Traf2- and Nck-interacting kinase (TNIK) is closely related to the cancer occurrence, development, and prognosis. TNIK plays an important role in regulating Wnt/β-catenin pathway, thus becoming a potential target for cancer treatment. Various small-molecule TNIK inhibitors with diverse structures and potent in vitro activities have been developed to treat tumors. However, no TNIK inhibitor has entered clinical phase mainly due to poor selectivity, toxicity, and unsatisfied in vivo anti-tumor efficiency. This review summarizes the research progress of small molecule inhibitors targeting TNIK, with the aim of giving some guidance for future research and development of small-molecule inhibitors.

In this study, ultra-performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS~E) was used to analyze the plasma components of Danzhi Xiaoyao Formula after oral administration. Forty-nine plasma components were found in the serum of rats by comparing the compound extract, drug-containing serum, and blank serum. Components, such as 6-hydroxycoumarin, poricoic acid F, deoxoglabrolide, 30-norhederagenin, kanzonol R, 3',6'-di-O-galloylpaeoniflorin, 16α-hydroxytrametenolic acid, 16-deoxyporicoic acid B, 3-O-acetyl-16α-hydroxytrametenolic acid, and 16α,25-dihydroxydehydroeburiconic acid, were first found in rat serum. Behavioral tests, including the tail suspension test, novel object recognition test, and novelty-suppressed feeding test, were conducted for behavioral analysis. It was confirmed that this formula had therapeutic effects on perimenopausal depression. Furthermore, in combination with the network pharmacology method, 53 core targets including MAPK1, HRAS, AKT1, EGFR, and ESR1 were screened, and these targets participated in 165 signaling pathways, including PI3K-AKT, AMPK, VEGFA, MAPK, and HIF-1. In summary, the potential effects of Danzhi Xiaoyao Formula in treating perimenopausal depression are associated with mechanisms in accelerating inflammation repair, improving neuroplasticity, affecting neurotransmitters, regulating estrogen levels, and promoting new blood vessel formation.
Animals ; Rats ; Chromatography, High Pressure Liquid ; Depression/drug therapy* ; Network Pharmacology ; Perimenopause ; Phosphatidylinositol 3-Kinases ; Drugs, Chinese Herbal/pharmacology* ; Molecular Docking Simulation

Objective:To investigate the clinical features of IgD multiple myeloma (MM) and the effect and prognosis of daratumumab-based combination therapy.Methods:The clinicopathological data of a IgD MM patient with disease progression and extramedullary infiltration treated with daratumumab in the Affiliated Hospital of Qingdao University in December 2019 were retrospectively analyzed.Results:The 74-year-old woman was diagnosed as IgD MM by bone marrow aspiration and immunofixation electrophoresis. The patient was given VD (bortezomib, dexamethasone), RD (lenalidomide, dexamethasone) and ID (ixazomib, dexamethasone) regimens. In June 2020, the patient developed multiple subcutaneous nodules, and she was assessed as progressive disease with extensive extramedullary infiltration. After treated with daratumumab-PAD (liposomal doxorubicin, bortezomib, dexamethasone) regimen, the patient's subcutaneous nodules were significantly reduced and partially disappeared, and the general condition was significantly improved. But the patient was in a cachexia state and finally died of the irregular treatment and disease progression.Conclusions:IgD MM has a low incidence and a short survival period, and there is no uniform standard treatment. The early application of daratumumab combined with proteasome inhibitors, immunomodulators, cytotoxic drugs and hematopoietic stem cell transplantation may improve the overall survival of patients.

