Personalized prognostic prediction tool for high-grade neuroendocrine cervical cancer: a SEER database analysis and single-center validation.

PURPOSE: Cervical high-grade neuroendocrine carcinoma (CHGNEC) is a rare but highly aggressive cancer. The purpose of this study is to develop a prognostic nomogram that can accurately predict the outcomes for CHGNEC patients. METHODS: We analyzed clinical data from the Surveillance, Epidemiology, and End Results (SEER) database of CHGNEC patients, including small-cell neuroendocrine carcinoma (SCNEC) and large-cell neuroendocrine carcinoma (LCNEC). We investigated patient characteristics and prognosis, and developed a prognostic nomogram model for cancer-specific survival in CHGNEC patients. External validation was conducted using real clinical cases from our hospital. RESULTS: Our study included 306 patients from SEER database, with a mean age of 49.9 ± 15.5 years. Most of the patients had SCNEC (86.9%). Among them, 170 died from the disease, while 136 either survived or died from other causes. Our final predictive model identified age at diagnosis, stage 1 status, stage 4 status, T1, N0, and surgery of the primary site as independent prognostic factors for CHGNEC. We validated our model using a group of 16 CHGNEC patients who underwent surgery at our center. The external validation showed that the prognostic nomogram had excellent discriminative ability, with an area under the receiver operating characteristic curve (AUC) of 0.76 (95% CI 0.49-1.00) for the prediction of 3-year cancer-specific survival (CSS) and an AUC of 0.85 (95% CI 0.62-1.00) for the prediction of 5-years CSS. The random survival forest model achieved an AUC of 0.80 (95% CI 0.56-1.00) for 3-years CSS and 0.91 (95% CI 0.72-1.00) for 5-years CSS, indicating its adequacy in predicting outcomes for CHGNEC patients. CONCLUSION: Our study provides an excellent nomogram for predicting the prognosis of CHGNEC patients. The prognostic nomogram can be a useful tool for clinicians in identifying high-risk patients and making personalized treatment decisions.

Development and validation of nomograms to recurrence and survival in patients with early-stage cervical adenocarcinoma.

PURPOSE: Cervical adenocarcinoma is one of the most common types of cervical cancer and its incidence is increasing. The biological behavior and treatment outcomes of cervical adenocarcinoma (CA) differ from those of squamous cell carcinoma (SCC). We sought to develop a model to predict recurrence and cancer-specific survival (CSS) deaths in CA patients. METHODS: 131 patients were included in model development and internal validation, and patients from the SEER database (N = 1679) were used for external validation. Multivariable Cox proportional hazards regression analysis was used to select predictors of relapse-free survival (RFS) and CSS and to construct the model, which was presented as two nomograms. Internal validation of the nomograms was performed using the bootstrap resampling method. RESULTS: Age, FIGO (International Federation of Gynecology and Obstetrics) stage, size of the tumor, lymph metastasis and depth of invasion were identified as independent prognostic factors for RFS, while age, FIGO stage, size of the tumor and number of positive LNs were identified as independent prognostic factors for CSS. The nomogram of the recurrence model predicted 2- and 5-year RFS, with optimism adjusted c-statistic of 75.41% and 74.49%. Another nomogram predicted the 2- and 5-year CSS with an optimism-adjusted c-statistic of 83.22% and 83.31% after internal validation; and 68.6% and 71.33% after external validation. CONCLUSIONS: We developed and validated two effective nomograms based on static nomograms or online calculators that can help clinicians quantify the risk of relapse and death for patients with early-stage CA.

Vaginal microbiota and HPV clearance: A longitudinal study.

Although vaginal microbiota (VM) may interact with human papillomavirus (HPV) infection and clearance, longitudinal data remain very limited. We aimed to investigate the association between VM at baseline and the clearance of high-risk HPV (HR-HPV) infection within 12 months. Cervical swabs were collected at diagnosis from 85 patients with HR-HPV infection and histologically confirmed cervical lesions, including cervicitis, low-grade squamous intraepithelial lesion and high-grade squamous intraepithelial lesion. Microbiome analysis was performed using 16S rRNA gene sequencing. Among the 73 women included in the analyses, HPV clearance was observed in 58.9% of the patients within 12 months. No significant difference was observed between the HPV-cleared and HPV-uncleared groups regarding age, disease stage, HPV subtype, VM community state types, and VM diversity (α and ß). Women with the depletion of enterococcus ASV_62 and enrichment in Lactobacillus iners at baseline were less likely to have HPV clearance at month 12. Further analysis revealed a significant negative association between high abundance of L. iners and HPV clearance in patients who received non-operative treatment (OR = 3.94, p = 0.041), but not in those who received operative treatment (OR = 1.86, p = 0.660). Our findings provide new evidence for the potential role of VM in the persistent HR-HPV infections.

