Intensity-Specific Physical Activity Measured by Accelerometer, Genetic Susceptibility, and the Risk of Kidney Stone Disease: Results From the UK Biobank.

RATIONALE & OBJECTIVE: Kidney stone disease (KSD), a significant healthcare problem within both developed and developing countries, has been associated with genetic risk factors. As well, an association between physical activity and KSD risk has been hypothesized but studies have yielded inconsistent findings. This study aimed to investigate the association between the intensity of physical activity and the incidence of KSD accounting for genetic risk. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: A total of 80,473 participants from the UK Biobank Study. EXPOSURES: Physical activity levels, including total physical activity (TPA), moderate-to-vigorous intensity physical activity (MVPA), and light-intensity physical activity (LPA), were measured using accelerometers and quantified using a machine learning model. A polygenic risk score (PRS) for KSD was also constructed. OUTCOMES: Individuals with KSD were identified using the International Classification of Diseases 10th Edition, and procedure codes for KSD surgery. ANALYTICAL APPROACH: A Fine and Gray survival model was used to estimate the associations of incident KSD with TPA, MVPA, LPA, and PRS (as categorical variables). Restricted cubic splines were used to examine potential non-linear associations within the fully adjusted models. RESULTS: During an average follow-up of 6.19 years, 421 participants developed KSD. Participants in the highest quartiles of TPA, MVPA, and LPA had lower adjusted rates of KSD compared to those in the lowest quartiles: HRs (95% confidence interval) of 0.50 (0.44, 0.56), 0.57 (0.51, 0.64), and 0.66 (0.59, 0.74), respectively. TPA, MVPA, and LPA were associated with lower risk of KSD in participants with low and high genetic predisposition for KSD. LIMITATIONS: Selection bias as participants who provided accelerometry data may have been more adherent to health care. CONCLUSION: Physical activity was negatively associated with the risk of KSD, regardless of the genetic risk. Future large studies are warranted to confirm and explain the mechanisms underlying these associations.

Research Progress on Benzimidazole Fungicides: A Review.

Benzimidazole fungicides are a class of highly effective, low-toxicity, systemic broad-spectrum fungicides developed in the 1960s and 1970s, based on the fungicidal activity of the benzimidazole ring structure. They exhibit biological activities including anticancer, antibacterial, and antiparasitic effects. Due to their particularly outstanding antibacterial properties, they are widely used in agriculture to prevent and control various plant diseases caused by fungi. The main products of benzimidazole fungicides include benomyl, carbendazim, thiabendazole, albendazole, thiophanate, thiophanate-methyl, fuberidazole, methyl (1-{[(5-cyanopentyl)amino]carbonyl}-1H-benzimidazol-2-yl) carbamate, and carbendazim salicylate. This article mainly reviews the physicochemical properties, toxicological properties, disease control efficacy, and pesticide residue and detection technologies of the aforementioned nine benzimidazole fungicides and their main metabolite (2-aminobenzimidazole). On this basis, a brief outlook on the future research directions of benzimidazole fungicides is presented.

The association between mammographic density and breast cancer risk in Chinese women: a systematic review and meta-analysis.

PURPOSE: Breast density has consistently been shown to be an independent risk factor for breast cancer in Western populations; however, few studies have evaluated this topic in Chinese women and there is not yet a unified view. This study investigated the association between mammographic density (MD) and breast cancer risk in Chinese women. METHODS: The PubMed, Cochrane Library, Embase, and Wanfang databases were systematically searched in June 2023 to include all studies on the association between MD and breast cancer risk in Chinese women. A total of 13,977 breast cancer cases from 14 studies were chosen, including 10 case-control/cross-sectional studies, and 4 case-only studies. For case-control/cross-sectional studies, the odds ratios (ORs) of MD were combined using random effects models, and for case-only studies, relative odds ratios (RORs) were combinations of premenopausal versus postmenopausal breast cancer cases. RESULTS: Women with BI-RADS density category II-IV in case-control/cross-sectional studies had a 0.93-fold (95% confidence interval [CI] 0.55, 1.57), 1.08-fold (95% CI 0.40, 2.94), and 1.24-fold (95% CI 0.42, 3.69) higher risk compared to women with the lowest density category. Combined RORs for premenopausal versus postmenopausal women in case-only studies were 3.84 (95% CI 2.92, 5.05), 22.65 (95% CI 7.21, 71.13), and 42.06 (95% CI 4.22, 419.52), respectively, for BI-RADS density category II-IV versus I. CONCLUSIONS: For Chinese women, breast cancer risk is weakly associated with MD; however, breast cancer risk is more strongly correlated with mammographic density in premenopausal women than postmenopausal women. Further research on the factors influencing MD in premenopausal women may provide meaningful insights into breast cancer prevention in China.

