Imputation strategies for low-coverage whole-genome sequencing data and their effects on genomic prediction and genome-wide association studies in pigs.

The uncertainty resulting from missing genotypes in low-coverage whole-genome sequencing (LCWGS) data complicates genotype imputation. The aim of this study is to find out an optimal strategy for accurately imputing LCWGS data and assess its effectiveness for genomic prediction (GP) and genome-wide association study (GWAS) on economically important traits of Large White pigs. The LCWGS data of 1 423 Large White pigs were imputed using three different strategies: (1) using the high-coverage whole-genome sequencing (HCWGS) of 30 key progenitors as the reference panel (Ref_LG); (2) mixing HCWGS of key progenitors with LCWGS (Mix_HLG) and (3) self-imputation in LCWGS (Within_LG). Additionally, to compare the imputation effects of LCWGS, we also imputed SNP chip data of 1 423 Large White pigs to the whole-genome sequencing level using the reference panel consisting of key progenitors (Ref_SNP). To evaluate effects of the imputed sequencing data, we compared the accuracies of GP and statistical power of GWAS for four reproductive traits based on the chip data, sequencing data imputed from chip data and LCWGS data using an optimal strategy. The average imputation accuracies of the Within_LG, Ref_LG and Mix_HLG were 0.9893, 0.9899 and 0.9875, respectively, which were higher than that of the Ref_SNP (0.8522). Using the imputed sequencing data from LCWGS with the Ref_LG imputation strategy, the accuracies of GP for four traits improved by approximately 0.31-1.04% compared to the chip data, and by 0.7-1.05% compared to the imputed sequencing data from chip data. Furthermore, by using the sequence data imputed from LCWGS with the Ref_LG, 18 candidate genes were identified to be associated with the four reproductive traits of interest in Large White pigs: total number of piglets born - EPC2, MBD5, ORC4 and ACVR2A; number of piglets born healthy - IKBKE; total litter weight of piglets born alive - HSPA13 and CPA1; gestation length - GTF2H5, ITGAV, NFE2L2, CALCRL, ITGA4, STAT1, HOXD10, MSTN, COL5A2 and STAT4. With the exception of EPC2, ORC4, ACVR2A and MSTN, others represent novel candidates. Our findings can provide a reference for the application of LCWGS data in livestock and poultry.

[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.

[Epidemiological and etiological characteristics of herpes pharyngitis in 3 prefectures in Jiangsu Province].

Objective: To analyze the epidemiological and etiological characteristics of herpes pharyngitis (HA) in three prefectures of Jiangsu Province, and provide evidence for the prevention and control of HA in Jiangsu. Methods: Three surveillance sentinel hospitals in Wuxi, Suzhou and Yancheng were selected from May 2018 to December 2022, and information related to HA visits and hospitalized cases was regularly collected from the hospital inpatient management system by age groups. Enterovirus nucleic acid detection was performed by RT-PCR, and sequencing analysis, identification of genotype subtypes, and phylogenetic analysis were performed on the sequences of the gene encoding the coat protein VP1 of the main prevalent strains. Results: A total of 57 709 HA cases were recorded in the sentinel hospitals in in Wuxi, Suzhou and Yancheng, which was 1.76 times higher than the reported cases of hand, foot and mouth disease during the same period (57 709/32 831).The percentage of HA hospitalizations was 1.35% (781/57 709), and the percentage of hospitalizations showed an increasing trend from year to year (χ2=62.79, P<0.001 ).The incidence peak of HA was during May-July. The cases were mainly children aged 12-59 months (67.07%, 38 708/57 709), with the highest case number in age group 36-59 months (34.40%, 19 852/57 709). The HA positivity rate was 33.82% (644/1 904); enterovirus A was predominant (54.04%, 348/644); of these, Coxsackievirus (CV)A6 accounted for the highest percentage (52.59%, 183/348), while CVA16 and CVA4 accounted for 24.71% (86/348) and 15.23% (53/348), respectively. All 10 CVA4 HA endemic strains belonged to the C2 gene subtype, and all 6 CVA6 HA endemic strains belonged to the D3a gene subtype; and were genetically closer to and related to the strains in some areas of China (Fujian Province, Guangzhou City, Jiangxi Province, Yunnan Province, Tianjin City, etc.). Conclusions: The disease burden of HA was heavy in 3 areas in Jiangsu, children in age group 12-59-month were mainly affected, and the annual incidence peak of HA was during May-July. The pathogens causing HA varied, but predominated by enterovirus A and had low intra-typical differentiation, and no new evolutionary branches were found, suggesting that it is necessary to include HA in foot and mouth disease surveillance or regarded as a notifiable communicable disease.

