Construction of a predictive model for the incidence of pulmonary tuberculosis in Nantong based on multivariate regression / 公共卫生与预防医学

Objective To establish a prediction model for tuberculosis incidence in Nantong area by multivariate regression analysis, and to provide theoretical support for the implementation of combined prevention work in this area. Methods A total of 37 338 registered patients with pulmonary tuberculosis in Nantong City from 2010 to 2021 were enrolled in the observation group. A total of 28,721 healthy people who underwent physical examination during the same period were selected as the control group. Results From 2010 to 2021, there were a total of 37 338 cases of pulmonary tuberculosis in central Nantong. From 2010 to 2015, more than 3,000 cases were reported annually, with the largest number (4 142 cases) in 2011, accounting for 11.09% of the total. The number of cases reported from 2016 to 2021 was all less than 3 000, and the number of cases reported from 2021 was the least , 1 803 cases, accounting for 4.83% of the total. The number of cases decreased each year in the past 12 years. The incidence of pulmonary tuberculosis in males was 70.97% (26 497 cases) and that in females was 29.03% (10 841 cases). In terms of age, the lowest incidence rate was 0.06% (23 cases) in the age group of 0-9 years old, and the highest incidence rate was 19.56% (7 304 cases) in the age group of 60-69 years old. Logistics regression analysis showed that male, age ≥60 years old, occupation as a farmer and smoking history were the risk factors for pulmonary tuberculosis (P < 0.05). ROC curve results showed that the AUC value of the risk prediction model for pulmonary tuberculosis in the Nantong area was 0.872, with a predictive sensitivity of 86.32% and a specificity of 89.21%. Conclusion There are many risk factors for pulmonary tuberculosis in Nantong area, and different factors interact and influence each other. The construction of a risk prediction model for pulmonary tuberculosis can better predict the clinical incidence, which is helpful to guide clinical diagnosis and treatment.

Predictors for muscle invasion of upper tract urothelial carcinoma / 中华泌尿外科杂志

Objective:To explore the predictors of upper tract urothelial carcinoma (UTUC) invading muscle.Methods:The preoperative clinical data of 169 patients with UTUC who underwent radical nephroureterectomy (RNU) in the Department of Urology, Second Hospital of Tianjin Medical University from August 2019 to September 2021 were retrospectively collected. The average age of the patients was (67.7±8.3)years. There were 95 male cases (56.2%).15 cases (15.8%) were with diabetes, 46 cases (48.4%) with hypertension, 68 cases (71.6%) with hematuria, 44 cases (46.3%) with renal pelvis tumor, 74 cases (77.9%) with hydronephrosis and 8 cases (8.4%) with multifocality. There were 15 (20.3%), with diabetes, 40(54.1%) with hypertension, 58(78.4%)with hematuria, 32(43.2%) with renal pelvis tumor, 60(81.1%) with hydronephrosis and 2(2.7%) with multifocality among 74 female patients(43.8%), respectively. Patients’ body mass index (BMI) was (24.2±3.2) kg/m 2.The tumor diameter was (3.4±1.8) cm. The average count of neutrophil (NEU) was (4.2±1.7) ×10 9/L, with monocyte (MON) (0.4±0.2) ×10 9/L, platelet (PLT) (237.8±75.3) ×10 9/L and lymphocyte (LYM) (1.7±0.5) ×10 9/L. Neutrophil-to-lymphocyte ratio (NLR) was 2.7±1.4. Mmonocyte-to-lymphocyte ratio (MLR) was 0.3±0.1 and platelet-to-lymphocyte ratio (PLR) was 151.1±59.6. The concentrations of hemoglobin (Hb) and fibrinogen (FIB) were (127.1±18.3) g/L and(3.5±1.0) g/L. Univariate logistic regression analysis was performed on all preoperative data, and a nomogram was established to predict UTUC invading muscle by stepwise regression combined with multivariate logistic analysis. Concordance index (C-index) was used to evaluate the accuracy of the model, and Hosmer-Lemeshow test was used to check the fit. Using 1000 bootstrap resampling to validate the model and draw calibration plot. Receiver operating characteristics (ROC) curves were used to determine the most appropriate cut-off point of the model to predict tumor invasion and evaluate its sensitivity and specificity. Results:In this study, there were 169 cases. Postoperative pathological results showed that 18 cases (10.6%) were of low grade and 151 cases (89.4%) were of high grade. There were 2 patients (1.2%) with pT a stage, 44 patients (26.0%) with pT 1 stage, 37 patients (21.9%) with pT 2 stage, 81 patients (47.9%) with pT 3 stage and 5 patients (3.0%) with pT 4 stage. According to tumor stage, 46 patients were included into non-muscle invasive disease (NMID, pT a/T is/T 1) group and 123 patients were included into muscle invasive disease (MID, pT 2/T 3/T 4) group. Univariate analysis showed that hydronephrosis ( OR=2.919, 95% CI 1.332-6.387, P=0.007) was significantly correlated with MID. Tumor location in ureter ( OR=1.898, 95% CI 0.960-3.800, P=0.067), higher NLR value ( OR=1.313, 95% CI 0.9901.832, P=0.082) and FIB concentration ( OR=1.436, 95% CI 1.008-2.125, P=0.056) might have potential association with MID. Stepwise regression method was used to screen out PLT, FIB and hydronefrosis as the optimal combination for MID prediction. multivariate analysis suggested that PLT decreasing ( OR=0.727, 95% CI 0.548-0.955, P=0.023), FIB increasing ( OR=1.629, 95% CI 1.084-2.552, P=0.025) and hydronephrosis ( OR=2.500, 95% CI 1.111-5.601, P=0.026) were independent predictors of MID.The C-index of the model constructed by the three factors was 0.682, and the P-value of the goodness of fit was 0.778. The ROC curve showed that the optimal cut-off point for the prediction of high-risk MID by the nomogram was 0.627, achieving 39.1% specificity, 88.6% sensitivity and 0.682 area under the curve (AUC). Conclusions:Preoperative decrease of PLT, increase of FIB and hydronephrosis were independent factors for predicting UTUC invading muscle.

