Recent advances in Pd-catalyzed asymmetric cyclization reactions.

Over the past few decades, there have been major developments in transition metal-catalyzed asymmetric cyclization reactions, enabling the convenient access to a wide spectrum of structurally diverse chiral carbo- and hetero-cycles, common skeletons found in fine chemicals, natural products, pharmaceuticals, agrochemicals, and materials. In particular, a plethora of enantioselective cyclization reactions have been promoted by chiral palladium catalysts owing to their outstanding features. This review aims to collect the latest advancements in enantioselective palladium-catalyzed cyclization reactions over the past eleven years, and it is organized into thirteen sections depending on the different types of transformations involved.

Prognostic Value of Left Ventricular Longitudinal Function and Myocardial Fibrosis in Patients With Ischemic and Non-Ischemic Dilated Cardiomyopathy Concomitant With Type 2 Diabetes Mellitus: A 3.0 T Cardiac MR Study.

BACKGROUND: Poorly controlled type 2 diabetes mellitus (T2DM) is known to result in left ventricular (LV) dysfunction, myocardial fibrosis, and ischemic/nonischemic dilated cardiomyopathy (ICM/NIDCM). However, less is known about the prognostic value of T2DM on LV longitudinal function and late gadolinium enhancement (LGE) assessed with cardiac MRI in ICM/NIDCM patients. PURPOSE: To measure LV longitudinal function and myocardial scar in ICM/NIDCM patients with T2DM and to determine their prognostic values. STUDY TYPE: Retrospective cohort. POPULATION: Two hundred thirty-five ICM/NIDCM patients (158 with T2DM and 77 without T2DM). FIELD STRENGTH/SEQUENCE: 3T; steady-state free precession cine; phase-sensitive inversion recovery segmented gradient echo LGE sequences. ASSESSMENT: Global peak longitudinal systolic strain rate (GLPSSR) was evaluated to LV longitudinal function with feature tracking. The predictive value of GLPSSR was determined with ROC curve. Glycated hemoglobin (HbA1c) was measured. The primary adverse cardiovascular endpoint was follow up every 3 months. STATISTICAL TESTS: Mann-Whitney U test or student's t-test; Intra and inter-observer variabilities; Kaplan-Meier method; Cox proportional hazards analysis (threshold = 5%). RESULTS: ICM/NIDCM patients with T2DM exhibited significantly lower absolute value of GLPSSR (0.39 ± 0.14 vs. 0.49 ± 0.18) and higher proportion of LGE positive (+) despite similar LV ejection fraction, compared to without T2DM. LV GLPSSR was able to predict primary endpoint (AUC 0.73) and optimal cutoff point was 0.4. ICM/NIDCM patients with T2DM (GLPSSR < 0.4) had more markedly impaired survival. Importantly, this group (GLPSSR < 0.4, HbA1c ≥ 7.8%, or LGE (+)) exhibited the worst survival. In multivariate analysis, GLPSSR, HbA1c, and LGE (+) significantly predicted primary adverse cardiovascular endpoint in overall ICM/NIDCM and ICM/NIDCM patients with T2DM. CONCLUSIONS: T2DM has an additive deleterious effect on LV longitudinal function and myocardial fibrosis in ICM/NIDCM patients. Combining GLPSSR, HbA1c, and LGE could be promising markers in predicting outcomes in ICM/NIDCM patients with T2DM. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: 5.

Pathogenic variations in MAML2 and MAMLD1 contribute to congenital hypothyroidism due to dyshormonogenesis by regulating the Notch signalling pathway.

