Lipotoxicity is a pivotal factor that initiates and exacerbates liver injury and is involved in the development of metabolic-associated fatty liver disease (MAFLD). However, there are few reported lipotoxicity inhibitors. Here, we identified a natural anti-lipotoxicity candidate, HN-001, from the marine fungus Aspergillus sp. C1. HN-001 dose- and time- dependently reversed palmitic acid (PA)-induced hepatocyte death. This protection was associated with IRE-1α-mediated XBP-1 splicing inhibition, which resulted in suppression of XBP-1s nuclear translocation and transcriptional regulation. Knockdown of XBP-1s attenuated lipotoxicity, but no additional ameliorative effect of HN-001 on lipotoxicity was observed in XBP-1s knockdown hepatocytes. Notably, the ER stress and lipotoxicity amelioration was associated with PLA2. Both HN-001 and the PLA2 inhibitor MAFP inhibited PLA2 activity, reduced lysophosphatidylcholine (LPC) level, subsequently ameliorated lipotoxicity. In contrast, overexpression of PLA2 caused exacerbation of lipotoxicity and weakened the anti-lipotoxic effects of HN-001. Additionally, HN-001 treatment suppressed the downstream pro-apoptotic JNK pathway. In vivo, chronic administration of HN-001 (i.p.) in mice alleviated all manifestations of MAFLD, including hepatic steatosis, liver injury, inflammation, and fibrogenesis. These effects were correlated with PLA2/IRE-1α/XBP-1s axis and JNK signaling suppression. These data indicate that HN-001 has therapeutic potential for MAFLD because it suppresses lipotoxicity, and provide a natural structural basis for developing anti-MAFLD candidates.

Objective:To evaluate the performance of the influenza surveillance network and compare the epidemic intensity of influenza during 2014-2020 in Shanghai.Methods:Based on the weekly reports of influenza-like illness (ILI) and laboratory-confirmed influenza cases from January 1, 2014 to December 31, 2020. This study first evaluated the data reporting and specimen collection of ILI cases for each sentinel hospital, and then calculated the percentage of ILI (ILI%), the proportion of specimens tested positive for influenza, and the incidence of influenza among all ILI outpatient and emergency visits to measure the epidemic intensity of influenza. Finally, seasonal autoregressive integrated moving average (ARIMA) model was applied to quantify the changes in epidemic intensity of influenza in 2020.Results:The proportion of influenza surveillance sentinel hospitals with a score of less than 5 in the evaluation of ILI data reporting and samples collection were 9.68% and 21.05% in 2020 in Shanghai, respectively. ILI% was estimated to be 1.51% (95% CI: 1.50%-1.51%) and 2.31% (95% CI: 2.30%-2.32%), respectively for 2014-2019 and 2020; the proportion of specimens tested positive was 24.27% (95% CI: 24.02%- 24.51%) and 7.15% (95% CI: 6.78%-7.54%), respectively; and the incidence of influenza was 3.66‰ (95% CI: 3.62‰-3.70‰) and 1.65‰ (95% CI: 1.57‰-1.74‰), respectively. ARIMA model showed that ILI% was increased by 45.25% in 2020 in Shanghai, and the proportion of specimens tested positive and the incidence of influenza were reduced by 78.45% and 51.80%, respectively. Conclusions:In 2020, the performance of influenza surveillance system has changed, ILI% has increased, the proportion of specimens tested positive and the incidence of influenza has decreased in Shanghai. The change in the quality of influenza surveillance is also a potential factor affecting the epidemic intensity of influenza. In the future, the quality control of influenza surveillance network still needs to be further strengthened.

Objective:To study the infection status and epidemiological characteristics of parainfluenza virus (PIV) in acute respiratory tract infection adult cases in Shanghai from 2015 to 2021, and to provide a scientific basis for preventing and controlling PIV.Methods:Acute respiratory tract infections were collected from 13 hospitals in Shanghai from 2015 to 2021. Relevant information was registered, and respiratory specimens were sampled to detect respiratory pathogens by multiplex PCR.Results:A total of 5 104 adult acute respiratory tract infection cases were included; the overall positive rate of the respiratory pathogens was 29.37% (1 499/5 104). The positive rate of PIV was 2.61% (133/5 104), compared with 2.32% (55/2 369) and 2.85% (78/2 735) in influenza-like cases (ILI) and severe acute respiratory infection (SARI) cases, respectively. Among them, PIV3 accounted for the highest proportion (62.41%, 83/133), followed by PIV1 (18.80%, 25/133), PIV2 (9.77%, 13/133), and PIV4 (9.02%, 12/133). The incidence of PIV-positive cases was mainly distributed in the first and second quarters, accounting for 62.41% (83/133). The difference in the incidence in each quarter was significant ( χ2=24.78, P<0.001). Mixed infection accounted for 18.80% (25/133) of 133 PIV-positive cases, the mixed infection rates of ILI and SARI were 18.18% (10/55) and 19.23% (15/78), respectively, and the main mixed pathogen of PIV was coronavirus 229E. Conclusions:There are a certain proportion of PIV-positive acute respiratory tract infection cases in Shanghai. It is necessary to strengthen the etiological surveillance in acute respiratory tract infection cases, especially the mixed infection of PIV and other pathogens.

