Signatures of immune cell infiltration for predicting immune escape and immunotherapy in cervical cancer.

The cervical cancer tumor microenvironment is a diverse and complex ecosystem. Tumor-immune cell infiltration (ICI) may influence immune escape and immunotherapeutic responses. However, the relationship between immune cell infiltrations, immune escape, and immunotherapy in cervical cancer has not been fully clarified. Here, Principal component analysis (PCA) and Tumor immune dysfunction and exclusion (TIDE) were applied to calculate individual ICI scores and probabilities of immune escape, respectively. Through the IMvigor210 and the Cancer Immunome Atlas (TCIA) datasets, we validated the different responses to immunotherapy in two subgroups of patients. Furthermore, therapeutic benefits of different patients were predicted by the pRRophetic package. We found that patients with high ICI scores were prone to immune escape due to the activated JAK-STAT signaling pathway, along with lower CD8+ T cells. High ICI scores patients could benefit more from anti-PD-L1 immunotherapy, and individuals with low scores may be better candidates for the anti-CTLA-4 treatment. Combinations of immunotherapies with targeted inhibitors may improve clinical efficacy and reduce the risk of tumor recurrence. The ICI model not only helps us enhance the cognition of immune escape, but also guides the application of immunotherapy in cervical cancer patients.

Quantifying the associations of the air pollutant SO2 on outpatient visits for conjunctivitis in Hangzhou, China.

The aim of this study is to further investigate the single and cumulative associations of SO2 on outpatient visits for conjunctivitis. Data from outpatient visits, air pollutants, and meteorology was collected by the Eye Center of the Second Affiliated Hospital of the Zhejiang University School of Medicine, the Environmental Protection Department of Zhejiang Province, and the Meteorological Administration of Zhejiang Province from July 1, 2014, to November 30, 2019. A Poisson generalized linear regression model (PGLM), combined with a distributed lag nonlinear model (DLNM), was employed to analyze the association between SO2 and outpatient visits for conjunctivitis using PM2.5 and NO2 as covariates. Of the 539,649 outpatients for conjunctivitis recruited for analysis, 58.1% were female. Obvious single associations of SO2 were observed in outpatient visits for conjunctivitis, which is consistent with our previous results using a time-stratified case crossover design. A delay in the associations of SO2 on outpatient visits for conjunctivitis was further confirmed, with the longest lag being 12 days. The strongest lag effect was found at lag 0-11 with RR95th vs 25th = 1.30 (1.24, 1.37), and RR90h vs 25th = 1.23 (1.18, 1.28). Furthermore, the results showed that old people may be more sensitive to the associations of SO2 than adults and the younger ones. Our study provides the first evidence that outpatient visits for conjunctivitis are positively associated with both single and cumulative air pollutant SO2 exposure, suggesting that people especially elders had better to decrease outdoor activities when the SO2 concentration is above safe level.

Barriers to healthcare workers reporting adverse events following immunization in Zhejiang province, China.

OBJECTIVES: A cross-sectional survey was conducted among healthcare workers (HCWs) to assess their knowledge, attitude, and reporting behavior in adverse event following immunization (AEFI) surveillance as well as to identify barriers. METHODS: A simple random sample of 170 vaccination clinics was selected and one HCW was informed to participate in this survey in each selected vaccination clinic. The survey was developed using a secure online platform and consisted of a structured online questionnaire. The distributions of the respondents' characteristics were presented. Training status, knowledge, attitude, and reporting behavior were compared between sub-groups of HCWs. Barriers and suggestions on AEFI reporting were also summarized. RESULTS: Of the 170 surveyed HCWs, 61.76% received the training on AEFI surveillance while 15.88% had no AEFI training at all. The higher level of knowledge and the more positive attitude and reporting behavior on AEFI surveillance were observed among HCWs with the longer working duration on AEFI surveillance, or among HCWs who received the training. The most critical barrier to reporting an AEFI was 'not being sure if the AEFI is related to the vaccine' (122, 71.76%). Other barriers were: 'I do not want to raise unnecessary public alarm about a vaccine' (105, 61.76%); 'reporting form or other method being too complicated' (65, 38.23%). CONCLUSION: The study findings highlighted the need to prioritize training on AEFI surveillance for HCWs. It is recommended that the development of the targeted interventions to strengthen AEFI surveillance system be required based on the barriers found in this study.

