Effect and mechanism of Bovis Calculus on ulcerative colitis by inhibiting IL-17/IL-17RA/Act1 signaling pathway / 中国中药杂志

This study aimed to elucidate the effect and underlying mechanism of Bovis Calculus in the treatment of ulcerative colitis(UC) through network pharmacological prediction and animal experimental verification. Databases such as BATMAN-TCM were used to mine the potential targets of Bovis Calculus against UC, and the pathway enrichment analysis was conducted. Seventy healthy C57BL/6J mice were randomly divided into a blank group, a model group, a solvent model(2% polysorbate 80) group, a salazosulfapyridine(SASP, 0.40 g·kg~(-1)) group, and high-, medium-, and low-dose Bovis Calculus Sativus(BCS, 0.20, 0.10, and 0.05 g·kg~(-1)) groups according to the body weight. The UC model was established in mice by drinking 3% dextran sulfate sodium(DSS) solution for 7 days. The mice in the groups with drug intervention received corresponding drugs for 3 days before modeling by gavage, and continued to take drugs for 7 days while modeling(continuous administration for 10 days). During the experiment, the body weight of mice was observed, and the disease activity index(DAI) score was recorded. After 7 days of modeling, the colon length was mea-sured, and the pathological changes in colon tissues were observed by hematoxylin-eosin(HE) staining. The levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6), and interleukin-17(IL-17) in colon tissues of mice were detected by enzyme-linked immunosorbent assay(ELISA). The mRNA expression of IL-17, IL-17RA, Act1, TRAF2, TRAF5, TNF-α, IL-6, IL-1β, CXCL1, CXCL2, and CXCL10 was evaluated by real-time polymerase chain reaction(RT-PCR). The protein expression of IL-17, IL-17RA, Act1, p-p38 MAPK, and p-ERK1/2 was investigated by Western blot. The results of network pharmacological prediction showed that Bovis Calculus might play a therapeutic role through the IL-17 signaling pathway and the TNF signaling pathway. As revealed by the results of animal experiments, on the 10th day of drug administration, compared with the solvent model group, all the BCS groups showed significantly increased body weight, decreased DAI score, increased colon length, improved pathological damage of colon mucosa, and significantly inhibited expression of TNF-α,IL-6,IL-1β, and IL-17 in colon tissues. The high-dose BCS(0.20 g·kg~(-1)) could significantly reduce the mRNA expression levels of IL-17, Act1, TRAF2, TRAF5, TNF-α, IL-6, IL-1β, CXCL1, and CXCL2 in colon tissues of UC model mice, tend to down-regulate mRNA expression levels of IL-17RA and CXCL10, significantly inhibit the protein expression of IL-17RA,Act1,and p-ERK1/2, and tend to decrease the protein expression of IL-17 and p-p38 MAPK. This study, for the first time from the whole-organ-tissue-molecular level, reveals that BCS may reduce the expression of pro-inflammatory cytokines and chemokines by inhibiting the IL-17/IL-17RA/Act1 signaling pathway, thereby improving the inflammatory injury of colon tissues in DSS-induced UC mice and exerting the effect of clearing heat and removing toxins.

Pathogenesis of Secondary Pulmonary Tuberculosis and Role of Cord Factor in Secondary Infection / 中国医学科学院学报

The primary and secondary tuberculosis features two completely different pathogenesis.At present,the pathogenesis of primary tuberculosis has been clear,whereas that of secondary tuberculosis remains unclear.In order to decipher the mechanism of secondary infection of

Research progress of effect of berberine in treatment of ulcerative colitis based on cell signaling pathway / 中国中药杂志

Berberine is the main extract of Coptis chinensis, and its anti-inflammatory, antioxidant, antibacterial and immunomodulatory effects have been confirmed by modern studies. Ulcerative colitis(UC) is a chronic, idiopathic inflammatory bowel disease with unknown etiology. Its causes involve genetics, intestinal microecology and mucosal immune system disorders. In this paper, literatures on relevant pathways and mechanism of berberine on ulcerative colitis in recent years were consulted and summarized to provide me-thods and ideas for developing berberine in the treatment of UC and exploring the mechanisms. The results showed that berberine protects the intestinal mucosal barrier, restores the body's normal immune response, and improves oxidative stress by regulating multiple signaling pathways, such as JAK-STAT, NK-κB, PI3 K-AKT, MAPK, Nrf2, ERS, and MLCK-MLC, so as to treat UC.

