BACKGROUND: In China, lung cancer remains the cancer with the highest incidence and mortality rate. Among early-stage lung adenocarcinomas (LUAD), the micropapillary (MPP) component is prevalent and typically exhibits high aggressiveness, significantly correlating with early metastasis, lymphatic infiltration, and reduced five-year survival rates. Therefore, the study is to explore the similarities and differences between MPP and non-micropapillary (non-MPP) components in malignant pulmonary nodules characterized by GGOs in early-stage LUAD, identify unique mutational features of the MPP component and analyze the relationship between the ZNF469 gene, a member of the zinc-finger protein family, and the prognosis of early-stage LUAD, as well as its correlation with immune infiltration. METHODS: A total of 31 malignant pulmonary nodules of LUAD were collected and dissected into paired MPP and non-MPP components using microdissection. Whole-exome sequencing (WES) was performed on the components of early-stage malignant pulmonary nodules. Mutational signatures analysis was conducted using R packages such as maftools, Nonnegative Matrix Factorization (NMF), and Sigminer to unveil the genomic mutational characteristics unique to MPP components in invasive LUAD compared to other tumor tissues. Furthermore, we explored the expression of the ZNF469 gene in LUAD using The Cancer Genome Atlas (TCGA) database to investigate its potential association with the prognosis. We also investigated gene interaction networks and signaling pathways related to ZNF469 in LUAD using the GeneMANIA database and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Lastly, we analyzed the correlation between ZNF469 gene expression and levels of immune cell infiltration in LUAD using the TIMER and TISIDB databases. RESULTS: MPP components exhibited a higher number of genomic variations, particularly the 13th COSMIC (Catalogue of Somatic Mutations in Cancer) mutational signature characterized by the activity of the cytidine deaminase APOBEC family, which was unique to MPP components compared to non-MPP components in tumor tissues. This suggests the potential involvement of APOBEC in the progression of MPP components in early-stage LUAD. Additionally, MPP samples with high similarity to APOBEC signature displayed a higher tumor mutational burden (TMB), indicating that these patients may be more likely to benefit from immunotherapy. The expression of ZNF469 was significantly upregulated in LUAD compared to normal tissue, and was associated with poor prognosis in LUAD patients (P<0.05). Gene interaction network analysis and GO/KEGG enrichment analysis revealed that COL6A1, COL1A1, COL1A2, TGFB2, MMP2, COL8A2 and C2CD4C interacted with ZNF469 and were mainly involved in encoding collagen proteins and participating in the constitution of extracellular matrix. ZNF469 expression was positively correlated with immune cell infiltration in LUAD (P<0.05). CONCLUSIONS The study has unveiled distinctive mutational signatures in the MPP components of early-stage invasive LUAD in the Asian population. Furthermore, we have identified that the elevated expression of mutated ZNF469 impacts the prognosis and immune infiltration in LUAD, suggesting its potential as a diagnostic and prognostic biomarker in LUAD.
Humans ; Lung Neoplasms/genetics* ; Adenocarcinoma of Lung/genetics* ; China ; Prognosis ; Transcription Factors

Objective:To investigate the immune reconstitution and its influencing factors in HIV/AIDS patients with antiretroviral therapy in Ningbo.Methods:The data were collected from HIV/AIDS patients of HIV/AIDS Comprehensive Response Information System in Ningbo during 2010-2020. The inclusion criteria of study subjects were HIV/AIDS patients aged 15 or above at initiation of antiretroviral therapy with duration of more than one year follow-up and baseline CD4 +T lymphocyte (CD4) counts completed. A retrospective cohort study was conducted to describe the epidemiological characteristics of the subjects, and univariate and multivariate Cox proportional risk regression models were used to analyze the influencing factors of immune reconstitution in HIV/AIDS patients. Results:A total of 3 851 HIV/AIDS patients were enrolled, in whom 3 185 were males (82.71%,3 185/3 851), 3 769 were in Han ethnic group (97.87%,3 769/3 851), and 1 333 had education level of junior high school (34.62%). Of the subjects, the age at initiation of antiretroviral therapy was (39.47±13.47) years. The median ( Q1, Q3) of follow-up time was 47 (25,77) months. The immune reconstitution after antiretroviral therapy accounted for 66.22% (2 550/3 851) in HIV/AIDS patients. Multivariate Cox proportional risk regression model results showed that, compared with HIV/AIDS patients receiving initial antiretroviral therapy at age ≥45 years, having baseline BMI <23.0 kg/m 2 and baseline CD4 counts <200 cells/μl, receiving initial antiretroviral therapy regimen of zidovudine+lamivudine+nevirapine (AZT+3TC+NVP), the immune reconstitution was more likely to occur in HIV/AIDS cases receiving initial antiretroviral therapy at age <30 years,having baseline BMI ≥23.0 kg/m 2 and baseline CD4 counts ≥200 cells/μl, receiving initial antiretroviral therapy regimen of AZT+3TC+efavirenz (EFV). Conclusions:Age at initial antiretroviral therapy, baseline BMI, baseline CD4 counts and initial regimens were the main factors affecting immune reconstitution. Therefore, it is necessary to start antiretroviral therapy as early as possible, conduct regular follow up and monitor CD4 levels, and pay attention to HIV/AIDS patients with older age and lower baseline BMI.