Identification of Senescence-Associated Biomarkers in Diabetic Glomerulopathy Using Integrated Bioinformatics Analysis.

Background: Cellular senescence is thought to play a significant role in the onset and development of diabetic nephropathy. The goal of this study was to explore potential biomarkers associated with diabetic glomerulopathy from the perspective of senescence. Methods: Datasets about human glomerular biopsy samples related to diabetic nephropathy were systematically obtained from the Gene Expression Omnibus database. Hub senescence-associated genes were investigated by differential gene analysis and Least Absolute Shrinkage and Selection Operator analysis. Cluster analysis was employed to identify senescence molecular subtypes. A single-cell dataset was used to validate the above findings and further evaluate the senescence environment. The relationship between these genes and the glomerular filtration rate was explored based on the Nephroseq database. These gene expressions have also been explored in various kidney diseases. Results: Twelve representative senescence-associated genes (VEGFA, IQGAP2, JUN, PLAT, ETS2, ANG, MMP14, VEGFC, SERPINE2, CXCR2, PTGES, and EGF) were finally identified. Biological changes in immune inflammatory response, cell cycle regulation, metabolic regulation, and immune microenvironment have been observed across different molecular subtypes. The above results were also validated based on single-cell analysis. Additionally, we also identified several significantly altered cell communication pathways, including COLLAGEN, PTN, LAMININ, SPP1, and VEGF. Finally, almost all these genes could well predict the occurrence of diabetic glomerulopathy based on receiver operating characteristic analysis and are associated with the glomerular filtration rate. These genes are differently expressed in various kidney diseases. Conclusion: The present study identified potential senescence-associated biomarkers and further explored the heterogeneity of diabetic glomerulopathy that might provide new insights into the diagnosis, assessment, management, and personalized treatment of DN.

Visible-Light-Enhanced Hydrogen Evolution through Anodic Furfural Electro-Oxidation Using Nickel Atomically Dispersed Copper Nanoparticles.

A novel copper nanoparticle variant, denoted as Cu98Ni2 NPs, which incorporate Ni atoms in an atomically dispersed manner, has been successfully synthesized via a straightforward one-pot electrochemical codeposition process. These nanoparticles were subsequently employed as an anode to facilitate the oxidation of furfural, leading to the production of hydrogen gas. Voltammetric measurements revealed that the inclusion of trace amounts of Ni atoms in the nanoparticles resulted in a pronounced synergistic electronic effect between Cu and Ni. Consequently, a 43% increase in current density at 0.1 V was observed in comparison to pure Cu NPs. Importantly, when the Cu98Ni2 NPs were irradiated with visible light, a remarkable current density enhancement factor of 505% at 0.1 V was achieved relative to that of pure Cu NPs in the absence of light. This enhancement can be attributed to localized surface plasmon resonance induced by visible light, which triggers photothermal and photoelectric effects. These effects collectively contribute to the significant overall improvement in the electrocatalytic oxidation of furfural, leading to enhanced hydrogen evolution.

TRAF7-targeted HOXA5 acts as a tumor suppressor in prostate cancer progression and stemness via transcriptionally activating SPRY2 and regulating MEK/ERK signaling.