Comparison of 3D-arterial spin labeling and digital subtraction angiography in the diagnosis of occlusion and collateral circulation in patients with acute ischemic stroke / 中国医师杂志

Objective:To explore the diagnostic value of 3D-arterial spin labeling (ASL) and digital subtraction angiography (DSA) in the occlusion and collateral circulation (CC) of patients with acute ischemic stroke (AIS).Methods:From January 2019 to June 2020, 53 cases of AIS patients with middle cerebral artery (MCA) occlusion in Langfang Hospital of Traditional Chinese Medicine were selected as the research objects. All patients underwent DSA and 3D ASL examination. According to the gold standard of DSA, the diagnostic value of proximal intra-arterial signal (IAS) in 3D-ASL was observed, and the clinical value of distal IAS in the diagnosis of lateral CC was observed. Univariate and multivariate logistic regression were used to identify risk factors for poor outcome in AIS patients.Results:There were 31 cases with good collateral circulation judged by DSA. Taking DSA as the gold standard, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of digital IAS in diagnosing CC status were 93.55%, 81.82%, 87.88%, 90.00% and 88.68%, respectively. The National Institutes of Health Stroke Scale (NIHSS) score of patients with good CC assessed by 3D-ASL was lower than that of patients with poor CC at admission, and the good prognosis rate at discharge was higher than that of patients with poor CC, with statistically significant difference (all P<0.05). There was no significant difference in clinical data between patients with good CC and those with poor CC, such as gender, age, history of atrial fibrillation, hypertension, diabetes, smoking, drinking, onset to treatment time, treatment methods, etc (all P>0.05). Univariate and multivariate analysis showed that poor CC assessed by ASL was a risk factor for poor prognosis in AIS patients ( OR=5.897, P<0.05). Conclusions:The proximal and distal IAS of 3D-ASL can provide important diagnostic clues for detecting arterial occlusion and collateral perfusion in patients with AIS, and the detection of CC by ASL is of great value for prognosis.

Effects of Banxia Shumi Decoction on 5-hydroxytryptamine receptor, 5-HT, and 5-HIAA of chronic insomnia rats with internal obstruction of phlegm-dampness / 国际中医中药杂志