Objective:To analyze the epidemiological characteristics of reinfection of 2019-nCoV and influencing factors, and provide evidence for effective prevention and control of COVID-19 epidemic.Methods:The incidence data of COVID-19 in Ningbo from January 1, 2020 to November 30, 2022 were collected from the infectious disease surveillance system of Chinese information system for disease control and prevention. The incidence of reinfection of 2019-nCoV was investigated by using questionnaire. logistic regression analysis was used to analyze the influences of gender, age, time interval from the first infection, history of underlying disease, 2019-nCoV vaccination dose and disease severity on the reinfection.Results:A total of 897 previous 2019-nCoV infection cases were investigated, of which 115 experienced the reinfection of 2019-nCoV, the reinfection rate was 12.82%. The interval between the two infections M( Q1, Q3) was 1 052 (504, 1 056) days. Univariate analysis showed that age, 2019-nCoV vaccination dose, history of underlying disease, type of 2019-nCoV variant causing the first infection, time interval from the first infection and severity of the first infection were associated with the reinfection rate (all P<0.05). Multivariate logistic regression analysis showed that the risk for reinfection in age group 30- years was higher than that in age group ≥60 years ( OR=2.10, 95% CI: 1.11-3.97). No reinfection occurred in those with time interval from the first infection of <6 months, and the risk for reinfection was higher in those with the time interval of ≥12 months than in those with the time interval of 6- months ( OR=6.68, 95% CI: 3.46-12.90). The risk for reinfection was higher in the common or mild cases than in the asymptomatic cases ( OR=2.64, 95% CI: 1.18-5.88; OR=2.79, 95% CI: 1.27-6.11). Conclusion:The time interval from the first infection was an important influencing factor for the reinfection of 2019-nCoV, and the probability of the reinfection within 6 months was low.

Objective: To investigate the origin of infection and risk factors of a case with SARS-CoV-2 infection associated with overseas countries in the Ningbo-Zhoushan Port, Zhejiang Province, so as to provide the evidence for improving the COVID-19 control measures at ports. Methods: Ningbo Center for Disease Control and Prevention ( CDC ) and Beilun CDC conducted case finding and epidemiological surveys immediately after being informed. The general information, history of vaccination and the travel during the latest 14 days were collected from the positive case, and all close contacts were tracked. Saliva samples were collected for SARS-CoV-2 nucleic acid testing and whole-genome sequencing, and the sequencing results were aligned with the GISAID's EpiCoV database. The origin of infection and transmission route of the positive case was investigated. Results: A case was identified positive for SARS-CoV-2 nucleic acid during company M's routine screening in the Ningbo-Zhoushan Port on August 10, 2021, and was confirmed positive for SARS-CoV-2 nucleic acid by Beilun CDC and Ningbo CDC on August 11. Whole-genome sequencing showed SARS-CoV-2 B.1.617.2 ( Delta ) variant, which shared the highest homology with the virus sequence uploaded by Russia on June, 2021 ( Russia/MOW-RII-MH27356S/2021 ). The case was a bundling worker for overseas container ships, and reported communicated with foreign boatmen and contacted materials without protected interventions on the SINOKOR AKITA Container Ship between August 4 and 5, 2021. This ship anchored at Vladivostok, Russia from July 27 to 29, anchored at Ningbo Harbor on August 4, and departed on August 5. Then, 11 boatmen from this ship were tested positive for SARS-CoV-2 nucleic acid on August 8. One asymptomatic case was reported in this epidemic; 254 close contacts and 617 secondary close contacts were identified, and all were tested negative for SARS-CoV-2 nucleic acid. No new cases with SARS-CoV-2 infections were detected until August 25, 2021, and the emergency response was therefore terminated. Conclusions The infection was a sporadic COVID-19 epidemic associated with overseas countries, which was caused by Delta variant infection through contacts with foreign boatmen or materials by a bundling worker in Ningbo-Zhoushan Port; fortunately, no epidemic spread occurred. Intensified closed-loop management and increased frequency of SARS-CoV-2 nucleic acid test among high-risk populations, and improving the precision and rapid emergency treatment of COVID-19 epidemics are required for the containment of COVID-19 at ports.

