Based on the literature study,the thoughts and possible therapeutic mechanism in treating male infertility from the perspective of spleen and kidney by regulating intestinal flora were explored.Disturbance of intestinal flora is one of the important factors leading to the development of male infertility,and the spleen and kidney have certain similarities to intestinal flora in the physiological function and pathological changes.Moreover,tonifying the kidney and strengthening the spleen can regulate the intestinal flora by fostering the growth of beneficial bacteria,inhibiting the reproduction of pathogenic bacteria,and protecting the barrier of the intestinal mucosa.Therefore,the possible therapeutic mechanisms in treating male infertility with the prescriptions for tonifying the kidney and strengthening the spleen to regulate intestinal flora are as follows:inhibiting the expression of inflammatory factors to reduce the inflammatory reaction of testicular tissues;improving the antioxidant capacity to alleviate the damage of spermatozoa caused by oxidative stress,and improving the bad mood to alleviate the impact of psychological stress on the reproductive system.The exploration of the thoughts for treating male infertility from the perspective of spleen and kidney by regulating intestinal flora may provide a new entry point for modern Chinese medicine clinical treatment of male infertility.

Objective:To investigate the feasibility, safety and reasonable operation of nasointestinal canal indwelling guided by miniature system in severe neurosurgery patients, and compare its advantages and disadvantages with traditional blind insertion.Methods:A prospective randomized controlled trial design was used to select 128 critically ill patients in need of enteral nutrition support at the Department of Neurosurgery, the First Affiliated Hospital of Nanjing Medical University from March 2022 to October 2023 by convenient sampling method. They were divided into blind insertion group and visualization group by random number table method, with 64 cases in each group. Nasointestinal canal indwelling was performed in the blind insertion group by traditional blind insertion method, and in the visualization group, nasointestinal canal indwelling was performed by indentations guided by the miniature visualization system. The success rate of initial catheterization, the time of catheterization, complications, changes of vital signs during catheterization and changes of nutritional indexes after catheterization were evaluated in 2 groups.Results:In the blind insertion group, there were 35 males and 29 females, aged (59.44 ± 13.84) years old. In the visualization group, there were 41 males and 23 females, aged (58.28 ± 12.08) years old. The success rate of the first catheter placement in the visual group was 96.8% (62/64), higher than that in the blind group 82.8% (53/64), and the difference was statistically significant ( χ2=6.94, P<0.05). The catheter placement time of the visualization group was (20.08 ± 2.69) min, which was shorter than that of the blind insertion group (38.19 ± 3.79) min, and the difference between the two groups was statistically significant ( t=29.99, P<0.05). There was no significant difference in the incidence of complications, changes of vital signs during catheterization and the changes of nutritional indexes after catheterization between two groups (all P>0.05). Conclusions:Compared with traditional blind nasointestinal canal indwelling, nasointestinal canal indwelling guided by the miniature visualization system can improve the success rate of the first catheterization and shorten the catheterization time. Although there is no difference in the complication rate, changes in vital signs during catheterization and changes in nutritional indexes after catheterization, it is believed that with the continuous development and upgrading of this technology, it will further reflect the advantages of this technology, which is worthy of further clinical trials and application.