BACKGROUND: In several countries, thyroid dyshormonogenesis is more common than thyroid dysgenesis in patients with congenital hypothyroidism (CH). However, known pathogenic genes are limited to those directly involved in hormone biosynthesis. The aetiology and pathogenesis of thyroid dyshormonogenesis remain unknown in many patients. METHODS: To identify additional candidate pathogenetic genes, we performed next-generation sequencing in 538 patients with CH and then confirmed the functions of the identified genes in vitro using HEK293T and Nthy-ori 3.1 cells, and in vivo using zebrafish and mouse model organisms. RESULTS: We identified one pathogenic MAML2 variant and two pathogenic MAMLD1 variants that downregulated canonical Notch signalling in three patients with CH. Zebrafish and mice treated with N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butylester, a γ-secretase inhibitor exhibited clinical manifestations of hypothyroidism and thyroid dyshormonogenesis. Through organoid culture of primary mouse thyroid cells and transcriptome sequencing, we demonstrated that Notch signalling within thyroid cells directly affects thyroid hormone biosynthesis rather than follicular formation. Additionally, these three variants blocked the expression of genes associated with thyroid hormone biosynthesis, which was restored by HES1 expression. The MAML2 variant exerted a dominant-negative effect on both the canonical pathway and thyroid hormone biosynthesis. MAMLD1 also regulated hormone biosynthesis through the expression of HES3, the target gene of the non-canonical pathway. CONCLUSIONS: This study identified three mastermind-like family gene variants in CH and revealed that both canonical and non-canonical Notch signalling affected thyroid hormone biosynthesis.

Effect of two different doses of nalbuphine for postoperative analgesia in children with cleft palate: a randomized controlled trial.

BACKGROUND: Cleft palate repair surgery may result in severe pain in the immediate postoperative period. The aim of this study is to compare the effects of different doses of nalbuphine for postoperative analgesia in children with cleft palate. METHODS: From November 2019 to June 2021, 90 children (45 males and 45 females, age 9-20 months old, ASA class I-II) were selected for palatoplasty. They were randomly divided into three groups: the control group (Group C), the N1 group (postoperative analgesia with 0.05 mg/kg/h nalbuphine) and the N2 group (postoperative analgesia with 0.075 mg/kg/h nalbuphine). Each group had 30 cases. Nalbuphine was not continuously infused in Group C but was continuously infused in Groups N1 and N2 at rates of 0.05 mg/kg/h and 0.075 mg/kg/h, respectively, for 24 h for postoperative analgesia. The FLACC analgesia score and Ramsay Sedation score were recorded at 10 min (T1), 30 min (T2), 2 h (T3), 12 h (T4) and 24 h (T5) after the operation. Adverse reactions such as nausea, vomiting and respiratory depression were observed and recorded. RESULTS: Compared with those in Group C, the FLACC scores in the N1 and N2 groups decreased significantly at T1-T5 (p < 0.05); the Ramsay Sedation score in the N1 group was significantly higher at T3 and T4 (p < 0.05), and that in the N2 group was significantly higher at T1-T5 (p < 0.05). Compared with that in the N1 group, the FLACC score in the N2 group was not significantly different, and the Ramsay Sedation score increased significantly at T5 (p < 0.05). CONCLUSION: Using 0.05 mg/kg/h Nalbuphine continuously for 24 h for postoperative analgesia in children with cleft palate has a better effect and fewer adverse reactions. TRIAL REGISTRATION: This study was registered at ChiCTR1900027385 (11/11/2019).

Palladium/TY-Phos-Catalyzed Asymmetric Heck/Tsuji-Trost Reaction of o-Bromophenols with 1,3-Dienes.

2,3-Dihydrobenzofurans are crucial building blocks in the synthesis of natural products and pharmaceutical molecules. However, their asymmetric synthesis has been a long-standing formidable challenge so far. In this work, we developed a highly enantioselective Pd/TY-Phos-catalyzed Heck/Tsuji-Trost reaction of o-bromophenols with various 1,3-dienes, allowing expedient access to chiral substituted 2,3-dihydrobenzofurans. This reaction features excellent regio- and enantiocontrol, high functional group tolerance, and easy scalability. More importantly, the demonstration of this method as a highly valuable tool for the construction of optically pure natural products (R)-tremetone and fomannoxin is highlighted.

Classification of quantum correlation using deep learning.

Quantum correlation, as an intrinsic property of quantum mechanics, has been widely employed to test the fundamental physical principles and explore the quantum-enhanced technologies. However, such correlation would be drowned and even destroyed in the conditions of high levels of loss and noise, which drops into the classical realm and renders quantum advantage ineffective. Especially in low light conditions, conventional linear classifiers are unable to extract and distinguish quantum and classical correlations with high accuracy. Here we experimentally demonstrate the classification of quantum correlation using deep learning to meet the challenge in the quantum imaging scheme. We design the convolutional neural network to learn and classify the correlated photons efficiently with only 0.1 signal photons per pixel. We show that decreasing signal intensity further weakens the correlation and makes an accurate linear classification impossible, while the deep learning method has a strong robustness of such task with the accuracy of 99.99%. These results open up a new perspective to optimize the quantum correlation in low light conditions, representing a step towards diverse applications in quantum-enhanced measurement scenarios, such as super-resolution microscope, quantum illumination, etc.

