Association of residential air pollution and green space with all-cause and cause-specific mortality in individuals with diabetes: an 11-year prospective cohort study.

BACKGROUND: To assess the long-term impact of residential air pollution and green space exposure on cause-specific mortality in individuals with type 2 diabetes mellitus (T2DM). METHODS: This study includes 174,063 participants newly diagnosed with T2DM from a prospective cohort in Shanghai, China, enrolled between 2011 and 2013. Residential annual levels of air pollutants, including fine (PM2.5) and coarse (PM2.5-10) particulate matter, nitrogen dioxide (NO2), along with the normalized difference vegetation index (NDVI), were derived from satellite-based exposure models. FINDINGS: During a median follow-up of 7.9 years (equivalent to 1,333,343 person-years), this study recorded 22,205 deaths. Higher exposure to PM2.5 was significantly associated with increased risks for all mortality outcomes, whilst PM2.5-10 showed no significant impacts. The strongest associations of PM2.5 were observed for diabetes with peripheral vascular diseases [hazard ratio (HR): 2.70; per 10 µg/m3 increase] and gastrointestinal cancer (2.44). Effects of NO2 became significant at concentrations exceeding approximately 45 µg/m³, with the highest associations for lung cancer (1.20) and gastrointestinal cancer (1.19). Conversely, each interquartile range increase in NDVI (0.10) was linked to reduced mortality risks across different causes, with HRs ranging from 0.76 to 1.00. The association between greenness and mortality was partly and significantly mediated by reduced PM2.5 (23.80%) and NO2 (26.60%). There was a significant and negative interaction between NO2 and greenness, but no interaction was found between PM2.5 and greenness. INTERPRETATION: Our findings highlight the vulnerability of individuals with T2DM to the adverse health effects of air pollution and emphasise the potential protective effects of greenness infrastructure. FUNDING: The 6th Three-year Action Program of Shanghai Municipality for Strengthening the Construction of Public Health System (GWVI-11.1-22), the National Key Research and Development Program (2022YFC3702701), and the National Natural Science Foundation of China (82030103, 82373532).

Preparation of phenol-formaldehyde composite modified with chitosan for the simultaneous removal of antibiotics and heavy metal ions in waters.

In current study, a new adsorbent based on aminated phenol-formaldehyde composite was prepared using chitosan as modifier. Various techniques were adopted to characterize the morphology and structure of the prepared adsorbent. Due to the abundant amino groups, the obtained adsorbent presented satisfactory adsorption performance towards fluoroquinolones (FQs) and heavy metal ions (including Cu2+, Cd2+ and Pb2+) by means of multiple forces including electrostatic, H-bonding, π-π stacking interactions (for FQs) and chelating force (for heavy metal ions). Studies about the adsorption kinetics, isotherm and thermodynamics were performed to inspect the adsorption behaviors of studied FQs and heavy metal ions on the new adsorbent. After optimizing the adsorption parameters, the obtained adsorbent were employed to remove FQs, Cu2+, Cd2+ and Pb2+ in various environmental waters. The removal rates for FQs and heavy metal ions were 91.8-98.6 % and 94.4-98.5 %, respectively, which were significantly higher than that obtained on unmodified phenol-formaldehyde resin (20.7-49.0 % for FQs and 35.1-43.0 % for heavy metal ions). At the same time, the adsorbent exhibited good preparation repeatability in different batches, acceptable stability and reusability. The current study well demonstrated the potential application of the new adsorbent in the simultaneous removal of organic and inorganic pollutants from aqueous waters.

Immunologic signatures of response and resistance to nivolumab with ipilimumab in advanced metastatic cancer.

Identifying pan-tumor biomarkers that predict responses to immune checkpoint inhibitors (ICI) is critically needed. In the AMADEUS clinical trial (NCT03651271), patients with various advanced solid tumors were assessed for changes in intratumoral CD8 percentages and their response to ICI. Patients were grouped based on tumoral CD8 levels: those with CD8 <15% (CD8-low) received nivolumab (anti-PD-1) plus ipilimumab (anti-CTLA4) and those with CD8 ≥15% (CD8-high) received nivolumab monotherapy. 79 patients (72 CD8-low and 7 CD8-high) were treated. The disease control rate was 25.0% (18/72; 95% CI: 15.8-35.2) in CD8-low and 14.3% (1/7; 95% CI: 1.1-43.8) in CD8-high. Tumors from 35.9% (14/39; 95% CI: 21.8-51.4) of patients converted from CD8 <15% pretreatment to ≥15% after treatment. Multiomic analyses showed that CD8-low responders had an inflammatory tumor microenvironment pretreatment, enhanced by an influx of CD8 T cells, CD4 T cells, B cells, and macrophages upon treatment. These findings reveal crucial pan-cancer immunological features for ICI response in patients with metastatic disease.