A Comparison with Adverse Events Following Immunization Associated with Sabin-Strains and Salk-Strains Inactivated Polio Vaccines in Zhejiang Province, China.

OBJECTIVES: One dose of Sabin-strains inactivated polio vaccine (IPV) was introduced into the Chinese immunization program on 1 May 2016. This study aimed to evaluate the safety of Sabin-strains IPV and provide a comparison with conventional Salk-strains IPV. METHODS: Adverse events following immunization (AEFI) records associated with Sabin-strains IPV and Salk-strains IPV were extracted from the national AEFI surveillance system (NAEFISS) from 1 May 2016 to 31 December 2020. The vaccination information on Sabin-strains IPV and Salk-strains IPV during the same period was obtained from the Zhejiang provincial immunization information system. Reporting rates of AEFI were calculated by age, city, severity of AEFI, categories of AEFI, and reaction categories and were compared between Sabin-strains IPV and Salk-strains IPV. RESULTS: In total, 3,861,758 doses of Sabin-strains IPV and 1,018,604 doses of Salk-strains IPV were administered during the study period. The overall AEFI reporting rate for Sabin-strains IPV (3.96/10,000 doses) was significantly lower than that for Salk-strains IPV (5.03/10,000 doses) due to the reporting rate of the minor vaccine product-related reaction following Sabin-strains IPV was significantly lower than that for Salk-strains IPV (2.76/10,000 doses vs. 3.83/10,000 doses). The most frequently reported symptoms/signs were fever, induration/swelling, and rash/urticaria. The most frequently reported serious AEFI with a causal relationship was febrile convulsion, with the reporting rates of 0.10/10,000 doses for Sabin-strains IPV and 0.08/10,000 doses for Salk-strains IPV. No significant difference was found in the reporting rates of the other serious AEFI between the two types of IPV. CONCLUSION: Most of the AEFI following Sabin-strains IPV and Salk-strains IPV were mild and common adverse reactions. The reporting rate of serious AEFI was not significantly different between Sabin-strains IPV and Salk-strains IPV. Sabin-strains IPV had a favorable safety profile and could be widely used.

Surveillance of adverse events following immunization of 13-valent pneumococcal conjugate vaccine among infants, in Zhejiang province, China.

OBJECTIVES: To evaluate the safety of 13-valent pneumococcal conjugate vaccine (PCV13) after its licensure. METHODS: Review and describe the AEFI reported to national adverse event following immunization surveillance system (NAEFISS) in Zhejiang province from 2017 to 2020. Reporting rates of AEFI were calculated by age, city, severity of AEFI, categories of AEFI, and reaction categories. The data mining algorithm used in this study was reporting odds ratio (ROR). A value of ROR-1.96SE >1 (standard error [SE]) was considered as the positive signal. RESULTS: NAEFISS received 3332 AEFI cases following PCV13, with a reporting rate of 17.58/10000 doses. Of the reported AEFI, 652 were serious AEFI cases and the reporting rate was 3.44 for serious AEFI. The reporting rate of fever was the highest among all the clinical diagnosis (7.39/10000 doses). The positive signals were obtained for injection site reaction (ROR-1.96SE: 1.55), hypotonic hyporesponsive episode (HHE) (ROR-1.96SE: 1.62) and febrile seizure (ROR-1.96SE: 1.52). CONCLUSION: The present results supported previous observations that the PCV13 administered as the four-dose schedule was generally well tolerated in Chinese infants as we did not identify any new/unexpected safety concern from the NAEFISS during a four-year time period.

Real-world safety profile of the 9-valent human papillomavirus vaccine: A study in Zhejiang, China from 2019 to 2021.

