， kidney， and thoracic aorta were alleviated in all the treatment groups， with the 6× goat horn- and antelope horn-containing Fufang Lingjiao Jiangya pills groups exhibited the best effect. Western blot and immunohistochemistry results showed that all the treatment groups exhibited down-regulated protein levels of AT1R， AGT， NF-κB p65， and TLR4 and up-regulated protein levels of ACE2 （P<0.05， P<0.01） compared with model group， with the 6×goat horn- and antelope horn-containing Fufang Lingjiao Jiangya pills groups showcasing the best effect. ConclusionReplacing antelope horn with 6×goat horn in Fufang Lingjiao Jiangya pills can achieve consistent blood pressure-lowering effect with the original prescription. The prescription may exert the effect by inhibiting the renin-angiotensin-aldosterone system （RAAS） and TLR4/NF-κB signaling pathways.

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 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.

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 analyze the epidemiological characteristics of overseas imported cases with coronavirus disease 2019 (COVID-19) in Zhejiang Province, so as to provide insights into containment of overseas imported COVID-19. Methods: The pertaining to overseas imported COVID-19 cases in Zhejiang Province during the period between January 1, 2020 and May 31, 2022 were captured from the Chinese Disease Prevention and Control Information System. The temporal, spatial and population distributions, the duration from entry to the first time of positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid test, and COVID-19 vaccination of overseas imported COVID-19 cases were analyzed using a descriptive epidemiological method. Results: A total of 1 535 overseas imported COVID-19 cases were reported in Zhejiang Province during the period between January 1, 2020 and May 31, 2022, including 596 confirmed cases and 939 asymptomatic infections, and all reported cases were imported from 102 countries and territories. Overseas imported COVID-19 cases were reported in each month during the period between March 2020 and May 2022 except May 2020, and the mean monthly number of reported overseas imported COVID-19 cases was 125 during the period between December 2021 and May 2022. Overseas imported COVID-19 cases were reported across 11 cities of Zhejiang Province, with the largest numbers reported in Hangzhou (978 cases) and Jiaxing cities (177 cases), and imported cases were reported in 76.09% of counties (districts) in Zhejiang Province. The overseas imported COVID-19 cases were predominantly identified among individuals with Chinese nationality (88.79%), at ages of 20 to 39 years (59.09%), and students (21.82%), workers (17.20%) and business servants (17.00%) were predominant occupations among the overseas imported COVID-19 cases. The median duration from entry to the first time of positive SARS-CoV-2 nucleic acid test was 3.98 (7.06) d during the period between January 1, 2020 and May 31, 2022, and was 3.23 (4.97) d during the period between December 1, 2021 and May 31, 2022, which was significantly shorter than that during the period between January 1, 2020 and November 30, 2021 (P<0.001). The proportion of normal and more severe types of COVID-19 was 15.69% among cases without COVID-19 vaccination, which was significantly higher than that (7.77%) among those receiving booster vaccination (χ2=5.345, P=0.021), but was not significantly different from that (12.65%) among those receiving full-dose vaccination (χ2=0.971, P=0.324). Conclusions Students with Chinese nationality, workers and business servants were predominant among overseas imported COVID-19 cases in Zhejiang Province until May 31, 2022. The duration from entry after December 1, 2021 to identification of overseas imported COVID-19 cases shortened, and booster COVID-19 vaccination facilitated the alleviation of severity of clinical symptoms. There is a long-term risk of overseas importation of COVID-19 in Zhejiang Province, and the containment of imported COVID-19 requires to be sustainably implemented among entry personnel.

