[Comprehensive assessment of mismatch repair and microsatellite instability status in molecular classification of endometrial carcinoma].

Objective: To explore the concordance and causes of different mismatch repair (MMR) and microsatellite instability (MSI) detection results in endometrial carcinoma (EC) molecular typing. Methods: A total of 214 EC patients diagnosed from January 2021 to April 2023 were selected at the Department of Pathology, Peking University Third Hospital. The immunohistochemistry (IHC) results of MMR protein were reviewed. Tumor specific somatic mutations, MMR germline mutations, microsatellite scores and tumor mutation burden (TMB) were detected by next-generation sequencing (NGS) with multi-gene panel. Methylation-specific PCR was used to detect the methylation status of MLH1 gene promoter in cases with deficient MLH1 protein expression. In cases with discrepant results between MMR-IHC and MSI-NGS, the MSI status was detected again by PCR (MSI-PCR), and the molecular typing was determined by combining the results of TMB and MLH1 gene promoter methylation. Results: (1) In this study, there were 22 cases of POLE gene mutation subtype, 55 cases of mismatch repair deficient (MMR-d) subtype, 29 cases of p53 abnormal subtype, and 108 cases of no specific molecular profile (NSMP). The median age at diagnosis of MMR-d subtype (54 years old) and the proportion of aggressive histological types (40.0%, 22/55) were higher than those of NSMP subtype [50 years old and 12.0% (13/108) respectively; all P<0.05]. (2) Among 214 patients, MMR-IHC test showed that 153 patients were mismatch repair proficient (MMR-p), 49 patients were MMR-d, and 12 patients were difficult to evaluate directly. MSI-NGS showed that 164 patients were microsatellite stable (MSS; equal to MMR-p), 48 patients were high microsatellite instability (MSI-H; equal to MMR-d), and 2 patients had no MSI-NGS results because the effective sequencing depth did not meet the quality control. The overall concordance between MMR-IHC and MSI-NGS was 94.3% (200/212). All the 12 discrepant cases were MMR-d or subclonal loss of MMR protein by IHC, but MSS by NGS. Among them, 10 cases were loss or subclonal loss of MLH1 and (or) PMS2 protein. Three discrepant cases were classified as POLE gene mutation subtype. In the remaining 9 cases, 5 cases and 3 cases were confirmed as MSI-H and low microsatellite instability (MSI-L) respectively by MSI-PCR, 6 cases were detected as MLH1 gene promoter methylation and 7 cases demonstrated high TMB (>10 mutations/Mb). These 9 cases were classified as MMR-d EC. (3) Lynch syndrome was diagnosed in 27.3% (15/55) of all 55 MMR-d EC cases, and the TMB of EC with MSH2 and (or) MSH6 protein loss or associated with Lynch syndrome [(71.0±26.2) and (71.5±20.1) mutations/Mb respectively] were significantly higher than those of EC with MLH1 and (or) PMS2 loss or sporadic MMR-d EC [(38.2±19.1) and (41.9±24.3) mutations/Mb respectively, all P<0.01]. The top 10 most frequently mutated genes in MMR-d EC were PTEN (85.5%, 47/55), ARID1A (80.0%, 44/55), PIK3CA (69.1%, 38/55), KMT2B (60.0%, 33/55), CTCF (45.5%, 25/55), RNF43 (40.0%, 22/55), KRAS (36.4%, 20/55), CREBBP (34.5%, 19/55), LRP1B (32.7%, 18/55) and BRCA2 (32.7%, 18/55). Concurrent PTEN, ARID1A and PIK3CA gene mutations were found in 50.9% (28/55) of MMR-d EC patients. Conclusions: The concordance of MMR-IHC and MSI-NGS in EC is relatively high.The discordance in a few MMR-d EC are mostly found in cases with MLH1 and (or) PMS2 protein loss or MMR protein subclonal staining caused by MLH1 gene promoter hypermethylation. In order to provide accurate molecular typing for EC patients, MLH1 gene methylation, MSI-PCR, MMR gene germline mutation and TMB should be combined to comprehensively evaluate MMR and MSI status.

[Meta-analysis of the effects of statins on the risk of chronic liver disease and hepatocellular carcinoma].

