Objective: To investigate the association between the distribution of tumor infiltrating lymphocytes (TIL) in EBV associated lymphoepitheliomatoid carcinoma (LELC) and the pathological subtypes of LELC, as well as the clinical significance of TIL distribution. Methods: The LELC patients with sufficient tumor tissues, complete clinical data and positive EBER, who visited Zhejiang Cancer Hospital, Hangzhou, China from January 2006 to October 2018, were selected. Various immunohistochemical markers (CD20, CD138, CD4, CD8, CD56 and FOXP3) were examined for TIL typing. Two pathologists reviewed the hematoxylin and eosin (HE) staining sections and interpreted the immunohistochemical results. Correlation analysis was used to evaluate the relationship between the distribution of TIL subgroups and LELC's pathological characteristics. Survival analyses were conducted to study the prognostic values of TIL subgrouping. Results: A total of 102 patients with EBV related LELC were included. 46 of them were classic LELC (c-LELC) with rich interstitial TIL, and 56 were non-classic LELC (n-LELC) with relatively fewer interstitial TIL. The results of TIL analysis showed that all subtypes of c-LELC were rich in TIL, with B lymphocytes as the dominant subgroup. The number of TIL in n-LELC was fewer than that in c-LELC, with T lymphocytes as the dominant subgroup. There was no significant difference in the distribution of plasma cells between the two groups. Survival analysis showed that the total number of TIL, and the infiltrations of CD20⁺B cells, CD4⁺T cells, and FOXP3⁺Treg cells were associated with better overall survivals (P=0.004, 0.003, 0.008 and 0.025, respectively) and disease-free survivals (P=0.011, 0.003, 0.038 and 0.041, respectively) in patients with LELC. Conclusions: The morphologic subtypes of EBV-related LELC have different tumor immune characteristics. The total number of TIL in the stroma of c-LELC is significantly higher than that of n-LELC. Interestingly, B lymphocytes are the dominant TIL in c-LELC, while T lymphocytes are the dominant TIL in n-LELC. The infiltration of TIL, CD20⁺B cells, CD4⁺T cells and FOXP3⁺Treg cells in LELC may suggest a better prognosis.
Humans ; Lymphocytes, Tumor-Infiltrating ; Herpesvirus 4, Human ; Clinical Relevance ; Prognosis ; Carcinoma, Squamous Cell/pathology* ; Forkhead Transcription Factors

Objective: To investigate the clinicopathological characteristics, immunohistochemical profiles, molecular features, and prognosis of subungual melanoma in situ (SMIS). Methods: Thirty cases of SMIS were collected in Fudan University Shanghai Cancer Center, Shanghai, China from 2018 to 2022. The clinicopathological characteristics and follow-up data were retrospectively analyzed. Histopathologic evaluation and immunohistochemical studies were carried out. By using Vysis melanoma fluorescence in situ hybridization (FISH) probe kit, combined with 9p21(CDKN2A) and 8q24(MYC) assays were performed. Results: There were 8 males and 22 females. The patients' ages ranged from 22 to 65 years (median 48 years). All patients presented with longitudinal melanonychia involving a single digit. Thumb was the most commonly affected digit (16/30, 53.3%). 56.7% (17/30) of the cases presented with Hutchinson's sign. Microscopically, melanocytes proliferated along the dermo-epithelial junction. Hyperchromatism and nuclear pleomorphism were two of the most common histological features. The melanocyte count ranged from 30 to 185. Most cases showed small to medium nuclear enlargement (29/30, 96.7%). Pagetoid spread was seen in all cases. Intra-epithelial mitoses were identified in 56.7% (17/30) of the cases. Involvement of nailfold was found in 19 cases, 4 of which were accompanied by cutaneous adnexal extension. The positive rates of SOX10, PNL2, Melan A, HMB45, S-100, and PRAME were 100.0%, 100.0%, 96.0%, 95.0%, 76.9%, and 83.3%, respectively. FISH analysis was positive in 6/9 of the cases. Follow-up data were available in 28 patients, and all of them were alive without disease. Conclusions: SMIS mainly shows small to medium-sized cells. High melanocyte count, hyperchromatism, nuclear pleomorphism, Pagetoid spreading, intra-epithelial mitosis, nailfold involvement, and cutaneous adnexal extension are important diagnostic hallmarks. Immunohistochemistry including SOX10 and PRAME, combined with FISH analysis, is valuable for the diagnosis of SMIS.
Male ; Female ; Humans ; Young Adult ; Adult ; Middle Aged ; Aged ; Skin Neoplasms/pathology* ; Prognosis ; Retrospective Studies ; In Situ Hybridization, Fluorescence ; China ; Melanoma/diagnosis* ; Nail Diseases/pathology* ; Antigens, Neoplasm