Ampicillin exacerbates acetaminophen-induced acute liver injury by inducing intestinal microbiota imbalance and butyrate reduction.

BACKGROUND AND AIMS: Antibiotics (ATBx) and acetaminophen (APAP) are widely used worldwide. APAP is the most common cause of acute liver injury (ALI) and might be used in combination with ATBx in clinics. However, the impact of ATBx on APAP-induced ALI has rarely been studied. METHODS: First, we compared the effects of seven ATBx on APAP-induced ALI. Then, we analysed faecal, serum and liver samples to investigate the impact of the gut microbiota on this process. Finally, we assessed the role of short-chain fatty acids in this process. RESULTS: In this work, we found that the ALI was significantly aggravated in the mice treated with ampicillin (Amp) instead of other ATBx. Amp exposure reduced the diversity and altered the composition of gut microbiota. The altered gut microbiota aggravated APAP-induced ALF, which was proven by faecal microbiota transplantation from ATBx-treated mice. Metagenomic analysis showed a significantly decreased Lactobacillus abundance in Amp-treated mice. Gavage with Lactobacillus, especially Lactobacillus rhamnosus, significantly reversed the severer ALF induced by APAP and Amp. Moreover, Lactobacillus supplementation increased butyrate-producing clostridia and lowered butyrate levels in Amp-treated mice. In accordance, butyrate supplementation could also alleviate Amp-aggravated ALI. In addition, inhibition of nuclear factor erythroid 2-related factor 2 counteracted the protective effect of butyrate on aggravated ALI induced by Amp and APAP. CONCLUSION: Together, this study revealed a potential health impact of Amp that may exacerbate liver damage when co-exposed to excess APAP.

Host ALDH2 deficiency aggravates nonalcoholic steatohepatitis through gut-liver axis.

Nonalcoholic steatohepatitis (NASH) is the major cause of liver dysfunction. Animal and population studies have shown that mitochondrial aldehyde dehydrogenase (ALDH2) is implicated in fatty liver disease. However, the role of ALDH2 in NASH and the underlying mechanisms remains unclear. To address this issue, ALDH2 knockout (ALDH2-/-) mice and wild-type littermate mice were fed a methionine-and choline-deficient (MCD) diet to induce a NASH model. Fecal, serum, and liver samples were collected and analyzed to investigate the impact of the gut microbiota and bile acids on this process. We found that MCD-fed ALDH2-/- mice exhibited increased serum pro-inflammation cytokines, hepatic inflammation and fat accumulation than their wild-type littermates. MCD-fed ALDH2-/- mice exhibited worsened MCD-induced intestinal inflammation and barrier damage, and gut microbiota disorder. Furthermore, mice receiving microbiota from MCD-fed ALDH2-/- mice had increased severity of NASH compared to those receiving microbiota from MCD-fed wild-type mice. Notably, the intestinal Lactobacillus was significantly reduced in MCD-fed ALDH2-/- mice, and gavage with Lactobacillus cocktail significantly improved MCD-induced NASH. Finally, we found that ALDH2-/- mice had reduced levels of bile salt hydrolase and specific bile acids, especially lithocholic acid (LCA), accompanied by downregulated expression of the intestinal FXR-FGF15 pathway. Supplementation of LCA in ALDH2-/- mice upregulated intestinal FXR-FGF15 pathway and alleviated NASH. In summary, ALDH2 plays a critical role in the development of NASH through modulation of gut microbiota and bile acid. The findings suggest that supplementing with Lactobacillus or LCA could be a promising therapeutic approach for treating NASH exacerbated by ALDH2 deficiency.

Separating Daily 1 km PM2.5 Inorganic Chemical Composition in China since 2000 via Deep Learning Integrating Ground, Satellite, and Model Data.

