Bacille Calmette-Guérin (BCG) vaccine is designed to provide protection against tuberculosis (TB). However, numerous epidemiological, clinical, and immunological studies have shown that BCG vaccination affects neonatal and infant mortality, which may be related to the reduction of TB-unrelated infections and diseases by BCG vaccine. We aimed to discuss the off-target effects of BCG vaccine on un-TB infections and diseases, as well as the potential mechanism and influencing factors. Literature was retrieved mainly from PubMed using medical subject headings "BCG, variations, and non-specific, heterologous or off-target". Studies have showed that BCG vaccination can prevent various heterologous infections, including respiratory tract infections, leprosy, and malaria, treat viral infections including human papillomavirus and herpes simplex virus infection as immunotherapy, and improve the immune responses as vaccine adjuvant. Besides, BCG vaccine can reduce the recurrence rate of non-muscle-invasive bladder cancer, and may provide protection against autoimmune diseases. These off-target effects of BCG vaccine are thought to be achieved by modulating heterologous lymphocyte responses or inducing trained immunity, which were found to be sex-differentiated and affected by the BCG vaccine strains, sequence or time of vaccination.

Objective:To investigate the impact of neuroendocrine function on postoperative complications and nutritional status in gastric cancer patients.Methods:Clinical data of 102 gastric cancer patients who underwent radical gastrectomy at the Department of General Surgery, First Affiliated Hospital of Soochow University, from Aug 2021 to Jun 2022 were retrospectively analyzed.Results:Among the 102 gastric cancer patients, 18 (17.6%) suffered from postoperative complications. Univariate analysis indicated that age, BMI, preoperative plasma ghrelin concentration, and preoperative hemoglobin levels were associated with early postoperative complications following radical gastrectomy. Multivariate analysis revealed that age, BMI, and preoperative plasma ghrelin concentration ( P<0.05) were independent risk factors for postoperative complications in gastric cancer patients. Differential analysis of ghrelin concentration demonstrated correlations with hemoglobin levels, skeletal muscle index, albumin, and creatinine, and a positive correlation with the skeletal muscle index. Conclusions:Reduced preoperative neuroendocrine hormone ghrelin concentration is an independent risk factor for postoperative complications in gastric cancer patients. Ghrelin concentration is correlated with the skeletal muscle index in these patients.

Objective:To explore the risk factors of postoperative depression in patients with esophageal cancer, and to develop a risk prediction model which providing a theoretical basis for the early detection of depression in high-risk groups by clinical staff.Methods:From September 2022 to March 2023, at the South Campus of Affiliated Hospital of Jiangnan University, 269 hospitalized patients with esophageal cancer (191 in depression group, 78 in non-depression group) were selected as the model construction set. From March to May 2023, at the South Campus of Affiliated Hospital of Jiangnan University, 78 hospitalized patients with esophageal cancer were selected as the external validation set. The patients with Beck depression inventory-Ⅱ score ≥5 and depression diagnosed by two experts (chief psychiatrists of the Department of Psychiatry of Affiliated Hospital of Jiangnan University) were considered as depression and included in the depression group, and the other patients were enrolled in the non-depression group. The general data, blood routine examination, high-sensitivity C-reactive protein (hs-CRP), blood electrolytes, blood lipids, clinical symptoms (gastroesophageal reflux, sleep disturbance, appetite, etc.) and depression score were compared between the depression group and the non-depression group. Independent sample t-test and Mann-Whitney U test were used for statistical analysis. Multiple logistic regression model was performed to analyze the independent risk factors of postoperative depression in patients with esophageal cancer, and a risk warning model was constructed. The Hosmer-Lemeshow test and receiver operating characteristic curve (ROC) were used to evaluate the fitting degree and predictive efficiency of the model, and the cross-validation method was used to verify the effectiveness of the model. Results:The incidence of postoperative depression in patients with esophageal cancer was 71.0% (191/269). The total white blood cell count, hs-CRP, blood phosphorus β 2 microglobulin and the proportion of sleep disorders of the depression group were higher than those of the non-depression group (1.3 (1.1, 5.4) ×10 9/L vs. 0.9 (0.3, 1.1) ×10 9/L, 75.8 (54.8, 102.1) mg/L vs. 60.8 (3.6, 61.5) mg/L, (1.33±0.32) mmol/L vs. (1.02±0.19) mmol/L, (2.17±0.72) mg/L vs.(2.12±0.49) mg/L, 84.3% (161/191) vs. 33.3% (26/78), and the differences were statistically significant ( Z=9.24, 7.88, t=9.24, χ2=67.87 t=1.98; all P<0.001); hemoglobin, total platelet count, high-density lipoprotein (HDL) and the proportion of poor appetite were lower than those of the non-depression group ((119.91±24.51) g/L vs. (122.09±22.97) g/L, (203.43±58.45)×10 9/L vs. (311.55±83.54)×10 9/L, (1.04±0.30) mmol/L vs. (1.43±0.23) mmol/L, 73.3% (140/191) vs. 84.6% (66/78)), and the differences were statistically significant ( t=-2.00, -8.42 and -8.48, χ2=3.96; P=0.047, <0.001, <0.001, =0.047). The results of multifactorial logistic regression model analysis showed that sleep disorder ( OR=3.976, 95% confidence interval (95% CI 1.601 to 9.872)), loss of appetite ( OR=0.271, 95% CI 0.092 to 0.791), white blood cell count ( OR=31.808, 95% CI 2.879 to 351.401), hs-CRP ( OR=1.031, 95% CI 1.017 to 1.044), platelet count ( OR=0.990, 95% CI 0.982 to 0.997), and HDL ( OR=0.017, 95% CI 0.001 to 0.242) were independent influencing factors of postoperative depression in patients with esophageal cancer. The formula of risk warning model was probability of depression=1-1/{1+ exp[1.544+ 1.380×sleep disturbance (yes=1, no=0)-1.307×loss of appetite (yes=1, no=0)-0.010×platelet count (×10 9/L)-4.063×HDL (mmol/L)+ 0.030×hs-CRP (mg/L)+ 3.460×white blood cell count (×10 9/L)]}. The results of Hosmer-Lemeshow test showed that the model has a good fit ( χ2=2.01, P=0.981), with an area under the ROC of 0.949, a sensitivity of 0.874, and a specificity of 0.872. The cross-validation of the external validation set showed that the accuracy of the risk warning model was 67.9%. Conclusion:This study is a preliminary study on the risk warning model of postoperative depression in patients with esophageal cancer, which provides a novel approach for screening depression in patients with esophageal cancer after surgery.

