Objective To investigate the potential mechanism by which dihydromyricetin(DHM)ameliorates diabetic nephropathy(DN),and to screen and validate its possible key molecular targets.Methods A DN model was established using db/db mice,and 100 mg/(kg·d)DHM was administered via gavage 5 d per week for totally 10 weeks.Renal morphological changes were observed after staining to evaluate the effects of DHM.GSE161885 and GSE270526 datasets were obtained from the Gene Expression Omnibus(GEO)database and analyzed in combination with the GeneCards database to screen for DN-related differentially expressed genes(DEGs).Protein-protein interaction(PPI)network and molecular docking were employed to predict potential DHM targets.Western blotting and immunofluorescence staining were performed to detect the effects of DHM on pyroptosis-related pathways in the renal tissues of db/db mice and in high glucose(HG)-induced human renal tubular epithelial cells(HK-2).The specific NLR family pyrin domain containing protein 3(NLRP3)inhibitor MCC950 was also used to validate the predicted mechanism.Results In vivo experiments showed that DHM significantly ameliorated renal pathological damage in db/db mice,alleviated glomerular hypertrophy and mesangial expansion,and markedly reduced Paller scores(P<0.001).Immunofluorescence staining revealed significantly weakened fluorescence signals for α-smooth muscle actin(α-SMA),fibronectin,and collagen Ⅰ in renal tissues.Western blot results showed that the expression levels of collagen Ⅰ,collagen Ⅲ,α-SMA,and transforming growth factor beta 1(TGF-β1)were significantly decreased(P<0.05).A total of 16 DN-related DEGs were identified.Enrichment analysis revealed that these genes were primarily enriched in pathways such as viral protein interactions,cytokine-cytokine receptor interaction,and the AGE-RAGE signaling pathway in diabetic complications,and were primarily involved in gene functions such as the positive regulation of lymphocyte-mediated immunity,positive regulation of adaptive immune response,and chemokine activity.Molecular docking confirmed NLRP3 as a potential target of DHM.In vivo validation showed that DHM significantly down-regulated gasdermin-D(GSDMD)fluorescence signals and inhibited the expression of pyroptosis-related proteins including NLRP3,Caspase 1,Cleaved-Caspase 1,interleukin 18(IL-18),and GSDMD(P<0.05).In vitro studies further confirmed that both DHM and the specific NLRP3 inhibitor MCC950 alleviate high glucose-induced fibrosis and pyroptosis in HIC-2 cells.Conclusion DHM can ameliorate the progression of DN,and its mechanism is related to inhibiting NLRP3 inflammasome-mediated pyroptosis,thereby alleviating renal inflammation and fibrosis.

Tumor cells can escape the surveillance and attack of the immune system, namely immune escape. In recent years, regulatory B (Breg) cell have attracted much attention in researches about tumor immunity. Breg cell plays an important role in tumor immune escape by secreted various cytokines. Mechanistic progress has been made in this field, which provides more targets and ideas for tumor clinical treatment. However, the phenotypic classification of Breg cells and its complex mechanism in tumor immunity still need to be systematically analyzed.

OBJECTIVES: To investigate the effects of formulated granules of Tianma Gouteng Yin (TGY) on motor deficits in a mouse model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced subacute Parkinson's disease (PD) and explore the possible molecular mechanisms. METHODS: Ninety C57BL/6 mice were randomized equally into 6 groups, including a control group, a PD model group, a NEC-1 (6.5 mg/kg) treatment group, two TGY treatment groups at 5 and 2.5 g/kg, and a Madopar (76 mg/kg) treatment (positive control) group. Mouse models of PD were established by intraperitoneal injection of MPTP (30 mg/kg) for 5 consecutive days with the corresponding treatments for 15 days. The mice were randomly selected for motor function tests. Western blotting was used to detect the changes in expressions of TH, α-syn, RIPK1, RIPK3 and MLKL in the striatum of the mice. Network pharmacology analysis and molecular docking studies were performed to explore TGY-mediated regulation of the necroptosis pathway for PD treatment. RESULTS: Compared with those in the control group, the PD model mice exhibited obvious motor deficits with significantly increased α-syn protein expression and lowered TH protein expression in the striatum. Treatment with NEC-1 obviously improved motor deficits, inhibited the necroptosis pathway, and alleviated the changes in TH and α‑syn proteins in PD mice. Network pharmacology and molecular docking analyses suggested that the therapeutic effect of TGY in PD was associated with the modulation of RIPK1, a key protein in the necroptosis pathway. In PD mouse models, TGY treatment at the two doses significantly improved motor deficits of the mice, increased TH expression, and decreased the expressions of α-syn and necroptosis-related proteins in the striatum. CONCLUSIONS TGY can effectively inhibit the necroptosis pathway, increase TH expression and decrease α-syn expression in the striatum to improve motor deficits in PD mice.
Animals ; Mice, Inbred C57BL ; Mice ; Necroptosis/drug effects* ; Drugs, Chinese Herbal/therapeutic use* ; Parkinson Disease/drug therapy* ; Disease Models, Animal ; Male