Objective: To identify BRAF V600E mutations in adult Wilms tumor (WT) with overlapping histologic features of metanephric adenoma (MA) and to investigate the clinicopathological features of adult WT. Methods: The clinical features of adult WT diagnosed at the Fudan University Shanghai Cancer Center, Shanghai, China from 2012 to 2021 were reviewed. HE-stained slides of all cases were reviewed by 2 expert pathologists. Representative tissues were selected for BRAF V600E immunohistochemical (IHC) staining and gene sequencing. Results: In adult WT with MA-like areas (cohort Ⅰ, n=6), 5 of the 6 cases were composed of epithelial-predominant and were positive for WT-1 and CD56, respectively, and all were positive for CD57. All 6 cases revealed highly variable Ki-67 indices, ranging from 1% in some areas to 60% in others. 5 of the 6 cases harbored a BRAF V600E mutation. All cases in cohort I were followed up for 23 to 71 months, and all survived. In classical adult WT without MA-like areas cohort (cohort Ⅱ, n=13), all 7 cases with available material were negative for BRAF by IHC and none of them had any BRAF mutation. Conclusions: BRAF V600E mutations are frequently present in adult WT with overlapping morphologically features of MA, but not in those without. More importantly, adult WTs with overlapping histologic features of MA may be an intermediate entity between typical MA and WT that may have a favorable prognosis and possible therapeutic targets.
Adult ; Humans ; Proto-Oncogene Proteins B-raf/genetics* ; China ; Wilms Tumor/genetics* ; Kidney Neoplasms/pathology* ; Mutation ; Adenoma/genetics* ; Biomarkers, Tumor/genetics*

Precision medicine became the key strategy in development priority of science and technology in China. The large population-based cohorts become valuable resources in preventing and treating major diseases in the population, which can contribute scientific evidence for personalized treatment and precise prevention. The fundamental question of the achievements above, therefore, is how to construct a large population-based cohort in a standardized way. The Chinese Preventive Medicine Association co-ordinated experienced researchers from Peking University and other well-known institutes to write up two group standards Technical specification of data processing for large population-based cohort study (T/CPMA 001-2018) and Technical specification of data security for large population-based cohort study (T/CPMA 002-2018), on data management. The standards are drafted with principles of emphasizing their scientific, normative, feasible, and generalizable nature. In these two standards, the key principles are proposed, and technical specifications are recommended in data standardization, cleansing, quality control, data integration, data privacy protection, and database security and stability management in large cohort studies. The standards aim to guide the large population-based cohorts that have been or intended to be established in China, including national cohorts, regional population cohorts, and special population cohorts, hence, to improve domestic scientific research level and the international influence, and to support decision-making and practice of disease prevention and control.
China ; Cohort Studies ; Delivery of Health Care ; Humans ; Population Surveillance ; Quality Control ; Reference Standards

