[Circ_0000263 improves radiosensitivity of Hela cells by inhibiting the activity of telomerase protein through miR-338-3p/TERT].

Objective: To explore the effect and molecular mechanism of circ_0000263 on HeLa cell activity, apoptosis, telomerase activity, and radiosensitivity. Methods: The Hela cells were divided into si-NC, si-circ, vector, circ_0000263, anti-NC, anti-miR-338-3p, miR-NC, miR-338-3p, si-circ+anti-NC, si-circ+ anti-miR-338-3p, si-circ+vector, si-circ+TERT, sh-NC, sh-circ groups. Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect the expressions of circ_0000263 and miR-338-3p. Cell clone formation array was used to detect cell survival; cell counting kit-8 (CCK-8) to detect cell proliferation; flow cytometry to detect apoptosis; western blot method to detect the expressions of proliferating cell nuclear antigen (PCNA), Cleaved-casp3, telomerase reverse transcriptase (TERT) proteins; double luciferase assay to detect the targeting relationships of circ_0000263 and miR-338-3p, miR-338-3p and TERT; telomere repeat amplification enzyme linked immunosorbent assay (TRAR-ELISA) to detect telomerase activity. Results: Circ_0000263 was highly expressed in Hela cells, miR-338-3p was low expressed, and TERT was highly expressed; circ_0000263 was also highly expressed in Hela cells treated with radiation (P＜0.05). Knockdown of circ_0000263 inhibited the clone formation and cell proliferation ability of HeLa cells, and enhanced the radiosensitivity and apoptosis of HeLa cells. In contrast, knockdown of circ_0000263 decreased PCNA protein expression level and enhanced Cleaved-casp3 protein expression level in HeLa cells (P＜0.05). The apoptosis rate in the si-circ group was (13.19±1.12)%, which was higher than (6.80±0.62)% of si-NC group (P＜0.05). The apoptosis rate in the si-circ+4 Gy group was (24.82±1.57)%, which was higher than (17.00±0.96)% of si-NC+4 Gy group (P＜0.05). Circ_0000263 targeted regulated miR-338-3p, and miR-338-3p targeted regulated TERT. MiR-338-3p was lowly expressed in HeLa cells, and knockdown of circ_0000263 elevated miR-338-3p expression level in HeLa cells. Circ_0000263 regulated TERT expression and inhibited telomerase activity through miR-338-3p. MiR-338-3p/TERT can restore the effect of circ_0000263 on the radiosensitivity of Hela cells. The apoptosis rate in the si-circ+anti-NC group was (27.37±0.89)%, which was higher than (18.22±1.18)% of the si-circ+anti-miR-338-3p group (P＜0.05). The apoptosis rate in the si-circ+vector group was (27.55±0.48)%, which was higher than (20.10±0.68)% of si-circ+TERT group (P＜0.05). After 72 hours of radiation by 4 Gy, the cell survival fraction of si-circ+anti-NC group was 0.41±0.02, which was lower than 0.66±0.03 of the si-circ+anti-miR-338-3p group (P＜0.05); the cell survival fraction of si-circ+vector group was 0.42±0.05, which was lower than 0.70±0.03 of si-circ+TERT group (P＜0.05). Conclusion: Inhibiting the expression of circ_0000263 supresses the proliferation of Hela cells by regulating miR-338-3p/TERT, promotes apoptosis, inhibits telomerase activity, increases the radiosensitivity of cancer cells, and provides a theoretical basis for improving the radiosensitivity of Hela cells.

[Efficacy of alternate mucosa-submucosa clip closure in preventing postoperative complications for patients with gastric mucosal lesions after endoscopic submucosal dissection].