Objective: To evaluate the relationship between the application of statins and the risk of hepatocellular carcinoma in patients with chronic liver disease. Methods: PubMed, the Cochrane Library, EMBASE, Web of science, WeiPu, Wanfang Med online, and China National Knowledge Infrastructure database were searched. The literatures about statins and the risk of hepatocellular carcinoma in patients with chronic liver disease were collected, with a search deadline of February 2020. Two researchers independently conducted literature screening, data extraction, quality evaluation and proofreading. RevMan5.3 software was used for data analysis. The I2 combined with χ (2) test was used to evaluate the heterogeneity. Funnel plots were used to evaluate the publication bias of the included literature. Results: A total of 12 articles were included. Statins application had significantly reduced the risk of hepatocellular carcinoma in patients with chronic liver disease (OR = 0.50, 95% CI: 0.43~0.58, P < 0.01). Subgroup analysis showed that statins had reduced the incidence rate of hepatocellular carcinoma in patients with chronic hepatitis B (OR = 0.56, 95% CI: 0.47~0.66, P < 0.01) and chronic hepatitis C (OR = 0.56, 95% CI: 0.45~0.71, P < 0.01). Lipophilic statins had significantly reduced the risk of chronic liver disease development to hepatocellular carcinoma (OR = 0.48, 95% CI: 0.39~0.59, P < 0.01), but hydrophilic statins did not reduce the incidence rate of chronic liver disease development to hepatocellular carcinoma, and the difference was not statistically significant (OR = 0.64, 95% CI: 0.36~1.14, P = 0.13). Conclusion: Statins can effectively reduce the risk of hepatocellular carcinoma development in patients with chronic liver disease, including chronic hepatitis B and C. Among them, the lipophilic statins have a significant preventive effect on the development of chronic liver disease to hepatocellular carcinoma, but hydrophilic statins have no obvious effect.

[Study on the health literacy and related factors of the cancer prevention consciousness among urban residents in China from 2015 to 2017].

Objective: To understand the health literacy and relevant factors of cancer prevention consciousness in Chinese urban residents from 2015 to 2017. Methods: A cross-sectional survey was conducted in 16 provinces covered by the Cancer Screening Program in Urban China from 2015 to 2017. A total of 32 257 local residents aged ≥18 years old who could understand the investigation procedure were included in the study by using the cluster sampling method and convenient sampling method. All local residents were categorized into four groups, which contained 15 524 community residents, 8 016 cancer risk assessment/screening population, 2 289 cancer patients and 6 428 occupational population, respectively. The self-designed questionnaire was used to collect the information of demographic characteristics and cancer prevention consciousness focusing on nine common risk factors, including smoking, alcohol, fiber food, food in hot temperature or pickled food, chewing betel nut, helicobacter pylori, moldy food, hepatitis B infection, estrogen, and exercise. The logistic regression model was adopted to identify the influencing factors. Results: The overall health literacy of the cancer prevention consciousness was 77.4% (24 980 participants), with 77.4% (12 018 participants), 79.9% (6 406 participants), 77.2% (1 766 participants) and 74.5% (4 709 participants) in each group (P<0.001). The correct response rates for nine risk factors ranged from 55.2% to 93.0%. The multivariate logistic regression analysis showed that compared with community residents, people with primary school level education or below, and the number of people living together in the family <3, the cancer risk assessment/screening intervention population, cancer patients, those with junior high school level educationor above and the number of people living in the family ≥3 had better health literacy of the cancer prevention consciousness (all P values <0.05). Compared with females, 39 years old and below, government-affiliated institutions or civil servants, from the eastern region, males, older than 40 years, company or enterprise employees, and from the middle or western region had worse health literacy of the cancer prevention consciousness (all P values <0.05). Conclusion: The health literacy of the cancer prevention consciousness in Chinese urban residents should be improved. The cancer screening intervention, gender, age, education, occupation, the number of people co-living in the family, and residential region were associated with the health literacy of the cancer prevention consciousness.

[Analysis on the consciousness of the cancer early detection and its influencing factors among urban residents in China from 2015 to 2017].

Objective: To understand the consciousness of the cancer early detection among urban residents and identify the influencing factors from 2015 to 2017. Methods: A cross-sectional survey was conducted in 16 provinces covered by the Cancer Screening Program in Urban China from 2015 to 2017. A total of 32 257 local residents aged ≥18 years old who could understand the investigation procedure were included in the study by using the cluster sampling method and convenient sampling method. All local residents were categorized into four groups, which contained 15 524 community residents, 8 016 cancer risk assessment/screening population, 2 289 cancer patients and 6 428 occupational population, respectively. Self-designed questionnaires were used to collect population, socioeconomic indicators, self-cancer risk assessment, regular participation in physical examination and other information. The multivariate logistic regression model was used to identify the factors of people who had not regularly participated in the regular physical examination in the past five years. Results: The self-assessment results of 32 357 residents showed that there were 27.54% (8 882) of total study population with self-reported cancer risk, 45.48% (14 671) without cancer risk and 26.98% (8 704) with unclear judgement on their own cancer risk. Among population with cancer risk, 79.84% (7 091) considered physical examination accounted. In the past five years, there were 21 105 (65.43%) residents participated in regular physical examination and 11 148 (34.56%) participated in non-scheduled one, respectively. The multivariate logistic regression analysis showed that compared with unmarried and western region residents, divorced, middle and eastern region residents had a stronger consciousness to participate in the regular physical examination (P<0.05). Compare with residents with annual household income less than 20 000 CNY in 2014, cancer risk assessment/screening intervention population, and self-assessment with cancer risk, residents with annual household income between 20 000 CNY and 59 000 CNY in 2014, occupational population, community residents, cancer patients, self-reported cancer-free risk, and self-assessment with unclear judgement of cancer risk were less likely to participate in the regular physical examination (all P values <0.05). Conclusion: From 2015 to 2017, the Chinese urban residents had a acceptable consciousness of the cancer early detection. The marital status, annual household income, population group and self-assessment of cancer risk were related to the consciousness of the cancer early detection of people who had not participated in the regular physical examination in the past five years.