Alterations of gut microbiota in patients with active pulmonary tuberculosis in China: a pilot study.

BACKGROUND: The aim of this study was to identify the differences in diversity, composition, and function of the gut microbiota between tuberculosis (TB) patients and healthy controls (HCs). METHODS: A cross-sectional study was conducted in three cities of China. Stool samples from 94 treatment-naive TB patients and 62 HCs were analyzed by 16S rRNA gene sequencing. TB patients were further divided into antibiotic-free and antibiotic-exposure according to their use of non-specific antibiotics before the TB diagnosis. RESULTS: Compared with HCs, antibiotic-free TB patients presented a different gut microbial community (P < 0.005) and decreased Shannon diversity (P < 0.005). Among TB patients, the relative abundances of short-chain fatty acid (SCFA)-producing genera such as Lachnospiraceae ND3007 group (log2(FC) = -2.74) were lower, while several conditional pathogen-related genera such as Enterococcus (log2(FC) = 12.05) and Rothia (log2(FC) = 6.322) were at higher levels. In addition, 41% of patients received antibiotics before TB diagnosis. Antibiotic exposure was correlated with an additional reduction in α diversity and depletion of SCFA-producing bacteria. Microbial functional analysis revealed that the biosynthesis capacity of amino acids and fatty acids was lower among TB patients compared to HCs. CONCLUSIONS: Significant alterations in gut microbiota composition and metabolic pathways of TB patients were observed. Antibiotic exposure could alter the gut microbiota of TB patients, which should be considered in anti-TB treatment.

Rising challenge of multidrug-resistant tuberculosis in China: a predictive study using Markov modeling.

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is on the rise in China. This study used a dynamic Markov model to predict the longitudinal trends of MDR-TB in China by 2050 and to assess the effects of alternative control measures. METHODS: Eight states of tuberculosis transmission were set up in the Markov model using a hypothetical cohort of 100 000 people. The prevalence of MDR-TB and bacteriologically confirmed drug-susceptible tuberculosis (DS-TB+) were simulated and MDR-TB was stratified into whether the disease was treated with the recommended regimen or not. RESULTS: Without any intervention changes to current conditions, the prevalence of DS-TB+ was projected to decline 67.7% by 2050, decreasing to 20 per 100 000 people, whereas that of MDR-TB was expected to triple to 58/100 000. Furthermore, 86.2% of the MDR-TB cases would be left untreated by the year of 2050. In the case where MDR-TB detection rate reaches 50% or 70% at 5% per year, the decline in prevalence of MDR-TB would be 25.9 and 36.2% respectively. In the case where treatment coverage was improved to 70% or 100% at 5% per year, MDR-TB prevalence in 2050 would decrease by 13.8 and 24.1%, respectively. If both detection rate and treatment coverage reach 70%, the prevalence of MDR-TB by 2050 would be reduced to 28/100 000 by a 51.7% reduction. CONCLUSIONS: MDR-TB, especially untreated MDR-TB, would rise rapidly under China's current MDR-TB control strategies. Interventions designed to promote effective detection and treatment of MDR-TB are imperative in the fights against MDR-TB epidemics.

Improved treatment outcome of multidrug-resistant tuberculosis with the use of a rapid molecular test to detect drug resistance in China.

OBJECTIVES: Numerous studies investigate the advantages of rapid molecular drug susceptibility testing (DST) in comparison to phenotypic DST, but the clinical impact on treating multi/extensively drug resistant TB(M/XDR-TB) is less studied. Therefore, we examined how molecular DST testing may improve MDR-TB treatment management and outcome in Chinese settings. METHODS: We performed a comparative study of patient cohorts before and after the implementation of molecular DST diagnosis with Genotype MTBDRsl/MTBDRplus assay in two Chinese hospitals. We collected clinical information including time to sputum culture conversion and final treatment outcome. RESULTS: In total, 242 MDR-TB patients were studied including 114 before (pre-implementation group) and 128 after the implementation (post-implementation group) of molecular DST. Time to MDR-TB diagnosis was significantly reduced for patients in the post-implementation group, as compared to the pre-implementation group (median,16 vs 62 days; P < 0.001). Patients with early available molecular DST results had a more rapid culture conversion (aHR1.94 95% CI: 1.37-2.73; median,12 vs 24 months, respectively; P < 0.001) and higher rate of treatment success (68% vs 47%, P < 0.01). CONCLUSIONS: The use of molecular DST in routine care for MDR-TB diagnosis as compared to phenotypic DST was associated with a decreased time to culture conversion and improved treatment outcome, highlighting its important clinical value.