The interaction effect between BMI, diabetes and age at diabetes onset on the risk of thyroid cancer: A population-based cohort study in Shanghai, China.

AIM: To determine the association of the presence of diabetes and, among persons with diabetes, the age at type 2 diabetes mellitus (T2DM) onset, BMI and the interactive effect with the subsequent thyroid cancer risk. MATERIALS AND METHODS: We conducted a population register-based longitudinal cohort study in Shanghai, including 428 568 persons with new-onset T2DM matched with the general population. The risk of thyroid cancer among subgroups was calculated based on standardized incidence ratio (SIR), hazard ratio (HR) and Cox proportional hazards models. RESULTS: In total, 1142 thyroid cancer cases were identified during 8 years of follow-up, with an incidence rate of 59.01/100 000 person-years and a higher risk (SIR = 1.21) compared with the general population. The earlier age at T2DM onset and higher BMI were associated with an increasing risk of thyroid cancer independently (onset age <50, SIR: 1.46; BMI ≥30.0 kg/m2, SIR: 1.93), with the highest risk in patients with both BMI ≥30.0 kg/m2 and onset age <50 years (SIR = 3.91, HR = 3.04). Among patients with T2DM onset age <60 years, SIR increased with higher BMI, while there were no trends when onset age ≥60 years. Among patients with BMI ≥25.0 kg/m2, SIR increased with an earlier onset age, whereas no trends were shown in the BMI <24.9 kg/m2 groups. Obese (BMI ≥30.0 kg/m2) patients had a significantly higher HR of thyroid cancer only when T2DM onset age <60 years. CONCLUSIONS: Both earlier age of T2DM onset (<50 years) and higher BMI (≥30 kg/m2) contributed to the higher risk of thyroid cancer. Patients with young-onset T2DM and obesity are considered more vulnerable to thyroid cancer development.

Lineage Replacement and Genetic Changes of Four HR-HPV Types during the Period of Vaccine Coverage: A Six-Year Retrospective Study in Eastern China.

OBJECTIVE: This study aimed to provide clinical evidence for lineage replacement and genetic changes of High-Risk Human Papillomavirus (HR-HPV) during the period of vaccine coverage and characterize those changes in eastern China. METHODS: This study consisted of two stages. A total of 90,583 patients visiting the Obstetrics and Gynecology Hospital of Fudan University from March 2018 to March 2022 were included in the HPV typing analysis. Another 1076 patients who tested positive for HPV31, 33, 52, or 58 from November 2020 to August 2023 were further included for HPV sequencing. Vaccination records, especially vaccine types and the third dose administration time, medical history, and cervical cytology samples were collected. Viral DNA sequencing was then conducted, followed by phylogenetic analysis and sequence alignment. RESULTS: The overall proportion of HPV31 and 58 infections increased by 1.23% and 0.51%, respectively, while infection by HPV33 and 52 decreased by 0.42% and 1.43%, respectively, within the four-year vaccination coverage period. The proportion of HPV31 C lineage infections showed a 22.17% increase in the vaccinated group, while that of the HPV58 A2 sublineage showed a 12.96% increase. T267A and T274N in the F-G loop of HPV31 L1 protein, L150F in the D-E loop, and T375N in the H-I loop of HPV58 L1 protein were identified as high-frequency escape-related mutations. CONCLUSIONS: Differences in epidemic lineage changes and dominant mutation accumulation may result in a proportional difference in trends of HPV infection. New epidemic lineages and high-frequency escape-related mutations should be noted during the vaccine coverage period, and regional epidemic variants should be considered during the development of next-generation vaccines.

MORF9-dependent specific plastid RNA editing inhibits root growth under sugar starvation in Arabidopsis.