[Analysis on the consciousness of the early cancer diagnosis and its related factors among urban residents in China from 2015 to 2017].

Objective: To understand the consciousness of the cancer early diagnosis among urban residents and identify the related factors from 2015 to 2017. Methods: A cross-sectional survey was conducted in 16 provinces covered by the Cancer Screening Program in Urban China from 2015 to 2017. A total of 32 257 local residents aged ≥18 years old who could understand the investigation procedure were included in the study by using the cluster sampling method and convenient sampling method. All local residents were categorized into four groups, which contained 15 524 community residents, 8 016 cancer risk assessment/screening population, 2 289 cancer patients and 6 428 occupational population, respectively. The general demographic characteristics, the consciousness of the cancer early diagnosis (whether people would have a willingness or encourage their relatives/friends to confirm the abnormal results once which were detected from the physical examination) and other information were collected by using the self-designed questionnaire. The non-conditional logistic regression model was used to identify the relateol factors related to the consciousness of the cancer early diagnosis. Results: As for residents with abnormal result from the physical examination, 89.29% (28 802) of residents would choose to seek medical treatment for further diagnosis. If their relatives/friends had abnormal results from the physical examination, 89.55% (28 886) of residents would encourage their relatives/friends to confirm the diagnosis in time. The non-conditional logistic regression model analysis showed that compared with the public institution staff/civil servants, annual household income less than 20 000 CNY, the western region and the cancer risk assessment/screening intervention population, the company staff, annual household income about 40 000 CNY and more, and the residents from the middle and eastern region had a stronger consciousness to seek further diagnosis; while the unemployed residents and community residents were less likely to seek further diagnosis (P<0.05). Conclusions: From 2015 to 2017, the Chinese urban residents had a good consciousness of the cancer early diagnosis. Occupation, annual household income, residential region and population group were related to the consciousness of the cancer early diagnosis.

[Analysis on the consciousness of the early cancer treatment and its influencing factors among urban residents in China from 2015 to 2017].

Objective: To understand the consciousness of the cancer early treatment and its demographic and socioeconomic factors. Methods: A cross-sectional survey was conducted in 16 provinces covered by the Cancer Screening Program in Urban China (CanSPUC) from 2015 to 2017. A total of 32 257 local residents aged ≥18 years old who could understand the investigation procedure were included in the study by using the cluster sampling method and convenient sampling method. All local residents were categorized into four groups, which contained 15 524 community residents, 8 016 cancer risk assessment/screening population, 2 289 cancer patients and 6 428 occupational population, respectively. The questionnaire collected personal information, the consciousness of the cancer early treatment and relevant factors. The Chi square test was used to compare the difference between the consciousness of the cancer early treatment and relevant factors among the four groups. The logistic regression model was used to analyze the influencing factors related to the consciousness of the cancer early treatment. Results: With the assumption of being diagnosed as precancer or cancer, 89.97% of community residents, 91.84% of cancer risk assessment/screening population, 93.00% of cancer patients and 91.52% of occupational population would accept active treatments (P<0.001). If the immediate family members were diagnosed as precancer or cancer, people who would encourage their family members to receive early treatment in the four groups accounted for 91.96%, 91.94%, 92.44% and 91.55%, respectively (P<0.001). The company employees, annual household income with 40 000 yuan and more and other three groups had a relatively better consciousness of the cancer early treatment (P<0.05). Male, widowed, unemployed and from the central and western regions had a relatively worse consciousness of the cancer early treatment (P<0.05). Conclusion: Residents in urban China participants had a good consciousness of the cancer early treatment. The marital status, occupation, annual household income and residential regions were major factors related to the consciousness of the cancer early treatment.

[Analysis on the health literacy of the cancer prevention and treatment and its related factors among urban residents in China from 2015 to 2017].

Objective: To understand the health literacy of the cancer prevention and treatment among urban residents of China, and explore the related factors. Methods: A cross-sectional survey was conducted in 16 provinces covered by the Cancer Screening Program in Urban China (CanSPUC) from 2015 to 2017. A total of 32 257 local residents aged ≥18 years old who could understand the investigation procedure were included in the study by using the cluster sampling method and convenient sampling method. All local residents were categorized into four groups, which contained 15 524 community residents, 8 016 cancer risk assessment/screening population, 2 289 cancer patients and 6 428 occupational population, respectively. The health literacy of the cancer prevention, early discovery, early diagnosis, early treatment and the demands of cancer prevention and treatment knowledge was analyzed. The level of health literacy among different groups were calculated and compared. The binary logistic regression model was used to analyze the influencing factors of the health literacy of the cancer prevention and treatment. Results: The level of health literacy of the cancer prevention and treatment was 56.97% among all study population; in each group it was 55.01% for community residents, 59.08% for cancer risk assessment/screening population, 61.99% for cancer patients and 57.31% for occupational population, respectively (P<0.001). The level of health literacy of the cancer prevention and treatment of residents aged 50 to 69 years old, other occupational groups, unmarried, the central and western region residents and the group with unclear self-assessment of cancer risk was significantly lower than that of residents younger than 40 years old, personnel of public institutions/civil servants, married, the eastern region residents and the group whose self-assessment without cancer risk (P<0.05) . The level of health literacy of cancer prevention and treatment of females, people who went to high school or over, cancer risk assessment/screening population, cancer patients and occupational population was significantly higher than that of males, people who had an education level of primary school or below and community residents (P<0.05) . Conclusion: The health literacy of the cancer prevention and treatment of urban residents in China was relatively high, but there was still room for improvement. Gender, age, educational level, occupation, region, marital status, self-assessment of cancer risk, and type of respondents were the key influencing factors of the health literacy of the cancer prevention and treatment. Male, 50-69 years old, lower educational level, central and western regions, unclear cancer risk self-assessment, and without specific environmental exposure to cancer prevention and treatment knowledge or related risk factors were the characteristics of the key intervention group of the health literacy of the cancer prevention and treatment.