Objective To investigate the effects of Shenling Baizhu San on hepatic lipid metabolism in mice with metabolic associated fatty liver disease(MAFLD)based on the KLF16/PPAR-α signaling pathway.Methods C57 BL/6 mice were randomly divided into normal group,model group and Shenling Baizhu San low-,medium-and high-dose groups(2.685,5.369,10.738 g·kg-1·d-1),with seven mice in each group.Except for the normal group,the mice in the other groups were given high-fat diet for 12 weeks to replicate the MAFLD model.After the modeling,intragastric administration was started once a day for five weeks.The body mass and liver coefficient of mice were measured.HE and oil red O staining were used to observe the pathological changes of liver tissue in mice.The levels of serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),triglyceride(TG)and total cholesterol(TC)were detected.The mRNA expression levels of PPAR-α,KLF16,FAS and SREBP-1c in liver tissue were detected by RT-qPCR.Results Compared with the normal group,the body mass,liver mass and liver coefficient of mice in the model group were significantly increased(P＜0.05,P＜0.01).The levels of serum TG,TC,ALT and AST were significantly increased(P＜0.001).There were a large number of vacuoles in the cytoplasm of the liver tissue,and a large number of red-stained lipid droplets appeared in the cytoplasm.The NAS pathological score and oil red O staining IOD value were significantly increased(P＜0.05,P＜0.001).The mRNA expressions of PPAR-α and KLF16 in liver tissue were significantly down-regulated(P＜0.01,P＜0.001),and the mRNA expressions of FAS and SREBP-1c was significantly up-regulated(P＜0.05,P＜0.001).Compared with the model group,the body mass,liver mass and liver coefficient of mice in the high-dose group of Shenling Baizhu San were significantly decreased(P＜0.05).The levels of serum TG,TC and ALT in the low-,medium-and high-dose groups of Shenling Baizhu San were significantly decreased(P＜0.05,P＜0.01,P＜0.001).The serum AST level of mice in the medium-and high-dose groups of Shenling Baizhu San was significantly decreased(P＜0.01,P＜0.001).The pathological changes of liver tissue in each administration group were significantly improved,and the orange-red lipid droplets in the cytoplasm of hepatocytes were significantly reduced.The NAS pathological score and oil red O staining IOD value of the high-dose group of Shenling Baizhu San were significantly reduced(P＜0.05,P＜0.01);the mRNA expressions of PPAR-α and KLF16 in liver tissue of mice in Shenling Baizhu San low-,medium-and high-dose groups were significantly up-regulated(P＜0.05,P＜0.01,P＜0.001),and the mRNA expressions of FAS and SREBP-1c were significantly down-regulated(P＜0.05,P＜0.01,P＜0.001).Conclusion Shenling Baizhu San can significantly improve hepatic lipid metabolism in MAFLD mice,and its mechanism may be related to transcriptional regulation of nuclear receptor KLF16/PPAR-α signaling pathway.