Objective: To analyze the efficacy of alternate titanium clip closure in preventing postoperative complications for patients with gastric mucosal lesions after endoscopic submucosal dissection (ESD). Methods: Clinical data of patients with gastric mucosal lesions who underwent ESD in the Department of Gastroenterology, Zhongda Hospital, Southeast University, were retrospectively collected from January 1, 2013 to August 31, 2023. According to the postoperative wound closure status, the patients were divided into completely closed group (complete closure of ESD wounds using alternate titanium clip closure), partially closed group (partial closure of ESD wounds), and unclosed group (without use of clips for treatment of ESD wounds). The incidence of postoperative complications as well as wound healing at 1 month and 3 months after surgery were compared among three groups, and the factors related to delayed bleeding after ESD for gastric mucosal lesions were analyzed through multiple logistic regression analysis. Results: A total of 846 patients were included, 430 cases in the completely closed group, including 300 males and 130 females, age [M (Q1, Q3)] was 65(56, 72) years old; one hundred and nine cases in unclosed group, including 78 males and 31 females, aged 66 (60, 71) years; and 307 cases in the partially closed group, including 214 males and 93 females, aged 66 (59, 71) years. The difference in the rate of delayed postoperative bleeding between the completely closed group [2.1% (9/430)] and the unclosed group [5.5% (6/109)] was not statistically significant (P=0.072), but both were lower than that of the partially closed group [9.4% (29/307), P<0.05)]. Further stratified analysis showed that, for the lesions located in the lower 1/3 of the stomach, the rate of postoperative bleeding was lower in the completely closed group than in the partially closed and unclosed groups [0.9% (2/222) vs 11.4% (4/35) vs 9.5% (7/74), respectively, P<0.001]. For lesions≥50 mm in length, the rate of postoperative bleeding was lower in the completely closed group than that in the partially closed and unclosed group[0 vs 11.8% (2/17) vs 20.5% (15/73), respectively, P=0.004]. The incidence of postoperative abdominal pain in the completely closed group [84.2% (363/430)] was lower than that in the unclosed group [97.2% (106/109)] and the partially closed group [95.4% (293/307), both P<0.001)]. The score of postoperative abdominal pain in the completely closed group [0 (0, 1)], was lower than that in the unclosed group [3 (2, 3)], and that in the partially closed group [2 (1, 3)] (both P<0.001). The wound healing rate of the completely closed group [80% (176/220)] was higher than that of the unclosed group [52.3% (33/63)] and the partially closed group [52.2% (83/159)] at 1 month postoperatively (both P<0.001); the healing rate of all three groups reached 100% at 3 months postoperatively. Multiple logistic regression analysis showed that the presence of ulcers or scars on the surface of the lesion (OR=2.930, 95%CI:1.503-5.712, P=0.002), and the diameter (OR=1.031, 95%CI:1.015-1.047,P<0.001) were related factors for postoperative bleeding. Conclusions: The alternate titanium clip closure surgery can reduce postoperative abdominal pain and shorten wound healing time in patients with gastric mucosal lesions after ESD surgery. The risk of postoperative bleeding can be reduced for lesions with a diameter≥50 mm and located in the lower 1/3 of the stomach.

[The association between visceral adipose thickness and gestational diabetes mellitus in the first trimester].

Objective: To investigate the association between visceral adipose tissue (VAT) thickness in early pregnancy and the risk of gestational diabetes mellitus (GDM). Methods: Based on the Qingdao Women and Children Health Cohort, pregnant women in the first trimester (11-13+6 weeks of gestation) were enrolled in this cohort study between May 2019 and October 2022. The VAT was measured in first trimester and determined as the distance from the inner margin of the rectus abdominis muscle to the anterior wall of the great artery using multi-functional color ultrasound. The 75 g oral glucose tolerance test (OGTT) results were followed up at 24-28 weeks and the participants were divided into GDM group and non-GDM group. The pregnant women were divided into 4 groups according to the VAT quartile. Log-binomial model and linear regression model were used to analyze the association between VAT and GDM/blood glucose. Results: A total of 3 686 pregnant women were included in this study, the mean age of participants was (30.56±4.05) years and 722 were diagnosed with GDM, with an incidence of 19.6%. The log-binomial regression model results showed that compared with VAT thickness Q1 (VAT<14.70 mm), the GDM risk in Q3 (21.65≤VAT≤29.69 mm) and Q4 (VAT ≥29.70 mm) increased by 34% [RR(95%CI): 1.34 (1.08-1.67)], and 61% [RR(95%CI): 1.61 (1.30-2.00)], respectively. Among women with gestational age<35 years old, compared with VAT thickness Q1, the risk of GDM increased by 42% in Q3 [RR(95%CI): 1.42 (1.22-1.65)] and 70% [RR(95%CI): 1.70 (1.46-1.98)] in Q4, whereas no associations were found in women with gestational age ≥35 years old (P>0.05). The association between VAT and GDM risk was only found in pregnant women with pre-pregnancy BMI <24.0 kg/m2, and the GDM risk increased by 57% [RR(95%CI): 1.57 (1.22-2.04)] in Q3 and 65% [RR(95%CI): 1.65 (1.24-2.19)] in Q4 compare with Q1. The results of multiple linear regression analysis showed that VAT was positively correlated with fasting blood glucose, 1-hour blood glucose after 75 g OGTT and 2-hours blood glucose after 75 g OGTT (all Pfor trend<0.001). Conclusion: High VAT thickness in early pregnancy is an independent risk factor for GDM, and the GDM risk increases with the raising of VAT depth.

[Research progress of vaccination status, efficacy and safety in children with tumor].

Malignant tumors in children are one of the most important diseases that threaten the health and quality of life of children and are the second most common cause of death in children.With the continuous improvement and progress of treatment technology, the long-term survival rate of children with tumor has been significantly improved, but both the disease itself and the treatment can impair the immune function of children, which makes them vulnerable to various infectious diseases and secondary serious complications, and even become a source of infection, endangering the health of others. Vaccination is the most cost-effective measure to prevent infectious diseases. For children with normal immune functions, the benefits of vaccination usually outweigh the disadvantages. However, there is a lack of detailed data on the vaccination situation, efficacy and safety of vaccine use for such immunocompromised tumor survivors, and there are no authoritative and uniform vaccination recommendations. This article reviewed and summarized the literature and consensus of some domestic and foreign scholars on current status of post-treatment vaccination status, efficacy and safety of vaccination for children with tumors after treatment, with the aim of providing a reference for the practice in this field in China.