Objective: To study the infection rate of secondary close contacts of COVID-19 patients, and assess the infection risk in the contacts. Methods: COVID-19 patients' close contacts (with a clear exposure time to index case) with negative nucleic acid test results and secondary close contacts were surveyed in continuous isolation and medical observation in this prospective study. The dynamic nucleic acid test results of the close contacts and secondary contacts of COVID-19 patients were collected to assess their risk of infection. Results: A total of 4 533 close contacts were surveyed, in whom 14 were confirmed as COVID-19 patients with overall secondary attack rate of 0.31%, and 4 201 secondary contacts were tracked, in whom no subsequent infections occurred. Conclusion: Close contacts of COVID-19 patients entered in centralized isolation for medical observation with negative nucleic acid tese results,the secondary close contacts of COVID-19 patients have no risk of infection.
COVID-19/epidemiology* ; Contact Tracing ; Humans ; Incidence ; Nucleic Acids ; Prospective Studies ; SARS-CoV-2

Objective : To investigate the factors of hyperglycemia among HIV/AIDS patients receiving antiretroviral therapy (ART) in Ningbo City. Methods : The demographic characteristics, ART and fasting blood glucose were collected from HIV/AIDS patients receiving ART in Ningbo City from 2005 to 2021 through the Ningbo Municipal ART Database. The fasting blood glucose levels were analyzed among HIV/AIDS patients receiving ART, and the factors affecting hyperglycemia were identified using a multivariable logistic regression model. Results : A total of 2 607 HIV/AIDS patients were enrolled, including 2 162 men (82.93%), and the participants had a mean age of (45.16±13.93) years, and had mean ART duration of 5.00 years (interquartile range, 5.00 years). The prevalence of hyperglycemia, impaired fasting glucose and diabetes was 22.59%, 13.62% and 8.98%, respectively. Multivariable logistic regression analysis showed that gender (male, OR=1.482, 95%CI: 1.120-1.961), age (30 years-, OR=2.062, 95%CI: 1.356-3.137; 45 years-, OR=3.697, 95%CI: 2.435-5.611; 60 years and older, OR=7.295, 95%CI: 4.722-11.268), WHO clinical staging of HIV diseases (stage Ⅱ, OR=1.415, 95%CI: 1.097-1.824; stage Ⅲ, OR=1.571, 95%CI: 1.139-2.168; stage Ⅳ, OR=1.488, 95%CI: 1.040-2.128, duration of HIV infections (7 to <10 years, OR=1.336, 95%CI: 1.004-1.777), treatment regimen (second-line regimen, OR=0.611, 95%CI: 0.472-0.792), and blood lipids (high TG, OR=1.665, 95%CI: 1.307-2.123; high TC, OR=1.415, 95%CI: 1.006-1.991; dyslipidemia, OR=2.597, 95%CI: 1.971-3.422) significantly correlated with hyperglycemia. Conclusions The overall prevalence of hyperglycemia was 22.59% among HIV/AIDS patients with ART in Ningbo City, and the prevalence of hyperglycemia correlated with gender, age, clinical staging of HIV infections, duration of HIV infections, treatment regimens and blood lipids among HIV/AIDS patients.

Objective: To analyze the trend in the mortality of liver cancer in Ningbo City from 2002 to 2021, so as to provide the evidence for improving the liver cancer control measures. Methods: The liver cancer mortality data in Ningbo City from 2002 to 2021 were collected from Ningbo Municipal Chronic Disease Surveillance System. The crude mortality and standardized mortality by the 2 000 national population census data of liver cancer were estimated, and the proportion of concomitant diseases was analyzed among all dead patients with liver cancer. In addition, the trends in liver cancer mortality were analyzed with annual percentage change (APC) and average annual percentage change (AAPC). Results: Both the crude and standardized mortality of liver cancer appeared a tendency towards a decline year by year in Ningbo City from 2002 to 2021, with AAPC of -3.47% (95%CI: -4.08% to -2.85%, P<0.001) and -6.56% (95%CI: -7.25% to -5.87%, P<0.001), and a the decline in liver cancer mortality was larger during the period between 2006 and 2021 than during the period between 2002 and 2006. The annual mean crude and standardized mortality of liver cancer was 35.39/105 and 20.98/105, and the crude mortality of liver cancer was 52.69/105 in men and 18.13/105 in women, respectively. After adjustment for age, the risk of liver cancer mortality was 3.03 (95%CI: 2.96-3.09) times greater among men than among women, and the mortality of liver cancer appeared a tendency towards a rise with age (χ2trend=45 684.254, P<0.001). Concomitant diseases were found among 9 985 dead cases with liver cancer (24.44%), and the concomitant diseases mainly included digestive system diseases (predominantly liver diseases) and infectious and parasitic diseases (predominantly virus hepatitis). Conclusions The mortality of liver cancer appeared a tendency towards a decline in Ningbo City from 2002 to 2021, and men and middle-aged and elderly residents were at high risk of liver cancer mortality. Digestive system diseases and infectious and parasitic diseases were predominant concomitant diseases among dead patients with liver cancer.