Objective:To observe the effects of Banxia Shumi Decoction on 5-HT 1AR, 5-HT 2AR, 5-HT, and 5-HIAA of chronic insomnia (CI) rats with internal obstruction of phlegm-damp (IOPD) type, to investigate the mechanisms of Banxia Shumi Decoction on resolving and draining dampness, guiding yang into yin and tranquilizing mind. Methods:A total of 48 Wistar rats were divided into control group, model group, Banxia Shumi Decoction low-dosage group, medium-dosage group, high-dosage group, and diazepam group according to random number table method, with 8 rats in each group. Except the control group, the CI with IOPD rats model were prepared by the method of "high-fat diet + single-platform water environment" in other groups. The rats in the Banxia Shumi Decoction low-, medium-, high-dosage group were treated with Banxia Shumi Decoction by gavage at the dose of 4.69, 9.38 and 18.75 g/kg respectively, the rats in the diazepam group were given 0.52 mg/kg diazepam aqueous solution by gavage, and the rats in the control group and model group were given the equal volume normal saline, once a day for consecutive 2 weeks. The mRNA expressions of 5-HT 1AR, 5-HT 2AR in rat brain stem were detected by qPCR, the protein expressions of 5-HT 1AR, 5-HT 2AR in rat brain raphe nucleus were detected by Western blot, and the contents of 5-HT and 5-HIAA in rat brain stem were determined by HPLC-MS. Results:Compared with model group, the expression of 5-HT 1AR mRNA significantly increased in the Banxia Shumi Decoction low-, medium-, high-dosage group, and diazepam group ( P<0.01); the expression of 5-HT 2AR mRNA significantly decreased in the Banxia Shumi Decoction high-dosage group and diazepam group ( P<0.05), and the expression of 5-HT 1AR and 5-HT 2AR significantly increased in the Banxia Shumi Decoction high-dosage group and diazepam group ( P<0.05 or P<0.01); 5-HT content significantly increased in the Banxia Shumi Decoction medium-, high-dosage group and diazepam group ( P<0.05 or P<0.01); 5-HIAA content significantly increased in the Banxia Shumi Decoction low-, medium-, high-dosage group, and diazepam group ( P<0.05 or P<0.01). Conclusion:Banxia Shumi Decoction may intervene CI with IOPD type and perform the actions of resolving and draining dampness, guiding yang into yin and tranquilizing mind by regulating the expressions of 5-HT 1AR, 5-HT 2AR, 5-HT and 5-HIAA.

Clinical application of G-iliac? iliac branch device in the treatment of common iliac artery aneurysm / 国际外科学杂志

Objective:To analyze the safety and efficacy of G-iliac? iliac branch device (IBD) in the treatment of common iliac artery aneurysm.Methods:The clinical data of 7 patients with common iliac artery aneurysm who were treated with G-iliac? IBD and internal iliac artery (IIA) preserved were retrospectively analyzed in the Department of Vascular Surgery, Beijing Friendship Hospital, Capital Medical University from June 2021 to June 2022, and the surgical effects and related complications were analyzed.Results:All 7 patients were male, aged from 57 to 80 years, with an average age of 70.9 years. There were 6 cases of abdominal aortic aneurysm combined with common iliac artery aneurysm and 1 case of simple common iliac artery aneurysm, all of them were successfully applied with G-iliac? IBD to preserve IIA. Cardiogenic shock occurred in 1 patient after the operation. 7 patients were followed up for 3-15 months, with an average of 8 months. During the follow-up period, the iliac artery and IIA stents were all patency, and there was no IBD-related endoleak, stent displacement, buttock claudication, sexual dysfunction, or aortic-related death. The diameter of abdominal aortic aneurysm and common iliac artery aneurysm were stable.Conclusion:For patients with common iliac artery aneurysm, preservation of IIA with G-iliac? IBD is a safe and effective technique with a high technical success rate and IIA patency rate, and has a low complication rate, but the long-term effect still requires more data and longer follow-up data to support.

Analysis of therapeutic effect on the spontaneous isolated superior mesenteric artery dissection with endovascular therapy / 国际外科学杂志

Objective:To discuss the clinical effect of endovascular treatment of 15 patients with spontaneous isolated superior mesenteric artery dissection(SISMAD).Methods:The clinical data of 15 patients with SISMAD treated with endovascular stent in Beijing Friendship Hospital Affiliated to Capital Medical University from January 2016 to July 2022 were collected and analyzed. The white blood cell, neutrophil percentage (NEUT%) and D-Dimer at admission, day 1 and day 3 after operation were analyzed and compared retrospectively. The time of abdominal pain at admission, YOO classification, angle from superior mesenteric artery to abdominal aorta(ASA), conservative treatment time, operation time, type and length of stent, vascular remodeling rate and long-term patency rate of stent were analyzed. The measurement data conforming to normal distribution was expressed as mean ± standard deviation ( ± s), t-test was used for comparison between the two groups. Measurement data of skewed distribution were expressed as M ( Q1, Q3), and non-parametric test was used for comparison between groups. Count data were expressed as rate or component ratio(%). The same variable was compared at different time points by repeated measurement data analysis of variance. Results:There were significant differences in white blood cell, NEUT% and D-Dimer between admission and postoperative day 3 in 15 patients. The time to admission for abdominal pain was 24.0(15.0, 78.0) hours. IVS type accounted for 46.7% of YOO type, and the ASA beyond 60° accounted for 66.7%. The conservative treatment time was (34.0±8.6) hours, moreover, the operation time was(153.0±37.8) min. Besides, self-expanding bare stent accounted for 85% of the stent types, moreover, the length of the stents beyond 60 cm was 50%. All patients were followed up for more than 24 months, and the vascular remodeling rate was(89.7±9.7)%.Conclusion:Endovascular self-expanding thin-wall stent placement has better vascular remodeling rate and patency rate for patients with IVS type.