Multiple organellar RNA editing factor (MORF) complex was shown to be highly associated with C-to-U RNA editing of vascular plant editosome. However, mechanisms by which MORF9-dependent plastid RNA editing controls plant development and responses to environmental alteration remain obscure. In this study, we found that loss of MORF9 function impaired PSII efficiency, NDH activity, and carbohydrate production, rapidly promoted nuclear gene expression including sucrose transporter and sugar/energy responsive genes, and attenuated root growth under sugar starvation conditions. Sugar repletion increased MORF9 and MORF2 expression in wild-type seedlings and reduced RNA editing of matK-706, accD-794, ndhD-383 and ndhF-290 in the morf9 mutant. RNA editing efficiency of ndhD-383 and ndhF-290 sites was diminished in the gin2/morf9 double mutants, and that of matK-706, accD-794, ndhD-383 and ndhF-290 sites were significantly diminished in the snrk1/morf9 double mutants. In contrast, overexpressing HXK1 or SnRK1 promoted RNA editing rate of matK-706, accD-794, ndhD-383 and ndhF-290 in leaves of morf9 mutants, suggesting that HXK1 partially impacts MORF9 mediated ndhD-383 and ndhF-290 editing, while SnRK1 may only affect MORF9-mediated ndhF-290 site editing. Collectively, these findings suggest that sugar and/or its intermediary metabolites impair MORF9-dependent plastid RNA editing resulting in derangements of plant root development.

Association Between Age at Diabetes Diagnosis and Subsequent Incidence of Cancer: A Longitudinal Population-Based Cohort.

OBJECTIVE: Diabetes presenting at a younger age has a more aggressive nature. We aimed to explore the association of age at type 2 diabetes mellitus (T2DM) diagnosis with subsequent cancer incidence in a large Chinese population. RESEARCH DESIGN AND METHODS: The prospective population-based longitudinal cohort included 428,568 newly diagnosed T2DM patients from 2011 to 2018. Participants were divided into six groups according to their age at diagnosis: 20-54, 55-59, 60-64, 65-69, 70-74, and ≥75 years. The incidence of overall and 14 site-specific cancers was compared with the Shanghai general population including 100,649,346 person-years. RESULTS: A total of 18,853 and 582,643 overall cancer cases were recorded in the T2DM cohort and the general population. The age-standardized rate of overall cancer in T2DM patients was 501 (95% CI: 491, 511) per 100,000 person-years, and the standardized incidence ratio (SIR) was 1.10 (1.09, 1.12). Younger age at T2DM diagnosis was associated with higher incidence of overall and site-specific cancers. SIRs for overall cancer with T2DM diagnosis at ages 20-54, 55-59, 60-64, 65-69, 70-74, and ≥75 years were 1.48 (1.41, 1.54), 1.30 (1.25, 1.35), 1.19 (1.15, 1.23), 1.16 (1.12, 1.20), 1.06 (1.02, 1.10), and 0.86 (0.84, 0.89), respectively. Similar trends were observed for site-specific cancers, including respiratory, colorectum, stomach, liver, pancreatic, bladder, central nervous system, kidney, and gallbladder cancer and lymphoma among both males and females. CONCLUSIONS: Our findings highlight the necessity of stratifying management for T2DM according to age of diagnosis. As with a range of vascular outcomes, age-standardized cancer risks are greater in earlier compared with later onset T2DM.

Immune-Related Colitis Is Associated with Fecal Microbial Dysbiosis and Can Be Mitigated by Fecal Microbiota Transplantation.

Colitis induced by treatment with immune-checkpoint inhibitors (ICI), termed irColitis, is a substantial cause of morbidity complicating cancer treatment. We hypothesized that abnormal fecal microbiome features would be present at the time of irColitis onset and that restoring the microbiome with fecal transplant from a healthy donor would mitigate disease severity. Herein, we present fecal microbiota profiles from 18 patients with irColitis from a single center, 5 of whom were treated with healthy-donor fecal microbial transplantation (FMT). Although fecal samples collected at onset of irColitis had comparable α-diversity to that of comparator groups with gastrointestinal symptoms, irColitis was characterized by fecal microbial dysbiosis. Abundances of Proteobacteria were associated with irColitis in multivariable analyses. Five patients with irColitis refractory to steroids and biologic anti-inflammatory agents received healthy-donor FMT, with initial clinical improvement in irColitis symptoms observed in four of five patients. Two subsequently exhibited recurrence of irColitis symptoms following courses of antibiotics. Both received a second "salvage" FMT that was, again, followed by clinical improvement of irColitis. In summary, we observed distinct microbial community changes that were present at the time of irColitis onset. FMT was followed by clinical improvements in several cases of steroid- and biologic-agent-refractory irColitis. Strategies to restore or prevent microbiome dysbiosis in the context of immunotherapy toxicities should be further explored in prospective clinical trials.

