ObjectiveTo analyze the pharmacodynamic activity of Bupleuri Radix processed with Trionyx sinensis blood in the treatment of Yin deficiency and study the spectrum-effect relationship of this medicine. MethodsHigh performance liquid chromatography was employed to establish the fingerprints of 15 batches of Bupleuri Radix processed with Trionyx sinensis blood， and the similarity was evaluated according to the SOP of Similarity Evaluation System of Chromatographic Fingerprint of TCM （version 2012）. A mouse model of Yin deficiency induced by thyroxine was established. The relationship between the active components and the effect on Yin deficiency was explored by grey correlation analysis and partial least squares method based on the changes in the serum levels of triiodothyronine （T3）， thyroxine （T4）， cyclic adenosine phosphate （cAMP）， and cyclic guanosine phosphate （cGMP）. The components screened out based on the spectrum-effect relationship were used for retrieval of the targets from the Traditional Chinese Medicine Systems Pharmacology and Analysis Database （TCMSP）， The Encyclopedia of Traditional Chinese Medicine （ETCM）， and Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP）. Furthermore， the Online Mendelian Inheritance in Man （OMIM）， GeneCards， TTD， DisGeNET， and Drugbank were employed to establish the active component-target against Yin deficiency network of Bupleuri Radix processed with Trionyx sinensis blood. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses were carried out for the core targets. Real-time PCR was conducted to verify the predicted key pathways and mechanisms. ResultsThe fingerprints of the 15 batches of Bupleuri Radix processed with Trionyx sinensis blood showed the similarities of 0.976-0.999 with the control fingerprint. Compared with the model group， the drug administration group showed elevated levels of T3 and T4 and lowered levels of cAMP， cGMP and cAMP/cGMP. The results of grey correlation analysis showed that active components in terms of the correlations followed the trend of saikosaponin B₁ > saikosaponin B₂ > saikosaponin C > saikosaponin D > saikosaponin A. The partial least squares analysis showed that saikosaponins A， D， B₁， and B₂ had higher VIP values. Network pharmacology predicted a total of 30 common targets， which were enriched in 276 GO terns and 115 KEGG pathways. The results of Real-time PCR showed that the model group had lower mRNA levels of Caspase-9， kinase insert domain receptor （KDR）， and mammalian target of rapamycin （mTOR） and higher mRNA level of mouse double minute 2 homolog （MDM2） than the blank group and the drug administration group. ConclusionBupleuri Radix processed with Trionyx sinensis blood has therapeutic effect on Yin deficiency syndrome， which provides a new idea for studying Bupleuri Radix processed with Trionyx sinensis blood.

OBJECTIVE To investigate the effects of Brassica rapa polysaccharide （BRP） on the Toll-like receptor 4 （TLR4）/ myeloid differentiation factor 88 （MyD88）/nuclear factor-κB （NF-κB）， AMP-activated protein kinase （AMPK）/sterol regulatory element-binding protein-1c （SREBP-1c） pathways， intestinal microbiota and liver metabolism of mice with alcoholic liver injury， and preliminarily elucidate its mechanism for improving alcoholic liver injury. METHODS Seventy-two mice were randomly divided into blank group （normal saline）， model group （normal saline）， bifendate group （positive control， 300 mg/kg） and BRP low-， medium- and high-dose groups （75， 150 and 300 mg/kg）. They were given relevant medicine intragastrically， once a day， for consecutive 9 d. After the last administration， mice in all groups except the blank group were gavaged with white liquor to establish an alcoholic liver injury model. The levels of alanine aminotransferase and aspartate aminotransferase in serum， total cholesterol， triglycerides， low-density lipoprotein cholesterol， interleukin-6， interleukin-1β， tumor necrosis factor- α and lipopolysaccharide， as well as protein expressions of TLR4， MyD88， NF-κB p65， phosphorylated NF-κB p65 （p-NF-κB p65）， AMPK， phosphorylated AMPK （p-AMPK）， and SREBP-1c were all detected； pathological morphological changes of liver tissue and colon were observed. 16S rRNA was used to detect the changes of intestinal microbiota in mice， and metabolomics 2022B02058） technology was used to detect the changes of liver metabolites. RESULTS Compared with model group， the above biochemical indicators and the protein expressions of TLR4， MyD88， p-NF-κB p65， and SREBP-1c in liver tissues were all significantly decreased （P＜0.05 or P＜0.01）， while the protein expression of p-AMPK was significantly increased （P＜0.05 or P＜0.01）. Pathological damage to liver and colon tissues was significantly improved. Medium dose of BRP could increase the relative abundance of Akkermansia， norank_f_Muribaculaceae and Lachnospiraceae_NK4A136_group in the intestinal contents of mice to a certain extent， and decrease the relative abundance of Lactobacillus and Escherichia-Shigella. A total of 9 differential metabolites were identified by metabolomics， including homogentisic acid， myristyl lysophosphatidylcholine， which were involved in pathways such as tyrosine metabolism. CONCLUSIONS BRP can regulate the relative abundance of beneficial flora， reduce the relative abundance of harmful flora， improve the structure of intestinal colonies， reduce the entry of pro-inflammatory mediator lipopolysaccharides into liver tissue， affect metabolic pathways such as tyrosine metabolism and the expression of TLR4/MyD88/NF- κB and AMPK/SREBP-1c signaling pathways in the liver， and ultimately improve alcoholic liver injury.