Homeobox A5 (HOXA5), a homeodomain transcription factor, is considered a tumor suppressor in cancer progression; however, its function in prostate cancer (PCa) remains unclear. This study focused on the relevance of HOXA5 in PCa progression. We identified the downregulation of HOXA5 in PCa tissues based on the TCGA database and further verified in 30-paired PCa and adjacent normal tissues. Functional studies revealed that HOXA5 upregulation impaired the stem-like characteristics and malignant behaviors of PCa cells in vitro and in vivo. Mechanistically, HOXA5 was found to be regulated by tumor necrosis factor receptor-associated factor 7 (TRAF7), a putative E3-ubiquitin ligase. We observed that TRAF7 was overexpressed in PCa and subsequently enhanced the degradation of HOXA5 protein via its ubiquitin ligase activity, contributing to the acquisition of an aggressive PCa phenotype. For its downstream mechanism, we demonstrated that sprouty RTK signaling antagonist 2 (SPRY2) served as a downstream target of HOXA5. HOXA5 could directly bind to the SPRY2 promoter, thereby regulating the SPRY2-mediated MEK/ERK signaling pathway. Silencing SPRY2 largely compromised the tumor-suppressive effect of HOXA5 in PCa progression and cancer stemness. Our findings highlight the previously-underappreciated signaling axis of TRAF7-HOXA5-SPRY2, which provides a novel prognostic and therapeutic target for PCa treatment.

Chidamide and Oxaliplatin Synergistically Inhibit Colorectal Cancer Growth by Regulating the RPS27A-MDM2-P53 Axis.

Purpose: The present study explored the anti-tumor effects of chidamide plus oxaliplatin on colorectal cancer (CRC) and examined its underlying mechanism. Material and Methods: First, the Combination Index (CI) of chidamide and oxaliplatin was evaluated via CCK-8 assay. Second, the effects of chidamide and oxaliplatin monotherapy and the combined treatment on cell proliferation, invasion, migration, and apoptosis were detected. Third, whole-transcriptome RNA sequencing (RNA-seq) was performed to seek the potential targeted gene by which chidamide plus oxaliplatin exerted anti-tumor effects. Fourth, the validation of the targeted gene and the signal pathway it regulated were performed. Finally, the anti-tumor effect of chidamide plus oxaliplatin on mice xenograft was examined. Results: Chidamide and oxaliplatin acted synergistically to inhibit CRC growth in vitro and in vivo (CI<1). Besides, compared with oxaliplatin monotherapy, chidamide could significantly enhance oxaliplatin-induced inhibition in cell proliferation, invasion, and migration, and promotion in HCT-116 and RKO cell apoptosis (P<0.05). The RNA-seq displayed that, compared to oxaliplatin monotherapy, RPS27A mRNA was evidently decreased in HCT-116 cells treated with chidamide plus oxaliplatin (P<0.001). Then, we found RPS27A was highly expressed in CRC tissues and CRC cell lines (P<0.001). Silence of RPS27A attenuated proliferation and induced apoptosis in HCT-116 and RKO cells via downregulation of MDM2 expression and upregulation of P53. Next, RPS27A overexpression could partially reverse chidamide plus oxaliplatin induced growth inhibition and apoptosis in HCT-116 and RKO cells (P<0.01). RPS27A overexpression could promote the upregulation of MDM2 and downregulation of P53 after the combined treatment of chidamide with oxaliplatin. Conclusion: Chidamide and oxaliplatin acted synergistically to suppress CRC growth by the inhibition of the RPS27A-MDM2-p53 axis.

Synthesis and Screening of Chemical Agents Targeting Viral Protein Genome-Linked Protein of Telosma Mosaic Virus.