[Comparison of ultrathin bronchoscopy with conventional bronchoscopy for the diagnostic value of peripheral pulmonary lesions].

Objective: To assess and compare the diagnostic efficacy of next-generation ultrathin bronchoscopy (UTB) and conventional bronchoscopy (CB), both combined with radial endobronchial ultrasound (r-EBUS), in the evaluation of peripheral pulmonary lesions (PPL). Methods: A cohort of 39 patients with PPL who underwent multimodal bronchoscopy at Dushu Lake Hospital, Soochow University, from June 1, 2021 to May 31, 2023 was consecutively enrolled. A single bronchoscopist performed multimodal bronchoscopies using CB (external diameter 4.9 mm or 5.9 mm, working channel diameter 2 or 3 mm, CB group) for transbronchial biopsy under r-EBUS guidance (rEBUS-TBLB), followed by UTB (external diameter 3 mm, working channel diameter 1.7 mm, UTB group) for transbronchial biopsy under r-EBUS guidance. Pathological findings and a 6-month clinical follow-up were used as the gold standard to compare the diagnostic yield of biopsy specimens, ultrasound characteristics, and localization rates of the two bronchoscope types. The aim was to evaluate the clinical application value of UTB combined with r-EBUS. Binary variables were analysed using the McNemar test for paired data. Continuous variables or ranked data were analysed using the Wilcoxon signed-rank test for paired data. Results: The diagnostic yields for UTB and CB groups were 66.67% (26/39) and 30.77% (12/39), respectively, with the UTB group significantly surpassing the CB group (χ2=10.56, P=0.001, 1-ß=0.968). r-EBUS with CB exhibited no visible lesion in 13 cases, adjacent to the lesion in 19 cases, and within the lesion in 7 cases.Substitution of UTB resulted in r-EBUS images changing from no visible lesion to adjacent to the lesion in 7 cases, from no visible lesion to within the lesion in 3 cases, and from adjacent to the lesion to within the lesion in 12 cases. The positioning of the r-EBUS probe in relation to the lesions improved significantly with UTB usage (Z=-4.46, P<0.001). Localization rates (number of patients with "within" or "adjacent to" the image/total number of patients) for UTB and CB were 92.30% (36/39) and 66.67% (26/39), respectively (χ2=8.10, P=0.002). UTB improved r-EBUS probe localization rates. The diagnostic yields of UTB were higher than CB for solid lesions, lesions>30 mm in diameter, non-upper lobar location, benign or malignant lesions and lesions with or without a bronchus sign. Conclusion: The UTB group demonstrated a significantly higher diagnostic yield than the CB group, providing superior r-EBUS probe images, and a significant diagnostic advantage for PPL.

[Incidence and case fatality rates of cardiovascular diseases in urban and rural community-dwelling populations in eastern, central and western regions of China].

Objective: To evaluate the incidence and case fatality rate of cardiovascular disease (CVD) among populations in urban and rural communities in eastern, central and western regions of China. Methods: The present study was based on the data of the Prospective Urban and Rural Epidemiology (PURE)-China cohort, which enrolled participants who had at least one follow-up visit and complete information on age and sex. Information on baseline demographics, cardiovascular risk factors, and prevention and treatment for CVD were collected. CVD and mortality events were documented using the standardized case report form of the PURE Global Study to assess the incidence and case fatality rate of CVD among populations in urban and rural communities in eastern, central and western China. Results: This study included a total of 47 262 community-dwelling participants (age: (51.1±9.6) years; female, n=27 529, 58.2%) from 115 urban and rural communities in 12 provinces across the eastern, central, and western regions of China. Over a follow-up period of 11.9 (9.5, 12.6) years, 2 686 deaths and 5 873 cardiovascular events were documented. The incidence of CVD was 11.90 (95%CI: 11.60-12.21)/1 000 person-years. A significant difference in CVD incidence was observed across regions (Ptrend<0.001), which was highest in the western provinces (13.99 (95%CI: 13.33-14.65)/1 000 person-years), intermediate in the eastern provinces (11.92 (95%CI: 11.52-12.33)/1 000 person-years), and lowest in the central provinces (8.87 (95%CI: 8.25-9.50)/1 000 person-years). The 1-year case fatality rate of CVD demonstrated an increasing trend from eastern to western regions (eastern: 10.20% (95%CI: 6.95-14.73); central: 13.50% (95%CI: 9.90-18.14); western: 18.62% (95%CI: 14.95-22.94); Ptrend<0.001). Moreover, the incidence of major CVD was consistently higher in rural areas compared with urban areas across eastern (P<0.001), central (P=0.01) and western (P<0.001)_regions, respectively. The 1-year case fatality rate in rural areas was also significantly higher compared with that in urban areas in both eastern (P<0.001) and western regions (P=0.02). Conclusions: The incidence and case fatality rate of CVD were high among middle-aged population in China, especially those in western regions with low socioeconomic levels and in rural areas.