Central nervous system (CNS) injuries, including stroke, traumatic brain injury, and spinal cord injury, are essential causes of death and long-term disability and are difficult to cure, mainly due to the limited neuron regeneration and the glial scar formation. Herein, we apply extracellular vesicles (EVs) secreted by M2 microglia to improve the differentiation of neural stem cells (NSCs) at the injured site, and simultaneously modify them with the injured vascular targeting peptide (DA7R) and the stem cell recruiting factor (SDF-1) on their surface via copper-free click chemistry to recruit NSCs, inducing their neuronal differentiation, and serving as the nanocarriers at the injured site (Dual-EV). Results prove that the Dual-EV could target human umbilical vascular endothelial cells (HUVECs), recruit NSCs, and promote the neuronal differentiation of NSCs in vitro. Furthermore, 10 miRNAs are found to be upregulated in Dual-M2-EVs compared to Dual-M0-EVs via bioinformatic analysis, and further NSC differentiation experiment by flow cytometry reveals that among these miRNAs, miR30b-3p, miR-222-3p, miR-129-5p, and miR-155-5p may exert effect of inducing NSC to differentiate into neurons. In vivo experiments show that Dual-EV nanocarriers achieve improved accumulation in the ischemic area of stroke model mice, potentiate NSCs recruitment, and increase neurogenesis. This work provides new insights for the treatment of neuronal regeneration after CNS injuries as well as endogenous stem cells, and the click chemistry EV/peptide/chemokine and related nanocarriers for improving human health.

Objective:To summarize the efficacy and safety of transurethral partial cystectomy combined with intravesical suturation in the treatment of bladder cancer.Methods:The clinical data of 28 patients with bladder cancer who were admitted in Zhengzhou People's Hospital from July 2020 to October 2021 were analyzed retrospectively. There were 22 males and 6 females, with the average age of (68.8±8.9) years old. Twenty cases were with single bladder tumor, and 8 cases were with multiple bladder tumors. The diameter of single bladder tumor measured by CT was less than 4 cm, with a median tumor diameter of 2.3(0.9, 2.8)cm. All 28 patients underwent transurethral partial cystectomy combined with intravesical suturation for the first time. Intraoperative intravesical instillation was conducted with 1 g gemcitabine. Bladder hot reperfusion treatment was performed with gemcitabine 2 g at 45℃ immediately after operation. The patients underwent reexamination with cystoscopy every 3 months after operation.Results:All the 28 patients successfully completed the operation. The average operation time was (128.3±16.3)min. No obturator nerve reflection was induced during operation. Muscularis tissue was found in all tumor pathological specimens after operation, among which 4 cases showed muscularis infiltration. Pathology of tumor basal and peripheral tissues showed tumor cell infiltration in 3 cases (1 case full-thickness infiltration, namely the incision margin was positive). The median continuous irrigation time of bladder after operation was 24.0(20.9, 25.0)h. The median time of indwelling catheter after operation was 6.5(6.0, 7.0)days, and one case developed severe bladder spasm. All patients were followed up, with a median follow-up of 7.5(4.0, 10.8) months.Postoperative recurrence occurred in 3 cases, all of which were ectopic recurrence in bladder.The 1-year recurrence rate was 10.7% (3/28).Conclusions:In the first surgical treatment of bladder cancer, transurethral partial cystectomy combined with intravesical suturation can provide accurate pathological staging, and low positive surgical margin rate. Immediate suturation of bladder wound during operation and immediate bladder perfusion chemotherapy can provide short bladder irrigation time, with few adverse reactions and low incidence of complications.