The viral protein genome-linked protein (VPg) of telosma mosaic virus (TeMV) plays an important role in viral reproduction. In this study, the expression conditions of TeMV VPg were explored. A series of novel benzenesulfonamide derivatives were synthesized. The binding sites of the target compounds and TeMV VPg were studied by molecular docking, and the interaction was verified by microscale thermophoresis. The study revealed that the optimal expression conditions for TeMV VPg were in Escherichia coli Rosetta with IPTG concentration of 0.8 mM and induction temperature of 25 °C. Compounds A4, A6, A9, A16, and A17 exhibited excellent binding affinity to TeMV VPg, with Kd values of 0.23, 0.034, 0.19, 0.086, and 0.22 µM, respectively. LYS 121 is the key amino acid site. Compounds A9 inhibited the expression of TeMV VPg in Nicotiana benthamiana. The results suggested that TeMV VPg is a potential antiviral target to screen anti-TeMV compounds.

Diagnostic value of mesenteric CTA combined with D-dimer level and inflammatory factor changes in severity of mesenteric artery embolism.

Objective: To investigate the value of mesenteric CTA combined with D-dimer (DD) level and inflammatory factor changes in evaluating the severity of mesenteric artery embolism. Methods: This is a retrospective study. The imaging data of mesenteric CTA and the levels of plasma DD and inflammatory factors in 120 patients with mesenteric artery embolism confirmed by DSA or surgery in Baoding No.1 Central Hospital were analyzed retrospectively from January 2021 to December 2022. The coincidence rate of CTA alone and CTA combined with DD and inflammatory factors with the results of surgery or DSA was compared and analyzed. The specificity, sensitivity and accuracy of CTA alone and CTA combined with DD and inflammatory factors in diagnosing superior mesenteric artery embolism were compared. The correlations of different severity of mesenteric artery embolism with DD and inflammatory factor levels were compared and analyzed. Results: There was a significant difference in the coincidence rate between CTA diagnosis and CTA combined with DD and inflammatory factors diagnosis (p= 0.01). And the sensitivity and accuracy of the latter were significantly higher than those of the former (sensitivity, p= 0.01; accuracy, p= 0.00). The levels of plasma DD, TNF-a, CRP and IL-6 in the intestinal wall thinning group were significantly higher than those in the thickening group (p= 0.00). The above indexes increased significantly in the decreased intestinal wall enhancement group compared with the increased intestinal wall enhancement group (p= 0.00). DD, TNF-ɑ, CRP and IL-6 levels increased with the increase in stenosis severity. Conclusion: Mesenteric CTA combined with plasma DD and inflammatory factor levels can effectively determine the severity of mesenteric arterial embolism, and provide a scientific basis for early clinical diagnosis and treatment.

Prospective comparison of extracorporeal shock wave lithotripsy and ureteroscopy in distal ureteral stones.

The optimal treatment modality of distal ureteral stones is controversial. Therefore, we conducted a prospective study to evaluate the efficacy, safety, and cost of early second shock wave lithotripsy (SWL) sessions versus ureterorenoscopy (URS) in patients with distal ureteral stones. This prospective study was conducted in a tertiary hospital from June 2020 to April 2022. Patients who underwent SWL or URS for distal ureteral stones were enrolled in this study. The stone-free rate (SFR), secondary treatment rate, complications, and costs were recorded. Propensity-score matching (PSM) analysis was also performed. A total of 1023 patients were included, of whom 68.4% (700) were treated with SWL and 31.6% (323) with URS. Based on PSM, SWL had an equivalent SFR (87.4% vs. 84.9%, P = 0.325) at one month after SWL and secondary treatment rate (10.7% vs.10.8%, P = 0.958) when compared with URS. Complications were rare and comparable between the SWL and URS groups (6.0% vs. 5.9%, P > 0.05), while the incidence of ureteral injuries (i.e., perforations) was higher in the URS group compared with the SWL group (1.3% vs. 0%, P = 0.019). The hospital stay was significantly shorter (1 day vs. 2 days, P < 0.001) and the costs considerably less (2000 RMB vs. 25,030 RMB; P < 0.001) in the SWL group compared with the URS group. This prospective study demonstrated that early second SWL sessions had equivalent efficacy in addition to reduced complication rates and costs compared with URS in patients with distal ureteral stones. Our findings may help guide clinical decision making.