Fine particulate matter (PM2.5) chemical composition has strong and diverse impacts on the planetary environment, climate, and health. These effects are still not well understood due to limited surface observations and uncertainties in chemical model simulations. We developed a four-dimensional spatiotemporal deep forest (4D-STDF) model to estimate daily PM2.5 chemical composition at a spatial resolution of 1 km in China since 2000 by integrating measurements of PM2.5 species from a high-density observation network, satellite PM2.5 retrievals, atmospheric reanalyses, and model simulations. Cross-validation results illustrate the reliability of sulfate (SO42-), nitrate (NO3-), ammonium (NH4+), and chloride (Cl-) estimates, with high coefficients of determination (CV-R2) with ground-based observations of 0.74, 0.75, 0.71, and 0.66, and average root-mean-square errors (RMSE) of 6.0, 6.6, 4.3, and 2.3 µg/m3, respectively. The three components of secondary inorganic aerosols (SIAs) account for 21% (SO42-), 20% (NO3-), and 14% (NH4+) of the total PM2.5 mass in eastern China; we observed significant reductions in the mass of inorganic components by 40-43% between 2013 and 2020, slowing down since 2018. Comparatively, the ratio of SIA to PM2.5 increased by 7% across eastern China except in Beijing and nearby areas, accelerating in recent years. SO42- has been the dominant SIA component in eastern China, although it was surpassed by NO3- in some areas, e.g., Beijing-Tianjin-Hebei region since 2016. SIA, accounting for nearly half (∼46%) of the PM2.5 mass, drove the explosive formation of winter haze episodes in the North China Plain. A sharp decline in SIA concentrations and an increase in SIA-to-PM2.5 ratios during the COVID-19 lockdown were also revealed, reflecting the enhanced atmospheric oxidation capacity and formation of secondary particles.

Exposure to parabens and semen quality in reproductive-aged men.

BACKGROUND: Parabens are common preservatives in personal care products, cosmetics, and medical goods. In the past few years, animal studies showed the male reproductive toxicity associated with some parabens. Yet, epidemiological studies have generated inconsistent findings and research rarely has focused on the mixture effects of the parabens. We aimed to explore the associations between individual paraben exposure as well as the mixture and semen quality parameters. METHODS: A total of 795 male partners from preconception couples were included in the study. Their urine samples were analyzed for the concentrations of six parabens, namely methyl paraben (MeP), ethyl paraben (EtP), propyl paraben (PrP), butyl paraben (BuP), benzyl paraben (BzP) and heptyl paraben (HeP). Multiple linear regression models and weighted quantile sum regression (WQS) models were utilized to assess the relationships between individual paraben exposure and paraben mixture with semen quality parameters, respectively. RESULTS: After adjusting for covariates, exposure to a paraben mixture was significantly associated with declining sperm concentration, total sperm count, and progressive motility, among which BuP was identified as the main contributor to sperm concentration and total sperm count while MeP to progressive motility. Results from multiple linear regression models were generally in line with the WQS analysis. CONCLUSIONS: Our results suggest negative associations between paraben mixture and sperm concentration, total sperm count, and sperm motility among reproductive-aged men.

Research on Two-Stage Semi-Active ISD Suspension Based on Improved Fuzzy Neural Network PID Control.

To better improve the ride comfort and handling stability of vehicles, a new two-stage ISD semi-active suspension structure is designed, which consists of the three elements, including an adjustable damper, spring, and inerter. Meanwhile, a new semi-active ISD suspension control strategy is proposed based on this structure. Firstly, the fuzzy neural network's initial parameters are optimized using the grey wolf optimization algorithm. Then, the fuzzy neural network with the optimal parameters is adjusted to the PID parameters. Finally, a 1/4 2-degree-of-freedom ISD semi-active suspension model is constructed in Matlab/Simulink, and the dynamics simulation is carried out for the three schemes using PID control, fuzzy neural network PID control, and improved fuzzy neural network PID control, respectively. The results show that compared with adopting PID control and fuzzy neural network PID control strategy, the vehicle body acceleration and tire dynamic loads are significantly reduced after using the grey wolf optimized fuzzy neural network PID control strategy, which shows that the control strategy proposed in this paper can significantly improve the vehicle smoothness and the stability of the handling.

Molecular Mechanisms of Noncoding RNA in the Occurrence of Castration-Resistant Prostate Cancer.