Application of a diagnosis flow draft based on appearance impression for detection of vulvar disease.

OBJECTIVES: The aims of this retrospective study were to evaluate the clinical applicability of the latest International Society for the Study of Vulvovaginal Disease (ISSVD) and International Federation for Cervical Pathology and Colposcopy (IFCPC) terminology for vulvar diseases, and to explore a new evaluation flow to optimize decision-making on diagnosis. METHODS: A total of 1,068 patients with 5,340 qualified vulvar images were evaluated by observers using 2011 ISSVD and 2011 IFCPC terminology systems. The sensitivity, specificity, positive predictive value, negative predictive value, Youden Index and Overall Diagnostic Value (ODV) were calculated for each finding in the two systems. Then the disease diagnosis order and a diagnosis flow draft (DFD) were obtained. RESULTS: A total of 15 kinds of vulvar diseases were diagnosed. The proportion of patients accompanied with cervical or vaginal intraepithelial neoplasia was highest (83.3 %) in vulvar Paget's disease group (p<0.001). Total area of lesions was larger in vulvar Paget's disease, lichen simplex chronicus and lichen sclerosus group (p<0.001). Among the top five findings of ODV, some findings inferred several (≥6) kinds of diseases, while some findings only exist in a certain disease. When the DFD was used, the agreement between the initial impression and histopathology diagnosis was 68.8 %, higher than those when ISSVD an IFCPC terminology systems used (p=0.028), and it didn't change with the experience of the observer (p=0.178). CONCLUSIONS: Based on the findings in ISSVD and IFCPC terminology systems, we explored a DFD for observers with different experience on the detection of vulvar disease.

Genetic variability analysis of human papillomavirus 58: Novel sublineage identification and persistent infection association.

This study aims to characterize the genetic variability of HPV58, identify novel lineages and sublineages, and explore the association between persistent/multiple HPV58 infections and genetic variation. In this study, samples from 124 women with HPV58 infection in Eastern China were collected and 81 isolates of E6 and L1 full-length genes were successfully amplified from 55 samples. We evaluated the diversity of genetic variants and performed correlation analyses between genetic variability and pathology, vaccination, multiple infections, and persistent infections. Among the E6 and L1 gene sequences collected, the dominant prevailing sublineages were A1 (46.2%) and A2 (23.1%). In addition, we found two potential novel sublineages denoted as the A4 and A5 sublineage. A total of 50 nucleotide substitutions, including 28 synonymous substitutions and 22 nonsynonymous substitutions, were observed in the E6 and L1 genes. Among them, variants with A388C/K93N substitutions in the E6 gene correlated with persistent infection (≥1 and ≥2 years) (p < 0.005), and C307T/C66C was associated with persistent infection (≥2 years) (p < 0.005). Notably, two mutations above were detected in the isolate from the patient with breakthrough vaccine infection. Our study found two novel sublineages and sites of genetic variability in multiple and persistent infection variants. In addition, we identified two mutational sites associated with persistent infection. This study provides new insight into the clinical characteristics of HPV 58 genetic variations and offers new ideas for research on next-generation vaccines in Eastern China.

Long-term effects of blood pressure 130-139/80-89 mmHg on all-cause and cardiovascular mortality among Chinese adults with different glucose metabolism.