[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.

Periodontitis and the risk of oral, gastric and esophageal cancers: a two-sample Mendelian randomization study.

BACKGROUND: Periodontitis is a common oral disease and the chronic inflammation caused by it may influence the development of cancers in the upper gastrointestinal tract. Many observational studies have established a relationship between the two, but the results are not entirely consistent. METHODS: Two-sample MR was performed using publicly available genome-wide association studies data for periodontitis, oral, gastric and oesophagal cancers. The Inverse Variance Weighting (IVW) method serves as the primary method, with MR Egger, Weighted Median, Simple Model and Weighted Model Algorithm methods as complementary methods to assess genetic causal associations. Cochran Q-test, MR-Egger regression and MR polytropic residuals and outliers were used to assess heterogeneity and horizontal pleiotropy. RESULTS: IVW results did not support a causal association between periodontitis and oral (OR = 1.00, 95% CI: 1.00, 1.00) and oesophagal cancer (OR = 1.00, 95% CI: 1.00, 1.00). Similarly, there was again no causal association between periodontitis and gastric cancer, which was integrated with an OR of 1.04 (95% CI: 0.97, 1.12). Complementary method results were consistent with IVW and heterogeneity and horizontal pleiotropy were not found in most studies. CONCLUSIONS: The findings of our MR study do not support a causal relationship between periodontitis and oral, gastric and oesophagal cancers.

[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.

[Associations of onset age, diabetes duration and glycated hemoglobin level with ischemic stroke risk in type 2 diabetes patients: a prospective cohort study].

Objective: To investigate the associations of onset age, diabetes duration, and glycated hemoglobin (HbA1c) levels with ischemic stroke risk in type 2 diabetes patients. Methods: The participants were from Comprehensive Research on the Prevention and Control of the Diabetes in Jiangsu Province. The study used data from baseline survey from December 2013 to January 2014 and follow-up until December 31, 2021. After excluding the participants who had been diagnosed with stroke at baseline survey and those with incomplete information on onset age, diabetes duration, and HbA1c level, a total of 17 576 type 2 diabetes patients were included. Cox proportional hazard model was used to calculate the hazard ratio (HR) and 95%CI of onset age, diabetes duration, and HbA1c level for ischemic stroke. Results: During the median follow-up time of 8.02 years, 2 622 ischemic stroke cases were registered. Multivariate Cox proportional risk regression model showed that a 5-year increase in type 2 diabetes onset age was significantly associated with a 5% decreased risk for ischemic stroke (HR=0.95, 95%CI: 0.92-0.99). A 5-year increase in diabetes duration was associated with a 5% increased risk for ischemic stroke (HR=1.05, 95%CI: 1.02-1.10). Higher HbA1c (per 1 standard deviation increase:HR=1.17, 95%CI: 1.13-1.21) was associated with an increased risk for ischemic stroke. Conclusion: The earlier onset age of diabetes, longer diabetes duration, and high levels of HbA1c are associated with an increased risk for ischemic stroke in type 2 diabetes patients.

[Efficacy and safety of chimeric antigen receptor T-cell therapy followed by allogeneic hematopoietic stem cell transplantation in 21 patients with Ph-like acute lymphoblastic leukemia].

Objective: To evaluate the efficacy and safety of chimeric antigen receptor T-cell (CAR-T) therapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with Ph-like acute lymphoblastic leukemia (Ph-ALL) . Methods: Patients with Ph-ALL who underwent CAR-T therapy followed by allo-HSCT from March 2018 to August 2023 at the First Affiliated Hospital of Soochow University were included, and their clinical data were retrospectively analyzed. Results: Of the 21 patients, 14 were male and 7 were female. The median age at the time of CAR-T therapy was 22 (6-50) years. Seven patients had ABL1-like rearrangements, and 14 had JAK-STAT rearrangements. Prior to CAR-T therapy, 12 patients experienced hematologic relapse; 7 were multiparameter flow cytometry minimal residual disease (MFC-MRD) -positive and 2 were MFC-MRD-negative. CAR-T cells were derived from patients' autologous lymphocytes. Nine patients were treated with CD19 CAR-T cells, and 12 were treated with CD19/CD22 CAR-T cells. After assessment on day 28 after CAR-T therapy, 95.2% of the patients achieved complete remission, with an MRD-negative remission rate of 75%. Nineteen patients developed grade 0-2 cytokine release syndrome (CRS) and 2 patients suffered grade 3 CRS, all cases of which resolved after treatment. All patients underwent allo-HSCT after CAR-T therapy. The median time from CAR-T therapy to allo-HSCT was 63 (38-114) days. Five patients experienced relapse after CAR-T therapy, including four with hematologic relapse and one with molecular relapse. The 3-year overall survival (OS) rates in the ABL1 and JAK-STAT groups were (83.3±15.2) % and (66.6±17.2) %, respectively (P=0.68) . The 3-year relapse-free survival (RFS) rates were (50.0±20.4) % and (55.6±15.4) % in the ABL1 and JAK-STAT groups, respectively. There was no significant difference in 3-year OS or RFS between the two groups. Conclusions: CAR-T therapy followed by allo-HSCT leads to rapid remission in most patients with Ph-ALL and prolongs leukemia-free survival.