Objective: To understand the infection status of HIV and related factors in men who have sex with men (MSM) in Shanxi province in 2010, 2015 and 2020. Methods: According to the sentinel surveillance protocol, continuous cross-sectional survey were conducted to collect the information about basic characteristics, general demographic characteristics, AIDS knowledge awareness, high-risk sexual behavior, sexually transmitted diseases, intervention services and HIV infection rate of the MSM in Shanxi in 2010, 2015 and 2020. Results: In 2010, 2015 and 2020, a total of 2 708 MSM were included in this study. There were significant differences in HIV infection rate among three years (χ²=23.76, P<0.001) with an increasing trend with year (trend χ² =17.34, P<0.001). The rates of anal sex, commercial sex and heterosexual behavior in the past 6 months were 77.62% (2 102/2 708), 5.91% (160/2 708) and 28.14% (762/2 708) respectively, and the rates of consistent use of condom were 52.52% (1 104/2 102), 63.13% (101/160) and 23.49%(179/762) respectively, and the rate of consistent condom use was low. Results from multivariate logistic regression analysis showed that different cities, having educational level of junior high school or below, being recruited through internet, voluntary counseling and testing, suffering from sexually transmitted diseases, occasional condom use in anal sex in the past 6 months were the correlative factors of HIV infection of MSM. Conclusions: The HIV infection rate of MSM in Shanxi increased year by year from 2010, 2015 to 2020. The HIV/AIDS-related risk behavior persisted, and the proportion of condomuse adherence was low, and the HIV detection rate was low in the MSM, so targeted and effective measures should be taken to promote the condom use adherence and regular HIV testing in MSM.
Cross-Sectional Studies ; HIV Infections/epidemiology* ; HIV Testing ; Homosexuality, Male ; Humans ; Male ; Prevalence ; Risk Factors ; Risk-Taking ; Sentinel Surveillance ; Sex Work ; Sexual Behavior ; Sexual and Gender Minorities ; Sexually Transmitted Diseases/epidemiology* ; Surveys and Questionnaires

OBJECTIVE: To explore the pharmacological mechanism of Bushen Huatan (BSHT) recipe in the treatment of polycystic ovary syndrome (PCOS). METHODS: The active ingredients in the component drugs of the recipe were screened through TCMSP, and their potential targets were predicted by PubChem and Swiss target prediction. Genecards and OMIM were used to screen the therapeutic targets in the treatment of PCOS. The drug targets and disease targets were corrected using Uniprot, and the intersection targets were obtained. The protein-protein interaction (PPI) network was constructed using STRING, and the intersection targets were analyzed with CytoNCA to screen the core targets. DAVID was used for GO enrichment analysis and KEGG pathway enrichment analysis, and the core components and core targets were verified using AutoDock. Animal experiment was performed to verify the results using a female C57BL/6J mouse model of PCOS, treated daily with 1 mg/kg BSHT recipe granule for 35 days, and the ovarian expressions of the core targets and pathways were detected using Western blotting. RESULTS: We identified a total of 125 potential active ingredients from the 14 component drugs in the recipe, 990 drug targets, 4759 PCOS targets and 434 intersection targets. The core active ingredients of the recipe included β -Sitosterol, kaempferol, and quercetin, whose core targets included PIK3CA, PIK3R1, APP, AKT1, and MAPK1. GO enrichment analysis highlighted such processes as drug reaction, negative regulation of apoptosis, and positive regulation of transcription from RNA polymerase Ⅱ promoter. The enriched KEGG pathways included primarily the cancer pathway and PI3K-Akt signaling pathway. Molecular docking showed that the core active ingredients had strong binding ability with the core targets. In the animal experiment, BSHT recipe was shown to improve the symptoms, down-regulate the expressions of PI3K and Akt proteins and up-regulate MAPK1 expression in the ovary of mice with PCOS. CONCLUSION The therapeutic mechanism of BSHT recipe for PCOS involves multiple active ingredients, multiple therapeutic targets and multiple pathways.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Female ; Mice ; Mice, Inbred C57BL ; Molecular Docking Simulation ; Network Pharmacology ; Phosphatidylinositol 3-Kinases ; Polycystic Ovary Syndrome/drug therapy*