Objective To investigate the value of carvedilol or propranolol in preventing rebleeding in patients with esophageal variceal bleeding(EVB)in liver cirrhosis.Methods Patients with EVB in liver cirrhosis were divided into the treatment group and the control group.The treatment group was treated with oral administration of carvedilol dispersible tablets,with an initial dose of 6.25 mg,bid.The control group was treated with oral administration of propranolol hydrochloride tablets,with an initial dose of 20 mg,bid.The treatment course of two groups was 1 year.The effects between two groups were compared.The rebleeding rate,and hemodynamics between two groups were compared treated after 6 months and 1 year of treatment.Safety that occurred during treatment were observed.Results The treatment group consisted of 64 patients,while the control group consisted of 61 patients.After treatment,the overall response rate in the treatment group was 93.75％(60 cases/64 cases),while the control group was 91.80％(56 cases/61 cases),without statistically significant difference between the groups(all P＞0.05).After 6 months of treatment,rebleeding rates in the treatment group and the control group were 4.69％(3 cases/64 cases)and 9.84％(6 cases/61 cases),without statistically significant difference between the groups(P＞0.05).After 1 year of treatment,rebleeding rates in the treatment group and the control group were 10.94％(7 cases/64 cases)and 24.59％(15 cases/61 cases),without statistically significant difference between the groups(P＜0.05).After 6 months of treatment,portal vein diameter(PVD)in the treatment group and the control group were(12.39±2.41)and(13.88±1.76)mm;splenic vein diameter(SVD)were(7.56±1.52)and(8.35±1.69)mm;mean blood flow velocity of portal vein(Vp)were(35.26±7.04)and(38.12±7.60)cm·s-1;mean blood flow velocity of splenic vein(Vs)were(20.03±4.11)and(22.34±4.69)cm·s-1.Compared with control group,the above indexes of treatment group had statistical significance(all P＜0.05).After 1 year of treatment,PVD in the treatment group and the control group were(11.87±2.52)and(13.15±2.04)mm;SVD were(7.33±1.48)and(8.22±1.55)mm;Vp were(33.96±6.75)and(37.46±6.83)cm·s-1;Vs were(19.26±4.33)and(21.55±4.47)cm·s-1.Compared with control group,the above indexes of treatment group had statistical significance(all P＜0.05).Adverse drug reactions in the treatment group included bradycardia,hypotension,dizziness,nausea and vomiting,while adverse reactions in the control group included bradycardia,hypotension,dizziness,drowsiness,nausea and vomiting,and skin rash.The total incidence of adverse drug reactions in the treatment group was 12.50％,while the control group was 27.87％,the differences were statistically significant(P＜0.05).Conclusion Compared to propranolol,carvedilol can better prevent rebleeding and relieve esophageal varices.

Objective This study aimed to understand the epidemic status and phylogenetic relationships of rotavirus group A(RVA)in the Pearl River Delta region of Guangdong Province,China. Methods This study included individuals aged 28 days-85 years.A total of 706 stool samples from patients with acute gastroenteritis collected between January 2019 and January 2020 were analyzed for 17 causative pathogens,including RVA,using a Gastrointestinal Pathogen Panel,followed by genotyping,virus isolation,and complete sequencing to assess the genetic diversity of RVA. Results The overall RVA infection rate was 14.59%(103/706),with an irregular epidemiological pattern.The proportion of co-infection with RVA and other pathogens was 39.81%(41/103).Acute gastroenteritis is highly prevalent in young children aged 0-1 year,and RVA is the key pathogen circulating in patients 6-10 months of age with diarrhea.G9P[8](58.25%,60/103)was found to be the predominant genotype in the RVA strains,and the 41 RVA-positive strains that were successfully sequenced belonged to three different RVA genotypes in the phylogenetic analysis.Recombination analysis showed that gene reassortment events,selection pressure,codon usage bias,gene polymorphism,and post-translational modifications(PTMs)occurred in the G9P[8]and G3P[8]strains. Conclusion This study provides molecular evidence of RVA prevalence in the Pearl River Delta region of China,further enriching the existing information on its genetics and evolutionary characteristics and suggesting the emergence of genetic diversity.Strengthening the surveillance of genotypic changes and gene reassortment in RVA strains is essential for further research and a better understanding of strain variations for further vaccine development.