ObjectiveTo conduct on-site epidemiological investigation， emergency response， tracing of infection source and analysis of a confirmed COVID-19 case of a foreign airline cargo service staff member in Shanghai’s international airport， aiming to provide reference for prevention of imported COVID-19 cases under regular prevention and control of COVID-19. MethodsA retrospective field epidemiological investigation was conducted to collect information of basic characteristics， illness onset， diagnosis， treatment， clinical manifestations， exposure history and risk factors within 14 days before onset， close contacts， close contacts of close contacts， and key places related to activity trajectories. Respiratory tract specimens of cases and contacts were collected for detection of SARS-CoV-2 by real time RT-PCR （rRT-PCR）. Emergency response， including infection source analysis and contact management， was conducted. ResultsThe case developed pharyngeal itch on July 28， 2021， and fever on the 30th， and went to the hospital for treatment twice on the 31st. Because his specimen was positive for SARS-CoV-2 by rRT-PCR on August 1， he was isolated and treated on August 2 and diagnosed as a confirmed case of COVID-19. The case was a foreign airline cargo service member at an international airport. The two regular nucleic acid screenings of him as a high-risk occupation on July 21 and 28 were negative. He did not leave Shanghai within 14 days before the onset of illness. During July 22nd and 23rd， he was repeatedly exposed during work to the high-risk environment that may have been contaminated by SARS-CoV-2 and had contact with the crew of foreign airlines， and the personal protection was not standardized. None of the 67 close contacts and 567 close contacts of close contacts in Shanghai showed symptoms during the 14-day medical quarantine， and the specimens of them were all negative for SARS-CoV-2 by rRT-PCR. The results of genome sequencing analysis showed that the genomic homology between the virus of the case and the one of recent domestic local epidemic and the recent imported cases was low， and the homology with the overseas Delta mutant strain was higher than that of the domestic Delta mutant strain. ConclusionThe situation of prevention of COVID-19 import is still serious. It is necessary to conduct regular nucleic acid screening for high-risk occupational groups， strengthen the diagnosis and reporting awareness of medical institutions， effectively implement the prevention and control measures for people， objects， and environment at international airports， and further enhance the public's awareness of personal protection.

Objective:To analyze the changes in the epidemiological characteristics of scarlet fever cases in Shanghai City before and after the outbreak of coronavirus disease 2019 (COVID-19), and to provide a reference for scientific prevention and control of scarlet fever.Methods:The information of scarlet fever reported cases in Shanghai City from January 2016 to June 2021 in the information system of Chinese Disease Prevention and Control was collected, and the differences in time trend, regional distribution, age and gender distribution of cases before and after the outbreak of COVID-19 in Shanghai City were analyzed by descriptive epidemiologic method.Results:The incidence rate of scarlet fever reported in 2016-2019 was (0.22-4.02)/100 000 in each month, with a median of 1.13/100 000. During January 2020 (the outbreak began in Shanghai City) and June 2021, the incidence rate of scarlet fever was (0.01-1.64)/100 000, with a median of 0.14/100 000, which was 12.39% of that before the outbreak of COVID-19. During February and June 2020, the monthly reported incidence rate of scarlet fever was (0.18-0.58)/100 000, showing an upward trend compared with the same period in 2020 ((0.01-0.05)/100 000). From 2016 to 2019, the annual reported incidence rate of each district was (0.55-65.48)/100 000, with a median of 9.57/100 000; while in 2020, the annual reported incidence rate of each district was (0.29-9.85)/100 000, with a median of 2.18/100 000, which was 22.78% of that before the outbreak of COVID-19. The incidence of scarlet fever dropped significantly. The incidence rate in Minhang District was still the highest. The cases were mainly four to eight years old, and there was no substantial difference of the proportions before and after COVID-19 pandemic, with the incidence rate of six years old group the highest. The proportion of male was more than female in reported case, while the male ratio in reported cases was not significantly different before and after COVID-19 pandemic.Conclusions:The incidence rate of scarlet fever in Shanghai City has dropped sharply after COVID-19 pandemic. The main epidemiological characteristics of the regional and population distribution of cases remain unchanged.