Protective Effect of Compatibility of Coptidis Rhizoma and Magnoliae Officinalis Cortex on Rat Model of Ulcerative Colitis and Influence of Apoptosis / 中国实验方剂学杂志

Objective:To study the protective effect of different doses of single-flavored Coptis， Magnoliae Officinalis Cortex， and their compatibility on ulcerative colitis （UC） model rats and the colonic B lymphoblastoma-2 associated X protein （Bax） and cysteine-containing aspartame-3（Caspase-3） protein， inflammatory cytokines， and other expressions. Method:The 120 healthy adult SD rats were randomly divided into blank group， model group， sulfasalazine group， Coptidis Rhizoma 2.00， 1.00， 0.50 g·kg-1 group， Magnoliae Officinalis Cortex 2.00， 1.00， 0.50 g·kg-1 group， Coptidis Rhizoma combine with Magnoliae Officinalis Cortex 4.00， 2.00， 1.00 g·kg-1 group， 12 groups with 10 rats in each group. The UC model was prepared by 2，4， 6-trinitrobenzene sulfonic acid/ethanol （TNBS/ethanol）. After 24 h of modeling， the rats were gavaged at 10 mL·kg-1 for one time/d. After modeling， the mental state， activity state， hair luster， stool characteristics， and blood in the stool of each group were observed. After continuous administration for 6 days， colon tissues and spleen were taken after the last administration for 24 h. The ratio of colonic weight to length and spleen index was calculated. The degree of colonic injury was evaluated according to the colonic mucosal injury index （CMDI） score criteria. the histopathological observation was performed using hematoxylin-eosin staining （HE）. The expression levels of tumor necrosis factor （TNF）-α， interleukin-6 （IL-6）， interleukin-10 （IL-10）， and myeloperoxidase （MPO） in the serum of Coptidis Rhizoma 2.00 g·kg-1 group， Magnoliae Officinalis Cortex 2.00 g·kg-1 group， Coptidis Rhizoma combine with Magnoliae Officinalis Cortex 4.00 g·kg-1 were detected by enzyme-linked immunosorbent assay（ELISA） in blank group and model group. Western blot was used to detect the expression of Bax and Caspase-3 proteins in the colon of rats. Result:Compared with blank group， rats in model group were sluggish and less active. The colon weight-length ratio， spleen index， CMDI， and colon tissue pathological damage increased significantly， and the expression of serum TNF-α， IL-6， and MPO increased significantly. Serum IL-10 expression levels were extremely significantly reduced （P<0.01）. Compared with model group， the sulfasalazine group， the Coptidis Rhizoma 2.00， 1.00 g·kg-1 group， the Magnoliae Officinalis Cortex 2.00 g·kg-1 group， and the three-dose groups of Coptidis Rhizoma combine with Magnoliae Officinalis Cortex， their colon weight-length ratio and CMDI were significantly reduced （P<0.05，P<0.01）. The colon weight length ratio and CMDI index of the Coptidis Rhizoma 0.50 g·kg-1 group， Magnoliae Officinalis Cortex 0.50 and 1.00 g·kg-1 group were not significantly different from the model group but compared with Coptidis Rhizoma and Magnolia 0.50 g·kg-1 group， the ratio of colon weight to length in the group of Coptidis Rhizoma combine with Magnoliae Officinalis Cortex 1.00 g·kg-1 group was significantly reduced （P<0.01）. Compared with model group， the spleen index of the sulfasalazine group， the Coptidis Rhizoma 2.00 g·kg-1， and the Coptidis Rhizoma combine with Magnoliae Officinalis Cortex 4.00 g·kg-1 group were significantly lower （P<0.05）， compared with model group， the sulfasalazine group， Coptidis Rhizoma 2.00， 1.00 g·kg-1 and Magnoliae Officinalis Cortex 2.00 g·kg-1， thre dose groups of Coptidis Rhizoma combine with Magnoliae Officinalis Cortex can significantly improve the depth and scope of histopathological damage and tissue necrosis. Compared with the model group， the preferred Coptidis Rhizoma 2.00 g·kg-1 group， Magnoliae Officinalis Cortex 2.00 g·kg-1　group， Coptidis Rhizoma combine with Magnoliae Officinalis Cortex 4.00 g·kg-1 group serum TNF-α， IL-6， MPO expression levels are extremely significantly reduced， the level of IL-10 increased significantly （P<0.01）．Compared with blank group， the expression of 　Bax and Caspase-3 protein in the colon of model group was significantly increased （P<0.01）. Compared with model group， the expression of Bax and Caspase-3 protein in preferred Coptidis Rhizoma 2.00 g·kg-1 group and Magnoliae Officinalis Cortex 2.00 g·kg-1 group， Coptidis Rhizoma combine with Magnoliae Officinalis Cortex 4.00 g·kg-1 group were significantly reduced （P<0.01）． Conclusion:The compatibility of single-flavored Coptidis Rhizoma， Magnoliae Officinalis Cortex， and Coptidis Rhizoma combine with Magnoliae Officinalis Cortex may improve the pathology of UC model rats induced by TNBS/ethanol by down-regulating the expression of Bax and Caspase-3 protein， inhibiting the release of inflammatory cytokines and promoting the release of anti-inflammatory factors injury， it plays a role in protecting colonic mucosa. The compatibility effect of Coptidis Rhizoma and Magnoliae Officinalis Cortex is better than that of single medicine， and Coptidis Rhizoma has a tendency to be better than Magnoliae Officinalis Cortex.