BACKGROUND: This study aimed to investigate the risks of all-cause and cardiovascular mortality associated with blood pressure (BP) levels of 130-139/80-89 mmHg in Chinese adults with different glucose metabolism, during a long-term follow-up of over 20 years. METHODS: A prospective population-based cohort of 2,132 adults in Shanghai was established in 2002 and followed for 21 years. The association between BP categories and mortality was assessed, and the risk was further analyzed using multiple Cox regression analysis by combining BP and blood glucose categories. RESULTS: The final analysis included 2,004 participants, with 397 all-cause and 166 cardiovascular mortality. The incidence of all-cause and cardiovascular mortality per 1,000 person-years for different BP categories were as follows: BP < 130/80 mmHg (4.5 and 1.3), 130-139/80-89 mmHg (7.7 and 2.9), and ≥ 140/90 mmHg or treated groups (19.9 and 8.7), respectively. After adjusting for age, sex, and other factors, BP ≥ 140/90 mmHg was significantly associated with a higher risk of mortality across different blood glucose categories. However, using BP < 130/80 mmHg and normoglycemia as the reference, a BP of 130-139/80-89 mmHg was significantly associated with higher risks of all-cause (hazard ratio 3.30 [95% confidence interval 1.48-7.38], P < 0.01) and cardiovascular mortality (9.60 [1.93-47.7], P < 0.01) in diabetes, but not in those with normoglycemia or prediabetes. CONCLUSIONS: BP of 130-139/80-89 mmHg may lead to a significantly higher risk of all-cause and cardiovascular mortality in Chinese adults with diabetes, but not in those with normoglycemia or prediabetes. This suggests that the targeted BP for people with diabetes should be < 130-139/80-89 mmHg.

Vaccine escape challenges virus prevention: The example of two vaccine-preventable oncogenic viruses.

Over the years, the pace of developing vaccines for HBV and HPV has never stopped. After more than 30 years of application, the HBV vaccine has reduced 80% of hepatocellular carcinoma (HCC). However, vaccine escape variants occur under selective pressure induced by widespread vaccination and antiviral therapy, which results in fulminant infection and horizontal transmission. Several mechanisms have been studied to explain HBV vaccine escape, including vaccine escape mutations (VEMs) in the major hydrophilic region, which leads to a decrease in the binding ability to neutralize antibodies and is the primary escape mechanism, protein conformational and N-linked glycosylation sites changes caused by VEMs, differences in genotype distribution, gene recombination, and some temporarily unknown reasons. However, effective solutions are still being explored. The HPV vaccine has also been proven to prevent 70%-90% of cervical cancer worldwide. Cases of HPV infection after being vaccinated have been observed in clinical practice. However, few researchers have paid attention to the mechanism of HPV vaccine escape. Thus, we reviewed the literature on vaccine escape of both HBV and HPV to discuss the mechanism of the virus escaping from vaccine protection and possible solutions to this problem. We analyzed the gap between studies of HPV and HBV and made prospects for further research in HPV vaccine escape.

Integration of peripheral blood- and tissue-based biomarkers of response to immune checkpoint blockade in urothelial carcinoma.

As predictive biomarkers of response to immune checkpoint inhibitors (ICIs) remain a major unmet clinical need in patients with urothelial carcinoma (UC), we sought to identify tissue-based immune biomarkers of clinical benefit to ICIs using multiplex immunofluorescence and to integrate these findings with previously identified peripheral blood biomarkers of response. Fifty-five pretreatment and 12 paired on-treatment UC specimens were identified from patients treated with nivolumab with or without ipilimumab. Whole tissue sections were stained with a 12-plex mIF panel, including CD8, PD-1/CD279, PD-L1/CD274, CD68, CD3, CD4, FoxP3, TCF1/7, Ki67, LAG-3, MHC-II/HLA-DR, and pancytokeratin+SOX10 to identify over three million cells. Immune tissue densities were compared to progression-free survival (PFS) and best overall response (BOR) by RECIST version 1.1. Correlation coefficients were calculated between tissue-based and circulating immune populations. The frequency of intratumoral CD3+ LAG-3+ cells was higher in responders compared to nonresponders (p = 0.0001). LAG-3+ cellular aggregates were associated with response, including CD3+ LAG-3+ in proximity to CD3+ (p = 0.01). Exploratory multivariate modeling showed an association between intratumoral CD3+ LAG-3+ cells and improved PFS independent of prognostic clinical factors (log HR -7.0; 95% confidence interval [CI] -12.7 to -1.4), as well as established biomarkers predictive of ICI response (log HR -5.0; 95% CI -9.8 to -0.2). Intratumoral LAG-3+ immune cell populations warrant further study as a predictive biomarker of clinical benefit to ICIs. Differences in LAG-3+ lymphocyte populations across the intratumoral and peripheral compartments may provide complementary information that could inform the future development of multimodal composite biomarkers of ICI response. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Analysis of publications on HPV genotype co-infection: a bibliometric study on existing research.