Objective: To describe the genetic structure of populations in different areas of China, and explore the effects of different strategies to control the confounding factors of the genetic structure in cohort studies. Methods: By using the genome-wide association study (GWAS) on data of 4 500 samples from 10 areas of the China Kadoorie Biobank (CKB), we performed principal components analysis to extract the first and second principal components of the samples for the component two-dimensional diagram generation, and then compared them with the source of sample area to analyze the characteristics of genetic structure of the samples from different areas of China. Based on the CKB cohort data, a simulation data set with cluster sample characteristics such as genetic structure differences and extensive kinship was generated; and the effects of different analysis strategies including traditional analysis scheme and mixed linear model on the inflation factor (λ) were evaluated. Results: There were significant genetic structure differences in different areas of China. Distribution of the principal components of the population genetic structure was basically consistent with the geographical distribution of the project area. The first principal component corresponds to the latitude of different areas, and the second principal component corresponds to the longitude of different areas. The generated simulation data showed high false positive rate (λ=1.16), even if the principal components of the genetic structure was adjusted or the area specific subgroup analysis was performed, λ could not be effectively controlled (λ>1.05); while, by using a mixed linear model adjusting for the kinship matrix, λ was effectively controlled regardless of whether the genetic structure principal component was further adjusted (λ=0.99). Conclusions: There were large differences in genetic structure among populations in different areas of China. In molecular epidemiology studies, bias caused by population genetic structure needs to be carefully treated. For large cohort data with complex genetic structure and extensive kinship, it is necessary to use a mixed linear model for association analysis.
China ; Genetic Structures ; Genome-Wide Association Study ; Humans ; Linear Models ; Principal Component Analysis

Objective: To evaluate the association of educational level with anthropometric measurements at different adult stages and their long-term changes in adults who participated in the second re-survey of China Kadoorie Biobank (CKB). Methods: The present study excluded participants who were aged >65 years, with incomplete or extreme measurement values, or with major chronic diseases at baseline survey or re-survey. The weight at age 25 years was self-reported. Body height, body weight and waist circumference at baseline survey (2004-2008) and re-survey (2013-2014) were analyzed. Results: The present study included 3 427 men and 6 320 women. Both body weight and waist circumference (WC) increased with age. From age 25 years to baseline survey (mean age 45.2±6.5), the mean weight change per 5-year was (1.70±2.63) kg for men and (1.27±2.10) kg for women. From baseline survey to re-survey (53.2±6.5), the mean changes per 5-year for body weight were (1.12±2.61) kg for men and (0.90±2.54) kg for women; and that for WC was (3.20±3.79) cm for men and (3.83±3.85) cm for women. Among women, low educational level was consistently associated with higher body mass index (BMI) and WC at age 25 years, baseline survey and re-survey. Among men, low educational level was associated with higher BMI at age 25 years. At baseline survey and re-survey, the educational level in men was not statistically associated with BMI; but men who completed junior or senior high school showed slight higher WC and increase of WC from baseline survey to re-survey than other male participants. Conclusions: Body weight and WC increased with age for both men and women. The associations of educational level with BMI and WC were different between men and women.
Adult ; Asian People/statistics & numerical data* ; Body Height ; Body Mass Index ; Body Weight ; China/epidemiology* ; Educational Status ; Female ; Humans ; Male ; Middle Aged ; Obesity/ethnology* ; Risk Factors ; Sex Distribution ; Waist Circumference/ethnology*