The safety profile of the 9-valent human papillomavirus vaccine (9vHPV) was evaluated based on the reporting rate of adverse events following immunization (AEFI) obtained from the passive surveillance data in Zhejiang. The 9vHPV AEFI reports in Zhejiang were collected and reviewed from the National Adverse Event Following Immunization Surveillance System (NAEFISS) from 2019 to 2021. Reporting rates of AEFI were analyzed under multiple aspects, including age, city, number of vaccinations, AEFI categories, and diagnosis categories. This study used the reporting odds ratio (ROR) for anomalous signal assessment. The NAEFISS collected 331 AEFI reports after administering 1,064,851 doses of 9vHPV, with a crude AEFI rate of 3.12/10,000 doses. The third dose had the highest reporting rate of minor vaccine-related reaction (n = 80, 3.06 per 10,000), followed by the first dose (n = 134, 2.98 per 10,000), and second dose (n = 76, 2.15 per 10,000). Fever/redness/induration was the most common minor adverse event (281 records, 2.64/10,000 doses). Nine cases of urticaria, ten cases of allergic rash, and ten cases of syncope were recorded. This study found a positive signal association between 9vHPV immunization and adverse events such as syncope, encephalitis, sterile abscess, and urticaria. This study did not identify any new emerging safety concerns. In the future, more research is needed to validate and further explore adverse reactions associated with 9vHPV.

Surveillance on the adverse events following immunization with the pentavalent vaccine in Zhejiang, China.

OBJECTIVES: The aim of this study is to describe the reporting rate of adverse events following immunization (AEFI) with pentavalent vaccine: diphtheria-pertussis-tetanus-poliomyelitis-Haemophilus influenzae type b (DPT-IPV/Hib), and to determine whether the reporting rate of AEFI following DPT-IPV/Hib was higher than the average level of the other vaccines. METHODS: Review and describe the AEFI reported to national adverse event following immunization surveillance system (NAEFISS) in Zhejiang province from 2015 to 2020. Reporting rates of AEFI were calculated by age, city, severity of AEFI, categories of AEFI, and reaction categories. The data mining algorithm used in this study was reporting odds ratio (ROR). A value of ROR­1.96SE >1 (standard error [SE]) was considered as positive signal. RESULTS: NAEFISS received 5726 AEFI reports following DTP-IPV/Hib, with a reporting rate of 20.01/10000 doses. Of the reported AEFI, 202 were serious vaccine product-related reactions, including two cases of anaphylactic shock, five cases of Guillain Barre Syndrome (GBS) and two cases of acute disseminated encephalomyelitis. The reporting rate of fever/redness/induration was the highest among all the clinical diagnosis (14.97/10000 doses). The positive signals were obtained for allergic rash (ROR-1.96SE: 1.36), febrile convulsion (ROR-1.96SE: 1.32) and GBS (ROR-1.96SE: 1.16). CONCLUSION: The present findings bolstered that the DTP-IPV/Hib administered as the four-dose schedule was generally well tolerated in Chinese infants as we did not identify any new/unexpected safety concern from the NAEFISS during a six-year timespan.

Oral care for intensive care unit patients without mechanical ventilation: protocol for a systematic review and meta-analysis.

BACKGROUND: Infection is a common problem and a major cause of morbidity and mortality for patients in intensive care units (ICUs). According to published meta-analyses, oral care has been found to reduce the risk of nosocomial pneumonia, and has been recommended to improve the oral environment for patients in ICUs. However, relatively little information is available about the effects of oral care in patients without ventilatory support in ICUs. Therefore, this review proposes to evaluate the effectiveness of oral care in preventing pneumonia in non-ventilated ICU patients. METHODS: Eight databases will be searched for relevant literature, including four Chinese and four English online databases, from their inception to the protocol publication date. Records obtained will be managed and screened via Endnote X7. All literature will be selected following pre-established inclusion criteria by two independent review authors to obtain quality trials. The quality of the included records will be evaluated according to the "risk of bias table", recommended by the Cochrane Handbook for Systematic Reviews of Interventions. All the data will be extracted by one author and checked by another. If there is any disagreement, a final agreement will be reached with a third reviewer via consultation. If there are missing data, the original authors will be emailed to ask for it. If enough data were collected, the data synthesis will be performed using Review Manager (RevMan5.3). Both a random effect model and a fixed effect model will be undertaken. A Bayesian meta-analysis will also be performed to estimate the magnitude of the heterogeneity variance and comparing it with the distribution using the WinBUGS software. Otherwise, the results will be reported narratively. The sources of heterogeneity will be determined using meta-regression and subgroup analysis if there is significant heterogeneity. A funnel plot will be used to assess publication bias if there are enough records included. The Cochrane Handbook for Systematic Reviews of Interventions will be followed throughout the system evaluation process. CONCLUSION: This review will provide evidence of oral care for intensive care unit patients without mechanical ventilation to prevent nosocomial pneumonia. TRIAL REGISTRATION: PROSPERO Research registration identifying number: CRD42020146932.