A synthetic Tn-BSA conjugate vaccine bearing chitotriose as built-in adjuvant.

Chitotriose (CTS), the hydrolysate of chitosan, is readily soluble in water because of the shorter chain lengths of the oligomers and the free amino groups in the d-glucosamine units. In the current study, we report the synthesis of novel conjugate vaccine Tn-BSA-CTS with chitotriose as built-in adjuvant, along with an evaluation of the effect of adjuvant chitotriose (CTS). Immunological evaluations of the resultant conjugate vaccine revealed that Tn-BSA-CTS could provoke the highest titers of IgG antibodies (102,400). The Tn-BSA-CTS conjugate remarkably enhanced both humoral and cellular immunity. The obtained results demonstrate the potential of CTS as a novel vaccine adjuvant in the development of antitumor vaccine and the covalent linkage of tumor vaccine to CTS might be available strategy to increase the efficacy against cancer.

Comparison of shock wave lithotripsy and ureteroscopy in patients with proximal ureteral stones under the COVID-19 pandemic.

PURPOSE: To compare the effectiveness, safety, and cost between ultrasound-guided shock wave lithotripsy (SWL) with an early second session protocol and ureteroscopy (URS) in patients with proximal ureteral stones using the propensity score matching (PSM) method based on a large prospective study. METHODS: This prospective study was conducted in a tertiary hospital from June 2020 to April 2022. Patients who underwent lithotripsy (SWL or URS) for proximal ureteral stones were enrolled. The stone-free rate (SFR), complications, and cost were recorded. PSM analysis was performed. RESULTS: A total of 1230 patients were included, of whom 81.1% (998) were treated with SWL and 18.9% (232) were treated with URS. After PSM, the SWL group had an equivalent SFR at one month (88.7 vs. 83.6%, P = 0.114) compared with the URS group. Complications were rare and comparable between the two groups, while the incidence of ureteral injuries was higher in the URS group compared with the SWL group (1.4 vs. 0%, P = 0.011). The hospital stay was significantly shorter (1 day vs. 2 days, P < 0.001), and the cost was considerably less (2000 vs. 25,053, P < 0.001) in the SWL group compared with the URS group. CONCLUSION: This prospective PSM cohort demonstrated that ultrasound-guided SWL with an early second session protocol had equivalent effectiveness but better safety and lower cost compared with URS in the treatment of patients with proximal ureteral stones, whether the stones were radiopaque or radiolucent. These results will facilitate treatment decisions for proximal ureteral stones.

Development and Validation of a Nomogram for Predicting Blood Pressure Change Failure in Patients with Pheochromocytoma and Concomitant Hypertension after Adrenalectomy.

(1) Background: Pheochromocytoma is a common cause of secondary hypertension, which is considered curable; nevertheless, some patients still suffer from hypertension after adrenalectomy. Therefore, we developed and validated a nomogram for predicting blood pressure change failure in patients with pheochromocytoma and concomitant hypertension after adrenalectomy. (2) Methods: The development cohort of this study consisted of 259 patients with pheochromocytoma who underwent adrenalectomy at our center between 1 January 2007 and 31 December 2018. Each patient's clinicopathologic data were recorded. LASSO (the least absolute shrinkage and selection operator) regression was used to reduce and select the features of the data. Furthermore, we used multivariate logistic regression analysis to develop the prediction model. An independent cohort of 110 consecutive patients from 1 January 2019 to 31 December 2021 was used for validation. The performance of this nomogram was assessed with regard to discrimination, calibration, and clinical usefulness. (3) Results: 40.9% and 46.4% of patients experienced blood pressure change failure in the development and validation cohorts of this study, respectively. We found that older patients with a longer duration of hypertension and concomitant cardiovascular events were more likely to suffer from blood pressure change failure. In the validation cohort, the model manifested great discrimination with an AUROC (area under the receiver operating characteristic) of 0.996 (p < 0.001) and good calibration (unreliability test, p = 0.359). Decision curve analysis demonstrated that the model was clinically useful. (4) Conclusions: This study presented a reliable nomogram that facilitated individualized preoperative prediction of blood pressure change failure after adrenalectomy in patients with pheochromocytoma, which may help decision-making in perioperative treatment and follow-up strategies.