[Analysis on the demand, access and related factors of cancer prevention and treatment knowledge among urban residents in China from 2015 to 2017].

Objective: To investigate the demand and access to the cancer prevention and treatment knowledge and related factors among urban residents in China from 2015 to 2017. Methods: A cross-sectional survey was conducted in 16 provinces covered by the Cancer Screening Program in Urban China from 2015 to 2017. A total of 32 257 local residents aged ≥18 years old who could understand the investigation procedure were included in the study by using the cluster sampling method and convenient sampling method. All local residents were categorized into four groups, which contained 15 524 community residents, 8 016 cancer risk assessment/screening population, 2 289 cancer patients and 6 428 occupational population, respectively. The self-designed questionnaire was used to collect the information of general demographic characteristics, the demand and access to cancer prevention and treatment knowledge, and the influencing factors of the attitude. The Chi-square test was used to analyze the difference of the demand of the cancer prevention knowledge among different groups and the corresponding factors of the cancer prevention and treatment knowledge were analyzed by using the logistic regression model. Results: The proportion of residents who need the cancer prevention and treatment knowledge was 79.5%. The demand rate of the inducement, symptom and diagnosis methods of cancer in the occupational population was highest, about 66.8%, 71.0% and 20.8%, respectively. The demand rate of treatment methods and cost in current cancer patients was the highest, about the 45.9% and 21.9%, respectively. The top three sources to acquire the cancer prevention and treatment knowledge were "broadcast or television" (69.5%), "books, newspapers, posters or brochures" (44.7%) and "family and friends" (33.8%). The multivariate analysis showed that compared with public institution personnel/civil servants, unmarried/cohabiting/divorced/widowed and others, annual household income less than 20 000 CNY, from the eastern region, people without cancer diagnosis and people with self-assessment of cancer risk, the demand rate of cancer prevention and treatment knowledge was higher in enterprise personnel/workers, married, annual household income between 60 000 CNY and 150 000 CNY, from the central region, people with cancer and people with unclear cancer risk (all P values <0.05). Conclusion: There was a high demand for the cancer prevention and treatment knowledge among urban residents in China from 2015 to 2017. The main access to the knowledge is from the radio or television. The occupation, marital status, annual household income, residential region, health status and risk of disease were the main factors of the demand of the cancer prevention and treatment knowledge.

[Molecular pathological diagnosis of twin pregnancy with complicated genetical characteristics].

Objective: To investigate the molecular pathological diagnostic strategy of twin pregnancy(TP) with complex genetic characteristics, using p57 immunohistochemistry and short tandem repeat (STR) genotyping. Methods: Ten cases of TP with suspected hydatidiform mole(HM) according to pathological morphology were collected in Peking University Third Hospital from 2015 to 2019, and were subject to p57 immunohistochemistry, STR genotyping and follow-up. Results: The age of ten patients ranged 23 to 36 years, with an average of 29.5 years. Seven patients accepted assisted reproductive techniques in this conception. Three patients with "divergent" p57 staining pattern were diagnosed as TP with complete HM by STR, in which one had a persistent trophoblastic disease. The villi of five patients were consistently positive for p57, but the genotyping result was polyploid and suspicious as TP. Four of them showed excessive paternal alleles at more than 40% of the loci, suggesting that concomitant partial moles could not be excluded. One patient was diagnosed as TP without HM according to the maternal allelic predominance at all loci in villi. Two patients with p57 "divergent" and "discordant" staining villi were genotyped as TP with mosaic conception. Conclusions: The correct identification of p57 staining pattern and accurate interpretation of STR genotyping results are important in diagnosing TP. It may assist pathologists in making a definite or likely diagnosis of TP with complex genetic features to fulfill clinical triage strategies and contribute to formulate a reasonable follow-up approach.

[Epidemiological analysis of viral hepatitis E in China, 2004-2017].