ObjectiveTo observe the effectivenss and safety of Yiqi Huoxue Formula （益气活血方） combined with surgery and sequential therapy of estrogen and progesterone for the treatment of intrauterine adhesion with syndrome of qi deficiency and blood stasis. MethodsSixty-four patients with intrauterine adhesions were recruited in Guang'anmen Hospital， China Academy of Chinese Medical Sciences during 1st June 2021 to 31st December 2022， and they were randomly divided into two groups， with 32 patients in each group， all receiving transcervical resection of adhesions （TCRA）. The control group was treated with sequential therapy of estrogen and progesterone after surgery， taking 1 tablet orally daily， estradiol tablets for the first 14 days， and estradiol dydrogesterone tablets for the last 14 days. In the treatment group， the postoperative treatment was combined with Yiqi Huoxue Formula on the basis of the treatment in the control group， and 1 dose was taken daily. The treatment course of both groups was 3 months. We observed the clinical effectiveness， syndrome scores of traditional Chinese Medicine （TCM）， endometrial thickness， uterine adhesion score， menstrual flow points， and the re-adhesion rate and pregnancy rate 3 months after the end of treatment of the two groups， and conducted evaluation on safety. ResultsThe total clinical effectiveness rates of the treatment group and the control group were 90.63% and 75.00%， respectively， significantly better in the treatment group （P＜0.05）. The endometrial thickness and menstrual flow of patients in both groups increased after treatment， and the scores of uterine adhesion and TCM syndrome scores decreased significantly （P＜0.05 or P＜0.01）. After treatment， the uterine adhesion score and TCM syndrome scores of the treatment group decreased significantly compared with the control group （P＜0.05）. The 6-month postoperative pregnancy rate in the treatment group was 37.50%， higher than the 12.50% in the control group （P＜0.05）. The re-adhesion rate was 3.13% in the treatment group and 9.38% in the control group， and the difference between the two groups was not statistically significant （P＞0.05）. No adverse events occurred in both groups. ConclusionYiqi Huoxue Formula combined with surgery and sequential therapy of estrogen and progesterone for treating intrauterine adhesion patients with syndrome of qi deficiency and blood stasis can promote endometrial recovery， increase menstrual flow， improve patients' clinical symptoms， and improve pregnancy rate， showing certain clinical effectiveness and safety.

Acute liver injury (ALI) is one of the common severe diseases in clinic, which is characterized by redox imbalance and inflammatory storm. Untimely treatment can easily lead to liver failure and even death. Rosmarinic acid (RA) has been proved to have anti-inflammatory and antioxidant activity, but it is not clear how to protect ALI through antioxidation and inhibition of inflammation. Therefore, this study explored the therapeutic effect and molecular mechanism of RA on ALI through in vitro and in vivo experiments. In the mouse ALI model, the effects of RA on liver function and inflammatory indexes were studied, the pathological changes of liver were observed by HE, the effect of RA on reactive oxygen species in liver was detected by fluorescence method, and the level of F4/80 in liver tissue was detected by immunohistochemical method. The levels of thioredoxin interacting protein (TXNIP), NOD-like receptor protein 3 (NLRP3) and cysteinyl aspartate specific proteinase-1 (CASPASE-1) in liver tissue were measured by Western blot. All animal welfare and experimental procedures follow the rules of the Animal Ethics Committee of Southwest Minzu University. In vitro, human hepatoma cell line HepG2 was used to establish the model of oxidative damage induced by H₂O₂. The cell viability was detected by CCK-8 method. The level of interleukin-1β (IL-1β) in the supernatant was detected by enzyme linked immunosorbent assay (ELISA), the activity of lactatede hydrogenase (LDH) was detected by LDH kit, and the level of ROS was detected by fluorescence probe DCFH-DA labeling. The mRNA expression of Txnip, Nlrp3, Caspase 1, Il1β was detected by real-time fluorescence quantitative PCR (qPCR), and the protein levels of nuclear factor erythroid-2 related factor 2 (NRF2), TXNIP, NLRP3 and CASPASE-1 were measured by Western blot. The results showed that compared with the model group, the degree of liver swelling, tissue injury, liver function index in RA group were significantly lower than those in model group. And RA significantly attenuated the increases of ROS in liver tissue. The expression levels of TXNIP, NLRP3 and CASPASE-1 in liver tissue were significantly lower than those in model group. Additionally, RA inhibited the expressions of F4/80 and IL-1β. In vitro experiment, compared with model group, RA effectively inhibited the secretion of IL-1β and LDH. The level of ROS also decreased significantly. RA inhibited the mRNA expressions of Txnip, Caspase 1, Il1β. Furthermore, RA significantly increased the expression level of NRF2 protein in nucleus, and decreased the expression level of TXNIP and NLRP3 protein. Specifically, with the addition of ML385, the effect of RA on NRF2, TXNIP, NLRP3, CASPASE-1 protein expression was reversed. Collectively, these findings suggested that RA may inhibit the production of ROS by promoting NRF2 nuclear transfer, and then reduce the activation of NLRP3 inflammatory bodies by TXNIP, reduce cell death and inflammatory response to prevent the liver injury.