Although several therapeutic options have been shown to improve survival of most patients with prostate cancer, progression to castration-refractory state continues to present challenges in clinics and scientific research. As a highly heterogeneous disease entity, the mechanisms of castration-resistant prostate cancer (CRPC) are complicated and arise from multiple factors. Among them, noncoding RNAs (ncRNAs), the untranslated part of the human transcriptome, are closely related to almost all biological regulation, including tumor metabolisms, epigenetic modifications and immune escape, which has encouraged scientists to investigate their role in CRPC. In clinical practice, ncRNAs, especially miRNAs and lncRNAs, may function as potential biomarkers for diagnosis and prognosis of CRPC. Therefore, understanding the molecular biology of CRPC will help boost a shift in the treatment of CRPC patients. In this review, we summarize the recent findings of miRNAs and lncRNAs, discuss their potential functional mechanisms and highlight their clinical application prospects in CRPC.

[Progress of physical therapy for chronic prostatitis/chronic pelvic pain syndrome].

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), as a common male urogenital system disease, has made significant progress in the field of physical therapy in recent years. With the characteristics of non-invasiveness, low side effects, clear effectiveness and high patient compliance, physical therapy has gradually become one of the vital methods for the treatment of CP/CPPS. In the physical therapy of chronic prostatitis, the commonly used methods mainly include prostate massage, biofeedback, magnetic therapy, ultrasound and shock wave therapy, hyperthermia, acupuncture and electrophysiological therapy. These methods ultimately alleviate the patient's pain and other discomfort symptoms through different physical effects. This article will summarize the latest research progress of physical therapy for CP/CPPS, analyze their mechanisms and their respective advantages and disadvantages, forthe reference in clinical treatment, and also inorderto provide new concepts and ideas for researchers.

[Intratesticular varicocele: Progress in research].

Intratesticular varicocele (ITV) is a relatively rare condition. Currently, there is no domestic literature available on this topic. This paper presents an overview of the epidemiology, diagnosis, differential diagnosis, impact on male reproductive health, and treatment of ITV with a review of recent foreign literature, aiming to gain a deeper insight into this condition.

[Correlation of serum and seminal plasma HCY levels with semen parameters in men and its effect on recurrent spontaneous abortion].

OBJECTIVE: To investigate the correlation of serum and seminal plasma homocysteine (Hcy) levels with semen parameters in men and its effect on recurrent spontaneous abortion (RSA) in their spouses. METHODS: The study included 103 males subjects undergoing preconception examination in the reproduction center from March 2022 to June 2023. According to whether their spouses had a history of RSA or not, we divided their subjects into an RSA (n = 43) and a non-RSA group (NRSA, n = 60), obtained their serum and seminal plasma Hcy levels and semen parameters, and analyzed their correlation. RESULTS: The serum Hcy level was significantly correlated with the sperm DNA fragmentation index (DFI) (r = 0.316, P = 0.005), but not with the seminal plasma Hcy level (r = －0.041, P = 0.723) and other semen parameters of the subjects (P > 0.05). There was no significant correlation between seminal plasma Hcy and semen parameters (P > 0.05). The median serum Hcy was significantly higher in the RSA than in the NRSA group (18.39 ï¼»13.02, 42.84ï¼½ vs 14.65 ï¼»12.00, 18.20ï¼½ µmol/L), with statistically significant difference in the overall distribution of serum Hcy between the two groups (Ｚ=－2.20, P = 0.028), so was the median sperm DFI in the former than in the latter group (25.00% ï¼»12.50%, 37.25%ï¼½ vs 13.00% ï¼»11.00%, 18.50%ï¼½), with statistically significant difference in the overall sperm DFI distribution between the two groups (Ｚ=－2.74, P = 0.006). CONCLUSION: The serum Hcy level was positively correlated with sperm DFI, and both serum Hcy and sperm DFI were significantly elevated in men with spousal RSA, which is expected to be used as a clinical screening indicator for males with spousal RSA.

[Mechanism of regulation of CNP rat model by oxalis decoction via cGAS-STING signaling pathway].