Analysis of the adverse events following immunization with inactivated quadrivalent influenza vaccine from 2018 to 2020 in Zhejiang province, with a comparison to trivalent influenza vaccine.

OBJECTIVES: To summarize reports to the national adverse event following immunization surveillance system (NAEFISS) following inactivated quadrivalent influenza vaccine (QIV) in Zhejiang province from 2018 to 2020. METHODS: We analyzed adverse events following immunization (AEFI) reports following QIV, with a comparison, with the AEFI reports following inactivated trivalent influenza vaccine (TIV). Reporting rates of AEFI were calculated by age, severity of AEFI, categories of AEFI, and reaction categories. The data mining algorithm used in this study was reporting odds ratio (ROR). A value of ROR­1.96SE >1 (standard error [SE]) was considered as positive signal. These reporting rates between vaccine types were compared through chi-square tests. RESULTS: NAEFISS received 514 AEFI reports following QIV and 536 reports following TIV, with a reporting rate of 13.66/100,000 100,000 doses/100,000 doses (χ2 = 7.11, P> .05). Of the 514 reports following QIV, 410 were vaccine product-related reactions and 51 were severe AEFI. Fever/redness/induration was the most frequent clinical diagnosis of the QIV AEFI, with a reporting rate of 12.42/100,000 doses in the age group of 3-17 years, and 12.44/100,000 doses in the age group of ≥18 years. The positive signal of QIV AEFI was observed for the allergic rash and asthma/wheezing. CONCLUSION: The present analysis did not identify any new/unexpected safety concerns. We suggested that NAEFISS continue to monitor the safety of QIV.

Post-licensure safety monitoring of quadrivalent human papillomavirus vaccine using the national adverse event following immunization surveillance system from Zhejiang province, 2018-2020.

OBJECTIVES: To evaluate the reporting rate of adverse events following immunization (AEFI) of the quadrivalent human papillomavirus vaccine (4vHPV) and to compare the reporting rate of AEFI following 4vHPV with those following other vaccines. METHODS: Review and describe the AEFI reported to national adverse event following immunization surveillance system (NAEFISS) in Zhejiang province from 2018 to 2020. Reporting rates of AEFI were calculated by age, city, severity of AEFI, categories of AEFI, and reaction categories. The data mining algorithm used in this study was reporting odds ratio (ROR). A value of ROR­1.96SE >1 (standard error [SE]) was considered as positive signal. RESULTS: NAEFISS received 238 reports after receipt of 4vHPV and 899,282 doses of 4vHPV were administered during the study period, with a crude reporting rate of 2.7/10000 doses. Fever/redness/induration (101 reports) was the most common event reported (1.12/10000 doses). Two cases of anaphylactic shock, three cases of Guillain Barre Syndrome and two cases of acute disseminated encephalomyelitis were reported. ROR showed positive signals for seizure (ROR­1.96SE: 2.1), syncope (ROR­1.96SE: 1.3), allergic rash (ROR­1.96SE: 1.6) and headache (ROR­1.96SE: 2.1). CONCLUSION: The present analysis did not identify new/unexpected safety concerns. Further epidemiological studies are required to systematically validate the data provided by NAEFISS.