[Safety and efficacy analysis of the removal of refractory esophageal self-expandable metal stents by stent-in-stent technique].

To evaluate the safety and efficacy of esophageal stent-in-stent (SIS) in patients with refractory esophageal self-expandable metal stents (SEMS). Case series study. Retrospective analysis was made on the patients with refractory esophageal SEMS treated with SIS technology in Zhongda Hospital Affiliated to Southeast University from June 2015 to June 2021. The success rate of stent removal and the incidence of adverse events were analyzed. A total of 12 patients were included, including 7 males and 5 females, aged 50-73 (62.7±8.5) years. The clinical success rate of the internal stents was 12/12, with the median retention time of [M(Q1, Q3), 64.5 (52.0, 90.8)] days. The postoperative displacement rate and severe stenosis incidence were 1/12 and 3/12, respectively. The esophageal stents were successfully removed in one endoscopic session in all patients. A small amount of mucous membrane extravasation occurred in all patients after SIS, and no patients died after 90 days of follow-up.

[Construction of a prediction model for predicting rebleeding in patients with obscure gastrointestinal bleeding after capsule endoscopy].

Objective: To explore the risk factors of rebleeding in patients with obscure gastrointestinal bleeding (OGIB) after capsule endoscopy (CE), and construct a model to predict rebleeding. Methods: The data of patients with OGIB who underwent CE in Zhongda Hospital Affiliated to Southeast University from July 2018 to September 2021 were retrospectively analyzed. Follow-up data were obtained via electronic medical records or telephone interviews. Univariate and multivariate Cox regression models were performed to figure out the risk factors of rebleeding in OGIB patients. Then the optimal prediction model was determined and presented as a nomogram. The model was evaluated by C statistic, calibration curve and decision curve analysis. Results: One hundred and thirty patients with OGIB were included, including 64 females and 66 males, aged (55.8±17.2) years (18-87 years), and 39 (30.0%) cases developed rebleeding during follow-up. Univariate and multivariate Cox regression model analysis showed the duration of more than 2 weeks OGIB (HR=3.70, 95%CI: 1.85-7.42, P<0.001), a history of previous gastrointestinal bleeding (HR=5.25, 95%CI: 2.00-13.81, P<0.001), positive CE findings (HR=3.72, 95%CI: 1.66-8.33, P=0.001), and the lowest hemoglobin level before CE<80 g/L (HR=2.00, 95%CI: 1.02-3.84, P=0.044) were risk factors for rebleeding, while specific treatment (HR=0.25, 95%CI: 0.11-0.54, P<0.001) was a protective factor. The corresponding scores of the above five predictive factors were: OGIB duration>2 weeks: 79 points; Previous history of gastrointestinal bleeding: 100 points; The result of CE was positive: 79 points; Specific treatment:-85 points; Minimum hemoglobin before CE<80 g/L: 41 points. The prediction model constructed from the above five variables had good discriminative capability (concordance index=0.798, 95%CI: 0.732-0.865). The calibration curves showed high consistency between nomogram-predicted probabilities and actual observations. The decision curves showed that when the threshold probability was above 0.04, the use of the nomogram to predict rebleeding provided a greater net benefit than the assumption of "all patients rebleeding or no patients rebleeding". Conclusion: The prediction model established in this study has a good ability to predic rebleeding in patients with OGIB after CE examination.

[Efficacy and safety of endoscopic submucosal dissection with additional radiotherapy for T1a-MM/T1b-SM esophageal squamous cell carcinoma].

Objective: To clarify the efficacy and safety of endoscopic submucosal dissection (ESD) with additional radiotherapy in T1a-MM/T1b-SM esophageal squamous cell carcinoma (ESCC). Methods: A retrospective analysis was conducted on 71 patients with T1a-MM/T1b-SM ESCC admitted to Southeast University Affiliated Zhongda Hospital from January 2015 to December 2019. The patients were divided into two groups based on the treatment method: the ESD group (ESD therapy alone) and the ESD-radiotherapy group (ESD combined radiotherapy). The follow-up duration after ESD was (44±17) months. The difference of disease-free survival (DFS) rate and overall survival (OS) rate between the two groups was compared by survival analysis, and the occurrence of complications was compared. Baseline variables of the two groups were compared and the influencing factors of DFS rate were analyzed by Cox proportional risk regression model. Results: There were 44 patients in the ESD-radiotherapy group [28 males, 16 females, aged (65±7) years] and 27 patients in the ESD group [18 males, 9 females, aged (67±9) years]. The results of survival analysis show that the 1, 3 and 5-year DFS rates of ESD-radiotherapy group were 95.5%, 92.9% and 77.4%, respectively, which were higher than those of ESD group 85.2%, 73.2% and 62.7% (all P<0.05). The 1, 3 and 5-year OS rates of the ESD-radiotherapy group were 100%, 94.7% and 94.7%, while those of the ESD group were 96.3%, 96.3% and 79.4%, respectively. The difference was not statistically significant (all P>0.05). Cox proportional hazard regression model analysis showed that ESD combined with radiotherapy (HR=0.19, 95%CI: 0.04-0.90, P=0.037), complete tumor resection (HR=0.25, 95%CI: 0.07-0.86, P=0.027), and vascular invasion (HR=12.06, 95%CI: 1.61-90.26, P=0.015) were the influencing factors of DFS rates. The most common complication of ESD was esophageal stenosis, and no grade 3 or higher radiation adverse reactions occurred after combined radiotherapy. Conclusion: ESD combined radiotherapy is an effective and safe therapeutic strategy for patients with T1a-MM/T1b-SM ESCC.