Abstract: Objective　To analyze the survival status of HIV/AIDS patients aged above 50 years receiving antiviral therapy (ART) in Shanxi Province from 2011 to 2019, and to provide evidence for further improvement of antiviral therapy. Methods　Basic information and follow-up information of HIV/AIDS patients aged above 50 years who first received HIV/AIDS antiviral therapy in Shanxi Province from 2011 to 2019 were collected. Excel database was established and SPSS23.0 software was used for analysis. Retrospective cohort study was conducted. Cox proportional risk regression model was used to analyze the factors influencing survival time. Results　A total of 1 183 subjects were included, of which 172 died, including 84(48.84%) from other causes, 74(43.02%) AIDS-related death and 14 (8.14%) from accidents, suicides and undetermined deaths. Setting AIDS-related deaths as an outcome event, life table analysis showed that the cumulative survival rates at 1, 3, 5, 7 and 9 years after receiving ART were 96.61%, 93.59%, 90.35%, 87.57% and 83.44%, respectively. Multivariate Cox proportional risk model analysis showed that the risk of death in patients aged 60-<70 years group and over 70 age group was 2.53 times (95%CI: 1.51-4.23) and 3.59 times (95%CI: 1.74-7.40) for patients aged the 50-<60 group , respectively. The risk of death in patients with baseline CD4+T lymphocyte (CD4) counts of ≥200/mm3, 50-<200 /mm3 was 0.22 times (95%CI: 0.12-0.41) and 0.37 times (95%CI: 0.21-0.67) for patients with CD4+T lymphocyte counts of <50/mm3. The risk of death in patients with opportunistic infections at baseline was 1.99 times (95%CI: 1.16-3.39) for patients without baseline opportunistic infections. Conclusions　The survival rate of HIV/AIDS patients aged above 50 who received antiviral therapy (ART) in Shanxi Province from 2011 to 2019 was relatively high. To further improve the quality of antiviral treatment in our province, the strategy of "early detection and early treatment" should be continued and improved in the future, and information collection of specific causes of non-AIDS-related deaths among this population should be further strengthened.

Objective:To evaluate the early effects of combined transaortic and transapical approach to septal myectomy in patients with complex hypertrophic obstructive cardiomyopathy(HOCM).Methods:We consecutively enrolled 20 complex HOCM patients who received transaortic and transapical myectomy in fuwai hospital from January 2019 to October 2019. Echocardiography was performed to compare left atrial size, left ventricular end diastolic diameter, peak left ventricular outflow gradient, ventricular septal thickness, mitral systolic anterior motion and mitral regurgitation grade before and after operation. Furthermore, pre-operative and post-operative electrocardiogram were also analyzed to determine the incidence of bundle branch block. Functional status was evaluated by New York Heart Association functional class.Results:Of the 20 complex hypertrophic cardiomyopathy patients, 7(35%) HOCM patients with long-segment septal hypertrophy more than 7cm, 4(20%) patients had both mid-ventricular obstruction and left ventricular outflow obstruction. Apical hypertrophic cardiomyopathy with LOVT obstruction was observed in 5 patients(25%) and aneurysm was found in 4(20%) HOCM patients. Postoperative thickness of ventricular septum was significantly decreased compared with that of preoperation[(21.1±3.6)mm vs.(13.4±3.1)mm]. Peak LOVT gradient or mid-ventricular gradient also significantly reduced after operation[(77.0±21.0) mmHg vs.(9.2±3.4) mmHg] or [(71.0±23.0) mmHg vs. 0 mmHg, 1 mmHg=0.133 kPa]; After surgery, mitral systolic anterior motion disappeared, mitral regurgitation degree reduced from (1.9±1.5) to (0.2±0.4); NYHA class improved from(2.1±0.2) to(1.3±0.5). New incidence of left bundle branch block occurred in 9 patients, and 1 patient developed complete bundle branch block and implanted permanent pacemaker. The 30-day survival was 100%.Conclusion:Combined transaortic and transapical septal myectomy is an effective and reasonably safe procedure for patients with complex hypertrophic obstructive cardiomyopathy.