Analysis of adverse events following immunization in Zhejiang, China, 2019: a retrospective cross-sectional study based on the passive surveillance system.

Objectives: This study summarizes passive surveillance data for adverse events following immunization (AEFI) in Zhejiang province.Methods: The AEFI reports and number of doses on all vaccines used were extracted from the national AEFI surveillance system and the immunization information system of Zhejiang province (ZJIIS). Reporting rates of AEFI were calculated by age, city, severity of AEFI, categories of AEFI, vaccine types, and reaction categories.Results: A total of 13,079 AEFI records were reported and 23,091,401 vaccine doses were administered, with a reporting rate of 56.64/100,000 doses for AEFI. The highest reporting rate of AEFI was observed among the infants <1 year of age (108.61/100,000 doses) and the lowest rate was observed among recipients aged ≥60 years. Most of the AEFI reports were vaccine product-related reactions (48.81/100,000 doses), and the lowest was vaccination errors (0.02/100,000 doses). The most frequently reported individual vaccine was DTP and Hib combined vaccine, with a reporting rate of 426.62/100,000 doses. The most frequently reported AEFI was fever/redness/induration (48.82/100,000 doses).Conclusion: Our findings illustrated the high level of vaccine safety since the majority of those reported were not serious, or coincidentally associated with vaccination. Furthermore, the national AEFI surveillance system should be continuously used as a surveillance tool for monitoring of AEFI.

Evaluating the vaccination coverage: validity of household-hold vaccination booklet and caregiver's recall.

BACKGROUND: We compared results from household data sources to medical record sources by using data from a vaccination coverage survey. METHODS: Vaccination coverage (VC) was calculated based on parental recall, household vaccination booklet, and Zhejiang provincial immunization information system (ZJIIS). We evaluated the accuracy of VC based on household sources (vaccination booklet and recall) assuming the medical record was accurate. Concordance, sensitivity, specificity, positive predictive value, and negative predictive value were estimated as well as the Kappa statistic was also used to evaluate the agreement between data sources. RESULTS: Among the 1,800 children identified in the household survey, all were registered in ZJIIS. VC estimated using the vaccination booklet alone was substantially lower than that based on medical records (net bias 3.4-16.7% in different age groups). VC based on parental recall ranged from 2.5% below (among children aged 1 year) to 16.7% points above (among children aged 6 years) than those based on medical records. Concordance was lowest for card estimates (32.5-45.5%). Sensitivity was <60% for all household sources, except for recall source. Specificity was lowest for recall estimates (14.5-42.6%). Positive predictive value was >75%, while negative predictive value was <50%, for all household sources. Kappa statistics generally indicated poor agreement between household and medical record sources. CONCLUSIONS: Household-retained vaccination booklets and parental recall were insufficient sources for evaluating the VC. Our findings emphasized the importance of taking interventions to make the vaccination booklet more consistent with the records from medical resource.

Increasing mortality caused by chronic obstructive pulmonary disease (COPD) in relation with exposure to ambient fine particulate matters: an analysis in Southeastern China.

The objective of this study was to investigate the association between ambient particulate matters (PMs) and chronic obstructive pulmonary disease (COPD) mortality. generalized additive mixed model was employed to investigate the effects of ambient fine and coarse PMs on COPD mortality using 13,066 deaths from 2014 to 2016 among six cities in Zhejiang Province in Southeastern China. The daily average death count due to COPD was 3, varying from 1 to 7 among six cities. The daily 24-h mean concentrations were diverse among cities, from 29.7 to 56.8 µg/m3 for PM2.5, 16.7 to 30.3 µg/m3 for PM2.5-10, and 50.3 to 87.1 µg/m3 for PM10, respectively. The analysis showed that daily exposure to PM2.5 and PM10 was associated with increased mortality due to COPD and that weak effects were observed between PM2.5-10 and COPD mortality. Our results provided solid evidence that the fine particles in air pollution have stronger functions on adverse health effects other than coarser particles in Southeastern China, which may be considered as a potential clinic target in PM-associated COPD.