Gegen Qinlian decoction has a wide range of clinical applications. However, there is a lack of systematic quality evaluation methods to ensure the safety and effectiveness of Gegen Qinlian decoction in clinical use. The UHPLC fingerprint and multi-component determination method of Gegen Qinlian decoction were established to provide scientific basis for the quality control and evaluation of Gegen Qinlian decoction. The chromatography was performed on a ZORBAX Eclipse Plus-C₁₈ column (150 mm × 4.6 mm, 3.5 μm) with mobile phase consisted of acetonitrile (A) - 20 mmol·L^-1 ammonium acetate (containing 0.8% acetic acid and 0.5% triethylamine) (B) and gradient elution at a flow rate of 1.0 mL·min^-1. The column temperature was 25 ℃, the detection wavelength was 260 nm, the fingerprint of 10 batches of Gegen Qinlian decoction was determined, and the similarity evaluation system of TCM chromatographic fingerprint was used for comprehensive analysis, and 9 components were quantitatively analyzed. In the fingerprint study of Gegen Qinlian decoction, a total of 18 peaks were obtained, 12 of which were identified by reference substances. Moreover, the similarity of 10 batches of Gegen Qinlian decoction was good, and all of them were greater than 0.99. In the multi-component quantitative analysis, the linear relationship between the nine components and the peak area was good (r ≥ 0.999) in the corresponding mass concentration range. The average recovery rate was 94.4%-100.3%, and the RSD was 0.1%-1.4%. The fingerprint of Gegen Qinlian decoction was studied under the same wavelength, and the content of 9 main components were determined by our established method. The method has high sensitivity and strong specificity, which provided a comprehensive scientific basis for the comprehensive evaluation of the quality of Gegen Qinlian decoction.

Background::There is a need for effective and safe therapies for psoriasis that provide sustained benefits. The aim of this study was to assess the efficacy and safety of tildrakizumab, an anti-interleukin-23p19 monoclonal antibody, for treating moderate-to-severe plaque psoriasis in Chinese patients.Methods::In this multi-center, double-blind, phase III trial, patients with moderate-to-severe plaque psoriasis were enrolled and randomly assigned (1:1) to receive subcutaneous tildrakizumab 100 mg or placebo at weeks 0 and 4. Patients initially assigned to placebo were switched to receive tildrakizumab at weeks 12, 16, and every 12 weeks thereafter. Patients in the tildrakizumab group continued with tildrakizumab at week 16, and every 12 weeks until week 52. The primary endpoint was the Psoriasis Area and Severity Index (PASI 75) response rate at week 12.Results::At week 12, tildrakizumab demonstrated significantly higher PASI 75 response rates (66.4% [73/110] vs. 12.7% [14/110]; difference, 51.4% [95% confidence interval (CI), 40.72, 62.13]; P <0.001) and Physician’s Global Assessment (60.9% [67/110] vs. 10.0% [11/110]; difference, 49.1% [95% CI, 38.64, 59.62]; P <0.001) compared to placebo. PASI 75 response continued to improve over time in both tildrakizumab and placebo-switching to tildrakizumab groups, reaching maximal efficacy after 28 weeks (86.8% [92/106] vs. 82.4% [89/108]) and maintained up to 52 weeks (91.3% [95/104] vs. 87.4% [90/103]). Most treatment-emergent adverse events were mild and not related to tildrakizumab. Conclusion::Tildrakizumab demonstrated durable efficacy through week 52 and was well tolerated in Chinese patients with moderate-to-severe plaque psoriasis.Trial registration::ClinicalTrials.gov, NCT05108766.