[Vaginal microbiota abnormalities in women with unexplained infertility and its treatment].

The vaginal microbiota is a complex and dynamic environment that plays an important role in the healthy reproduction of women. The mechanism of unexplained infertility is not yet clear, and the imbalance and low stability of vaginal microbiota may be related to unexplained infertility. Taking probiotic composite preparations to restore normal vaginal microbiota may be a safe and natural method for treating unexplained infertility. This article reviews the probiotic composite preparations used in the treatment of unexplained infertility both domestically and internationally, including the isolation site of the bacterial species, the use method of the composite preparation, the course of treatment, and the final therapeutic effect, aiming to provide a basis for the clinical application of probiotic composite preparations in the treatment of unexplained infertility.

[Progress in the pharmacological treatment of tobacco dependence in special populations].

Schizophrenic and pregnant smokers with tobacco dependence had always been excluded from most large treatment trials for nicotine dependence. As weight gain was found to be common after smoking cessation, obese people were more likely to have a reduced willingness to quit smoking and an increased risk of relapse. This article reviewed the latest research progress in pharmacological treatment of tobacco dependence in schizophrenia, pregnant women, and obese people.

[Analysis of the burden of disease attributable to high temperature exposure in China and globally from 1990 to 2019].

Objective: To analyze the burden of disease attributable to high temperature exposure in China and globally from 1990 to 2019, and to study the current burden of disease in relevant populations. Methods: In October 2021, based on data from the global burden of disease 2019 (GBD 2019) study, population attributable fraction (PAF), number of deaths, mortality, disability-adjusted life year (DALY) and DALY rate of Chinese and global populations with different ages and genders in 1990 and 2019 were extracted and analyzed. The rate of change was calculated, the mortality rate was normalized by the age structure of the world standard population, and the causes of disease burden caused by high temperature exposure of Chinese residents were analyzed. Results: In 2019, compared with 1990, the PAF of Chinese and global population decreased by 43.98% and 12.41% respectively, the number of deaths increased by 29.55% and 49.40% respectively, the crude mortality rate increased by 7.81% and 3.30% respectively, the DALY decreased by 48.12% and 14.41% respectively, and the DALY rate decreased by 56.82% and 40.82% respectively. The mortality rate of the ≥70 age group was higher than that of other groups. The disease burden indicators such as PAF, standardized mortality and DALY attributable to high temperature exposure in men were higher than those in women. In 2019, the main cause of DALY affected by high temperature exposure in Chinese population was ischemic heart disease (84400 person-years), and the main cause of death was ischemic heart disease (4900 cases). Conclusion: The burden of diseases attributable to high temperature exposure is still serious in China and the world at large. Targeted interventions should be formulated for men, the elderly and people with occupational exposure, and a sound surveillance system should be established to reduce the burden of diseases caused by high temperature exposure.

[Detection of drug resistance genes of mycobacterium tuberculosis by rolling circle amplification technique with multicolor fluorescent probes].

The aim of this study was to construct a simple, rapid and ultra-sensitive optical biosensing technique based on rolling circle amplification (RCA), and to apply it to multiple detection of drug-resistant genes of mycobacterium tuberculosis. The common mutation sites of isoniazid, rifampicin and streptomycin resistance genes are katG315 (AGC➝ACC), rpoB531 (CAC➝TAC) and rpsL43 (AAG➝AGG). For these three gene sites, from February 2020 to May 2021, in the Department of Laboratory Medicine of the First Affiliated Hospital of Army Military Medical University, the padlock probe (PLP), primers and capture probes were designed. And a solid-phase RCA constant temperature amplification reaction system based on magnetic beads was constructed and the experimental parameters were optimized. The RCA products were accurately captured by the multicolor fluorescent probes (Cy3/Cy5/ROX), and the single-tube multiple detection of three mutation genes was realized. The sensitivity, specificity and linear range of this method were further verified. The results showed that the response range of katG315 in the same reaction system ranged from 1.0 pmol/L to 0.1 nmol/L. The response range of rpoB531 and rpsL43 ranged from 1.0 pmol/L to 50.0 pmol/L and 1.0 pmol/L to 20.0 pmol/L, and the method had good specificity and sensitivity, and could accurately identify single base mutations in mixed targets, with the minimum detection limit as low as 1.0 pmol/L. The recoveries of simulated serum samples were 95.0%-105.2%. In conclusion, the constant temperature amplification multiple detection method constructed in this study can quickly realize the single-tube multiple detection of three drug resistance mutation sites. This technology is low-cost, simple and rapid, and does not rely on large equipment, providing a new analysis method for pathogen drug resistance gene detection.