OBJECTIVE: To investigate the therapeutic mechanism of oxalis decoction on CNP rats by regulating cGAS-STING signaling pathway. METHODS: Thirty specific pathogen-free SD male rats were randomly divided into normal control group (NC), model control group (MC), and oxalis decoction group (OD),with 10 rats in each group.The left and right anterior abdominal lobes of each group were surgically exposed.The normal control group was injected by the same volume of normal saline.After the model was successfully established,the OD group was given ï¼»9.37g/(kg·d)ï¼½ by gavage once a day, and the NC and MC groups were given ï¼»0.01/(mｌ/g)ï¼½ normal saline by gavage. From the 7th day of administration, the body weight of the rats in each group was recorded every 7 days for dynamic comparison. After 50 days of administration, the prostate index of the rats in each group was calculated, the morphological and pathological changes of the prostate tissue were observed by HE staining,and the expression levels of tumor necrosis factorα(TNF-α), interleukin-1ß(IL-1ß)and IL-6 in serum were detected by ELISA. RT-qPCR was used to detect the mRNA expression of cGAS, STING, TRAF6 and HSP70 in prostate tissue of rats in each group. RESULTS: Versus the NC group and OD group, the prostate organ index in MC group was significantly higher than that in other groups (P<0.01). Versus the NC group, the HE staining results of the MC group showed that the prostate gland structure was disordered, and the interstitial and acinar epithelium were extensively edema, accompanied by a large number of lymphocyte infiltration, cell swelling, loose cytoplasm, and a small number of foam cells. Versus the MC group, HE staining showed that the edema of interstitial and acinar epithelial cells in the rat prostate tissue was reduced after the OD group intervention, and the inflammatory cell infiltration in the interstitium was significantly reduced.Versus to NC group, the expression levels of TNF-α,IL-1ßandIL-6 in MC group were significantly increased（P<0.01 ).Versus to MC group,the expression levels of TNF-α, IL-1ß and IL-6 in OD group were decreased (P<0.05). Versus the NC group, the mRNA expression of cGAS, STING and TRAF6 in the MC group was significantly up-regulated,and HSP70mRNA was significantly down-regulated(P<0.01).Versus the MC group,the OD group had significantly decreased mRNA expression of cGAS, STING and TRAF6 and significantly increased mrna expression of HSP70(P<0.05). CONCLUSIONS: CNP has autoimmune disorders that cause inflammatory responses.The key target for CNP treatment is to regulate innate immunity.The treatment with oxalis decoction can significantly improve the prostate organ index and pathological changes in CNP rats, which may be related to the down-regulation of cGAS-STING innate immune signaling pathway and the inhibition of inflammatory mediators secretion.

[Action mechanisms of Xiaoluowan (II) in the treatment of epididymitis: A network pharmacology-based study].

OBJECTIVE: To explore the potential action mechanisms of Xiaoluowan (II) (XLW-II) in the treatment of epididymitis through a network pharmacology approach. METHODS: We searched various databases for relevant targets associated with epididymitis and XLW-II and obtained the common targets of epididymitis and XLW-II on the Venny platform. We acquired the protein-protein interactions (PPI) using the STRING data and had them visualized with the Cytoscape software. After topological analysis, we retrieved the key targets, followed by gene ontology (GO) and KEGG pathway enrichment analyses using the DAVID database. RESULTS: A total of 2 38 drug targets, 2 150 disease targets and 85 common targets were identified. The core targets for the treatment of epididymitis with XLW-II identified by PPI network analysis included TNF, IL6, IL1B, MMP9, AKT1, PTGS2 and TP53. GO function analysis revealed the involvement of the common targets in such biological processes as response to hypoxia, regulation of apoptotic processes, inflammatory response, and positive regulation of the MAPK cascade. KEGG pathway analysis suggested that the signaling pathways such as the cancer pathway, PI3K-Akt pathway, protein glycosylation pathway in cancer, Ras pathway and chemokine pathway might be related to the action mechanisms of XLW-II in the treatment of epididymitis. CONCLUSION: The potential targets and signaling pathways of Xiaoluowan (II) in the treatment of epididymitis were identified on the basis of network pharmacology, which has provided a novel insight into its action mechanisms and offered a new direction for further relevant studies.

[Exploring the mechanism of levocarnitine in the treatment of epididymitis based on network pharmacology and molecular docking technology].