Regulation Mechanism of m6A Methylation Modification in the Development of Prostate Cancer / 中国生物化学与分子生物学报

N6-adenosine methylation, a form of methylation of the adenosine N6 site, is often found in eukaryotic mRNA and is one of the most common forms of internal RNA modification. Studies have shown that m6A affects cellular biological processes by regulating gene expression; also the regulators of m6A play a key role in the occurrence and development of various cancers. Prostate Cancer (PCa) is a common malignant tumor in men, and the risk of the disease in men over 60 years of age is increasing year by year. With the aging population, the number of PCa can be expected to continue to rise. In recent years, the role of m6A in tumorigenesis has received widespread attention, but studies on m6A methylation modification in PCa are still limited; therefore, it is particularly important to further explore the relationship between m6A methylation and PCa. In this paper, we review the recent research progress on the role, mechanism, and application of m6A methylation modification in PCa, especially the detailed review of the mechanism of METTL3, FTO, YTHDF2, three classical m6A-related regulatory proteins in PCa; and the potential application of m6A in advanced PCa (e. g., destructive resistant prostate cancer, bone metastatic prostate cancer). From the perspective of methylation modification, this paper may provide some clues to find effective therapeutic strategies for early diagnosis, treatment, and prognosis of PCa, and more theoretical references to achieve individualized treatment.

Liraglutide inhibits high glucose-induced cardiomyocyte hypertrophy via modulating autophagy and Na / 中国药理学通报

Aim To investigate the mechanism through which liraglutide (LRG) inhibited high glucose (HG)-induced cardiomyocyte hypertrophy. Methods Cultured H9c2 were divided into control (CON) group, HG group, low-, middle- and high-dose LRG (LRG-L, LRG-M and LRG-H) groups, LRG-H + autophagy inhibitor trimethyladenine (3-MA) group. The relative cell surface change was assessed phalloidin staining. Membrane bound Na, K

Distinct mononuclear diploid cardiac subpopulation with minimal cell-cell communications persists in embryonic and adult mammalian heart / 医学前沿

A small proportion of mononuclear diploid cardiomyocytes (MNDCMs), with regeneration potential, could persist in adult mammalian heart. However, the heterogeneity of MNDCMs and changes during development remains to be illuminated. To this end, 12 645 cardiac cells were generated from embryonic day 17.5 and postnatal days 2 and 8 mice by single-cell RNA sequencing. Three cardiac developmental paths were identified: two switching to cardiomyocytes (CM) maturation with close CM-fibroblast (FB) communications and one maintaining MNDCM status with least CM-FB communications. Proliferative MNDCMs having interactions with macrophages and non-proliferative MNDCMs (non-pMNDCMs) with minimal cell-cell communications were identified in the third path. The non-pMNDCMs possessed distinct properties: the lowest mitochondrial metabolisms, the highest glycolysis, and high expression of Myl4 and Tnni1. Single-nucleus RNA sequencing and immunohistochemical staining further proved that the Myl4+Tnni1+ MNDCMs persisted in embryonic and adult hearts. These MNDCMs were mapped to the heart by integrating the spatial and single-cell transcriptomic data. In conclusion, a novel non-pMNDCM subpopulation with minimal cell-cell communications was unveiled, highlighting the importance of microenvironment contribution to CM fate during maturation. These findings could improve the understanding of MNDCM heterogeneity and cardiac development, thus providing new clues for approaches to effective cardiac regeneration.

Relationship between serum reproductive hormones and sperm parameters and surgical outcomes in Micro-TESE / 现代泌尿外科杂志