New research progress of percutaneous coronary intervention strategy in acute ST elevation myocardial infarction / 心血管康复医学杂志

Percutaneous coronary intervention (PCI) has become routine therapeutic measure for ST elevation myo-cardial infarction (STEMI).Along with deepening research on PCI ,a lot of interventional programs are summa-rized in clinic .Thrombus aspiration during emergency PCI is used to treat most patients with heavy thrombus bur-den ,but major adverse cardiovascular events still occur in some of these patients after PCI .The present article mainly discussed interventional program selection based on thrombus burden degree ,and explored correlation be-tween residual thrombus volume and prognosis after thrombus aspiration .

Therapeutic effect of subhypothermia treatment combined cisternal nimodipine perfusion on cerebral vasospasm after subarachnoid hemorrhage / 心血管康复医学杂志

Objective :To explore therapeutic effect of subhypothermia combined cisternal nimodipine perfusion (CNP) on cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH).Methods :A total of 92 patients with CVS after SAH treated in our hospital from Feb 2014 to May 2016 were selected .The patients were randomly and e-qually divided into subhypothermia group (received subhypothermia treatment ) and combined treatment group (re-ceived subhypothermia treatment combined CNP) ,both groups were treated for 3 d .Therapeutic effect ,Glasgow coma scale (GCS) score ,middle cerebral artery (MCA) mean blood flow velocity ,serum levels of tumor necrosis factor (TNF)-α ,high sensitive C reactive protein (hsCRP) and interleukin (IL)-6 before and after treatment , and incidence rate of adverse events were compared between two groups .Results : Compared with before treat-ment ,after treatment ,there was significant rise in GCS score ,and significant reductions in MCA mean blood flow velocity ,serum levels of TNF-α ,hsCRP and IL-6 in two groups , P＝ 0.001 all ;compared with subhypothermia group after treatment ,there was significant rise in GCS score [ (10.26 ± 2.14) scores vs .(12.35 ± 2.56) scores] , and significant reductions in MCA mean blood flow velocity [(97.48 ± 18.20) cm/s vs.(89.74 ± 18.40) cm/s] ,se-rum levels of TNF-α [(0.56 ± 0.17) ng/ml vs.(0.34 ± 0.11) ng/ml] ,hsCRP [(186.75 ± 15.19) ng/L vs.(173.24 ± 15.23) ng/L] and IL-6 [ (10.41 ± 2.06) ng/L vs .(8.51 ± 2.13) ng/L] in combined treatment group ,P＜0.05 or ＜0. 01. Total effective rate of combined treatment group was significantly higher than that of subhypothermia group (91.30% vs.71.74%) , P＝0.016 ;and incidence rate of adverse events was significantly lower than that of subhypothermia group (6.52% vs.21.74%) ,P＝0.032 .Conclusion :Subhypothermia treatment combined cisternal nimodipine perfusion can effectively reduce MCA blood flow velocity ,relieve inflammation and improve therapeutic effect with less adverse events ,which is worth extending .