Prospective comparison of extracorporeal shock wave lithotripsy versus flexible ureterorenoscopy in patients with non-lower pole kidney stones under the COVID-19 pandemic.

Both shock wave lithotripsy (SWL) and flexible ureterorenoscopy (F-URS) are recommended as the first choice for non-lower pole kidney stones. Therefore, we conducted a prospective study to evaluate the efficacy, safety, and cost of SWL versus F-URS in patients with solitary non-lower pole kidney stones ≤ 20 mm under the COVID-19 pandemic. This prospective study was conducted in a tertiary hospital from June 2020 to April 2022. Patients who underwent lithotripsy (SWL or F-URS) for non-lower pole kidney stones were enrolled in this study. The stone-free rate (SFR), retreatment rate, complications, and cost were recorded. Propensity score-matched (PSM) analysis was performed. A total of 699 patients were finally included, of which 81.3% (568) were treated with SWL and 18.7% (131) underwent F-URS. After PSM, SWL showed equivalent SFR (87.9% vs. 91.1%, P = 0.323), retreatment rate (8.6% vs. 4.8%, P = 0.169), and adjunctive procedure (2.6% vs. 4.9%, P = 0.385) compared with F-URS. Complications were scarce and also comparable between SWL and F-URS (6.0% vs 7.7%, P > 0.05), while the incidence of ureteral perforation was higher in the F-URS group compared with the SWL group (1.5% vs 0%, P = 0.008). The hospital stay was significantly shorter (1 day vs 2 days, P < 0.001), and the cost was considerably less (1200 vs 30,083, P < 0.001) in the SWL group compared with the F-URS group. This prospective cohort demonstrated that SWL had equivalent efficacy with more safety and cost benefits than F-URS in treating patients with solitary non-lower pole kidney stones ≤ 20 mm. During the COVID-19 pandemic, SWL may have benefits in preserving hospital resources and limiting opportunity for virus transmission, compared to URS. These findings may guide clinical practice.

Application value of coaxial puncture needle (technique) in ultrasound-guided puncture biopsy of peripheral pulmonary masses.

This study aims to investigate the effect of ultrasound (US)-guided coaxial puncture needle in puncture biopsy of peripheral pulmonary masses. In this retrospective analysis, 157 patients who underwent US-guided percutaneous lung biopsy in our hospital were divided into a coaxial biopsy group and a conventional biopsy group (the control group) according to the puncture tools involved, with 73 and 84 patients, respectively. The average puncture time, number of sampling, sampling satisfaction rate, puncture success rate and complication rate between the 2 groups were compared and discussed in detail. One hundred fifty-seven patients underwent puncture biopsy, and 145 patients finally obtained definitive pathological results. The overall puncture success rate was 92.4% ([145/157]; with a puncture success rate of 97.3% [71/73] from the coaxial biopsy group and a puncture success rate of 88.1% [74/84] from the conventional biopsy group (P < .05). For peripheral pulmonary masses ≤3 cm, the average puncture time in the coaxial biopsy group was shorter than that in the conventional biopsy group, and the number of sampling, sampling satisfaction rate and puncture success rate were significantly higher than those in the conventional biopsy group (P < .05). There was no significant difference in the complication rate between the 2 groups (P > .05). For peripheral pulmonary masses >3 cm, the average puncture time in the coaxial biopsy group was still shorter than that in the conventional biopsy group (P < .05). The differences between the 2 groups in the number of sampling, satisfaction rate of the sampling, the success rate of puncture and the incidence of complications were not significant (P > .05). US guided coaxial puncture biopsy could save puncture time, increase the number of sampling, and improve the satisfaction rate of sampling and the success rate of puncture (especially for small lesions) by establishing a biopsy channel on the basis of the coaxial needle sheath. It provided reliable information for the diagnosis, differential diagnosis and individualized accurate treatment of lesions as well.