【Objective】 To investigate the current status of incision sites to obtain intact specimens in laparoscopic nephrectomy by urologists in China, so as to provide reference for the standardized procedure. 【Methods】 During Jun.20, 2021 and Jul.4, 2021, more than 20 000 urologists in a WeChat group were surveyed with a questionnaire. The general data, incision sites and related complications were statistically analyzed. 【Results】 A total of 601 valid questionnaires were collected, covering urologists from 31 provinces, autonomous regions and municipalities. Surgical approaches: 68 urologists chose trans-abdominal approach, 432 chose posterior abdominal space approach, 101 chose both surgical approaches. Incision sites: 97 urologists chose lumbar transverse incision, 202 chose dorsal oblique incision of the waist, 119 chose ventral oblique incision, 93 chose the paramedian incision, 112 chose the lower abdominal oblique incision (Gibson), 11 chose the transverse lower abdominal incision (Pfannenstiel), 7 chose the median incision of the lower abdomen, 2 chose the median incision in the upper abdomen, 15 chose axillary midline direct incision; 399 chose to cut off the muscles, and 202 chose not to. Complications: 232 urologists reported pain after 2 weeks, 369 reported no pain; 325 reported numbness after 2 weeks, 276 reported no numbness; 66 reported incisional hernia, 535 reported no hernia. 【Conclusions】 Chinese urologists tend to choose retroperitoneoscopic nephrectomy and waist incision to obtain intact specimens. Transperitoneal laparoscopic nephrectomy has a variety of incisions for intact specimens. There is no standardized incision sites to obtain intact specimens.

OBJECTIVE To conduct the pharmacoeconomic evaluation of empagliflozin in the treatment of heart failure with reduced ejection fraction （HFrEF），and to provide evidence-based reference for rational drug use and medical and healthy decision-making. METHODS A Markov model was used to perform a cost-effectiveness analysis of the regimen of empagliflozin in the treatment of HFrEF ，and to evaluate the cost and effectiveness of standard treatment plan plus empagliflozin （empagliflozin group）vs. standard treatment plan （standard treatment group ）. Clinical parameters were obtained from the EMPEROR-Reduced study；cost and utility data came from the published literatures. The cycle of the model was 1 month and the simulation time was 20 years. Single-factor sensitivity analysis and probability sensitivity analysis were performed to validate the results of cost-effectiveness analysis. RESULTS Compared with the standard treatment group ，each additional quality-adjusted life year in the empagliflozin group cost 37 995.94 yuan more ，which was less than China ’s 1 time GDP per capita in 2020（72 447 yuan）. The results of single factor sensitivity analysis showed that steady-state hospitalization rate of 2 groups was the most important factor affecting the incremental cost-effectiveness ratio . The results of probability sensitivity analysis showed that when the willingness-to-pay threshold （WTP）was 1 time GDP per capita in 2020（72 447 yuan），the probability of empagliflozin group with cost-effectiveness advantage was 58.8％；when the WTP was 3 times GDP per capita in 2020（217 341 yuan），the probability of empagliflozin group with cost-effectiveness advantage was 63.8％. CONCLUSIONS Compared with standard treatment plan alone，standard treatment plan plus empagliflozin is more cost-effective in the treatment of HFrEF. However ，the economic probability is not high.