Longitudinal profiling of gut microbiome among tuberculosis patients under anti-tuberculosis treatment in China: protocol of a prospective cohort study.

BACKGROUND: Anti-tuberculosis therapy requires at least six-month treatment with continuous administration of combined antibiotics, including isoniazid, rifampicin, pyrazinamide, and ethambutol. The long-term exposure to antibiotics could cause consequent changes in gut microbiota, which may alter the gastrointestinal function and drug absorption in patients, thereby affect the outcome of treatment. The study aims to characterize the longitudinal changes of gut microbiota among tuberculosis (TB) patients under standardized first-line treatment and provide an understanding of the association between alterations in gut microbiota composition and unfavorable clinical outcomes. METHODS: The study is a multicenter, observational prospective cohort study. Three study sites are purposively selected in the western (Sichuan Province) and eastern (Jiangsu Province and Shanghai) parts of China. Three-hundred patients with bacteriologically confirmed pulmonary TB are enrolled. All eligible patients should be investigated using structured questionnaires before treatment initiation; and be followed up during the treatment at Day-14, Month-2, Month-5, the end of treatment and the sixth month after ending therapy. Stool samples are to be collected at each visit, consisting of six stool samples from each patient. Additionally, 60 healthy volunteers from Sichuan province and Shanghai city will be recruited as healthy controls to form the baseline of patient gut microbiota in the Chinese population. The dynamic changes of gut microbiota in terms of alpha diversity, beta diversity, taxonomic composition are to be illustrated individually from the time at diagnosis until the sixth month after therapy is completed. Furthermore, the diversity and component of gut microbiota will be compared between the groups with and without unfavorable treatment outcome in terms of adverse effect and treatment failure. DISCUSSION: Studies on the clinical manifestations, adverse reactions, and gut microbiota alterations will provide scientifically-sound evidence on the impact of gut microbiota alterations on TB treatment outcomes. The study is not only useful for guiding personalized TB treatment but also sheds light on the effects of continuous antibiotics administration on gut microbiota. TRIAL REGISTRATION: Chinese Clinical Trial Registry, trial ID: ChiCTR1900023369, May 24, 2019. Retrospectively registered.

[Analysis of spatiotemporal patterns and influential factors for mushroom poisoning in Hunan Province in 2015].

OBJECTIVE: To understand the spatial distribution of mushroom poisoning in Hunan Province and its influential factors, and to provide the evidence for control of the mushroom poisoning.
 Methods: The surveillance data for mushroom poisoning cases from 122 counties in Hunan Province in 2015 were collected. Based on geographical information system database, spatial autocorrelation analysis and spatial regression analysis (via OpenGeoDa) was conducted.
 Results: The incidence of mushroom poisoning in Hunan Province in 2015 was 2.94/100 000. Global Moran's I values was 0.315 (P<0.05). Local spatial autocorrelation analysis indicated that Ningxiang, Xiangtan, Shaoyang, Lingling, Jiahe, and Linwu districts et al were "positive hotspot" regions. Guzhang, Hecheng, Dingcheng, Yueyang districts et al were "negative hotspot" regions. Spatial regression analysis revealed that the reported incidence of mushroom poisoning was positively correlated with the annual average temperate (Z=2.145, P=0.032), the number of health care institutions per capita (Z=2.352, P=0.019), and the number of students enrollment in secondary schools (Z=4.309, P<0.001). It was negatively associated with the number of school staff and workers of secondary schools (Z=-2.626, P=0.009).
 Conclusion: The spatial distribution of mushroom poisoning cases in Hunan Province in 2015 is highly clustered. Mushroom poisoning cases are more prevalent in the middle and southern regions and less prevalent in the northern areas of the province. The annual average temperate and the number of students enrollment in secondary schools demonstrate a certain positive influence on the distribution of mushroom poisoning in Hunan.

Comprehensive analysis on diagnostic value of circulating miRNAs for patients with ovarian cancer.