Purpose: To identify the bibliometric information of Human papillomavirus (HPV) genotype co-infection in certain literature database over the past two decades. Methods: Web of Science was used as the main database to identify all eligible articles focusing on HPV genotype co-infection at the date of October 16, 2022. From this journal database, we identified 463 articles on HPV genotype co-infection, conducted statistical analysis according to the author, journal, publication year and month, country or region, keyword and impact factor. Results: The articles included in our analysis were published between 1994 and 2022. The index of citations per year ranged from 170.4 to 13.1. These articles were from 78 countries or regions, with most publications from the United States (n = 73), followed by China (n = 65) and Italy (n = 50). The journal that contributed the most publications on HPV heterotypic gene co-infection was PLOS ONE with a total of 29 articles, followed by JOURNAL OF MEDICAL VIROLOGY (n = 28), INFECTIOUS AGENTS AND CANCER (n = 14) and JOURNAL OF CLINICAL VIROLOGY (n = 12). Among existing research in the field of HPV co-infection, we found that epidemiological distribution and infection mechanism has been the two major topics for scholars, and studies on detection methods for HPV multiple genotypes were also included. Conclusion: Over decades, epidemiological studies and mechanism investigationhas been the central topics when it comes to HPV genotypes co-infection. Studies on HPV co-infection remained relatively insufficient, mainly stays in qualitative level while detailed infection data and high quality literature publications were still lack of valuable discussion.

Stem cell-like T cell depletion in the recurrent head and neck cancer immune microenvironment.

Human papilloma virus (HPV)-related oncogenesis in head and neck cancer establishes a local microenvironment rich with immune cells, however the composition of the microenvironment in recurrent disease following definitive treatment is poorly understood. Here, we investigate the composition and spatial relationships between tumor and immune cells in recurrent head and neck cancer following curative intent chemoradiotherapy. Multiplexed immunofluorescence with 12 unique markers, through two multiplex immunofluorescent panels, was performed to evaluate 27 tumor samples including 18 pre-treatment primary and 9 paired recurrent tumors. Tumor and immune cell populations were phenotyped and quantified using a previously validated semi-automated digital pathology platform for cell segmentation. Spatial analysis was conducted by evaluating immune cells within the tumor, peri-tumoral stroma, and distant stroma. Initial tumors in patients with subsequent recurrence were found to be enriched in tumor associated macrophages and displayed an immune excluded spatial distribution. Recurrent tumors after chemoradiation were hypo-inflamed, with a statistically significant reduction in the recently identified stem-like TCF1+ CD8 T-cells, which normally function to maintain HPV-specific immune responses in the setting of chronic antigen exposure. Our findings indicate that the tumor microenvironment of recurrent HPV-related head and neck cancers displays a reduction in stem-like T cells, consistent with an immune microenvironment with a reduced ability to mount T-cell-driven anti-tumor immune responses.

Risk factors of LEEP margin positivity and optimal length of cervical conization in cervical intraepithelial neoplasia.

Background: The conization length for cervical precancerous lesions is essential for treatment but is left undetermined. This study aims to explore the reasonable and optimal conization length in patients with different types of cervical transformation zones (TZs) to reach the treatment outcome of margin negative in the surgery. Methods: From July 2016 to September 2019, a multi-center prospective case-control study with or suspicion of cervical precancer was enrolled from five medical centers in Shanghai, China. The clinical characteristics, cytology, human papillomavirus (HPV), histopathology, and details of cervical conization were recorded. Results: A total of 618 women were enrolled in this study; 6.8% (42/618) had positive internal (endocervical and stromal) margins and 6.8% (42/618) had positive external (ectocervical) margins of loop electrosurgical excision procedure (LEEP) specimen. Comparing the positive internal margin group with the negative group, age (p = 0.006) and cytology (p = 0.021) were significantly different. Multivariate logistic regression analysis showed that the risk factors for positive internal margin were cytology ≥ high-grade squamous intraepithelial lesion (HSIL) (odds ratio (OR) 3.82, p = 0.002) and age (OR 1.11, p < 0.001). The positive internal margin rate was 2.7%, 5.1%, and 6.9% in TZ1, TZ2, and TZ3, respectively, while the positive external margin was 6.7%, 3.4%, and 1.4%, respectively. In the TZ3 group, the HSIL positive internal margin of the 15-16-mm group (10.0%, 19/191) was significantly greater than in TZ1 (2.7%, 4/150) (p = 0.010) and TZ2 (5.0%, 9/179) (p = 0.092); when excision length increases to 17-25 mm, the positive internal margin rate dramatically decreased to 1.0% (1/98). Conclusion: A cervical excision length of 10-15 mm is reasonable for TZ1 and TZ2 patients, while 17-25 mm is optimal for TZ3 excision with more negative internal margins.