Objective:To investigate the infection rate in close contacts of COVID-19 patients before and after the last negative nucleic acid test, evaluate the effect of dynamic nucleic acid test in determining the infectivity of COVID-19 patients.Methods:Dynamic nucleic acid test results of COVID-19 cases were collected in a retrospective cohort study. COVID-19 cases with negative nucleic acid test results before their first positive nucleic acid tests were selected as study subjects. Close contacts of the index cases and the secondary close contacts were kept isolation for medical observation to assess their risk of infection.Results:This study included 89 confirmed cases from two local COVID-19 epidemics in Ningbo. A total of 5 609 close contacts were surveyed, the overall infection rate was 0.20%. No close contacts of the COVID-19 cases before the last negative nucleic acid test were infected, and the infection rate in the close contacts of the COVID-19 cases after the last negative nucleic acid test was 1.33%, all of these close contacts lived together with the index cases. No secondary close contacts were infected.Conclusion:COVID-19 patient becomes infectious after the last nucleic acid is negative, and has no infectivity before the last nucleic acid negative.

Objective:To investigate the local epidemic of COVID-19 caused by 2019-nCoV Delta variant in Zhenhai district of Ningbo, identify the transmission chain and provide reference for the prevention and control of COVID-19 epidemic.Methods:The incidence data of COVID-19 in Zhenhai from 6 to 18 December, 2021 were collected in field investigation. Field epidemiological investigation was conducted to understand the epidemiological characteristics of COVID-19 cases and analyze the transmission chains.Results:The first case might be infected with 2019-nCoV through direct or indirect exposure when passing through a medium-risk area, then a family cluster was caused, and the epidemic spread through close contacts of family members with others such as work, daily life, and moxibustion. The epidemic lasted for 14 days, and 74 confirmed COVID-19 cases were reported. The median incubation period was 4.0(3.0,5.8)d. All the cases were in a chain of transmission for more than 6 generations, and the intergenerational interval was 3.5(2.0,5.3)d. The gene sequencing result indicated that the pathogen was Delta AY.4 variant of 2019-nCoV. Both the epidemiological investigation and the gene sequencing results supported that the local COVID-19 epidemic in Zhenhai was associated with the COVID-19 epidemic in Shanghai.Conclusions:The transmission chain of this epidemic was clear. Delta AY.4 variant has obvious characteristic to cause case clusters in families, places with poor ventilation, and residential communities. It is suggested to strengthen the health management in key areas and key populations, and increase the frequency of nucleic acid testing.

Objective: To analyze the epidemiological characteristics of coronavirus disease 2019 （COVID-19） cases reported in Ningbo from January 22 to February 22, 2020, so as to provide guidance for the prevention and control of the COVID-19 epidemic. Methods: The confirmed cases of COVID-19 reported by Ningbo were selected from National Diseases Prevention and Control Information System to analyze the epidemiological characteristics by descriptive epidemiological method, including time, spatial and population distribution, clinical symptoms and exposure history. Results: A total of 157 confirmed cases of COVID-19 were reported and there was no death. The first confirmed case was reported on January 22. On the incidence curve, the peak was from January 22 to February 4, with a maximum of 15 cases in a single day. The incidence curve presented sustained human-to-human transmission. The number of the cases showed a declining trend from February 5. The confirmed cases were reported in all 10 counties（cities or districts）,among which 69（43.95%）cases were reported in Haishu District. The confirmed cases were mainly 30-69 years old,accounting for 78.34%;were mainly farmers,household workers and retired people,accounting for 59.87%;and were mainly clinically mild,accounting for 87.90%.There were 51 imported cases, accounting for 32.48%. The initial confirmed case was a local case. In the early stage of the epidemic, local cases and imported cases prevalent together,which was due to the outbreak caused by the large-scale buddhist activity on January 19.This event resulted in 67 confirmed cases and 15 asymptomatic cases. There totally reported 22 clusters with 138 （87.90%）confirmed cases. Conclusions In the early stage of the COVID-19 epidemic in Ningbo, the imported cases and local cases prevalent at the same time. Most of the cases were female, aged from 30 to 69 years, and their occupation were farmers, household workers and retired people. With comprehensive measures taken, the epidemic of COVID-19 in Ningbo have been under control.