[The relationship between peripheral blood mitochondrial DNA copy number and incident risk of liver cancer: a case-cohort study].

Objective: To investigate the association between peripheral blood mitochondrial DNA copy number (mtDNAcn) and incident risk of liver cancer. Methods: At the baseline of Dongfeng-Tongji (DFTJ) cohort, 27 009 retirees were recruited from Dongfeng Motor Corporation in 2008. After excluding people without baseline DNA, with current malignant tumor and loss of follow-up, 1 173 participants were randomly selected into a sub-cohort by age-and gender-stratified sampling method at a proportion of 5% among all retirees. A total of 154 incident liver cancer cases identified from the cohort before December 31, 2018 (4 cases had been selected into the sub-cohort) were selected to form the case cohort of liver cancer. For the above 1 323 participants, their baseline levels of mtDNAcn in peripheral blood cells were measured by using quantitative real-time PCR method. The restricted cubic spline analysis was used to fit the shape of the association between baseline mtDNAcn and incident risk of liver cancer. The weighted Cox proportional hazards model was used to estimate the hazard ratio (HR) and 95%CI. Results: In this case-cohort study, the median follow-up time was 10.3 years. The restricted cubic spline analysis indicated that the relationship between peripheral blood mtDNAcn and incident risk of liver cancer followed a U-shaped pattern (Pnon-linear<0.05). All case-cohort population were divided into four subgroups by sex-specific quartiles of mtDNAcn levels among sub-cohort participants, when compared to participants in the Q2 subgroup of mtDNAcn, those in the Q1 subgroup (HR=2.00,95%CI:1.08-3.70) and Q4 subgroup (HR=4.11,95%CI:2.32-7.26) both had a significantly elevated risk of liver cancer, while those in the Q3 subgroup (HR=1.05,95%CI:0.54-2.05) had not. There were no significant multiply interaction effects of aging, gender, tobacco smoking, alcohol drinking and history of chronic hepatitis on the above association (Pinteraction>0.05). Conclusion: Both extremely low and high baseline level of mtDNAcn in peripheral blood cells are associated with an increased risk of incident liver cancer, but the underlying mechanisms need to be further clarified.

[Surgical treatment of primary liver cancer:a report of 10 966 cases].

Objective: To summarize the experience of surgical treatment of primary liver cancer. Methods: The clinical data of 10 966 surgically managed cases with primary liver cancer, from January 1986 to December 2019 at Hepatobiliary Center, the First Affiliated Hospital of Nanjing Medical University, were retrospectively analyzed. The life table method was used to calculate the survival rate and postoperative recurrence rate. Log-rank test was used to compare the survival process of different groups, and the Cox regression model was used for multivariate analysis. In addition, 2 884 cases of hepatocellular carcinoma(HCC) with more detailed follow-up data from 2009 to 2019 were selected for survival analysis. Among 2 549 patients treated with hepatectomy, there were 2 107 males and 442 females, with an age of (56.6±11.1) years (range: 20 to 86 years). Among 335 patients treated with liver transplantation, there were 292 males and 43 females, with an age of (51.0±9.7) years (range: 21 to 73 years). The outcomes of hepatectomy versus liver transplantation, anatomic versus non-anatomic hepatectomy were compared, respectively. Results: Of the 10 966 patients with primary liver cancer, 10 331 patients underwent hepatectomy and 635 patients underwent liver transplantation. Patients with liver resection were categorized into three groups: 1986－1995(712 cases), 1996－2008(3 988 cases), 2009‒2019(5 631 cases). The 5-year overall survival rate was 32.9% in the first group(1986－1995). The 5-year overall survival rate of resected primary liver cancer was 51.7% in the third group(2009-2019), among which the 5-year overal survival rates of hepatocellular carcinoma, intrahepatic cholangiocarcinoma and mixed liver cancer were 57.4%, 26.6% and 50.6%, respectively. Further analysis was performed on 2 549 HCC patients with primary hepatectomy. The 1-, 3-, 5-, and 10-year overall survival rates were 88.1%, 71.9%, 60.0%, and 41.0%, respectively, and the perioperative mortality rate was 1.0%. Two hundred and forty-seven HCC patients underwent primary liver transplantation, with 1-, 3-, 5-, and 10-year overall survival rates of 84.0%, 64.8%, 61.9%, and 57.6%, respectively. Eighty-eight HCC patients underwent salvage liver transplantation, with the 1-, 3-, 5-, and 10-year overall survival rates of 86.8%, 65.2%, 52.5%, and 52.5%, respectively. There was no significant difference in survival rates between the two groups with liver transplantation (P>0.05). Comparing the overall survival rates and recurrence rates of primary hepatectomy (2 549 cases) with primary liver transplantation (247 cases), the 1-, 3-, 5-, and 10-year overall survival rates in patients within Milan criteria treated with hepatectomy and transplantation were 96.3%, 87.1%, 76.9%, 54.7%, and 95.4%, 79.4%, 77.4%, 71.7%, respectively (P=0.754). The 1-, 3-, 5-year recurrence rates were 16.3%, 35.9%, 47.6% and 8.1%, 11.7%, 13.9%, respectively(P<0.01). The 1-, 3-, 5-, 10-year overall survival rates in patients with no large vessels invasion beyond the Milan criteria treated with liver resection and transplantation were 87.2%, 65.9%, 53.0%, 33.0% and 87.6%, 71.8%, 71.8%, 69.3%, respectively(P=0.003); the 1-, 3-, 5-year recurrence rate were 39.2%, 57.8%, 69.7% and 29.7%, 36.7%, 36.7%, respectively (P<0.01). The 1-, 3-, 5-, and 10-year overall survival rates in patients with large vessels invasion treated with liver resection and transplantation were 62.1%, 36.1%, 22.2%, 15.0% and 62.9%, 31.8%,19.9%, 0, respectively (P=0.387); the 1-, 3-, 5-year recurrence rates were 61.5%, 74.7%, 80.8% and 59.7%, 82.9%, 87.2%, respectively(P=0.909). Independent prognostic factors for both overall survival and recurrence-free survival rates of HCC patients treated with liver resection included gender, neoadjuvant therapy, symptoms, AST, intraoperative or postoperative blood transfusion, tumor number, tumor size, cirrhosis, macrovascular invasion, microvascular invasion, and pathological differentiation. Propensity score matching analysis of 443 pairs further showed that there was no significant difference in overall survival rate between anatomical liver resection and non-anatomical liver resection(P=0.895), but the recurrence rate of non-anatomical liver resection was higher than that of anatomical liver resection(P=0.035). Conclusions: In the past decade, the overall survival rate of HCC undergoing surgical treatment is significantly higher than before. For HCC patients with good liver function reservation, surgical resection can be performed first, and salvage liver transplantation can be performed after recurrence. The effect of salvage liver transplantation is comparable to that of primary liver transplantation. As for the choice of liver resection approaches, non-anatomical resection can reserve more liver tissue and can be selected as long as the negative margin is guaranteed.