Objective:To explore the prevalence and influencing factors of mental violence in intimate partner violence.Methods:A total of 900 people, who aged 18 to 65 with marriage or love experience, were selected from Xinjiang Uygur Autonomous Region using stratification cluster method. A self-designed questionnaire for general information, the brief conflict tactics scale 2 (CTS-2), perceived stress scales (PSS) and personality diagnostic questionnaire-4+ (PDQ-4+ ) were used for questionnaire investigation. The influencing factors of mental violence were analyzed by binary logistic regression analysis model using SPSS 17.0 software.Results:The scores of CTS-2, PPS and PDQ-4+ were (21.46±6.38), (42.48±18.91), and (3.05±0.62), respectively. In the past one year, the incidence of abusing partners, emotional violence, destroying each other's goods and threatening to hit each other in mental violence were 41.67% (375/900), 33.44% (301/900), and 8.44% (76/900), respectively. Based on the scores of three items, the incidence of mental violence was 55.44% (499/900). Multi-factor logistic regression analysis showed age≤29 ( β=0.57, OR=2.53, 95% CI=1.11-5.99), male ( β=0.64, OR=3.68, 95% CI=1.22-4.56), rural ( β=0.12, OR=2.49, 95% CI=1.17-5.36), moderate and severe drinking ( β=0.33, OR=2.87, 95% CI=2.57-6.63), higher perceived stress level ( β=0.51, OR=1.05, 95% CI=1.03-1.09), personality factors deviate ( β=0.43, OR=2.26, 95% CI=2.13-2.39), lower marital satisfaction ( β=0.18, OR=2.05, 95% CI=1.03-8.76), behavior control over partner ( β=0.16, OR=2.55, 95% CI=1.68-3.69), economic control over partners ( β=0.19, OR=1.36, 95% CI=1.28-1.55) were risk factors of mental violence in intimate partner violence, while individual opposed attitude towards violence ( β=0.29, OR=0.88, 95% CI=0.80-0.94) was the protective factor of mental violence in intimate partner violence. Conclusion:The annual incidence of mental violence is high. Therefore, it is necessary to focus on the young, male, rural and personality deviant people. The incidence of mental violence may be reduced by reducing the individual's perceived stress level, drinking level, behavior control and economic control over partners, and strengthening the marital satisfaction and the individual's opposition to violence.

Objective:To investigate changes in the expression of Cosmc and T-synthase in peripheral B lymphocytes and in serum levels of galactose-deficient IgA1 (Gd-IgA1) in patients with Henoch-Sch?nlein purpura (HSP) .Methods:From January to August 2014, 56 patients with HSP were collected from outpatient or inpatient department of dermatology and venereology in the Second Hospital of Hebei Medical University, and were divided into 4 groups, including skin type group (22 cases) , joint type group (9 cases) , abdominal type group (12 cases) and renal type group (13 cases) . Twenty healthy volunteers served as healthy controls. Real-time fluorescence-based quantitative PCR was performed to determine the mRNA expression of Cosmc and T-synthase in peripheral B lymphocytes, and a lectin-based enzyme-linked immunosorbent assay (ELISA) to detect the serum level of Gd-IgA1. Comparisons among multiple groups were performed using one-way analysis of variance or Kruskal-Wallis H test, multiple comparisons were performed using least significant difference (LSD) - t test or Nemenyi test, and correlation analysis was performed using Spearman rank correlation analysis. Results:There was a significant difference in the duration from disease onset to the clinic visit ( χ2= 26.19, P < 0.05) among the skin type group (6.27 ± 3.09 d) , joint type group (5.56 ± 3.05 d) , abdominal type group (6.75 ± 3.75 d) , and renal type group (26.23 ± 14.12 d) , and the duration from disease onset to the clinic visit was significantly longer in the renal type group than in the other 3 groups (all P < 0.05) . The Cosmc mRNA expression significantly differed among the skin type group, joint type group, abdominal type group, renal type group and healthy control group (0.849 ± 0.239, 0.767 ± 0.181, 0.719 ± 0.183, 0.459 ± 0.121, 1.146 ± 0.232, F= 23.37, P < 0.05) , was significantly lower in the 4 patient groups than in the healthy control group ( P < 0.01) , and lower in the renal type group than in the other 3 patient groups (all P < 0.01) . There was no significant difference in the T-synthase mRNA expression in peripheral B lymphocytes among the patient groups and healthy control group ( F= 1.05, P > 0.05) . The serum level of Gd-IgA1 significantly differed among the skin type group, joint type group, abdominal type group, renal type group and healthy control group ( F= 7.06, P < 0.05) . Moreover, the Gd-IgA1 level was significantly higher in the patient groups than in the healthy control group (all P < 0.05) , and higher in the renal type group than in the other 3 patient groups (all P < 0.05) . The serum level of Gd-IgA1 in the HSP patients was significantly and negatively correlated with the mRNA expression of Cosmc ( rs=-0.50, P < 0.01) . Conclusion:Decreased mRNA expression of Cosmc and increased serum levels of Gd-IgA1 were observed in patients with HSP, and there was a negative correlation between the two indices.

