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.

Forensic Analysis of 72 Cases with Multiple Organ Dysfunction Syndrome Caused by Traffic Accidents / 法医学杂志

Objective To investigate the epidemiological and forensic characteristics of multiple organ dysfunction syndrome （MODS） after severe trauma and explore the reference indexes for determining traumatic MODS. Methods In terms of the number of organs or systems involved in MODS, the number of failures of each organ or system, the first failing organ and the survival time after organ failure, 72 cases of MODS death caused by traffic accidents were retrospectively analyzed. The cases were divided into two groups according to the mean injury severity score （ISS）. The t test was used to analyze the differences in the number of organs or systems involved in MODS in the two groups. Chi-square test was used to analyze the differences in the types of first failing organs and the differences between the two groups in the number of cases of organ or system failure involved in MODS. Wilcoxon signed-rank test was used to analyze the differences between the two groups in survival time of MODS after trauma. Kaplan-Meier survival curve was drawn and Log-Rank test was performed. Results The number of MODS involved organs or systems after trauma in ISS≤35 group was 3-5, and 2-4 in the ISS>35 group （P<0.05）. The cases of MODS organ or system failure after trauma occurred more in brain and lung in the two groups. The first failing organ after trauma was mainly the lung or kidney. The median time of first organ failure after trauma was 2.00 d, the median survival time of MODS after trauma in ISS≤35 group was 6.00 d, and 2.33 d in ISS>35 group （P<0.05）. The survival curve of ISS≤35 group was relatively high and declined gradually, while the survival curve of ISS>35 group was relatively low and the decline was steep （P<0.05）. Conclusion The epidemiological and forensic characteristics of MODS caused by traffic accidents have certain specificity. The ISS and the forensic characteristics of MODS at ISS>35 can be used as reliable reference indexes for evaluation of the causal relationship among trauma, MODS and death.

Cardioprotective Effect of Three Borneol Prevention and Administration on AMI Model Rats / 中国实验方剂学杂志

Objective::The effects of three different doses of borneol on acute myocardial infarction (AMI) model rats and the effects on oxidative stress factors were compared to provide reference for elucidation of the dose-effect relationship and mechanism of anti-myocardial infarction. Method::Healthy adult male SPF SD rats were randomly divided into sham operation group, model group, solvation model group, nitroglycerin group, Borneolum high, medium and low dose(0.6, 0.3, 0.15 g·kg-1) group, l-Borneolum and Borneolum syntheticum high, medium, low dose(0.2, 0.1, 0.05 g·kg-1) group, a total of 13 groups, 20 in each group. Gavage was performed at 20 mL·kg-1 once a day for 3 days of continuous preventive administration. The sham operation group and the model group were given the same volume of distilled water, and the solvation model group was given the same volume of 5% polysorbate 80.On the third day of the pre-administration, 30 minutes after the last dose, the left anterior descending coronary artery was ligated to make a model, and the successful rats were treated for 3 days. BL-420N biological system analyzer was used to record the ST-segment amplitude and hemodynamic changes. Rat body weight and cardiac weight were weighed to calculate cardiac viscera coefficients, 2, 3, 5-triphenyl tetrazolium chloride (TTC) staining was used to calculate the myocardial infarction rate. Hematoxylin-eosin (HE) staining was used to evaluate the degree of myocardial pathological damage. According to the kit requirements, serum levels of lactate dehydrogenase (LDH), aspartate amino-transaminase (AST), creatine kinase isoenzyme (CK-MB) and oxidative stress factors superoxide dismutase (SOD), malondialdehyde (MDA) were detected. Result::Compared with the sham operation group, the ST segment amplitude of the model group significantly increased after 5 minutes, the left ventricular diastolic blood pressure (LVDP) value increased significantly, and the measured maximum shortening velocity (Vpm) value of the left ventricular myocardial contraction component significantly decreased. The organ coefficient and myocardial infarction rate were extremely significantly increased, and the myocardial pathological tissue was severely damaged. The serum CK-MB, AST, LDH, and MDA contents were significantly increased (P<0.05, P<0.01). Compared with the solvation model group, the Borneolum and l-Borneolum in the middle and low, and the Borneolum syntheticum high dose groups could significantly inhibited the abnormal elevation of ST segments at different time points. The Borneolum and l-Borneolum high, medium, low, and Borneolum syntheticum high dose groups significantly increased the left ventricular systolic blood pressure (LVSP) value and decrease the LVDP value (P<0.01). The Borneolum medium, low, and l-Borneolum high, medium, Borneolum syntheticum high dose groups significantly increased the maximum rate of left ventricular pressure rise (dp/dt max) and Vpm value (P<0.05, P<0.01). The Borneolum and l-Borneolum medium, low dose groups significantly reduced rat cardiac organ coefficients. The Borneolum high, medium, low and l-Borneolum, Borneolum syntheticum medium, low dose groups significantly improved myocardial infarction in rats (P< 0.05, P<0.01). The Borneolum low, l-Borneolum high, medium, and Borneolum syntheticum high groups also significantly improved the degree of pathological damage (P<0.01). High dose of l-Borneolum significantly reduced CK-MB content, medium and low dose of l-Borneolum significantly reduced AST activity, medium and low dose of l-Borneolum, high, medium and low dose of Borneolum syntheticum significantly reduced LDH activity (P<0.05, P<0.01). Serum SOD activity of rats in l-Borneolum high, medium, and Borneolum syntheticum high dose groups increased significantly (P<0.05, P<0.01). Serum MDA levels in Borneolum high, medium, low, and l-Borneolum high, middle dose groups significantly decreased (P<0.01). Conclusion::Three kinds of borneol in different dose groups can play different degrees of myocardial protection. Under the experimental conditions, there was a trend of l-Borneolum>Borneolum>Borneolum syntheticum in improving the efficacy of myocardial infarction, the dose-effect of Borneolum was negatively correlated, Borneolum syntheticum was positively correlated, and no significant dose-effect relationship between l-Borneolum.