[The efficacy and safety of ticagrelor versus clopidogrel in elderly patients with acute coronary syndrome undergoing percutaneous coronary intervention].

Objective: To compare the efficacy and safety of ticagrelor and clopidogrel in elderly Chinese patients with acute coronary syndrome (ACS) underwent percutaneous coronary intervention (PCI) in the real world. Methods: This study is a post-hoc analysis of a single center, retrospective cohort study. Between March 2016 and March 2018, elderly (age≥65) ACS patients who underwent PCI in the General Hospital of Northern Theater Command were included in the study. The patients were grouped according to P2Y12 receptor inhibitor. The primary endpoints of this study were ischemic events during the 2-year follow-up, which were defined as the composite of cardiac death, myocardial or stroke. The secondary efficiency endpoints included all-cause death and BARC 2, 3, 5 bleeding events. Results: A total of 4 022 elderly (mean age: (71.5±5.3) years) ACS patients were included in this study. Based on the choice of P2Y12 receptor inhibitor, patients were divided into clopidogrel (n=3 201) and ticagrelor (n=821) groups. Incidences of ischemic events (3.2% (26/821) vs. 5.6% (179/3 201), P=0.005) at 2 years were significantly lower in ticagrelor group compared to clopidogrel group. BARC 2, 3, 5 bleeding events (1.7% (14/821) vs. 1.6% (52/3 201), P=0.818) were comparable between the two groups. The incidence of all-cause death (1.5% (12/821) vs. 4.1% (132/3 201), P=0.005) were also lower in the ticagrelor group compared to the clopidogrel group. Clinical outcomes were consistent after adjusting for confounding factors, the incidence of ischemic events (HR= 0.637, 95%CI 0.409-0.991, P=0.046) and all-cause mortality (HR=0.402, 95%CI 0.213-0.758, P=0.005) was significantly lower in the ticagrelor group compared with the clopidogrel group. Risk of BARC 2, 3, 5 bleeding events were similar between the two groups (HR=0.957, 95%CI 0.496-1.848, P=0.897). Conclusion: In real-world clinical practice, for elderly patients with ACS undergoing PCI, ticagrelor use might reduce the incidence of long-term ischemic events and all-cause death without increasing the risk of bleeding.

ERα-dependent stimulation of LCN2 in uterine epithelium during mouse early pregnancy.

Maintenance of a suitable uterine milieu is important for embryo development and subsequent implantation during early pregnancy. High estrogen level in proestrous and estrous stages is essential for uterine anti-bacterial activity during preimplantation period. Lipocalin-2 is an essential molecule which prevents bacterial infection by sequestering iron. In this study, the highest expression of lipocalin-2 is observed in the endometrial epithelium on day 1 of normal pregnancy and pseudopregnancy, which exhibit a similar hormone scenario. By injecting the agonists for estrogen receptor α and estrogen receptor ß in ovariectomized mice, we found estrogen receptor α is the dominant member for estrogen regulation on lipocalin-2 expression. Estrogen treatment in estrogen receptor α-knockout mice further confirmed the role of estrogen receptor α. Using published data from whole-genome estrogen receptor α binding site assay, significant estrogen receptor α recruitment peaks are found at the downstream of lipocalin-2 gene after estrogen treatment. Furthermore, to study the anti-bacterial activity of lipocalin-2 in uterus, Escherichia coli is injected to mimic bacterial infection. Our results showed an obvious induction of lipocalin-2 in Escherichia coli-treated group. Taken together, this study indicates estrogen regulation of lipocalin-2 in uterine epithelium is mediated by estrogen receptor α, and lipocalin-2 may have anti-bacterial activity during early pregnancy.