【Objective】 To investigate the relationship between serum reproductive hormones and sperm parameters and outcomes of micro-testicular sperm extraction (Micro-TESE). 【Methods】 Clinical data of 1 091 patients treated in our hospital during Jan. and Dec.2021 were retrospectively analyzed. According to the sperm concentration,the patients were divided into non-obstructive azoospermia (NOA) group (group A,n=418),normal sperm concentration group (group B,n=615),mild to moderate oligospermia group (group C,n=18),severe oligospermia group (group D,n=18),and obstructive azoospermia group (group E,n=22). In group A,244 cases treated with Micro-TESE were grouped into the sperm-acquired group (Micro-TESE positive group,n=82) and non-sperm-acquired group (Micro-TESE negative group,n=162),and according to the pathological types of testicular tissue,the patients were divided into normal testicular tissue with hypospermatogenesis group (HYPO group,n=129),maturation arrest group (MA group,n=10),and support-only cell syndrome group (SCO group,n=122). Differences in semen parameters and reproductive hormone levels were compared,and relationship between reproductive hormones and sperm parameters and Micro-TESE outcomes was determined with Pearson correlation analysis. 【Results】 In the sperm concentration subgroup,the testicular volume of group A was lower than that of group B and group E (P<0.05); the levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH) in group A were the highest (P<0.05),but the level of testosterone (T) was the lowest (P<0.05); the levels of anti-mullerian hormone (AMH) and serum inhibin B (INHB) in group A were lower than those in group B and group E (P<0.05),the normal sperm morphology rate in group B was higher than that in group A and group E (P<0.05); the percentage of forward moving sperm in group B was the highest (P<0.05). Pearson correlation analysis revealed that sperm concentration,normal sperm morphology rate,and percentage of forward moving sperm were negatively correlated with age,FSH,LH (P<0.05),and positively correlated with testicular volume,T,AMH,and INHB (P<0.05). NOA patients were grouped according to testicular histology and pathology. The INHB in the SCO group was the smallest of the three groups (P<0.05); the FSH and LH levels in the SCO group were higher than those in the MA group (P<0.05),while the 17β-estradiol (E2) levels in the HYPO group were higher than those in the SCO group (P<0.05). NOA patients were grouped according to the results of Micro-TESE surgical treatment. There was a statistically significant difference in AMH and INHB levels between the Micro-TESE positive and negative groups (P<0.05). The binary logistic regression analysis of factors affecting the Micro-TESE outcomes of NOA patients showed AMH was negatively correlated with the Micro-TESE outcome (OR=0.904,95%CI:0.91-1.08,P<0.05). 【Conclusion】 Age,FSH,LH,AMH,and INHB are correlated with sperm concentration,normal sperm morphology rate,and percentage of forward moving sperm. The INHB level was the lowest in the SCO group. The results of Micro-TESE in patients with NOA can be predicted by serum AMH level.

Factors influencing the sperm retrieval rate of microdissection testicular sperm extraction in patients with nonmosaic Klinefelter syndrome / 亚洲男科学杂志(英文版)

To investigate the factors affecting the sperm retrieval rate of microdissection testicular sperm extraction (micro-TESE) in patients with nonmosaic Klinefelter syndrome (KS), 64 patients with nonmosaic KS who underwent micro-TESE in the Center for Reproductive Medicine of Peking University Third Hospital (Beijing, China) between January 2016 and December 2017 were included in the study. Data on medical history, physical examination and laboratory examination results, and micro-TESE outcomes were collected. Patients were divided into two groups according to micro-TESE outcomes. The following factors were compared between the two groups by the Mann‒Whitney U test or Student's t-test based on the distribution (nonnormal or normal) of the factors: age, testicular size, follicle-stimulating hormone level, luteinizing hormone level, testosterone level, and anti-Müllerian hormone level. The overall success rate of sperm retrieval was 50.0%. Correlation analysis showed that testicular volume was positively correlated with testosterone level. Using a logistic regression model, age and anti-Müllerian hormone levels were found to be better predictors for the sperm retrieval rate than the other parameters.

Optic cup and disc segmentation model based on linear attention and dual attention / 生物医学工程学杂志

Glaucoma is one of blind causing diseases. The cup-to-disc ratio is the main basis for glaucoma screening. Therefore, it is of great significance to precisely segment the optic cup and disc. In this article, an optic cup and disc segmentation model based on the linear attention and dual attention is proposed. Firstly, the region of interest is located and cropped according to the characteristics of the optic disc. Secondly, linear attention residual network-34 (ResNet-34) is introduced as a feature extraction network. Finally, channel and spatial dual attention weights are generated by the linear attention output features, which are used to calibrate feature map in the decoder to obtain the optic cup and disc segmentation image. Experimental results show that the intersection over union of the optic disc and cup in Retinal Image Dataset for Optic Nerve Head Segmentation (DRISHTI-GS) dataset are 0.962 3 and 0.856 4, respectively, and the intersection over union of the optic disc and cup in retinal image database for optic nerve evaluation (RIM-ONE-V3) are 0.956 3 and 0.784 4, respectively. The proposed model is better than the comparison algorithm and has certain medical value in the early screening of glaucoma. In addition, this article uses knowledge distillation technology to generate two smaller models, which is beneficial to apply the models to embedded device.