Tissue-specific features of the T cell repertoire after allogeneic hematopoietic cell transplantation in human and mouse.

T cells are the central drivers of many inflammatory diseases, but the repertoire of tissue-resident T cells at sites of pathology in human organs remains poorly understood. We examined the site-specificity of T cell receptor (TCR) repertoires across tissues (5 to 18 tissues per patient) in prospectively collected autopsies of patients with and without graft-versus-host disease (GVHD), a potentially lethal tissue-targeting complication of allogeneic hematopoietic cell transplantation, and in mouse models of GVHD. Anatomic similarity between tissues was a key determinant of TCR repertoire composition within patients, independent of disease or transplant status. The T cells recovered from peripheral blood and spleens in patients and mice captured a limited portion of the TCR repertoire detected in tissues. Whereas few T cell clones were shared across patients, motif-based clustering revealed shared repertoire signatures across patients in a tissue-specific fashion. T cells at disease sites had a tissue-resident phenotype and were of donor origin based on single-cell chimerism analysis. These data demonstrate the complex composition of T cell populations that persist in human tissues at the end stage of an inflammatory disorder after lymphocyte-directed therapy. These findings also underscore the importance of studying T cell in tissues rather than blood for tissue-based pathologies and suggest the tissue-specific nature of both the endogenous and posttransplant T cell landscape.

Prevalence trends and disease burden of diabetes and prediabetes in Chinese adults of Shanghai.

BACKGROUND: To estimate secular trends and disease burden of diabetes and prediabetes among Chinese adults. METHODS: Three population-based surveys were performed among Chinese adults in Shanghai in 2002-2003 (n = 12 302), 2009 (n = 7414), and 2017 (n = 18 960). Diabetes and prediabetes were defined using the 1999 World Health Organization (WHO) criteria. Cochran-Armitage trend test was used to examine the trends in prevalence, awareness, and glycemic control status. Disability adjusted life years (DALYs) were estimated to evaluate the disease burden of diabetes-related complications using the population attribution fraction approach based on published data. RESULTS: The age-adjusted prevalence of diabetes increased during the 15-year period (p for trend <.001) and reached 23.0% (95% CI: 22.1 ~ 24.0%) in men and 15.7% (95% CI: 15.1 ~ 16.4%) among women in 2017. The prevalence of impaired glucose tolerance peaked in 2009, whereas that of impaired fasting glucose increased continuously (p for trend <.001). The awareness of diabetes was found to increase and the glycemic control rates decreased over the three surveys. The estimated DALYs of diabetes complications were found to have increased rapidly due to the increasing prevalence of diabetes and the decreasing glycemic control rates. CONCLUSIONS: Prediabetes and diabetes affect a considerable proportion of Chinese adults in Shanghai. Our results highlight the necessary to strengthen the community healthcare system in China to guarantee extensive management of diabetes and prediabetes.

The possible impact of novel mutations in human papillomavirus 52 on the infection characteristics.

Human papillomavirus 52 (HPV52) infection is prevalent in the Chinese population, and variations in HPV52 show correlations with oncogenicity. However, no specific variation in HPV52 was reported to show relevancy to infection characteristics. In this study, we retrieved 222 isolates of E6 and L1 full-length genes from 197 Chinese women with HPV52 infection. After sequence alignment and phylogenetic tree construction, we found that 98.39 % of the collected variants belonged to the sublineage B2 and two variants displayed incongruence between the phylogenetic tree of E6 and L1. The analysis of the infection pattern showed that the presence of C6480A/T mutation in the L1 gene was associated with single infection (P=0.01) and persistent infection (P=0.047) of HPV52, while the A6516G nucleotide change was relevant to transient infection (P=0.018). Our data also indicated that variations T309C in the E6 gene and C6480T, C6600A in L1 were more commonly presented in patients with high-grade cytology (P<0.05). One HPV52 breakthrough infection after vaccination was identified, which hinted at the immune escape post-vaccination. Young coitarche age and non-condom usage were correlated to multiple infections. This study provided insight into the polymorphism of HPV52 and revealed the impact of variations in HPV52 on its infection characteristics.