Based on the principle of "kidney suffers from dryness and can be moistened by pungent drugs", this article discussed the pathogenesis and treatment of chronic kidney disease-associated pruritus (CKD-aP), and believed that this disease begins with deficiency of kidney qi, and dampness, blood stasis, cold, heat, and turbid toxin are the symptoms, which ultimately leads to the kidney's inability to transport fluids, and develops into "dryness of kidney". It suggested that the treatment of CKD-aP should be "using pungent drugs to moisten" as the core, according to the stage of development of the disease and the contradiction of the primary and secondary, respectively, the use of pungency-warm (heat) declination, pungent-cold (cool) declination of the treatment, to help to restore the normal transmission of fluid operation, qi and blood, and promote fluids to reduce dryness, so as to promote the recovery of the disease.

Objective To investigate the association between microvariants at locus DYS570 and Y-SNPs haplogroup.Methods 89 Y-SNPs and 34 Y-STRs in AIYSNP42,AIYSNP47 and YfilerTM Platinum kits were used to detect the genotype of 116 microvariants at locus DYS570 in Kunming,and the Set-B kit was used to detect the core repeat sequences of the DYS570 locus.The data were statistically analyzed by direct counting method.Then,a network map was drawn by Network 10.2,in order to visualize the genetic information of the sample.Results The results demonstrated that 111 DYS570/18.3-21.3 samples had a core repeat sequence of TTT[TITC]18-21,belonging to subgroup O2a2b1a1a1a4-F14494.A DYS570/20.3 sample had a core repeat sequence of[TTTC]15TTC[TTTC]5,belonging to O2a1b1a1a1a1e-F1365 subgroup.A DYS570/17.1 sample had a core repeat sequence of[TTTC]17 T,belonging to the O2a1b1a1a1a-F11 subgroup.Three DYS570(19.2)samples had[TTTC]3 TT[TTTC]16,belonging to the D1a1a-M15 haplogroup.Conclusion The results indicated that the microvariant with the same core repeat structure at locus DYS570 was associated with haplogroups,and the ancestry origin of samples can be inferenced from microvariant characteristics during the practice of forensic medicine.

Objective:To study the short-term clinical outcomes of different courses of antenatal corticosteroids (ACS) for preterm twins.Methods:From January 2017 to December 2021, preterm twins with gestational age (GA) 24-34 weeks admitted to the neonatal ward of our hospital and received ACS were retrospectively studied. The infants were assigned into single-course group, partial-course group and multiple-course group according to ACS courses. The short-term clinical outcomes were compared among the groups. SPSS software version 25.0 was used for statistical analysis.Results:A total of 286 infants were enrolled in this study, including 128 in single-course group, 89 in partial-course group and 69 in multiple-course group. Compared with single-course group, the risks of neonatal respiratory distress syndrome (RDS) in both partial-course group ( OR=2.332, 95% CI 1.028-5.293, P=0.043) and multiple-course group ( OR=3.872, 95% CI 1.104-13.584, P=0.034) were higher. The birth length in multiple-course group ( β=-0.016, 95% CI -0.029 - -0.002, P=0.024) was lower than single-course group. Conclusions:The risks of neonatal RDS in preterm twins are higher in partial-course and multiple-course of ACS. A full course of ACS should be used to prevent neonatal RDS until further evidence of effectiveness is available.

Objective:To investigate the influential factors of adverse pregnancy outcomes in women with subchorionic hematoma.Methods:A total of 101 women with subchorionic hematoma who received treatment in the People's Hospital of Xinjiang Uygur Autonomous Region from January 2017 to June 2020 were included in this study. They were divided into a control group and an adverse pregnancy outcome group according to whether there was an adverse pregnancy outcome. The epidemiological characteristics, hematoma characteristics observed on ultrasound images, and pregnancy outcomes were compared between the two groups.Results:There was no significant difference in the number of women who used assisted reproductive technology between the control and adverse pregnancy outcome groups [6 (8.0%) vs. 8 (30.7%), χ2 = 8.38, P = 0.004]. There was a significant difference in hematoma volume between adverse pregnancy outcome and control groups [(4.12 ± 0.61) mL vs. (6.36 ± 0.87) mL, t = 6.73, P = 0.009]. There was a significant difference in the number of patients who had obstetric complications between control and adverse pregnancy outcome groups [11 (14.7%) vs. 16 (61.5%), χ2 = 21.66, P = 0.001]. There was a significant difference in the number of patients who had hematomas located at the edge of the placenta between the control and adverse pregnancy outcome groups [15 (20.0%) vs. 12 (46.2%), χ2 = -4.81, P = 0.001]. Conclusion:Women who use assisted reproductive technology for pregnancy, have obstetric complications, or have a subchorionic hematoma with hematoma at the edge of the placenta are more likely to experience a miscarriage. Therefore, women of childbearing age should actively treat the primary disease and be alert to the occurrence of placental abruption.