Objective: To examine the prevalence of 'healthy lifestyle' from data extracted from the China Kadoorie Biobank (CKB) of 0.5 million adults from ten areas across China. Methods: After excluding participants with self-reported histories of coronary heart disease, stroke or cancer, a total of 487 198 participants at baseline (2004-2008) and 22 604 participants at second survey (2013- 2014), were included for analysis. 'Healthy lifestyle' was defined as haing the following characteristics: a) never smoking or having stopped smoking for reasons other than illness; b) alcohol drinking <25 g/day (men)/<15 g/day (women); c) diet rich in vegetables, fruits, legumes and fish, but low in red meat; d) upper quarter of the physical activity level; e) body mass index of 18.5-23.9 kg/m(2) and waist circumstance <85 cm (men)/80 cm (women). We calculated the healthy lifestyle scores (HLS) by counting the number of all the healthy lifestyle factors, with a range from 0 to 6. Results: At baseline, prevalence rates of the above five healthy lifestyles (except physical activity) were 70.6%, 92.6%, 8.7%, 52.6% and 59.0%, respectively, with the mean HLS being 3.1±1.2. Most participants (81.4%) had2-4 healthy components, while only 0.7% (0.2% in men and 1.0% in women) of all the participants had all six healthy lifestyles. Participants who were women, at younger age, with more schooling and rural residents, were more likely to adhere to the healthy lifestyle. After ten years, the mean HLS showed a slight decrease. Conclusion: The prevalence of optimal lifestyles in Chinese adults appeared extremely low. Levels of 'healthy lifestyle' varied greatly among those populations with different socio-demographic characteristics across the ten areas in China.
Adult ; Asian People/statistics & numerical data* ; China ; Female ; Healthy Lifestyle ; Humans ; Life Style ; Male ; Prevalence ; Risk Factors

Objective: To analyze the pathogenic surveillance programs and related factors on bacillary dysentery in Beijing, 2008-2017, to provide evidence for the practices of diagnosis, treatment and prevention of the disease. Methods: Analysis was conducted on surveillance data of bacillary dysentery, collected from the surveillance areas of national bacillary dysentery in Beijing. Shigella positive rate of stool samples were used as the gold standard while detection rate of Shigella, diagnostic accordance rate and resistance were computed on data from the surveillance programs. Chi-square test was used to compare the rates and unconditional logistic regression was used to analyze the related factors of Shigella infection. Results: Both the reported incidence rate on bacillary dysentery and detection rate of Shigella in diarrhea patients showed significantly decreasing trend, from 2008 to 2017. The accordance rate of bacillary dysentery was only 7.80% (111/1 423). Shigella sonnei was the most frequently isolated strain (73.95%, 159/215) followed by Shigella flexnery. Results from the multivariate logistic regression of Shigella positive rate revealed that among those patients who were routine test of stool positive vs. routine test of stool positive (OR=1.863, 95%CI: 1.402-2.475), onset from July to October vs. other months'time (OR=7.271, 95%CI: 4.514-11.709) temperature ≥38 ℃vs. temperature <38 ℃(OR=4.516, 95%CI: 3.369-6.053) and age from 6 to 59 years old vs. other ages (OR=1.617, 95%CI: 1.085-2.410), presenting higher positive detection rates of Shigella from the stool tests. The resistant rates on ampicillin and nalidixic acid were 97.57% (201/206) and 94.90% (186/196), both higher than on other antibiotics. The resistant rates on ciprofloxacin (16.33%, 32/196), ofloxacin (9.57%, 11/115) and on amoxilin (15.05%, 31/206) were relatively low. The resistant rate appeared higher on Shigella flexnery than on Shigella sonnei. The proportion of strains with resistance on 3 more drugs, was 30.00%(21/70). Conclusions: The diagnostic accordance rate of bacillary dysentery in Beijing was low, with severe resistance of Shigella. Our findings suggested that clinicians should take multiple factors into account in their practices about epidemiological history, clinical symptom and testing results for diarrhea patients.
Adolescent ; Adult ; Anti-Bacterial Agents/therapeutic use* ; Beijing/epidemiology* ; Child ; China/epidemiology* ; Dysentery, Bacillary/prevention & control* ; Feces/microbiology* ; Humans ; Middle Aged ; Population Surveillance/methods* ; Sentinel Surveillance ; Shigella/isolation & purification* ; Shigella flexneri/isolation & purification* ; Shigella sonnei/isolation & purification* ; Young Adult