Objective: To investigate the characteristics of public health emergencies and related information in schools of Zhejiang Province from 2012 to 2021, so as to provide insights into the management of public health risks in schools. Methods: The public health emergencies and related information in schools of Zhejiang Province during the period from 2012 to 2021 were retrieved from the Public Health Emergency Management Information System of Chinese Disease Prevention and Control Information System. The type, temporal distribution and regional distribution of the events and the type of schools were analyzed, and the trends in disease attack rates were evaluated. Results: A total of 1 284 public health emergencies and related information were reported in schools of Zhejiang Province from 2012 to 2021, accounting for 72.34% of all public health emergencies and related information, and a total of 40 562 cases were reported, accounting for 87.72% of all cases; no death was recorded. There were 1 276 infectious disease events reported, accounting for 99.38%, and norovirus enteritis (649 cases), varicella (281 cases), influenza (181 cases), hand, foot and mouth disease (94 cases) and mumps (22 cases) were predominant infectious diseases, accounting for 95.56% of all public health emergencies and related information in schools. The number of public health emergencies and related information in schools peaked during the period between March and June (361 events, 28.12% of all events) and the period between November and December each year from 2012 to 2021 (629 events, 48.99% of all events), and the events occurred across 11 cities of Zhejiang Province, with the largest number of events reported in Hangzhou City (507 events). In addition, there were 627, 328 and 242 events reported in primary schools, kindergartens, and middle schools, accounting for 93.22%, and the events predominantly occurred in city schools. Nevertheless, there were no significant changes in the trends for attack rates of norovirus enteritis, varicella, influenza and hand, foot and mouth disease and mumps in schools of Zhejiang Province from 2012 to 2021. Conclusions Norovirus enteritis, varicella, influenza, hand, foot and mouth disease and mumps were the predominant types of public health emergencies and related information in schools of Zhejiang Province from 2012 to 2021, and the largest number of events were reported in primary schools.

Objective:To evaluate the clinical value and effect of the application of computer navigation system in orbital-zygomatic fibrous dysplasia.Methods:From March 2016 to December 2018, 16 patients with orbital-zygomatic fibrous dysplasia admitted to Shanghai 9th People’s Hospital, Shanghai Jiao Tong University School of Medicine were included in this study. CT scans and computer aided designs were finished preoperatively. By mirrored and compared with the healthy side, preoperative-designed lesion removal area was determined and surgical regions were highlighted. Digital reference frame was fixed rigidly to patient’s forehead. After accurate registration, lesion area was removed with the aid of surgical navigation system according to preoperative-designed plan restrictively through lower eyelid-intraoral approach. The symmetric morphology of orbital-zygomatic region was analyzed postoperatively. Zygomaxillare, oribitale, zygomaticand lower orbital point of zygomatic maxillary were marked both in preoperative and postoperative three-dimensional reconstructions, and the distance between them and mid-sagittal plane was measured. Paired- t tests were applied in this study for symmetric analysis. Results:In this study, 16 patients with orbital zygomatic bone fiber dysplasia assisted by computer navigation were included, consisted of 12 males and 4 females, ranging from 18 years old to 35 years old. The differences of preoperative symmetric analysis in zygomaxillare, oribitale, zygomatic had statistical significance( P<0.01). The difference of preoperative symmetric analysis in lower orbital point of zygomatic maxillary had no statistical significance( P>0.05). The differences of postoperative symmetric analysis in zygomaxillare, oribitale, zygomatic and lower orbital point of zygomatic maxillary had no statistical significance( P>0.05). The difference in zygomaxillare decreased from(10.1±6.2) mm to(2.7±6.4) mm. The difference in oribitale(ORI)decreased from(7.7±4.6) mm to(1.9±3.9) mm. The difference in zygomatic decreased from(8.5±7.5) mm to(0.7±1.5)mm. The difference in lower orbital point of zygomatic maxillary decreased from(1.9±3.5) mm to(0.6±2.1) mm. The morphology of the affected side and the healthy side was symmetrical. The contour was natural and no postoperative complications occurred. The postoperative satisfaction rate was high. Conclusions:Computer navigation system can solve the problem of limited exposure of lower eyelid-intraoral approach in orbital-zygomatic fibrous dysplasia and significantly improve the accuracy, effectiveness and safety during surgery.