Objective To investigate the association of the DYS527a/b and DYF387S1a/b multi-allele pattern with Y-SNP haplogroups.Methods Samples from 295 unrelated males who carrying the DYS527a/b multi-allele pattern were amplified by the YFilerPlus? kit.The genotypes of their frequency distributions,including three multi-copy loci(DYS527a/b,DYF387S1a/b,DYS385a/b)and other single-copy loci were obtained.The DYS527a/b multi-allele pattern and their haplotypes were examined for the associations with Y-chromosome haplogroups using the AIYSNP42 kit,which contains 42 Y-SNP loci.Based on the above results,the association between the DYS527a/b multi-allele patter and its constituent Y-STR haplotypes and related haplogroups was discussed.Results Among the 295 samples,the DYS527a/b tri-allele pattern and tetra-allele pattern accounted for 97.29%and 2.71%respectively,while the DYF387S1a/b tri-allele pattern and tetra-allele encompassed 54.24%and 4.75%.Null allele was detected in DYS448 in 13.22%of the samples.Here,7 Y-SNPs were deticted such as O-M175 and C-M131 which encompassed 45.76%and 45.08%.The haplogroups of R1-M173,N-M231,D1-M174,J-M304 and F-M89 were less than 13 cases,with frequencies ranging from 4.41%～0.34%.There were Y-STR genotypes differences among haplogroups,as haplogroup O-M175 was represented by 4 genotypes of Y-STR profiles characterized by DYS385a/b(12/12,as well as 12/17,12/18,12/19),DYS392(13),DYS593(16)and DYS393(12),and haplogroup C-M130 was characterized by DYS527a/b(19/20/21),DYS385a/b(11),DYS593(17),DYS390(23),Y_GATA_H4(11),and DYS444(13)and so on.Conclusion The DYS527a/b multi-allele pattern is frequently observed in the Kunming population with haplogroup C-M130.In the samples from haplogroups O,C,R1 and N,the DYS527a/b and DYF387S1a/b haplotypes frequently exhibit the multi-allele pattern.Given the frequencies of different haplogroups and the association between Y-SNP haplogroups and Y-STR loci,it could be helpful to look for more details in the paternal lineage search.

OBJECTIVE To explore the mechanism of modified Xianfang huoming decoction in the treatment of sepsis- induced liver injury from the perspective of gut microbiota and metabolites. METHODS Sixty SD rats were divided into blank group （normal saline）， model group （normal saline）， positive control drug group （Dexamethasone tablet， 5.0 mg/kg）， modified Xianfang huoming decoction high-dose， middle-dose and low-dose groups （6.0， 3.0， 1.5 g/kg， calculated by crude drug） according to equilibrium-partitioning approach of body mass， with 10 rats in each group. They were given relevant drug/normal saline 10 mL/ kg， once a day， for consecutive 14 days. After the last medication， except for blank group， other groups were given intraperitoneal injection of lipopolysaccharide 10 mg/kg to induce sepsis model. Twelve hours after modeling， serum levels of inflammatory indexes in rats [interleukin-1β （IL-1β）， IL-6， tumor necrosis factor-α （TNF-α）] and liver function indicators [total cholesterol （TC）， triglyceride （TG）， aspartate transaminase （AST）， alanine transaminase （ALT）] were detected. The changes of gut microbiota and liver metabolites in rats were analyzed by 16S rRNA technology and liver metabolomics. RESULTS Modified Xianfang huoming decoction could significantly improve the indexes of serum inflammatory indexes and liver function in rats with sepsis-induced liver injury （P＜0.05 or P＜0.01）； there was a significant callback effect on the relative abundance of 11 genera of bacteria （such as Akkermansia， Lactobacillus and Bilophila） among the 5 dominant phyla（P＜0.05 or P＜0.01）. Twelve metabolites related to liver injury caused by sepsis were identified， such as glycine cholic acid， phosphatidylcholine， taurine （P＜0.05 or P＜0.01）， mainly involving glycerol phospholipid metabolism， purine metabolism and primary bile acid metabolism. CONC LUSIONS Modified Xianfang huoming decoction can improve liver injury induced by sepsis by regulating gut microbiota and liver metabolites.