Objective: To analyze the changing epidemiological characteristics of hepatitis E cases in China, in order to promote in preventing and controlling hepatitis E. Methods: Data of hepatitis E and outbreaks reported through national notifiable diseases reporting system were analyzed from 2004 to 2017, but data of Hongkong, Macau and Taiwan were not included. Data of hepatitis E were divided into three phases as 2004-2007, 2008-2011 and 2012-2017, representing eight years before, four years before and years after the postmarketing of hepatitis E vaccine. Linear regression was used for analyzing the trend of hepatitis E, improved muster method was used for analyzing the seasonal intensity. Results: From 2004 to 2017, 329 519 hepatitis E cases were reported and the annual incidence were increasing from 1.27/100 000 to 2.10/100 000 (t=6.87, P<0.001). The concentrations of hepatitis E during 2004-2007, 2008-2011 and 2012-2017 were 17.43, 16.06, 11.17, respectively, with low seasonal intensity. Number of cases reported by Jiangsu, Guangdong and Zhejiang accounted for 31.54% of national cases. The incidence were lower in central (1.45/100 000) and western (1.11/100 000) region than that in eastern region (2.67/100 000), but were increasing continuously. There was an increasing trend of incidence with growing ages (t=7.85, P<0.001). The incidence was higher than 2/100 000 among cases aged ≥40, and was the highest (5.22/100 000) in the age group of 65-69 years old. Farmers, retired persons, houseworkers and unemployees accounted for 67.46% of total cases. A total of 7 outbreaks were reported, among which 3 were in nursing homes. Conclusion: The incidence of hepatitis E in central and western regions were increasing continuously and the surveillance should be strengthened. There was higher risk among middle-aged population, farmers and nursing homes, so strategy for immunization among those population was in great need.

Biomarker assessment of the CBCSG006 trial: a randomized phase III trial of cisplatin plus gemcitabine compared with paclitaxel plus gemcitabine as first-line therapy for patients with metastatic triple-negative breast cancer.

Background: CBCSG006 trial reported the superior efficacy of cisplatin plus gemcitabine (GP) regimen than paclitaxel plus gemcitabine (GT) regimen as first-line treatment of metastatic triple-negative breast cancer (mTNBC). This study focused on the updated survival data and the explorations of potential biomarkers for efficacy. Patients and methods: Germ-line mutations of homologous recombination (HR) panel, BRCA1/2 included, were evaluated in 55.9% (132/236) patients. PD-L1 expression was evaluated in 48.3% (114/236) patients. A nonparametric sliding-window subpopulation treatment effect pattern plot (STEPP) methodology was used to analyze the absolute survival benefits. All statistical tests were two-sided. Results: Median progression-free survival (PFS) was 7.73 [95% confidence interval (CI) 6.46-9.00] months for GP arm and 6.07 (95% CI 5.32-6.83) months for GT arm (P = 0.005). No significant difference in overall survival (OS) was observed. There was significant interaction between HR status and treatment for PFS and status of HR deficient significantly correlated with higher objective response rate (ORR) and longer PFS in GP arm than in GT arm (71.9% versus 38.7%, P = 0.008; 10.37 versus 4.30 months, P = 0.011). There was no significant interaction between germ-line BRCA1/2 (gBRCA1/2) status and treatment for PFS. Patients with gBRCA1/2 mutation had numerically higher ORR and prolonged PFS in GP arm than in GT arm (83.3% versus 37.5%, P = 0.086; 8.90 versus 3.20 months, P = 0.459). There was no significant interaction between PD-L1 status and treatment for PFS, and no significant differences in ORR, PFS or OS between two arms regardless of PD-L1 status. In STEPP analysis, patients with lower composite risks had more absolute benefits in PFS than those with higher composite risks. Conclusions: GP regimen has superior efficacy than GT regimen as first-line chemotherapy for mTNBC patients. Germ-line mutations of BRCA1/2 and HR panel are possible biomarkers for better performance of cisplatin-based regimens. A composite risk model was developed to guide patient selection for GP treatment in TNBC patients. Trial registration: ClinicalTrials.gov, NCT01287624.

The epidemiology of hepatitis B virus infection in women of reproductive age in highly endemic areas in China.

We describe the epidemiology of hepatitis B virus (HBV) infection among women of reproductive age residing in areas of China that are highly endemic for chronic HBV, and provide evidence useful for decision-makers to guide strategies for preventing mother-to-child transmission of HBV, and assess the impact of perinatal transmission PMTCT by projecting HBsAg prevalence trends without interventions. We conducted a cross-sectional HBV serological survey of women, 15-49 years of age, residing in Fujian, Guangdong, Guangxi and Hainan provinces. Demographic and other subject-level data were collected in face-to-face interviews, after which we obtain blood specimens. Specimens were tested for HBV sero-markers by ELISA (Beijing Wantai Biological Pharmacy), and HBV DNA was tested with PCR (Hunan Sansure Biotech). Weighted HBsAg and HBV (either HBsAg+ or anti-HBc+ indicating either present or past infection) prevalences were 11.82% and 57.16%, respectively. Among the HBsAg-positive women, 27% were also HBeAg positive. The proportion of individuals with HBV DNA loads >105 IU/mL declined with increasing age. Among HBsAg-negative women, 0.9% had occult HBV infection. The prevalence of chronic HBV infection among reproductive women in these highly endemic provinces is high, posing a threat to maternal health and risk of mother-to-child transmission. Prevention of mother-to-child transmission remains critically important.