[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.

[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.

[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.

[Obstructive sleep apnea and type 2 diabetes: a bidirectional Mendelian randomization study].

Objective: This study aims to explore the causal relationship between obstructive sleep apnea (OSA) and type 2 diabetes (T2D) using bidirectional Mendelian randomization (MR). Methods: The genetic data related to OSA were obtained from the FinnGen Biobank (Ncase=16, 761, Ncontrol=201, 194) in the Genome-wide association study (GWAS). Three single nucleotide polymorphism (SNP) were screened out as instrumental variable (IV) of OSA. The genetic data related to T2D were derived from a large Meta-analysis of GWAS (Ncase=62, 892, Ncontrol=596, 424), 114 SNP were selected as IV of T2D. Multiple MR methods were used for analysis and inverse variance weighted (IVW) was performed as main method. The sensitivity of MR analytic results was analyzed using MR-Egger and other methods, and the IV was evaluated using F-value statistics. Results: MR analysis showed that OSA was significantly associated with increased risk of T2D (OR=2.016, 95%CI: 1.185-3.429, P<0.05). There was no significant relationship between T2D and OSA risk (OR=1.030, 95%CI: 0.980-1.082, P=0.238). There was heterogeneity in both-way results (OSA➝T2D, P=1.808×10-11; T2D➝OSA, P=1.729×10-7), and no horizontal pleiotropy (OSA➝T2D, P=0.477; T2D➝OSA, P=0.349). IV of OSA and T2D-selected in the study were strong instrumental variables (F statistics of OSA=20.543; F statistics of T2D=30.117). Conclusion: Our results supported that OSA was a risk factor for T2D, but T2D had no significant impact on the incidence of OSA. Blood glucose monitoring and diabetes screening in OSA patients might be beneficial to the early detection and intervention of T2D.

[Clinical efficacy and safety of venetoclax combined with multidrug chemotherapy in the treatment of 15 patients with relapsed or refractory early T-cell precursor acute lymphoblastic leukemia].

Objective: To explore the efficacy and safety of Venetoclax combined with multidrug chemotherapy in patients with relapsed or refractory early T-cell precursor acute lymphoblastic leukemia (R/R ETP-ALL) . Methods: This study retrospectively analyzed 15 patients with R/R ETP-ALL who received Venetoclax combined with multidrug chemotherapy from December 2018 to February 2022. Among them, eight cases were combined with demethylated drugs, four cases were combined with demethylated drugs and HAAG chemotherapy regimen, two cases were combined with demethylated drugs and CAG regimen, and one case was combined with Cladribine. Specific usage and dosage of Venetoclax: 100 mg on day 1, 200 mg on day 2, 400 mg on day 3-28, orally; when combined with azole antifungal drugs, dosage was reduced to 100 mg/d. Results: Fifteen patients (10 males and 5 females) with R/R ETP-ALL were treated with Venetoclax and multidrug chemotherapy with a median age of 35 (12-42) years old. Of 4 refractory and 11 relapsed patients, the efficacy was evaluated on the 21th day following combined chemotherapy: the overall response rate, the complete response (CR) rate, and the CR with incomplete hematological recovery (CRi) rate were 67.7% (10/15), 60.0% (9/15), and 6.7% (1/15), respectively. For the overall study population, the 12-month overall survival (OS) rate was 60.0%, and the median OS was 17.7 months. The disease-free survival (DFS) rate of all CR patients at 12 months was 60.0%, and the median DFS did not reach. About 14 patients had Ⅲ-Ⅳ hematological toxicity, but these adverse reactions were all controllable. No adverse reaction in the nervous system and tumor lysis syndrome occurred in this study, and no adverse reaction of organs above grade Ⅲ occurred. Conclusion: Venetoclax combined with multidrug chemotherapy may be a safe and promising treatment option for patients with R/R ETP-ALL.

[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.

[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.

[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.