【Objective】 To explore the effects and the possible mechanism of RNA targeting membrane-bound prostaglandin E2 synthase l（mPGES- 1）on proliferation，apoptosis and drug resistance of leukemia cell line K562/A.【Methods】RNA interference was used to inhibit the expression of mPGES-1 of K562/A cells. Four groups were set up as follows：untreated group（K562/A），negative control group after interference（K562/A-NC），group after interference（K562/ A-KD），and group after interference with exogenous PGE2（K562/A-KD+PGE2）.Cell viability was assessed by CCK-8 assay. Cell apoptosis was analyzed by flow cytometry. Concentration of PGE2 was detected by ELISA. Proteins expression was detected by western blot.【Results】The expression of mPGES- 1 in K562/A cells was significantly down- regulated and the synthesis of PGE2 decreased（P < 0.000 1）after RNA interference. After RNA interference，the proliferation of K562/A cells was inhibited and apoptosis increased，and the sensitivity to chemotherapy drugs was enhanced（P < 0.05）. Meanwhile，the expression of β-catenin and MDR1 was decreased（P < 0.01）. Exogenous PGE2 could reverse the effect of RNA interference on proliferation ，apoptosis and drug sensitivity in K562/A cells（P < 0.05），and up-regulate the expression of β-catenin and MDR1（P < 0.01）. XAV939，an inhibitor of β-catenin，could down-regulate the expression of β- catenin and MDR1 in an dose- dependent pattern in K562/A cells（P < 0.05）.【Conclusions】RNA interference of mPGES- 1 could inhibit proliferation，induce apoptosis and reverse drug resistance in K562/A cells. The mechanism was related to reducing the synthesis of PGE2 and thus down- regulating the expression of β- catenin and MDR1. Wnt/β- catenin signal pathway may participate in the regulation of MDR1 by mPGES-1/PGE2.

Objective:To observe effect of ginsenoside Rh₂ (GRh₂) on the invasion and migration of colon cancer resistant cells HCT116/L-OHP and its specific mechanism. Method:Cell counting kit-8 (CCK-8) assay was used to detect the inhibitory effect of different concentrations of GRh₂ (0, 2.5, 5, 10, 20, 40 mg·L^-1) on HCT116/L-OHP cell proliferation, scratch assay, Transwell assay and adhesion assay were used to detect the effects of GRh₂ (0, 2.5, 5, 10 mg·L^-1) on cell migration, invasion and adhesion. The protein expression levels of E-cadherin and matrix metalloproteinase-9(MMP-9) were examined by Western blot. Result:Compared with control group, GRh₂(5, 10, 20, 40 mg·L^-1) significantly inhibited the proliferation of HCT116/L-OHP cells in a dose-dependent manner(P<0.05, P<0.01); Compared with the control group, the scratch healing rate of GRh₂ group (5, 10 mg·L^-1) was significantly decreased (P<0.05, P<0.01), the number of cells passing through the chamber of GRh₂ group was significantly decreased (P<0.05, P<0.01), cell migration and invasive ability were significantly inhibited in a dose-dependent manner. The number of adherent cells in GRh₂ group was significantly reduced (P<0.05, P<0.01), and the cell adhesion ability was significantly inhibited. Compared with the control group, GRh₂ (10, 20, 30 mg·L^-1) promoted E-cadherin protein expression (P<0.05, P<0.01), while protein expression of MMP-9 was inhibited (P<0.01). Conclusion:GRh₂ can significantly inhibit the invasion and migration of HCT116/L-OHP in colon cancer cells, and its potential mechanism may be related to the promotion of E-cadherin and the inhibition of MMP-9 expression in a dose-dependent manner.

Objective To analyze the spatial point pattern distribution characteristics of hemorrhagic fever with renal syndrome (HFRS) in Jingzhou city, Hubei province during the two seasons spring- summer and autumn-winter of 2017, to discuss its high incidence area and reason, and to provide basis for the resource allocation of public health. Methods The analytical data was collected from Infectious Disease Reporting Information System in China, and the spring-summer season was from March to August of 2017, while the autumn-winter was from the September of 2017 to the February of 2018. The Ripley's K-function and kernel density estimation were applied to analyze the spatial point pattern distribution and compare the distribution characteristics of spatial point pattern between the two seasons. Results In 2017, 133 cases of HFRS were reported in Jingzhou city, including the spring- summer and autumn-winter two pick incidences. The strongest aggregation distance was 17.77km in spring-summer season, and 14.40 km in autumn-winter season. The spatial gathering center was located in the north of Jianli County in spring-summer, and it moved to the south of Jiangling County and Shashi District in autumn-winter. Conclusions The key areas for the prevention and control of HFRS in Jingzhou City are Jiangling County, the southern part of Shashi District and the northern part of jianli county. The key groups are the residents of the urban-rural junction in the southern part of Shashi City, residents along the route of large-scale projects, and farmers engaged in agricultural planting or crayfish breeding in the gathering areas.