We performed a meta-analysis to assess the diagnostic accuracy of circulating miRNA for patients with ovarian cancer. We systematically searched several online databases, including PubMed, Web of Science, Chinese National Knowledge Infrastructure, and Wanfang from inception to February 20, 2017. We used the bivariate mixed-effect models to pool positive likelihood ratios, negative likelihood ratios, diagnostic odds ratios and their 95% CI confidence intervals (CIs). We used the Quality Assessment of Diagnostic Accuracy Studies 2 for quality assessment of diagnostic accuracy studies. This meta-analysis included ten studies with the number of 1356 participants. The pooled sensitivity and specificity were 0.75 (95%CI: 0.69-0.80) and 0.75 (95%CI: 0.69-0.81). We also calculated the positive likelihood ratios (3.03, 95%CI: 2.44-3.76), and negative likelihood ratios (0.33, 95%CI: 0.27-0.41). The diagnostic odds ratio was 9.09 (95%CI: 6.51-12.69). The summary receiver operator characteristic was 0.82 (95%CI: 0.78-0.85). Sensitivity analysis showed similar results. No publication bias existed (t=0.380, P=0.712). The diagnostic ability of miRNAs were moderate for ovarian cancer. Further research was required to obtain accurate results.

Prevalence of intimate partner violence (IPV) during pregnancy in China: A systematic review and meta-analysis.

BACKGROUND: Intimate partner violence (IPV) is the most common form of violence against women worldwide. IPV during pregnancy is an important risk factor for adverse health outcomes for women and their offspring. However, the prevalence of IPV during pregnancy is not well understood in China. The objective of this study was to estimate the pooled prevalence of IPV during pregnancy in China using a systematic review and meta-analysis. METHODS: Systematic literature searches were conducted in PubMed, Web of Science, CNKI, Wanfang, Weipu and CBM databases to identify relevant articles published from the inception of each database to January 31, 2016 that reported data on the prevalence of IPV during pregnancy in China. The Risk of Bias Tool for prevalence studies was used to assess the risk of bias in individual studies. Owing to significant between-study heterogeneity, a random-effects model was used to calculate the pooled prevalence and corresponding 95% confidence interval, and then univariate meta-regression analyses were performed to investigate the sources of heterogeneity. Subgroup analysis was conducted to explore the risk factors associated with IPV during pregnancy. RESULTS: Thirteen studies with a total of 30,665 individuals were included in this study. The overall pooled prevalence of IPV during pregnancy was 7.7% (95% CI: 5.6-10.1%) with significant heterogeneity (I2 = 97.8%, p < 0.001). The results of the univariate meta-regression analyses showed that only the variable "sample source" explained part of the heterogeneity in this study (p < 0.05). The characteristics "number of children" and "unplanned pregnancy" were determined as risk factors for experiencing violence during pregnancy. CONCLUSIONS: The prevalence of IPV during pregnancy in China is considerable and one of the highest reported in Asia, which suggests that issues of violence against women during pregnancy should be included in efforts to improve the health of pregnant women and their offspring. In addition, a nationwide epidemiological study is needed to confirm the prevalence estimates and identify more risk factors for IPV during pregnancy.

Prevalence of attention deficit/hyperactivity disorder among children and adolescents in China: a systematic review and meta-analysis.

BACKGROUND: Attention deficit/hyperactivity disorder (ADHD), the most common childhood neurobehavioural disorder, can produce a series of negative effects on children, adolescents, and even adults as well as place a serious economic burden on families and society. However, the prevalence of ADHD is not well understood in China. The goal of this study was to estimate the pooled prevalence of ADHD among children and adolescents in China using a systematic review and meta-analysis. METHODS: A systematic literature search was conducted in PubMed, Web of Science, MEDLINE, CNKI, Wanfang, Weipu and CBM databases, and relevant articles published from inception to March 1, 2016, that provided the prevalence of ADHD among children and adolescents in China were reviewed. The risk of bias in individual studies was assessed using the Risk of Bias Tool for prevalence studies. Pooled-prevalence estimates were calculated with a random-effects model. Sources of heterogeneity were explored using subgroup analyses. RESULTS: Sixty-seven studies with a total of 275,502 individuals were included in this study. The overall pooled-prevalence of ADHD among children and adolescents in China was 6.26% (95% CI: 5.36-7.22%) with significant heterogeneity (I2 = 99.0%, P < 0.001). The subgroup analyses showed that, the variables "geographic location" and "source of information" partially explained of the heterogeneity in this study (P < 0.05). The prevalence of ADHD-I was the highest of the subtypes, followed by ADHD-HI and ADHD-C. CONCLUSIONS: The prevalence of ADHD among children and adolescents in China is generally consistent with the worldwide prevalence and shows that ADHD affects quite a large number of people under 18 years old. However, a nationwide study is needed to provide more accurate estimations.