High sodium diet on the prevalence and mortality of gastric cancer in Xi'an / 公共卫生与预防医学

Objective To investigate the effect of high sodium diet on the prevalence and mortality of gastric cancer in Xi'an , and to provide reference for its clinical treatment and prevention. Methods A questionnaire survey was conducted on 604 inpatients in tertiary hospitals in Xi'an from 2018 to 2020, and data including medical history, medication use, daily sodium intake and gastric cancer incidence were collected. A one-year follow-up was completed, and all-cause mortality was recorded during the follow-up period. Results A total of 604 cases , there were 81 cases of gastric cancer and 523 cases of non-gastric cancer, with a prevalence rate of 13.41%. Among patients with gastric cancer, 49 (8.11%) were male and 32 (5.30%) were female. There were 9 cases (1.49%) aged 30-40 years, 14 cases (2.32%) aged 41-50 years, 27 cases (4.47%) aged 51-60 years and 31 cases (5.13%) aged 60 years and above. The gastric cancer and non-gastric cancer patients yielded no statistical difference in terms of age, gender and medical history (P>0.05), while the proportion of sodium intake was significantly higher in gastric cancer patients than in non-gastric cancer patients (P<0.05). Logistics analysis showed that high sodium diet was a risk factor for the development of gastric cancer (P<0.05). The proportion of high sodium diets was 40.89% (247/604) in all selected individuals, 72.84% (59/81) in gastric cancer patients and 35.95% (188/523) in non-gastric cancer patients. The proportion of patients on a high sodium diet demonstrated statistical difference between gastric cancer and non-gastric cancer patients (P<0.05). One-year follow-up showed that 58 of 81 gastric cancer patients survived (71.60%) and 23 died (28.40%), including 20 survivors (34.48%) and 17 deaths (73.91%) on a high-sodium diet. Significant difference was found in the proportion of patients on high sodium diet between dead and surviving gastric cancer patients (P<0.05). Conclusion The prevalence and mortality rate of gastric cancer caused by high sodium diet is high among residents in Xi'an , clinical guidance on sodium intake is of great importance to patients.

The protective effects and underlying mechanisms of dapagliflozin on diabetes-induced testicular dysfunction / 亚洲男科学杂志(英文版)

Male diabetic individuals present a marked impairment in fertility; however, knowledge regarding the pathogenic mechanisms and therapeutic strategies is unsatisfactory. The new hypoglycemic drug dapagliflozin has shown certain benefits, such as decreasing the risk of cardiovascular and renal events in patients with diabetes. Even so, until now, the effects and underlying mechanisms of dapagliflozin on diabetic male infertility have awaited clarification. Here, we found that dapagliflozin lowered blood glucose levels, alleviated seminiferous tubule destruction, and increased sperm concentrations and motility in leptin receptor-deficient diabetic db/db mice. Moreover, the glucagon-like peptide-1 receptor (GLP-1R) antagonist exendin (9-39) had no effect on glucose levels but reversed the protective effects of dapagliflozin on testicular structure and sperm quality in db/db mice. We also found that dapagliflozin inhibited the testicular apoptotic process by upregulating the expression of the antiapoptotic protein B-cell lymphoma 2 (BCL2) and X-linked inhibitor of apoptosis protein (XIAP) and inhibiting oxidative stress by enhancing the antioxidant status, including total antioxidant capacity, total superoxide dismutase (SOD) activity, and glutathione peroxidase (GPx) activity, as well as decreasing the level of 4-hydroxynonenal (4-HNE). Exendin (9-39) administration partially reversed these effects. Furthermore, dapagliflozin upregulated the glucagon-like peptide-1 (GLP-1) level in plasma and GLP-1R expression by promoting AKT8 virus oncogene cellular homolog (Akt) phosphorylation in testicular tissue. Exendin (9-39) partially inhibited Akt phosphorylation. These results suggest that dapagliflozin protects against diabetes-induced spermatogenic dysfunction via activation of the GLP-1R/phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Our results indicate the potential effects of dapagliflozin against diabetes-induced spermatogenic dysfunction.

Ethics considerations on brain-computer interface technology / 生物医学工程学杂志

The development and potential application of brain-computer interface (BCI) technology is closely related to the human brain, so that the ethical regulation of BCI has become an important issue attracting the consideration of society. Existing literatures have discussed the ethical norms of BCI technology from the perspectives of non-BCI developers and scientific ethics, while few discussions have been launched from the perspective of BCI developers. Therefore, there is a great need to study and discuss the ethical norms of BCI technology from the perspective of BCI developers. In this paper, we present the user-centered and non-harmful BCI technology ethics, and then discuss and look forward on them. This paper argues that human beings can cope with the ethical issues arising from BCI technology, and as BCI technology develops, its ethical norms will be improved continuously. It is expected that this paper can provide thoughts and references for the formulation of ethical norms related to BCI technology.