[A cross-sectional study of the clinical features and physician visit patterns at onset of immunoglobulin G4 related disease].

OBJECTIVE: To comprehend clinical features and patient's physician visit patterns at onset of immunoglobulin G4 related disease (IgG4RD). METHODS: In the study, 100 patients with IgG4RD who received treatments in the Department of Rheumatology and Immunology of Peking University People's Hospital from Apr. 1st, 2017 to Apr. 1st, 2018 were investigated, including gender, age, height, body weight, age of onset, physician visit history, primary history and how did the disease affected their life, etc. RESULTS: In this 100 IgG4RD cohort (57 males and 43 females), the male/female ratio was 1:0.75, the mean age of onset was (51.51±12.9) years, and the median duration was 49 months (ranging from 4 to 231 months). The onset age of males was significantly older than that of females (P<0.01). The manifestations showed that up to 69% patients had submaxillay glands lesion, 59% patients had lacrimal glands lesion, 28% patients had pancreas involvement and 28% patients had parotid glands involvement. The females had more lacrimal glands involvement (P<0.05). 62% patients were complicated with anaphylactic disease. The primary physician visit departments concentrated upon general surgery department (19/100), oral and maxillofacial surgery department (17/100), rheumatology and immunology department (16/100), ophthalmology department (15/100) and gastroenterology department (10/100). The departments where the confirmed diagnose was made concentrated upon rheumatology department (67/100),oral and maxillofacial surgery department (16/100) and gastroenterology department (7/100). The mean diagnosis duration after 2010 was (16.96±2.163) months, significantly shorter than that before 2010, which was (113.3±11.01) months. Before the definite diagnose was made, 43% patients underwent surgeries and 12% patients had more than one time surgeries. The patients whose first-visit department was a surgery department were more likely to undergo surgeries (P<0.01). 18% patients (18/100) stated that the disease had affected their work. CONCLUSION: In this cohort of the IgG4RD patients, female is common and has earlier onset age than male. The major manifestations of IgG4RD are salivary glands, lacrimal glands and pancreas involvement. The common chief complains are salivary glands and lacrimal glands enlargement. Accompanied by anaphylactic disease is a marked manifestation of this disease. Delayed diagnoses are not rare, though this situation has been improved since 2010, and more attention still should be paid to the disease.

[A typical investigation on the status of diagnosis and reporting of hepatitis B inpatients in non-surveillance hospitals in three provinces in China, 2015].

Objective: To review the consistency of diagnosis and reporting of hepatitis B (HB) patient in non-surveillance hospitals in three provinces and analyze the influencing factors. Methods: In 2016, using typical survey methods, we carried out a hospital-based pilot study in three provinces: Fujian, Hainan and Gansu. In each province, we chose two hospitals with grade 3 and grade 2 respectively in each province, using the following criteria: (1) in 2015, the hospital reported a greater number of hepatitis B cases compared the hospital-based provincial mean; (2) the hospital had an advanced laboratory information system (LIS) with access to HBsAg test results; (3) the hospital had an electronic hospital information system (HIS) which linked to the LIS via the inpatient medical record number; (4) general hospital; (5) non-surveillance hospitals for hepatitis B. Using national notifiable infectious disease reporting system (NNDRS), we chose all HB patients who were reported by the investigated hospitals in 2015, and we linked NNDRS HBV case-reports with patient-data from hospital information systems (HIS) to review the diagnosis, and then to compare the consistency of reviewed diagnosis and NNDRS report diagnosis, which we made a descriptive analysis. We used multivariable logistic regression to examine factors associated with misclassification of case-reports to NNDRS. Results: We found the NNDRS report accuracy was 47.11% (669) among 1 420 eligible inpatient hepatitis B inpatients. Of the 352 reported acute HBV cases, 6.53% (23) were consistent with our medical record review, the accuracy rate for level 2 hospitals and level 3 hospitals was 9.42% (21) and 1.55% (2), respectively. Of the1 068 reported chronic HBV cases, 60.49% (646) were consistent with our medical record review, the accuracy rate for level 2 hospitals and level 3 hospitals was 57.92% (106) and 60.02% (540), respectively. Compared to primary diagnosis of HB patients, the OR(95%CI) for mis-report was 29.36 (19.21-44.76) in non-primary diagnosis of HB patients. Compared to Fujian Province, the mis-report risk was higher in Hainan province and Gansu Province, with the values of OR (95%CI) being 2.33 (1.58-3.44) and 20.38 (11.29-36.78), respectively; compared to level 3 hospitals, the OR (95%CI) for mis-report was 2.38 (1.66-3.42) for level 2 hospitals; compared to HB related wards, the OR (95%CI) for mis-report was 1.45 (1.04-2.01) in non-HB-related wards. Conclusion: In some non-surveillance areas of China, the consistency between hepatitis B diagnosed in hospital and reported in NNDRS was low. Factors affecting the accuracy of HB surveillance data in NNDRS were level 2 hospitals, non-liver disease departments and nonprimary diagnosis of HB.