Effect of Yuanzhisan on Learning and Memory Abilities and Food Intake of AD Rats Based on Ghrelin Level of Cerebrointestinal Peptide / 中国实验方剂学杂志

Objective:Through the preparation of Alzheimer's disease （AD） rat model， the effect of Yuanzhisan on the expression of Ghrelin was observed， and the possible mechanisms in preventing and treating AD were discussed. Method:A total of 120 SD rats were randomly divided into sham-operated group， model group， donepezil group（1.02 mg·kg-1）， and high， medium and low-dose Yuanzhisan groups （12，6，3 g·kg-1）， with 20 rats in each group， including half male and half female. The rats in sham-operated group were injected with normal saline （NS）， and the rats in other groups were injected with β-amyloid 1-40 （Aβ1-40） in hippocampus to induce the AD rat model. During the 10-week continuous gavage， the food intake of rats in each group was observed and recorded. After the end of gavage， learning and memory abilities of rats were tested by Morris water maze. The whole brain and the gastric body and antrum were collected， the pathologic changes in the CA1 area of hippocampus was assessed by hematoxylin-eosin （HE） staining， and the expression of Ghrelin was detected by immunohistochemistry. Result:Compared with the sham-operated group， the escape latency time of model group rats increased （P<0.01），while times across platform， retention time in effective area and movement distance decreased （P<0.01）. The disorder of neurons， the decrease of the neuronal number， and the pyknosis of nucleus were observed in hippocampal CA1 area. The food intake of male and female rats decreased significantly （P<0.05，P<0.01）. The expression of Ghrelin in hippocampal CA1 area and gastric mucosa decreased significantly （P<0.01）. Compared with the model group， the escape latency time of rats in each treatment group was significantly shortened （P<0.05，P<0.01），whereas times across platform， retention time in effective area and movement distance increased （P<0.05，P<0.01）. The pathologic change was improved markedly， and the daily food intake of rats in high and medium-dose Yuanzhisan groups increased significantly （P<0.05，P<0.01）. The protein expression of Ghrelin in hippocampal CA1 area and gastric mucosa increased significantly in each Yuanzhisan group （P<0.05，P<0.01）. Conclusion:Yuanzhisan can effectively improve the learning and memory abilities of AD rats and increase the daily intake， which may be related to its up-regulation of Ghrelin content in hippocampal CA1 area and gastric mucosa.

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.

Forensic pathological analysis on 23 cases of fatal pulmonary thromboembolism / 法医学杂志

OBJECTIVE@#To analyze the forensic pathological characteristics of sudden death caused by pulmonary thromboembolism and the chronological transformation of thrombus and explore the assessment method of the causal relationship between previous trauma and the following fatal PTE episode.@*METHODS@#All the 23 cases reviewed here were collected from our institute files from the year of 1998 to 2008.@*RESULTS@#Trauma, surgery and braking etc. were all risky factors of PTE. Of these cases, 12 cases were caused by trauma, 21 cases were caused by surgery and 22 cases died in hospitals which were often happened one or two weeks after injury or one week's postoperative time. Of all the cases, 6 cases had single attack of thrombus and the rest 17 cases had the recurrence of thrombus. The number of the leg deep vein to be the embolic source was 16 cases which were often seen in the left leg.@*CONCLUSION@#It is important to confirm the embolic source, trauma, surgery and chronological events in determing the sudden death with PTE.

Analysis of death caused by postpartum hemorrhage / 法医学杂志

OBJECTIVE@#To analyze the pathological characteristics and the death reasons due to postpartum hemorrhage, and to help to deal with the obstetrical medical tangles.@*METHODS@#Thirty-two cases of death caused by postpartum hemorrhage encountered in our department since 1995 had been collected and retrospectively analyzed.@*RESULTS@#Death caused by postpartum hemorrhage could be divided into single factor and multi-factor, with 81.25% due to single factor, 12.50% multi-factor, and 6.25% unknown reason. The single factors included uterine atony, retained placenta, placenta increta, laceration of the lower genital tract, and coagulation defects. The multi-factor included a combination of two or more factors mentioned above.@*CONCLUSION@#The causes of death due to postpartum hemorrhage should be analyzed according to the clinical characteristics of the postpartum hemorrhage and the autopsy examination.