Postoperative corneal topography generation based on attention mechanism and Pix2Pix network / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To explore the use of attention mechanism and Pix2Pix generative adversarial network to predict the postoperative corneal topography of age-related cataract patients undergone femtosecond laser arcuate keratotomy.METHODS:In this retrospective case series study, the 210 preoperative and postoperative corneal topographies from 87 age-related cataract patients(105 eyes)undergoing femtosecond laser arcuate keratotomy at Shanxi Eye Hospital between March 2018 and March 2020 were selected and divided into a training set(180)and a test set(30)for model training and testing. The peak signal-to-noise ratio(PSNR), structural similarity(SSIM)and Alpins astigmatism vector analysis were used to compare the accuracy of postoperative corneal topography prediction under different attention mechanisms.RESULTS:The model based on attention mechanism and Pix2Pix network can predict postoperative corneal topography, among which the model based on Self-Attention mechanism has the best prediction effect, with PSNR and SSIM reaching 16.048 and 0.7661, respectively. There were no statistically significant differences in the difference vector, difference vector axis position, surgically induced astigmatism, and correction index between real and generated corneal topography on the 3mm and 5mm rings(all P&#x003E;0.05).CONCLUSION:Based on the Self-Attention mechanism and Pix2Pix network, the postoperative corneal topography can be well predicted, which can provide reference for the surgical planning and postoperative effects of ophthalmic clinicians.

Microdeletions and vertical transmission of the Y-chromosome azoospermia factor region / 亚洲男科学杂志(英文版)

Spermatogenesis is regulated by several Y chromosome-specific genes located in a specific region of the long arm of the Y chromosome, the azoospermia factor region (AZF). AZF microdeletions are the main structural chromosomal abnormalities that cause male infertility. Assisted reproductive technology (ART) has been used to overcome natural fertilization barriers, allowing infertile couples to have children. However, these techniques increase the risk of vertical transmission of genetic defects. Despite widespread awareness of AZF microdeletions, the occurrence of de novo deletions and overexpression, as well as the expansion of AZF microdeletion vertical transmission, remains unknown. This review summarizes the mechanism of AZF microdeletion and the function of the candidate genes in the AZF region and their corresponding clinical phenotypes. Moreover, vertical transmission cases of AZF microdeletions, the impact of vertical inheritance on male fertility, and the prospective direction of research in this field are also outlined.

Infective endocarditis in pregnancy: A case report / 北京大学学报(医学版)

Infective endocarditis in pregnancy is extremely rare in clinical practice. Guidelines addressing prophylaxis and management of infective endocarditis do not extensively deal with concomitant pregnancy, and case reports on infective endocarditis are scarce. Due to increased blood volume and hemodynamic changes in late pregnancy, endocardial neoplasms are easy to fall off and cause systemic or pulmonary embolism, respiratory, cardiac arrest and sudden death may occur in pregnant women, the fetus can suffer from intrauterine distress and stillbirth at any time, leading to adverse outcomes for pregnant women and fetuses. The disease is dangerous and difficult to treat, which seriously threatens the lives of mothers and babies. Early diagnosis and reasonable treatment can effectively improve the prognosis of patients. The most important method for the treatment of infective endocarditis requires early, adequate, long-term and combined antibiotic therapy. Moreover, surgical controversies regarding indication and timing of treatment exist, especially in pregnancy. In terms of the timing of termination of pregnancy, the timing of cardiac surgery, and the method of surgery, individualized programs must be adopted. A pregnant woman with 30+5 weeks of gestation is reported. She was admitted to hospital due to intermittent chest tightness, suffocation and fever, with grade Ⅲ cardiac insufficiency. Imaging revealed large mitral valve vegetation, 22.0 mm×4.1 mm and 22.0 mm×5.1 mm, respectively, and severe valve regurgitation. Mitral valve perforation was more likely, blood culture suggested Staphylococcus epidermidis infection, after antibiotic conservative treatment, the effect was poor. After the joint consultation including cardiology, neonatology, interventional vascular surgery, anesthesiology, and obstetrics, the combined operation of obstetrics and cardiac surgery was performed in time. The heart was blocked for 60 minutes, the bleeding was 1 200 mL, the newborn was mildly asphyxiated after birth, and the birth weight was 1 890 g. Nine days after the operation, the patient was discharged from the hospital, and the newborn was discharged with the weight of 2 020 g. Critical cases like this require a thorough weighing of risks and benefits followed by swift action to protect the mother and her unborn child. An optimal outcome in a challenging case like this greatly depends on effective interdisciplinary communication, informed consent of the patient, and concerted action among the specialists involved.