Prospective Comparison of Local Anesthesia with General or Spinal Anesthesia in Patients Treated with Microscopic Varicocelectomy.

It is unclear whether local anesthesia (LA) is a viable and safe alternative to general anesthesia (GA) or spinal anesthesia (SA) for microscopic varicocelectomy. As a result, we designed a prospective trial to compare the pain relief, complications, and cost of LA with GA or SA in subinguinal microscopic varicocelectomy (MSV), using the propensity score matching method (PSM). This prospective study was conducted in a tertiary hospital from February 2021 to April 2022. Patients who underwent subinguinal MSV for varicocele were enrolled. The perioperative visual analog scale (VAS) scores, anesthesia-associated side effects, and cost data were recorded, and PSM analysis was performed. Finally, 354 patients were included, of whom 61.0% (216) were treated with LA, and 39.0% (138) underwent GA or LA. After PSM, the patients in the LA group exhibited lower VAS scores both three hours and one day after surgery, and a lower incidence of postoperative analgesic requirement; a lower ratio of patients who experienced anesthesia-associated side effects was also observed in the LA group, compared with the GA or SA group (all p < 0.001). The rate of perioperative satisfaction for patients was higher, the hospital stays and days to return to normal activity were shorter, and the cost was less in the LA group than in the patients in the GA or SA group (all p < 0.001). This prospective PSM cohort demonstrated that LA has the advantages of perioperative pain relief, reduced anesthesia-associated side effects, and cost, compared with GA or SA. It indicated that LA is an effective and safe technique for subinguinal MSV, and may guide clinical practice.

Nomogram for predicting spontaneous pregnancy after microscopic varicocelectomy in infertile men with normal hormone.

INTRODUCTION: The current challenge for the treatment of varicocele is identifying patients who could benefit the most from surgery. We aimed to develop and validate a nomogram for predicting spontaneous pregnancy following microscopic varicocelectomy in infertile men, based on a large cohort. METHODS: Two hundred eighty-two consecutive patients who underwent microscopic varicocelectomy from January 2018 to December 2020 were enrolled as participants in the study. Xiang Hua center (206 patients) as a development cohort. Hu Nan center (76 patients) as a validation cohort. Patient clinicopathologic data were recorded. Multivariate logistic regression was used to build a predictive model with regression coefficients. Then, backward stepwise selection was applied, and the likelihood ratio test with Akaike's information criterion was used as the stopping rule. The performance of this predictive model was assessed for discrimination, calibration, and clinical usefulness. RESULTS: Predictors of this model included the age of female partners, diameter of veins, initial and increased total progressively motile sperm count. The model demonstrated good discrimination with an AUROC of 0.925 (p < 0.001) and calibration (Unreliability test, p = 0.522) in the validation cohort. Furthermore, the model was clinically useful, according to decision curve analysis. CONCLUSIONS: Our findings indicated that younger female partners, larger diameter of veins, higher initial and increased total progressively motile sperm count were significant predictors of spontaneous pregnancy in infertile men, post microscopic varicocelectomy. This nomogram may assist in individual decision-making on the treatment strategy of varicocele preoperatively and improve the treatment outcome.

Application of sutureless technique in total anomalous pulmonary venous connection repair.

The sutureless technique was initially used for the treatment of postoperative pulmonary vein obstruction (PVO) in patients with total anomalous pulmonary venous connection (TAPVC). However, as the effectiveness of the sutureless technique has been confirmed and widely developed, the sutureless technique has been used for the primary treatment of high-risk children with TAPVC who are at high risk of PVO. Compared with traditional surgery, the sutureless technique significantly reduces the incidence of postoperative PVO, re-intervention rate due to PVO, and postoperative mortality, but there are potential complications such as pericardial and confluent venous anastomosis, phrenic nerve damage, air embolism. In addition, the sutureless technique is not effective in dealing with the progressive stenosis of the pulmonary veins after sutureless surgery and diffuse stenosis of extrapulmonary proximal veins and intrapulmonary veins. These make the efficacy and safety of this procedure controversial. This paper reviews the research status of the sutureless technique in TAPVC repair at home and abroad over the years.