In clinical follow-up studies, hazard ratio (HR) is routinely used to quantify the differences between-groups, however, it is being estimated by the Cox procedure. HR, the ratio of two hazard functions has abstract meaning only and is in lack of the context to give an intuitive explanation of the survival of patients and the assumption of proportional hazards (PH) must be satisfied. Under this context, the restricted mean survival time (RMST) can be used as a relatively effective measure or index of statistics. This paper introduces the RMST-based statistical analysis methods, including estimation of RMST and its difference, hypothesis testing and regression analysis. The application of RMST in data analysis is also introduced. All the evidence demonstrates that RMST can be used as an effective analytical tool with straightforward interpretation. RMST is also more effective than HR in comparing differences between groups, when non-PH is observed. Therefore, RMST is suggested to be stated along with HR in the process of disease efficacy evaluation and prognosis analysis. Cooperation and complement of the two, a precise reflection on the characteristics of data can be expected.
Clinical Trials as Topic ; Endpoint Determination/methods* ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Prognosis ; Proportional Hazards Models ; Regression Analysis ; Survival Rate/trends* ; Treatment Outcome

OBJECTIVE: To explore the relationship between physiological parameters changes and severe heatstroke induced by 5-km armed cross-country training. METHODS: A total of 521 male officers and soldiers from a special team who participated in the summer training of 5-km armed cross-country training from year 2016 to 2017 were enrolled. All trainees participated in 5-km armed cross-country training in high temperature and humidity environment of ambient temperature > 32 centigradeand (or) relative humidity > 65%. The trainees were divided into two groups according to the incidence of severe heatstroke in the course of training. The age, enlistment time, constitution score, body mass index (BMI), external environment (ambient temperature, relative humidity, wind speed, heat index) of trainees of the two groups, and the change rates of arterial blood oxygen saturation (SaO₂), body temperature, pulse and blood pressure within 5 minutes after the 5-km armed cross-country training were compared between the two groups. The risk factors of severe heatstroke were screened by two classified Logistic regression analysis, and the predictive value of various risk factors of severe heatstroke was analyzed by the receiver operator characteristic curve (ROC). RESULTS: In 521 trainees of 5-km armed cross-country training, 29 trainees suffered from severe heatstroke accounting for 5.57%. There was no significant difference in the age, enlistment time, constitution score, BMI, or external environment during 5-km armed cross-country training between severe heatstroke group and non-severe heatstroke group. Compared with those without severe heatstroke, the descending rates of body temperature, pulse, blood pressure and SaO₂ increased rate within 5 minutes after 5-km armed cross-country training of severe heatstroke trainees were significantly decreased [temperature descending rate: (0.67±0.30)% vs. (1.43±1.28)%, pulse descending rate: (7.53±5.21)% vs. (13.48±8.07)%, blood pressure descending rate: (9.28±6.84)% vs. (19.42±7.73)%, SaO₂ increased rate: (0.51±0.39)% vs. (1.50±1.43)%, all P < 0.01]. Two classification Logistic regression analysis showed that the temperature descending rate [odds ratio (OR) = 0.485, 95% confidence interval (95%CI) = 0.289-0.817], pulse descending rate (OR = 0.903, 95%CI = 0.845-0.965), blood pressure descending rate (OR = 0.841, 95%CI = 0.790-0.896), and SaO2 increased rate (OR = 0.421, 95%CI = 0.250-0.711) were the risk factors for severe heatstroke during 5-km armed cross-country training (all P < 0.01). ROC curve analysis showed that temperature descending rate [area under ROC curve (AUC) = 0.659, 95%CI = 0.604-0.714], pulse descending rate (AUC = 0.730, 95%CI = 0.762-0.900), blood pressure descending rate (AUC = 0.831, 95%CI = 0.659-0.801), SaO₂ increased rate (AUC = 0.711, 95%CI = 0.655-0.767) could be used for the incidence of severe heatstroke prediction during 5-km armed cross-country training (all P < 0.01), and the predicted value was the same. CONCLUSIONS Under the same conditions, the severe heatstroke during 5-km cross-country training is closely related to the descending rates of body temperature, pulse, and blood pressure as well as SaO₂ increased rate within 5 minutes after the training, whose predictive values for severe heatstroke were the same.
Blood Pressure ; Heart Rate ; Heat Stroke ; Hot Temperature ; Humans ; Male ; Risk Factors