The Effect of Iodine Status on the Risk of Thyroid Nodules: A Cross-Sectional Study in Zhejiang, China.

OBJECTIVE: The aim of this study was to explore whether iodine nutrition is associated with the risk of thyroid nodules among adult population in Zhejiang Province, China. METHODS: A cross-sectional study was conducted in the general population aged 18 years or older. A total of 2,710 subjects received physical examination, questionnaires, and thyroid ultrasonography. Urinary iodine concentration (UIC) and thyroid hormone levels were measured and documented for each subject. 4 multiple logistic regression models adjusted for other risk factors were applied to analyze the association between iodine nutrition and thyroid nodules. RESULTS: The prevalence of thyroid nodules was 15.5% among all adults. As indicated by all 4 models, subjects with UIC varying from 200 µg l-1 to 399 µg l-1 had lower risk of thyroid nodules compared with those with relatively low UIC (<100 µg l-1), with approximately 37-57 percent reduction in risk. Moreover, subjects with UIC between 100 and 199 µg l-1 had a decreased risk of thyroid nodules in model 1 and 2 (OR = 0.75, 95% CI, 0.58-0.97; OR = 0.75, 95% CI, 0.58-0.97, respectively). However, there was no significant difference of risk in thyroid nodules between subjects with high UIC (≥400 µg l-1) and low UIC (<100 µg l-1). Furthermore, intake of iodized salt was inversely associated with risk of thyroid nodules, with approximately 69-77 percent reduction in risk. CONCLUSION: The relationship between UIC and the risk of thyroid nodules is U-shaped. Consumption of noniodized salt is an independent risk factor of thyroid nodules.

Characterization and health risk assessment of PM2.5-bound polycyclic aromatic hydrocarbons in 5 urban cities of Zhejiang Province, China.

In 2015, we measured polycyclic aromatic hydrocarbons (PAHs) in atmospheric fine particulate matter (PM2.5) collected from 5 cities in Zhejiang Province. The mean toxic equivalent quotient (TEQ) values of benzo(a)pyrene (BaP) ranged between 1.2-3.1 ng/m3. The BaP-TEQ displayed seasonal trends, such that winter > spring and autumn > summer. During the winter, the most abundant individual PAHs were 4-6ring PAHs (84.04-91.65%). The median daily intake of atmospheric PAHs ranged between 2.0-7.4 ng/day for all populations, with seasonal trends identical to that of BaP-TEQ. The 95th incremental lifetime cancer risk (ILCR) values induced by PM2.5-bound PAHs were far lower than 10-6 for all populations. The data suggested that the pollution levels in the 5 Zhejiang Province cities were higher than the Chinese National Ambient Air Quality Standard (NAAQS). In the future, relevant measures should be taken to control atmospheric PAHs, especially 4-6 ring PAHs. The data also revealed no obvious cancer risk for populations residing in these 5 cities of Zhejiang Province.

Acute effects of air pollution on respiratory disease mortalities and outpatients in Southeastern China.

The objective of this study was to investigate the potential association between air pollutants and respiratory diseases (RDs). Generalized additive models were used to analyze the effect of air pollutants on mortalities or outpatient visits. The average concentrations of air pollutants in Hangzhou (HZ) were 1.6-2.8 times higher than those in Zhoushan (ZS), except for O3. In a single pollutant model, the increased concentrations of PM2.5, NO2, and SO2 were strongly associated with deaths caused by RD in HZ, while PM2.5 and O3 were associated with deaths caused by RD in ZS. All air pollutants (PM2.5, NO2, SO2, and O3) were strongly associated with outpatient visits for RD in both HZ and ZS. In multiple pollutant models, a significant association was only observed between PM2.5 and the mortality rate of RD patients in both HZ and in ZS. Moreover, strong associations between SO2, NO2, and outpatient visits for RD were observed in HZ and ZS. This study has provided evidence that both the mortality rates and outpatient visits for RD were significantly associated with air pollutants. Furthermore, the results showed that different air pollutant levels lead to regional differences between mortality rates and outpatient visits.