[Matrix metalloproteinase-3 in patients with systemic lupus erythematosus and its significance in differentiating disease activity from pulmonary infections].

The purpose of this study is to investigate the matrix metalloproteinase-3 (MMP-3) levels in patients with systemic lupus erythematosus (SLE) and its significance in identifying disease activity and pulmonary infections. A total of 122 SLE patients were enrolled, including 21 with pulmonary infections, 16 with arthritis, 26 with nephritis, 10 with vasculitis, and 23 healthy controls. Serum MMP-3, C-reactive protein (CRP), serum amyloid A (SAA), and haptoglobin (HPT) levels were measured in all subjects. The results showed that the levels of MMP-3 in SLE combined with pulmonary infections [(230.10±44.92) µg/L], arthritis [(140.20±20.76) µg/L], nephritis [(155.40±23.36) µg/L] were higher than those in SLE only [(91.74±10.47) µg/L]. The levels of MMP-3 [(210.30±45.71) µg/L], CRP [(12.11±5.21) mg/L], HPT [(1.57±0.23) g/L] in active SLE combined with pulmonary infections were higher than those inactive SLE without pulmonary infections including MMP-3 [(124.00±15.22) µg/L], CRP [(7.76±2.96) mg/L], HPT [(0.89±0.09) g/L]. The levels of CRP [(10.03±2.70) mg/L], SAA [(89.22±36.77) mg/L] in active SLE with pulmonary infections and CRP[(7.76±2.96) mg/L], SAA [(60.22±19.7) mg/L] in active SLE without pulmonary infections were higher than CRP [(1.90±0.39) mg/L], SAA [(17.60±3.89) mg/L] in stable SLE with pulmonary infections. It suggests that the levels of CRP and SAA are elevated in active SLE with pulmonary infections. Serum MMP-3 in combination with CRP may assist in differentiating from SLE pulmonary infections.

[Elimination of hepatitis C, our progress, challenges and hopes].

Hepatitis C infection is a serious public health threat, and the World Health Organization has recommended the elimination of public health threats from viral hepatitis, including hepatitis C, by 2030. Many countries and regions are actively exploring strategies and models to eliminate the public health threat of hepatitis C. It is estimated that there are at least 7.6 million cases of chronic hepatitis C in China, with both diagnosis and treatment rates far away to 2030 target. China's government, social organizations and doctors at different levels are also actively exploring the mode of eliminating the public health threat of hepatitis C in China, including the main mode supported by national standards, government-led mode, social institution undertaking and government-supported mode, medical alliance mode, screening in high-prevalence areas and services contracted with family doctors. China can have a lessons learning from international and ourselves experience, particularly as "Test and treat all based on needs and demand" strategy in Covid-19 control, finally achieve eliminate the public health threat of hepatitis C as soon as possible.

[Diagnostic value of liver stiffness measurement for the evaluation of liver fibrosis in nonalcoholic fatty liver].

Objective: To investigate the clinical and diagnostic value of liver stiffness measurement (LSM) for the evaluation and comparison of aspartate aminotransferas/platelet ratio index (APRI), fibrosis 4 indexes (FIB-4) and NAFLD fibrosis score (NFS) with liver fibrosis staging in relation to nonalcoholic fatty liver disease (NAFLD). Methods: 103 cases with NAFLD who met the inclusion criteria confirmed by liver biopsy were selected for retrospective analysis. The results of serological tests and LSM were recorded. The APRI, FIB-4 and NFS were calculated. The accuracy and applicability of four liver fibrosis models in the diagnosis of liver fibrosis in NAFLD patients were compared with the receiver operating characteristic curve (ROC), and the diagnostic cut-off value of LSM was established. Results: Varying degrees of LSM, APRI, FIB-4 and NFS had shown positive correlations with the increasing degree of liver fibrosis. Among them, LSM was positively correlated with the degree of liver fibrosis, and the correlation coefficient was r = 0.727, P < 0.0001. Consistent with this, the area under the receiver operating characteristic curve, sensitivity, and specificity of LSM diagnosis of liver fibrosis in different stages was significantly higher than APRI, FIB-4 and NFS. Area under receiver operating characteristic curve of LSM was 0.862 and 0.928 for significant liver fibrosis (f ≥ 2), and advanced liver fibrosis (f ≥ 3). Conclusion: LSM has a good diagnostic exclusion value for NAFLD-induced fibrosis, and its sensitivity and specificity are better than APRI, FIB-4 and NFS.