Objective To discuss the safety and efficacy of inserting ureterovesical reimplantation by means of laparoscopy associated with six-stitch suture.Methods There was an retrospective analysis on operation videos and clinical data for 16 participants of inserting ureterovesical reimplantation by means of laparoscopy associated with six-stitch suture with the period from March in 2012 to September in 2015. And these were statistically analyzed including the operation time, intraoperative bleeding volume, postoperative drainage volume, removal time of drainage tube, admission time after operation and the incidence of postoperative complications of vesicoureteric reflux and stenosis.Results The operations of 16 participants were completed successfully without converting to open surgery. The operation time was 60 ~ 125 min (Mean time: 85 min); intraoperative bleeding volume was 20 ~ 50 ml (Mean volume: 32 ml); postoperative drainage volume was 60 ~ 400 ml (Mean volume: 106 ml); removal time of drainage tube was 3 ~ 6 d (Mean time: 4.2 d) and admission time after operation was 7 ~ 10 d (Mean time: 8.5 d). There was the follow-up with 6 ~ 18 months (Mean time: 12 months) for participants. No anastomotic stenosis was present. In addition, one participant was suffered from mild vesicoureteric relfux. And there was no aggravation during 18 months.Conclusions The inserting ureterovesical reimplantation by means of laparoscopy associated with six-stitch suture was safe and effective. It was found that the operation time was significantly shortened and the incidence of postoperative complications of vesicoureteric relfux and anastomotic stenosis was not increased. By contrast, the six-stitch suture could reduce the incidence of anastomotic stenosis.

Objective To investigate the effect of N-myc downstream regulated gene 2 (NDRG2) on the apoptosis of bladder cancer cells by regulating the signal transducer and activator of transcription 3(STAT3) signaling pathway.Methods The expression level of NDRG2 in human bladder cancer cell BIU-87 and immortalized cell SV-HUC-1 was detected by Western blot.NDRG2 over expression vector and empty vector control (pcDNA3.1),siRNA-NDRG2,siRNA control were transfected into BIU-87 cells.After transfected 48 h,the expression level of NDRG2,Cleaved caspase 3,STAT3,p-STAT3,JAK2,p-JAK2 were detected by Western blot,the cell proliferation and apoptosis were measured by MTT and flow cytometry.After adding inhibitor AG490 of 45 μmol/L in cultured BIU-87 cells,MTT assay was used to detect cell proliferation and flow cytometry was used to detect the cell apoptosis,Western blot to detect the expression level of Cleaved caspase 3,STAT3,p-STAT3,JAK2,p-JAK2.Results The expression level of NDRG2 in bladder cancer cells was higher than that in bladder epithelial cells.The cell survival rate of pcDNA3.1/NDRG2 group was lower than that of pcDNA3.1 group,the difference was statistically significant (P ＜ 0.01).The cell survival rate of siRNA-NDRG2 group was higher than that of siRNA control group (P＜ 0.01).The apoptosis rate of pcDNA3.1/NDRG2 group was higher than that of pcDNA3.1 group (P ＜ 0.01).The apoptosis rate of NDRG2 siRNA group was lower than that of siRNA control group (P ＜ 0.01).The level of p-STAT3 and p-JAK2 in pcDNA3.1/NDRG2 group was lower than that in pcDNA3.1 group (P＜ 0.01).The survival rate and apoptosis rate of BIU-87 cells cultured with AG490 were in agreement with the trend of pcDNA3.1/NDRG2 after transfection.Conclusions NDRG2 could promote the apoptosis of bladder cancer cells,and its mechanism may be related to STAT3 signaling pathway.