Acute Toxoplasma gondii infection affects the reproductive function of male mice / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the influence of acute Toxoplasma gondii infection on the reproductive function of male mice.</p><p><b>METHODS</b>Twenty-six adult male mice were randomized into an infection and a control group of equal number. Acute Toxoplasma gondii infection was induced in the testes of the former, while abdominal injection of normal saline given to the latter. Cell imprints and pathological sections were obtained to observe the pathological changes and Toxoplasma gondii invasion in the spermatogenic cells and to compare the testicular LDH-X, sperm concentration and motility and the number of deformed spermatozoa between the two groups.</p><p><b>RESULTS</b>The testicular LDH-X, sperm concentration and motility and the number of deformed spermatozoa were 53.19 +/- 18.04, (15.01 +/- 2.42) x 10(6)/ ml, (8.26 +/- 2.57) % and (17.69 +/- 11.91) % in the infection group, as compared with 68.71 +/- 17.79, (23.87 +/- 6.66) x 10(6)/ ml, (13.21 +/- 2.82) % and (11.30 +/- 6.60) % in the control, with significant differences between the two groups (P < 0 05).</p><p><b>CONCLUSION</b>Acute Toxoplasma gondii infection affects the reproductive function of male mice.</p>

A study on the inhibitory effect on transplanted tumor growth expressing HCV NS3 protein by HCV minigene vaccine based on invariant chain substitution in mice / 中华肝脏病杂志

<p><b>OBJECTIVES</b>To establish a transplanted tumor producing HCV NS3 protein in mice and study the therapeutic effect of minigene vaccine based on invariant chain substitution.</p><p><b>METHODS</b>SP2/0-NS3 cells expressing HCV NS3 antigen were injected subcutaneously into BALB/ c mice. After three days of inoculation, different therapeutical reagents were injected intramuscularly into different groups of mice. The boost immunization was carried out two weeks after the first immunization. The efficiency of HCV NS3 Th1 minigene vaccine was estimated after 60 days observation.</p><p><b>RESULTS</b>For saline, pCI-neo, pHCV-NS3 and pHCV-NS3-Th1 treated groups, the induction period needed for tumor growth was 16.17+/-2.55, 14.40+/-1.82, 16.75+/-2.36, and 24.00+/-5.57 days (t =2.623, P =0.034 vs saline, t =3.713, P =0.010 vs pCI-neo and t =2.425, P =0.045 vs pHCV-NS3) respectively. The tumorigenesis rates were 100%, 100%, 57.1% (8/14, chi2 = 6.190, P = 0.013 vs saline and chi2 = 6.608, P = 0.010 vs pCI-neo) and 46.7% (7/15, chi2 = 9.707, P = 0.002 vs saline and chi2 = 10.311, P = 0.001 vs pCI-neo ) respectively. The survival rates were 0, 0, 50.0% (7/14, chi2 = 5.787, P = 0.016 vs saline and chi2 = 9.333, P = 0.002 vs pCI-neo) and 53.3% (8/15, chi2 = 6.651, P = 0.010 vs saline and chi2 = 10.311, P = 0.001 vs pCI-neo) respectively. The average tumor diameter of the pHCV-NS3-Th1 treated group was significantly smaller compared with the control groups and the pHCV-NS3 treated group (P =0.001). Moreover, the average survival time of tumor-bearing mice immunized with pHCV-NS3-Th1 was 6 days longer compared with the saline treated group, 12 days longer compared with the pCI-neo treated group (P =0.001), and 6 days compared with the pHCV-NS3 treated group.</p><p><b>CONCLUSION</b>HCV NS3 Th1 epitope vaccine might be a potential biotherapy candidate against HCV infection.</p>