Objective To explore the feasibility and rationality of advanced integrated two-stage laparoscopic simulation training course in standardized training of surgical residents.Methods From December 2019 to December 2021,the advanced integrated two-stage laparoscopic simulation training course was carried out among 2019-2020 surgical residents who received standardized training in our hospital.The course was divided into two stages.In the first stage,BEST(best essential surgical technology training)course,adopted Darwin? endoscopic training system,Tianyan? endoscopic training system,Microport? 3D laparoscopic training system and simple simulative models were used.The second stage,BEST PLUS course,same platform as that in BEST course and in vitro animal models were used.The questionnaire survey method(before and after class questionnaire)was adopted to evaluate the curriculum setting,such as curriculum form,simulators,teaching method,time arrangement,curriculum difficulty,training effect,curriculum satisfaction and so on.Results A total of 37 surgical residents completed the two-stage course training and the questionnaire survey.The overall satisfaction rate with the curriculum setting was 100%.There were 32 residents(86.5%)thought that first stage training course could significantly improve their clinical skills,35 residents(94.6%)thought that second stage training course could significantly improve their clinical skills,and 36 resident(97.3%)thought that the first stage curriculum could significantly help them improve performance in the second stage curriculum.Conclusions The trainees had a high degree of recognition and satisfaction for the advanced integrated two-stage laparoscopic simulation training course.The overall design of course was reasonable and feasible,and was attractive to trainees.

NAD(P)H: quinone oxidoreductase 1 (NQO1) is a flavin protease highly expressed in various cancer cells. NQO1 catalyzes a futile redox cycle in substrates, leading to substantial reactive oxygen species (ROS) production. This ROS generation results in extensive DNA damage and elevated poly (ADP-ribose) polymerase 1 (PARP1)-mediated consumption of nicotinamide adenine dinucleotide (NAD⁺), ultimately causing cell death. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the NAD⁺ salvage synthesis pathway, emerges as a critical target in cancer therapy. The concurrent inhibition of NQO1 and NAMPT triggers hyperactivation of PARP1 and intensive NAD⁺ depletion. In this study, we designed, synthesized, and assessed a novel series of proqodine A derivatives targeting both NQO1 and NAMPT. Among these, compound T8 demonstrated potent antitumor properties. Specifically, T8 selectively inhibited the proliferation of MCF-7 cells and induced apoptosis through mechanisms dependent on both NQO1 and NAMPT. This discovery offers a promising new molecular entity for advancing anticancer research.
Humans ; NAD/metabolism* ; Cell Line, Tumor ; Reactive Oxygen Species/metabolism* ; Nicotinamide Phosphoribosyltransferase/metabolism* ; Cytokines/metabolism* ; Quinones ; Oxidoreductases

Objective:To investigate the alteration of m6A demethylase AlkB homolog 5 (ALKBH5) expression and its impact on form-deprivation myopia (FDM) retina in guinea pigs.Methods:Thirty normal SPF grade 3-week-old tricolor guinea pigs were randomly divided into normal control group and experimental group, with 15 in each group.In the experimental group, the right eyes were covered as FDM group and the left eyes uncovered were set as self-control group.Ocular biometry was performed at one-week intervals from baseline to week 4 of the experiment.Spherical equivalent was detected by streak retinoscopy and axial length was measured by A-scan ultrasonography.Animals were sacrificed after 4 weeks of modeling.The distribution and expression of ALKBH5 protein in the guinea pig retina was detected by immunohistochemical and immunofluorescence staining.Expression of ALKBH5 mRNA and protein in guinea pig retina was detected by real-time fluorescence quantitative PCR and Western blot, respectively.The use of animals in ophthalmic and vision research followed the tenets of Animal Research in Vision and Ophthalmology, and the study was approved by the Ethics Committee of North Sichuan Medical College (No.2023087).Results:At weeks 2, 3, and 4 after myopia induction, diopters and axial lengths were significantly higher in the FDM group than in the normal control group and the self-control group (all at P<0.001). Immunohistochemistry and immunofluorescence assays showed that ALKBH5 protein was expressed in the retinal nerve fiber layer, rod/cone photoreceptor cells, and retinal pigment epithelium (RPE) layer, and was highly expressed in the retinal nerve fiber layer and RPE layer.The relative ALKBH5 immunofluorescence intensity in the normal control group, self-control group and FDM group was 1.000±0.204, 0.874±0.076 and 0.571±0.053, respectively, which was lower in the FDM group than in the normal control and self-control groups, showing statistically significant differences ( t=4.069, P=0.006; t=5.176, P=0.014). After 4 weeks of modeling, ALKBH5 mRNA and protein expressions were significantly lower in FDM group than in normal control and self-control groups (both at P<0.01). Conclusions:The expression of m6A demethylase ALKBH5 is decreased in the retina of FDM guinea pigs, suggesting that ALKBH5 and related m6A methylation modification may be involved in the development and progression of myopia.