Abstract: Objective　To investigate the distribution characteristics of HCV genotypes and subtypes in patients with HIV (human immunodeficiency virus, HIV)/HCV co-infection in Kunming based on the nucleocapsid protein gene sequence of HCV (hepatitis C virus). Methods　Serum was collected from HIV/HCV co-infected patients with household registration in 14 county-level cities, districts and counties under the jurisdiction of Kunming, who admitted to Yunnan Provincial Infectious Disease Hospital from March to August 2019. The viral RNA was extracted from the serum, reverse transcribed to synthesize cDNA, and the HCV nucleocapsid protein gene-specific primers were used for nested PCR amplification. The positive amplification products were sequenced, bioinformatics software such as DNAstar and MEGAX were used for sequence analysis. Results　A total of 64 samples from co-infected patients with clinical diagnosis of suspected HIV/HCV were collected and amplified by HCV nucleocapsid protein gene-specific primers, of which 17 samples were amplified positively. The results of sequence analysis showed that the sequences of 9 cases were located in the same evolutionary branch as the HCV 3b subtype sequence, and the nucleotide homology was 93.3%-95.2%; the sequences of 5 cases were located in the same evolutionary branch as the HCV 1b subtype sequence, and the nucleotide homology was 96.8%-97.6%; the sequence of one case and the subtype sequence of HCV 3a gene were located in the same evolutionary branch, and the nucleotide homology was 95.2%; the sequence of one case and HCV 6n gene subtype sequence were located in the same evolutionary branch, and the nucleotide homology was 97.9%; One case was located in the same evolutionary branch as the HCV 6u gene subtype sequence, and the nucleotide homology was 98.4%. Conclusions　HCV 1b, HCV 3a, HCV 3b, HCV 6n and HCV 6u genotypes or subtypes of HCV are prevalent in Kunming, and HCV 3b is the most prevalent genotype.

Based on GC-MS and network pharmacology, the active constituents, potential targets, and mechanism of essential oil from Gleditsiae Fructus Abnormalis(EOGFA) against cerebral ischemia/reperfusion(I/R) injury were explored, and the effective constituents were verified by experiment. To be specific, GC-MS was used identify the constituents of the volatile oil. Secondly, the targets of the constituents and disease were predicted by network pharmacology, and the drug-constituent-target network was constructed, followed by Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment of the core targets. Molecular docking was performed to investigate the binding affinity between the active constituents and the targets. Finally, SD rats were used for experimental verification. The I/R injury model was established, and the neurological behavior score, infarct volume, and pathological morphology of brain tissue were measured in each group. The content of interleukin-1β(IL-1β), interleukin-6(IL-6), and tumor necrosis factor-alpha(TNF-α) was determined by enzyme-linked immunosorbent assay(ELISA), and the protein expression of vascular endothelial growth factor(VEGF) by Western blot. A total of 22 active constituents and 17 core targets were screened out. The core targets were involved in 56 GO terms and the major KEGG pathways of TNF signaling pathway, VEGF signaling pathway, and sphingolipid signaling pathway. Molecular docking showed that the active constituents had high affinity to the targets. The results of animal experiment suggested that EOGFA can alleviate the neurological impairment, decrease the cerebral infarct volume and the content of IL-1β, IL-6 and TNF-α, and down-regulate the expression of VEGF. The experiment verified the part results of network pharmacology. This study reflects the multi-component, multi-target, and multi-pathway characteristics of EOGFA. The mechanism of its active constituents is related to TNF and VEGF pathways, which provides a new direction for in-depth research on and secondary development of Gleditsiae Fructus Abnormalis.
Animals ; Rats ; Rats, Sprague-Dawley ; Network Pharmacology ; Oils, Volatile ; Gas Chromatography-Mass Spectrometry ; Interleukin-6 ; Molecular Docking Simulation ; Tumor Necrosis Factor-alpha ; Vascular Endothelial Growth Factor A ; Reperfusion Injury ; Cerebral Infarction