Objective:To identify the gene mutations associated with facial cleft-related orbital hypertelorism in 3 pairs of monozygotic twins with different phenotypes (with/without hypertelorism) and to investigate their mechanisms.Methods:From May 2014 to May 2019, 3 pairs of monozygotic twins, 2 males and 4 females, aged 5-18 years, were treated in Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, one with normal orbital distance and widening of orbital distance was caused by facial fissure. Among the twins, there was 1 case of orbital hypertelorism and the other case of without orbital hypertelorism, and the hypertelorism was caused by facial cleft. To screen for mutations in hypertelorism, whole genome sequencing was performed on 3 pairs of twins. The Sanger method was used to sequence the exons of 33 patients with facial fissure associated hypertelorism and 50 healthy individuals in the same period to identify the genes selected by the whole genome sequencing. The periosteal tissues were obtained from patients and healthy people during plastic surgery. The cells were cultured, the activity of alkaline phosphatase was measured, and the osteogenic differentiation was identified by alizarin red staining, real-time quantitative PCR and Western blotting were used to detect the mRNA and protein expression of signal transduction pathways in periosteal cells.Results:Whole genome sequencing analysis showed that in all three sets of twins, a new synonymous mutation (c.1479G>A, p. Q493Q) was found in the MAML3. In Sanger exon sequencing, 17(51.5%) of 33 patients with hypertelorism carried the mutation, while no mutation was detected in 50 normal controls. The result of periosteum-derived cytology showed that the expression of MAML3 mRNA and protein in the patient-derived cells was lower than that in the healthy-derived cells. Three, 7, 14 days after osteoinduction, the ALP activity in the cells from the patients was higher than that from the healthy subjects (8.540±1.450, 20.740±2.514, 24.090±3.213 vs. 5.268±0.482, 11.680±1.527, 13.200±0.592; all P<0.05). Fourteen days after osteoinduction, the result of alizarin red staining showed that there were more erythema formation in the cells from the patients than those from the healthy subjects, these result suggest that MAML3 mutation may lead to over-differentiation of human periosteal-derived cells. The mRNA and protein expression levels of hes1 and hes5 downstream of the Notch signal pathway were down-regulated in the periosteal cells of the patients, while Wnt3a and β-catenin mRNA and protein expression levels were up-regulated in the Wnt signal pathway. Conclusions:The MAML3 gene (c.1479G>A, p. Q493Q) mutation is one of the causative genes of facial cleft-related hypertelorism. Notch and Wnt/β-catenin signaling pathway play an important role in the pathogenesis of hypertelorism.

Objective:To evaluate the clinical value and effect of the application of computer navigation system in orbital-zygomatic fibrous dysplasia.Methods:From March 2016 to December 2018, 16 patients with orbital-zygomatic fibrous dysplasia admitted to Shanghai 9th People’s Hospital, Shanghai Jiao Tong University School of Medicine were included in this study. CT scans and computer aided designs were finished preoperatively. By mirrored and compared with the healthy side, preoperative-designed lesion removal area was determined and surgical regions were highlighted. Digital reference frame was fixed rigidly to patient’s forehead. After accurate registration, lesion area was removed with the aid of surgical navigation system according to preoperative-designed plan restrictively through lower eyelid-intraoral approach. The symmetric morphology of orbital-zygomatic region was analyzed postoperatively. Zygomaxillare, oribitale, zygomaticand lower orbital point of zygomatic maxillary were marked both in preoperative and postoperative three-dimensional reconstructions, and the distance between them and mid-sagittal plane was measured. Paired- t tests were applied in this study for symmetric analysis. Results:In this study, 16 patients with orbital zygomatic bone fiber dysplasia assisted by computer navigation were included, consisted of 12 males and 4 females, ranging from 18 years old to 35 years old. The differences of preoperative symmetric analysis in zygomaxillare, oribitale, zygomatic had statistical significance( P<0.01). The difference of preoperative symmetric analysis in lower orbital point of zygomatic maxillary had no statistical significance( P>0.05). The differences of postoperative symmetric analysis in zygomaxillare, oribitale, zygomatic and lower orbital point of zygomatic maxillary had no statistical significance( P>0.05). The difference in zygomaxillare decreased from(10.1±6.2) mm to(2.7±6.4) mm. The difference in oribitale(ORI)decreased from(7.7±4.6) mm to(1.9±3.9) mm. The difference in zygomatic decreased from(8.5±7.5) mm to(0.7±1.5)mm. The difference in lower orbital point of zygomatic maxillary decreased from(1.9±3.5) mm to(0.6±2.1) mm. The morphology of the affected side and the healthy side was symmetrical. The contour was natural and no postoperative complications occurred. The postoperative satisfaction rate was high. Conclusions:Computer navigation system can solve the problem of limited exposure of lower eyelid-intraoral approach in orbital-zygomatic fibrous dysplasia and significantly improve the accuracy, effectiveness and safety during surgery.