Objective:To evaluate the value of combined measurement of urinary insulin-like growth factor-binding protein 7 (IGFBP7) and urinary metalloproteinase inhibitor-2 (TIMP-2) in the early diagnosis and prognosis of cardiac surgery-associated acute kidney injury (CSA-AKI).Methods:From March 2018 to June 2018, cardiac surgery patients admitted to the cardiac macrovascular surgery department of the First Affiliated Hospital of Nanjing Medical University were prospectively included, and the blood creatinine was monitored to observe the presence of acute kidney injury (AKI). The prognostic information of the patients was collected, including in-hospital dialysis, in-hospital death, complete recovery of kidney function at discharge, death in one year after surgery, and progression to chronic kidney disease. The levels of urine IGFBP7 and TIMP-2 at 6 h, 24 h and 48 h after cardiac surgery were detected by enzyme linked immunosorbent assay (ELISA), and the urine creatinine (Cr) was also measured. Moreover, receiver operating characteristic curves (ROC) were plotted and the areas under the curves ( AUC) were calculated to evaluate the predictive value and prognostic value of urinary [TIMP-2]·[IGFBP7] (T*I for short) and urine T*I/urine Cr 2 in CSA-AKI. Results:A total of 74 patients with age of (58.43±10.91) years old and 47 males, were enrolled in this study, of which 24 cases (32.4%) had AKI and 10 cases (13.5%) had stage 2-3 AKI. Compared with the non-AKI group, the AKI group had significantly higher levels of urine T*I levels at 6 h and 24 h (both P<0.05). The AUC of T*I at 24 h predicting for AKI was 0.71(95% CI 0.59-0.81, P=0.001, cutoff value 0.020, sensitivity 79.2%, specificity 56.0%), while the AUC for stage 2-3 AKI was 0.85 (95% CI 0.75-0.92, P<0.001, cutoff value 0.083, sensitivity 70.0%, specificity 90.6%). Urinary T*I normalized for urinary creatinine excretion did not show better predictive value. In addition, of T*I at 24 h predicting for poor hospitalization outcome, renal recovery, and one year postoperative death, the AUC was 0.82(95% CI 0.71-0.90, P=0.001), 0.80(95% CI 0.66-0.86, P<0.001), and 0.81(95% CI 0.70-0.89, P=0.047), respectively. Conclusion:The combined detection of TIMP-2 and IGFBP7 in urine is expected to be a biomarker for early diagnosis of CSA-AKI and has certain clinical value in predicting the prognosis of CSA-AKI.

Objective:To evaluate narrow band imaging-magnifying endoscopy (NBI-ME) for the further assessment of lesions of low-grade intraepithelial neoplasia (LGIN) in the gastric biopsy.Methods:Data of 180 patients who underwent NBI-ME before endoscopic submucosal dissection (ESD) for biopsy of gastric LGIN at the First Affiliated Hospital of Soochow University from January 2017 to October 2020 were analyzed retrospectively. Taking the pathological results after ESD as the gold standard, the sensitivity, the specificity, the positive predictive value, the negative predictive value, and the accuracy of NBI-ME in predicting the pathological upgrading of gastric LGIN lesions after ESD were calculated, and the receiver operator characteristic (ROC) curve was drawn.Results:Among 180 gastric LGIN lesions, 115 (63.89%) were pathological upgraded and 65 (36.11%) were not after ESD. There were 10 missed diagnoses, 19 misdiagnoses, and 151 correct diagnoses in NBI-ME examination before ESD. The sensitivity, the specificity, the positive predictive value, the negative predictive value, and the accuracy of NBI-ME in predicting the pathological upgrading of gastric LGIN lesions after ESD were 91.3% (105/115), 70.8% (46/65), 84.7% (105/124), 82.1%(46/56) and 83.9% (151/180), respectively. The area under the ROC curve was 0.810 (95% CI: 0.737-0.883). Conclusion:Further NBI-ME examination of gastric LGIN lesions diagnosed by biopsy pathology can accurately predict whether the lesions have pathological upgrading after ESD, which is of important guiding significance for the patients to choose the treatment strategy of further follow-up or endoscopic resection.