OBJECTIVE: To explore the potential mechanism of action of levocarnitine in the treatment of epididymitis based on network pharmacology and experimental research. METHODS: The target proteins related to epididymitis and levocarnitine were retrieved through multiple databases, and the common targets were obtained using Venny software. The protein-protein interactions were obtained using the STRING database. Cytoscape software was used for visualization, and key targets were selected after topological analysis. GO and KEGG pathway enrichment analysis was performed using the DAVID database. Molecular docking was performed using Autodock Vina. RESULTS: A total of 130 drug targets and 2 151 disease targets were obtained, with 47 common targets. Protein-protein interaction network analysis identified core targets of levocarnitine in the treatment of epididymitis, including AKT1, HSP90AA1, ALB, CASP3, GSK3B, and GSR. KEGG pathway analysis suggested that metabolic pathways, lipid metabolism and atherosclerosis, cancer pathways, fluid shear stress and atherosclerosis, measles, chemical carcinogens-reactive oxygen species, purine metabolism, PI3K-Akt, and other signaling pathways may be associated with the mechanism of levocarnitine in the treatment of epididymitis. CONCLUSION: This study revealed through network pharmacology that levocarnitine may act on multiple signaling pathways by targeting AKT1, HSP90AA1, ALB, CASP3, GSK3B, GSR, etc., thereby potentially exerting therapeutic effects on epididymitis.

[Research on the mechanism of Miao ethnicity medicine formula of Oxalis corniculata against chronic non-bacterial prostatitis].

Objective： To explore the mechanism of Miao ethnicity medicine formula of Oxalis corniculata against chronic non-bacterial prostatitis. Methods: The rat model of chronic abacterial prostatitis was induced by stimulation with 2% sterile carrageenan solution. After modeling, the rats were randomly divided into two groups, Model control group (Model group) and oxalis group. Another normal control group was set up. The rats in the Model group and the normal control group were given 0.01ml/g normal saline by gavage, and the rats in the oxalis alis group were given 1ml/100g (1 g/kg) of Oxalis corniculata L warm water decoction by gavage once a day for 28 days. Twenty-four hours after the last administration, 10ml blood was collected from the abdominal aorta of the rats, and prostate tissue samples were collected from the rats. hematoxylin-eosin (HE) staining was used to observe the morphological structure of the prostate in normal and prostatitis rats. ELISA was used to detect the levels of serum and prostate cytokines. The protein expressions of 4-HNE , ALDH2 and FGF2 were detected by Western blot. Results: Compared with the blank group, the model group showed obvious hyperplasia of fibrous tissue in the interstitium of the prostate tissue, disordered glandular structure, papillary hyperplasia of epithelial cells in the acini, infiltration of a small amount of lymphocytes, monocytes and other inflammatory cells in the acini, and increased pathological scores. The protein expressions of 4-HNE , ALDH2 , MCP-1 and FGF2 in prostate tissue were significantly increased. Compared with the model group, the prostate tissue of the oxalis group was slightly damaged, with a small amount of fibrous hyperplasia and inflammatory cell infiltration. The protein expressions of 4-HNE , ALDH2 , MCP-1 and FGF2 were decreased in prostate tissue. Conclusion： Oxalis corniculata L can effectively repair the pathological morphology of prostate tissue in rats with CNP, and its mechanism may be related to activating 4-HNE protein and reducing oxidative stress injury of prostate tissue in rats.

[Mechanism of Xiaoluanwan(II) in treating mouse epididymitis through the regulation of NLRP3 inflammasome].

OBJECTIVE: This study aimed to investigate the mechanism of Xiaoluanwan(II) in treating lipopolysaccharide(LPS)-induced epididymitis and its impact on the NLRP3 inflammasome. METHODS: The murine epididymitis model was established through local injection of LPS. The study included a control group (n=5), a model group (n=5), a model group treated with Xiaoluanwan(II) (Ⅱ) (n=5), and a saline group treated with Xiaoluanwan(II) (n=5). After 14 consecutive days of oral administration of Xiaoluanwan(II) or physiological saline, pathological changes in the epididymal tissues, expression levels of NLRP3 inflammasome and Caspase-1, as well as associated protein levels were examined. RESULTS: Compared to the model group, Xiaoluanwan(II) significantly alleviated inflammatory cell infiltration and lesions, as evidenced by a reduction in the protein expression levels of NLRP3, Caspase-1, Cleaved-Caspase-1, IL-1ß, IL-18, GSDMD, and p-p38 MAPK (P<0.05 or P<0.01), thereby mitigating the inflammatory response. CONCLUSION: Xiaoluanwan(II) alleviates epididymal inflammation and ameliorates mouse epididymal epithelial injury by modulating the NLRP3-mediated cell pyroptosis pathway.