The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.How-ever,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive rela-tionship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met's anti-proliferative effects were blocked by AMPK inhibitor or YAP1 over-expression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.

Schistosomiasis was once hyper-endemic in Yunnan Province. Following concerted efforts for over 70 years, remarkable achievements have been made for schistosomiasis control in the province. In 2004, the Mid- and Long-term Plan for Schistosomiasis Prevention and Control in Yunnan Province was initiated in Yunnan Province, and the target for transmission control of schistosomiasis was achieved in the province in 2009. Following the subsequent implementation of the Outline for Key Projects in Integrated Schistosomiasis Control Program (2009—2015) and the 13th Five - year Plan for Schistosomiasis Control in Yunnan Province, no acute schistosomiasis had been identified in Yunnan Province for successive 12 years, and no local Schistosoma japonicum infections had been detected in humans, animals or Oncomelania hupensis snails for successive 6 years in the province by the end of 2020. The transmission of schistosomiasis was interrupted in Yunnan Province in 2020. This review summarizes the history of schistosomiasis, changes in schistosomiasis prevalence and progress of schistosomiasis control in Yunnan Province, and proposes the future priorities for schistosomiasis control in the province.

Objective To predict the potential geographic distribution of Oncomelania hupensis in Yunnan Province using random forest (RF) and maximum entropy (MaxEnt) models, so as to provide insights into O. hupensis surveillance and control in Yunnan Province. Methods The O. hupensis snail survey data in Yunnan Province from 2015 to 2016 were collected and converted into O. hupensis snail distribution site data. Data of 22 environmental variables in Yunnan Province were collected, including twelve climate variables (annual potential evapotranspiration, annual mean ground surface temperature, annual precipitation, annual mean air pressure, annual mean relative humidity, annual sunshine duration, annual mean air temperature, annual mean wind speed, ≥ 0 ℃ annual accumulated temperature, ≥ 10 ℃ annual accumulated temperature, aridity and index of moisture), eight geographical variables (normalized difference vegetation index, landform type, land use type, altitude, soil type, soil textureclay content, soil texture-sand content and soil texture-silt content) and two population and economic variables (gross domestic product and population). Variables were screened with Pearson correlation test and variance inflation factor (VIF) test. The RF and MaxEnt models and the ensemble model were created using the biomod2 package of the software R 4.2.1, and the potential distribution of O. hupensis snails after 2016 was predicted in Yunnan Province. The predictive effects of models were evaluated through cross-validation and independent tests, and the area under the receiver operating characteristic curve (AUC), true skill statistics (TSS) and Kappa statistics were used for model evaluation. In addition, the importance of environmental variables was analyzed, the contribution of environmental variables output by the models with AUC values of > 0.950 and TSS values of > 0.850 were selected for normalization processing, and the importance percentage of environmental variables was obtained to analyze the importance of environmental variables. Results Data of 148 O. hupensis snail distribution sites and 15 environmental variables were included in training sets of RF and MaxEnt models, and both RF and MaxEnt models had high predictive performance, with both mean AUC values of > 0.900 and all mean TSS values and Kappa values of > 0.800, and significant differences in the AUC (t = 19.862, P < 0.05), TSS (t = 10.140, P < 0.05) and Kappa values (t = 10.237, P < 0.05) between two models. The AUC, TSS and Kappa values of the ensemble model were 0.996, 0.954 and 0.920, respectively. Independent data verification showed that the AUC, TSS and Kappa values of the RF model and the ensemble model were all 1, which still showed high performance in unknown data modeling, and the MaxEnt model showed poor performance, with TSS and Kappa values of 0 for 24%(24/100) of the modeling results. The modeling results of 79 RF models, 38 MaxEnt models and their ensemble models with AUC values of > 0.950 and TSS values of > 0.850 were included in the evaluation of importance of environmental variables. The importance of annual sunshine duration (SSD) was 32.989%, 37.847% and 46.315% in the RF model, the MaxEnt model and their ensemble model, while the importance of annual mean relative humidity (RHU) was 30.947%, 15.921% and 28.121%, respectively. Important environment variables were concentrated in modeling results of the RF model, dispersed in modeling results of the MaxEnt model, and most concentrated in modeling results of the ensemble model. The potential distribution of O. hupensis snails after 2016 was predicted to be relatively concentrated in Yunnan Province by the RF model and relatively large by the MaxEnt model, and the distribution of O. hupensis snails predicted by the ensemble model was mostly the joint distribution of O. hupensis snails predicted by RF and MaxEnt models. Conclusions Both RF and MaxEnt models are effective to predict the potential distribution of O. hupensis snails in Yunnan Province, which facilitates targeted O. hupensis snail control.