Incidence and risk factors for late complications after the arterial switch operation.

OBJECTIVE: The purpose of this study was to evaluate our institution's 16-year arterial switch operation (ASO) experience and to determine early and late mortality and late morbidity, as well as the need for reoperation and catheter intervention, and finally, to explore risk factors for late complications and reintervention. METHODS: The clinical data of 185 transposition of the great arteries (TGA) patients who received ASO treatment in our center from January 2006 to January 2022 were continuously included for retrospective study. RESULTS: There were 13 early deaths (7.03%), 5 late deaths (3.01%), and 6 lost to follow-up. The median follow-up time for the 166 hospitalized survivors was 88.5 (2190) months. Moderate or above new aortic valve regurgitation (NAR; in this article, NAR represents moderate or greater reflux unless otherwise specified) occurred in 19 cases (11.45%), and aortic root dilation (ARD) occurred in 28 cases (16.87%). Late right ventricular outflow tract obstruction (RVOTO) occurred in 33 cases (19.88%). There were 18 patients (10.84%) who underwent late re-intervention, and the most common indication for intervention was RVOTO, followed by recurrent aortic coarctation in patients undergoing concurrent arch repair and NAR or ARD. Receiver operating characteristics analysis found that NAR had the strongest predictive power for ARD, followed by RVOTO, followed by bicuspid native pulmonary valve (BPV), and aorto-pulmonary diameter mismatch (APDMM) was the weakest. Multivariate analysis showed that APDMM, previous pulmonary artery banding (PAB), and mild NAR at discharge were independent risk factors for late NAR and ARD. Low surgical weight was an independent risk factor specific to NAR, and BPV was an independent risk factor specific to ARD. Older surgical age and ARD were independent risk factors for late RVOTO. Older surgical age, operation before 2014, late RVOTO, and late ARD were independent risk factors for late intervention. No reintervention events for coronary dysfunction were found in the late stage, but one patient occurred myocardial infarction due to coronary embolism after reoperation. CONCLUSION: Early and late survival rates after ASO in TGA patients have been remarkably improved in recent decades. Increased rates of NAR, ARD, recurrent coarctation of the aorta, and RVOTO as children age are major future outcomes of concern and may imply more late reinterventions. Careful follow-up of neo-aortic valve and root function is imperative, especially in patients with APDMM, previous PAB, mild NAR at discharge, low surgical weight, and BPV structures.

Ångstrom-scale silver particles potently combat SARS-CoV-2 infection by suppressing the ACE2 expression and inflammatory responses.

The SARS-CoV-2 pandemic has become a severe global public health event, and the development of protective and therapeutic strategies is urgently needed. Downregulation of angiotensin converting enzyme 2 (ACE2; one of the important SARS-CoV-2 entry receptors) and aberrant inflammatory responses (cytokine storm) are the main targets to inhibit and control COVID-19 invasion. Silver nanomaterials have well-known pharmaceutical properties, including antiviral, antibacterial, and anticancer properties. Here, based on a self-established metal evaporation-condensation-size graded collection system, smaller silver particles reaching the Ångstrom scale (AgÅPs) were fabricated and coated with fructose to obtain a stabilized AgÅP solution (F-AgÅPs). F-AgÅPs potently inactivated SARS-CoV-2 and prevented viral infection. Considering the application of anti-SARS-CoV-2, a sterilized F-AgÅP solution was produced via spray formulation. In our model, the F-AgÅP spray downregulated ACE2 expression and attenuated proinflammatory factors. Moreover, F-AgÅPs were found to be rapidly eliminated to avoid respiratory and systemic toxicity in this study as well as our previous studies. This work presents a safe and potent anti-SARS-CoV-2 agent using an F-AgÅP spray.