A retrospective analysis of ovarian stimulation with letrozole in women undergoing artificial insemination by donor.

The aim of this retrospective study was to determine the clinical pregnancy rate in women undergoing letrozole ovarian stimulation and artificial insemination by donor (AID). Between 2012 and 2015, 130 natural cycles, 939 letrozole cycles and 130 letrozole plus gonadotrophin cycles were conducted. Letrozole cycles were divided into three groups according to LH concentration on the day of HCG administration (LH <10 mIU/ml and follicle size ≥18 cm; LH ≤10 to <20 mIU/ml; and LH ≥20 mIU/ml). Pregnancy rates were 17.3%, 22.4% and 26.8%, respectively (P = 0.012). In women given 10 mIU/ml LH or more, logistic regression identified oestradiol (OR 1.002, 95% CI, 1.000 to 1.004, P = 0.029) and leading follicle size (OR 0.861, 95% CI, 0.772 to 0.960, P = 0.007) as significant predictive factors of pregnancy rate; the higher the oestradiol and the smaller the follicles, the better the pregnancy rate. The pregnancy rate was significantly higher in the letrozole plus gonadotrophin group than the letrozole group (P = 0.04). Better pregnancy rates can be achieved if LH surge occurs before HCG administration, especially with higher oestradiol and lower follicle size; treatment with letrozole plus gonadotrophin was significantly more effective than letrozole alone in AID.

Oridonin Induces Apoptosis in Human Nasopharyngeal Carcinoma Cells Involving ROS Generation.

Oridonin, an ent-kaurene diterpenoid isolated from the traditional Chinese herb Rabdosia rubescens, has been reported to be a potent cytotoxic agent against a wide array of cancer cells. However, its effect on human nasopharyngeal carcinoma (NPC) cells has not been well investigated. The present study aimed to explore the anti-tumour effect of oridonin in NPC cells and its underlying mechanisms. Cell viability was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay and colony formation assay. Apoptosis, mitochondrial membrane potential (MMP), reactive oxygen species (ROS), and expression of apoptosis-related proteins were analysed by flow cytometry with propidium iodide staining, JC-1 staining, DCFH-DA staining, and Western blot analysis, respectively. The results showed that oridonin concentration-dependently inhibited the cell viability, decreased the colony formation, and enhanced the apoptotic rate in NPC cells. Further, oridonin-induced apoptosis was mediated by the mitochondrial pathway in NPC cells, which was confirmed by the loss of MMP, downregulation of anti-apoptotic Bcl-2 family protein Mcl-1 and Bcl-2, upregulation of pro-apoptotic Bcl-2 family member Bax, and activation of caspase-3 and PARP. Notably, the augmented ROS generation played an essential role in oridonin-induced apoptosis in NPC cells, as the apoptosis-inducing effect was attenuated by ROS scavenger N-acetyl-L-cysteine. These results indicate that oridonin triggers apoptosis through the ROSmediated mitochondrial pathway in NPC cells. This study supports oridonin to be an interesting candidate drug for the treatment of human NPC.

Association between the interleukin-1ß C-511T polymorphism and periodontitis: a meta-analysis in the Chinese population.

The association between the interleukin-1 beta (IL-1ß) C-511T (or rs16944) polymorphism and periodontitis remains inconclusive, even though there have been previous studies on this association. To assess the effects of IL-1ß C-511T variants on the risk of development of periodontitis, a meta-analysis was performed in a single ethnic population. Studies, published up to December 2015, were selected for the meta-analysis from PubMed and Chinese databases. The associations were assessed with pooled OR and 95%CI. This meta-analysis identified 8 studies, including 1276 periodontitis cases and 1558 controls. Overall, a significant association between the IL-1ß C-511T polymorphism and periodontitis was found in the Chinese population (TT vs CC: OR = 1.48, 95%CI = 1.19-1.85; TT + CT vs CC: OR = 1.50, 95%CI = 1.25-1.81; T vs C: OR = 1.33, 95%CI = 1.06-1.68). In the subgroup analyses based on geographical area(s), source of controls, and type of periodontitis, significant results were obtained for the association between IL-1ß C-511T variants and periodontitis. Our meta-analysis indicated that the IL-1ß C-511T polymorphism may be a genetic susceptibility factor for periodontitis in the Chinese population. This marker could be used to identify Chinese individuals at a high risk for periodontitis.

[The epidemiological characteristics of HBV susceptibility in 1-29 years old young people in China in 2006 and 2014: based on the national sero-survey data analysis].