Effect of Buyang Huanwutang on Keap1/Nrf2/HO-1 Antioxidant Signaling Pathway in Rats with Idiopathic Pulmonary Fibrosis / 中国实验方剂学杂志

ObjectiveTo study the effect of Buyang Huanwutang on Kelch-like Ech-related protein 1 （Keap1）/nuclear factor E2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） antioxidant signaling pathway in rats with idiopathic pulmonary fibrosis （IPF） and explore the mechanism of this prescription in the treatment of IPF. MethodForty SPF-grade male SD rats were assigned into a sham operation group， a model group， a Buyang Huanwutang group， and a nintedanib group according to random number table method， with 10 rats in each group. IPF rat model was established by intratracheal infusion of bleomycin （0.005 g·kg-1） in other groups except the sham operation group. Buyang Huanwutang group was administrated with Buyang Huanwutang (14.84 g·kg-1)，intragastric administration of nitedanib suspension (0.1 g·kg-1)，sham operation group and model group were given equal volume of normal saline， for 28 days. After lung function test， serum and lung tissue samples were collected. Hematoxylin-eosin （HE） staining and Masson trichrome staining were employed to observe the pathological changes of the lung tissue. The content of hydroxyproline （HYP） in lung tissue was detected. The levels of malondialdehyde （MDA） in serum and lung tissue， and the activities of superoxide dismutase （SOD）， glutathione peroxidase （GSH-Px） and catalase （CAT） were determined. The mRNA and protein levels of Keap1， Nrf2， and HO-1 was determined by Real-time fluorescent quantitative polymerase chain reaction， immunohistochemical staining， and Western blot. ResultCompared with the sham operation group， the modeling increased the resistance and elasticity and decreased the compliance of respiratory system （P<0.01）， elevated the lung index， pathological score， and HYP content in lung tissue （P<0.01）， and enriched MDA in serum and lung tissue， while it decreased the activities of SOD， GSH-Px， and CAT （P<0.01）. Furthermore， the modeling down-regulated the mRNA and protein levels of Keap1 and up-regulated those of Nrf2 and HO-1 in lung tissue （P<0.01）. Compared with the model group， Buyang Huanwutang decreased the resistance and elasticity and increased the compliance of respiratory system （P<0.01）， lowered the lung index， pathological score， and HYP content in lung tissue （P<0.01）， and reduced MDA in serum and lung tissue， while it increased the activities of SOD， GSH-Px， and CAT （P<0.01）. Additionally， Buyang Huanwutang down-regulated the expression of Keap1 and up-regulated that of Nrf2 and HO-1 in lung tissue （P<0.05， P<0.01）. ConclusionBuyang Huanwutang can activate Keap1/Nrf2/HO-1 signaling pathway to enhance the antioxidant capacity and slow down the pathological process of IPF in rats.

Repurposing econazole as a pharmacological autophagy inhibitor to treat pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is characterized by the highest mortality among carcinomas. The pathogenesis of PDAC requires elevated autophagy, inhibition of which using hydroxychloroquine has shown promise. However, current realization is impeded by its suboptimal use and unpredictable toxicity. Attempts to identify novel autophagy-modulating agents from already approved drugs offer a rapid and accessible approach. Here, using a patient-derived organoid model, we performed a comparative analysis of therapeutic responses among various antimalarial/fungal/parasitic/viral agents, through which econazole (ECON), an antifungal compound, emerged as the top candidate. Further testing in cell-line and xenograft models of PDAC validated this activity, which occurred as a direct consequence of dysfunctional autophagy. More specifically, ECON boosted autophagy initiation but blocked lysosome biogenesis. RNA sequencing analysis revealed that this autophagic induction was largely attributed to the altered expression of activation transcription factor 3 (ATF3). Increased nuclear import of ATF3 and its transcriptional repression of inhibitor of differentiation-1 (ID-1) led to inactivation of the AKT/mammalian target of rapamycin (mTOR) pathway, thus giving rise to autophagosome accumulation in PDAC cells. The magnitude of the increase in autophagosomes was sufficient to elicit ER stress-mediated apoptosis. Furthermore, ECON, as an autophagy inhibitor, exhibited synergistic effects with trametinib on PDAC. This study provides direct preclinical and experimental evidence for the therapeutic efficacy of ECON in PDAC treatment and reveals a mechanism whereby ECON inhibits PDAC growth.