Objective:To discuss the challenges and problems of the prevention and control of emerging infectious diseases in Shanghai as a megacities.Methods:An imported case of cutaneous anthrax occurred in Shanghai on May 30, 2019. Shanghai Municipal Center for Disease Control & Prevention conducted an epidemiological investigation and treatment of the cases; after this case, the data of patients with cutaneous anthrax were collected, and an epidemiological study was conducted. Meanwhile, the wound and blood samples of the patient were collected for laboratory testing.Results:Of the seven wound samples of the patient, 6 were positive for the Bacillus anthracis nucleic acid test, and the double serological test results showed a 4-fold increase in the titer of anthrax antibodies. Shanghai CDC conducted an epidemiological investigation of the confirmed cases and observed its contacts. After treatment, the patients recovered, and no other issues appeared among the 19 contacts. Conclusions:Shanghai must strengthen the training of clinicians on emerging infectious diseases to achieve early detection, diagnosis, and treatment of imported infectious diseases and reduce the incidence, spread, and death of the diseases. At the same time, multi-department joint prevention and control are needed to prevent and control secondary cases.

Objective:To study the epidemiological characteristics and mixed infection of adenovirus in acute respiratory tract infections in Shanghai from 2015 to 2019, and to provide scientific basis for the prevention and control of adenovirus.Methods:Acute respiratory tract infections were collected from 3 hospitals in Shanghai from 2015 to 2019. Relevant information was registered and respiratory specimens were sampled for detection of respiratory pathogens by multiplex PCR.Results:A total of 1 543 cases of acute respiratory tract infection were included. The positive rate of adenovirus was 2.92%(45/1 543), the positive rates of influenza like illness (ILI) and severe acute respiratory illness (SARI) were 2.74%(29/1 058) and 3.30%(16/485), respectively. The positive rate of ILI during January-May 2019 was 5.43%(7/129), higher than that in the same period of 2015- 2018 (0.52%-4.48%) (Fisher’s exact test value=8.92, P=0.036). The incidence of adenovirus-positive cases was mainly distributed in the first and second quarters, accounting for 62.22% (28/45). The difference of the incidence of adenovirus-positive cases in each quarter was significant ( χ2= 12.52, P=0.006). The positive rate in the second quarter was highest (6.03%), which was higher than that in other quarters (1.89%-2.93%). There were significant differences among different age groups ( χ2=16.94, P=0.001), and the positive rate decreased with age ( χ2=10.16, P=0.001). The positive rate of 13-19 years old group (9.43%) was higher than that of other age groups (1.48%-4.81%). The positive rate of student group (12.07%) was higher than that of other occupations (2.61%). The difference was systematic ( χ2=11.53, P=0.001). Mixed infection accounted for 31.11% (14/45) of 45 adenovirus positive cases. The mixed infection rates of ILI and SARI were 34.48% (10/29) and 25.00% (4/16), respectively. Among 14 cases of mixed infection, the main mixed infection pathogens of adenovirus were influenza A virus and coronavirus. Conclusion:Adenovirus surveillance should be further strengthened in adolescents with a focus on students and other key groups in the second quarter.

Objective:To analyze the epidemiological characteristics of a cluster of 5 confirmed COVID-19 cases related with the transmission in incubation period of initial case, and find out the infection source and transmission chain.Methods:According to "The Prevention and Control Protocol for Coronavirus Disease 2019 (Third Edition)" issued by the National Health Commission, a field epidemiological survey was conducted for the 5 cases in January 2020. Nasopharyngeal swabs and sputum samples were collected from them for the detection of 2019-nCoV by real time RT-PCR. Multi prevention and control measures were taken, such as tracking and screening close contacts, medical isolation observation, investigating the epidemiological link, analyzing transmission chain.Results:Case 1, who had common environmental exposure with other COVID-19 cases, got sick on 20 January, 2020 and was confirmed on 1 February. Case 2 became symptomatic on 22 January and was confirmed on 27 January. Case 3 got sick on 25 January and was confirmed on 30 January. Case 4 had illness onset on 20 January and was confirmed on 1 February. Case 5 got sick on 23 January and was confirmed on 31 January. Among the 5 cases, case 2 died and the illness of other cases were effectively controlled. After exclusion of other common exposure factors, case 1 had a 6-hour meeting with case 2 and case 3 on 19 January. Case 2 and case 3 might be infected by case 1 during the incubation period. It is the key point for epidemiological investigation.Conclusion:The epidemiological investigation indicates that the transmission might occur in the incubation period of COVID-19 case, close attention should be paid to it in future COVID-19 prevention and control.