Objective: To analyze the epidemiological characteristics of HBV susceptible people in 1-29 years old people in 2006 and 2014 in China. Method: Data is from the 2006 and 2014 national sero-survey, and both of them were conducted in 160 disease surveillance points of 31 provinces (excluding Hong Kong, Macao Special Administrative Region and Taiwan province) in China. We used the centralized face-to face investigation method to collect basic information including birth date, gender, ethnicity, resident place, hepatitis B vaccination (HepB) history and so on, and 5 ml venous blood was collected for all subjects to test the sero-markers of HBsAg, anti-HBs and anti-HBc. We definite the HBV susceptible people as the HBsAg, anti-HBs and anti-HBc all negative together. And we use chi-square to analyze the epidemiological characteristics of HBV susceptibility in 1-29 years old young people in 2006 and 2014, and use multiple factors logistic regression to analyze the affect factors on HBV susceptible appearing in people with HepB vaccination. Result: In 2006 and 2014 sero-surveys, the investigated 1-29 year-old people were 49 849 and 31 713, respectively. And compared with 2006, the proportion of HBV susceptible people with HepB among 1-29 in 2014 increased from 20.87% (10 401) to 28.55% (9 055) (χ(2)=630.69, P<0.001); and the proportion of susceptible people without HepB decreasing from 15.02% (7 485) to 7.66% (2 460) (χ(2)=953.73, P<0.001). Compared with Han nationality, the high risk of susceptible appearing in minority people after HepB vaccination (OR=1.38). And compared with less than 3 doses HepB vaccination, the more than 3 doses vaccination could reduce the anti-HBs disappearing rate (OR=0.68); Compared with one year after last dose vaccination, the 2-4 years interval (OR=3.33) and more than 5 years interval (OR=6.53) would have high risk for anti-HBs disappearing. All above were P<0.001. In western area, the proportion of susceptible people without HepB (9.58%, 1 047/2 460) was higher than the proportion in eastern (6.30%, 657/2 460) and middle area (7.30%, 756/2 460) (P<0.001). Conclusion: The HepB coverage maintained in high level in 1-4 years old children. The HBV susceptible proportion mainly concentrated in 15-29 years old people, and the immunization gap was in western, rural areas and minority peoples.

[Analysis on sero-epidemiological characteristics of hepatitis B virus among people born during 1994-2001 before and after hepatitis B vaccine catch-up vaccination, China].

Objective: To analyze the sero-epidemiological characteristics of hepatitis B virus among people born during 1994-2001, conducted by the national hepatitis B sero-epidemiological surveys in 2006 and 2014. Methods: Based on the data of the two national hepatitis B sero-epidemiological surveys in 2006 and 2014, people born during 1994-2001 were included into our analysis as this study subjects. The two surveys were conducted in 160 disease surveillance points of 31 provinces (not including Hong Kong, Macao and Taiwan) in China. Face-to-face interviews with the subject by door to door or on the investigation site were conducted by trained staff using standard questionnaires to obtain basic information including birth date, sex, ethnicity, resident place and so on. And then 5 ml venous blood was collected. Enzyme-linked immunosorbent assay (ELISA) reagents were used for HBsAg, anti-HBs and anti-HBc measurements and Abbott micro-particle enzyme immunoassay (MEIA) reagents was used to confirm test. We analyzed HBsAg, anti-HBs and anti-HBc positive rate by gender, ethnicity, urban/rural, eastern/central/western region, birth years and compared the distribution of serum epidemiological characteristics in 2006 and 2014. Results: 19 821 and 4 712 people born during 1994-2001 were involved in 2006 and 2014 national serosurveys of China, respectively. For the people born during 1994-2001, HBsAg positive rate were 2.02% (95% CI: 1.82%-2.21%) in 2014 and 1.95% (95% CI: 1.56%-2.35%) in 2006. Anti-HBc positive rate were 7.94% (95%CI: 7.17%-8.71%) in 2014 and higher than that in 2006 (6.49%, 95%CI: 6.15%-6.83%), especially for the female (8.31%, 95% CI: 7.20%-9.43%), urban (7.45%, 95% CI: 6.38%-8.52%), western region (11.25%, 95%CI: 9.79%-12.71%), minority people (16.02%, 95%CI: 13.47%-18.57%) in 2014 were higher than that of the female (6.29%, 95% CI: 5.81%-6.78%), urban (4.82%, 95% CI: 4.40%-5.24%), western region (7.97%, 95% CI: 7.31%-8.63%), minority people (11.88%, 95% CI: 10.66%-13.00%) in 2006 respectively. Anti-HBs positive rate were 57.80% (95%CI: 57.11%-58.48%) in 2014 and 59.13% (95%CI: 57.72%-60.53%) in 2006. Anti-HBs positive rate of rural (58.80%, 95% CI: 56.83%-60.78%),western region (58.50%, 95% CI: 56.23%-60.78%), minority people (57.20%, 95% CI: 53.76%-60.63%) in 2014 was higher than of rural (52.62%, 95% CI: 51.64%-53.61%),western region (51.73%, 95% CI: 50.54%-52.96%),minority people (41.14%, 95%CI: 39.28%-43.00%) in 2006. Conclusion: Anti-HBc positive rate among people born during 1994-2001 in 2014 survey showed a rising tendency than in 2006. The risk of HBV infection was existed. Hepatitis B vaccine catch-up in childhood was necessary.