ObjectiveTo discuss the effects of continuing nursing on the living condition of patients with severe craniocerebral injury in neurosurgery department.Methods A total of 303 patients with severe craniocerebral injury from January 2008 to December 2009 in neurosurgery department of Huai'an First People's Hospital,Nanjing Medical University were randomly divided into the control group (140 cases) and the intervention group (163 cases). Patients in the control group were followed up once by the phone at the first week after discharge. There was no longer follow-up after the first week and patients could call or visit hospital in case of problems. Patients in the intervention group received continuing nursing intervention by telephone follow-up visit,the establishment of continuing nursing WeChat group,family visit and the establishment of brain club. Patients were followed up from the first week after discharge until the death of patients or December 2015. Survival rate of two groups was evaluated by survival analysis.Results The survival rate of patients in the intervention group and the control group were 78.8% and 62.3%,which were calculated by the Kaplan-Meier method. The survival rate of patients in the intervention group was significantly higher than that in the control group (χ2=33.91,P<0.05).Conclusions Continuing nursing helps to improve the survival situation of patients with severe craniocerebral injury in the process of time.

Objective:To investigate the incidence rate of upper digestive tract cancer in Cixian, China, a particular area with high inci-dence of esophageal cancer. Methods:Statistical analysis was performed on the 2003-2012 incidence data of upper digestive tract can-cer in Cixian. The annual incidence rate, Chinese population standardized incidence rate (the bid rate), and structure of world popula-tion standardized incidence rate (referred to as the world standard rate) were calculated. The incidence data were divided into two groups according to period (2003-2007 and 2008-2012), and different age groups were compared. Results:From 2003 to 2012, the in-cidence of upper gastrointestinal cancer was 165.36/10 million. The 2003-2007 crude incidence rate was 171.55/10 million), whereas 2008-2012 crude incidence rate was 151.41/10 million which has reduced over the last five years. Esophageal cancer incidence from 2003 to 2012 had a crude incidence rate of 108.05/10 million during the two periods (from 2003 to 2007, the incidence rate was 116.87/10 million;and from 2008 to 2012, 99.58/10 million), the crude incidence rate of the latter 5-year period has declined obvious-ly. From 2003 to 2012, the overall crude incidence rate of cardia cancer was 31.21/10 million, comparison of two peaiods (from 2003 to 2007 was 29.11/10 million, and 2008-2012, 33.23/10 million) indicated that the level of measurement of the latter period in-creased. At the same period, the overall incidence rate of gastric cancer was 26.10/10 million, comparison of the two periods (2003-2007 the crude incidence rate was 25.57/10 million, 2008-2012 was 26.60/10 million) indicated that the level of the parameter in the latter 5 years increased slightly. Conclusion:The incidence of esophageal cancer in Cixian decreased significantly, but the area remains to have the highest incidence rate of cardiac cancer morbidity. The incidence rate of distal gastric cancer increased significantly in males but decreased slightly in females, which suggests that early diagnosis and treatment of gastric cardia and distal stomach cancer is extremely important.

BACKGROUND: Preliminary studies have indicated that Shexiang Baoxin Pill (MUSKARDIA) has a coronary artery dilation effect and increases the coronary blood flow, relieving the symptoms of angina. This study aimed to evaluate the benefit of MUSKARDIA on patients with stable coronary artery disease (CAD) and diabetes mellitus (DM). METHODS: This was a subgroup analysis of a multicenter, randomized, placebo-controlled phase IV trial. CAD patients with a medical history of DM or baseline fasting blood glucose (FBG) ≥7.0 mmol/L were grouped according to the treatment (standard therapy plus MUSKARDIA or placebo). The primary outcome was major adverse cardiovascular events (MACEs), which was the composite outcome of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. The secondary outcome was the composite outcome of all-cause death, non-fatal myocardial infarction, non-fatal stroke, hospitalization for unstable angina or heart failure, and coronary angioplasty. RESULTS: MACEs occurred in 2.6% (9/340) and 4.8% (18/376) of patients in the MUSKARDIA and placebo groups, respectively ( P  = 0.192). Secondary composite outcome was significantly less frequent with MUSKARDIA than with placebo (15.3% [52/340] vs . 22.6% [85/376], P  = 0.017). Risk of MACEs (hazard ratio [HR] = 0.69, 95% confidence interval [CI]: 0.31-1.57) was comparable between two groups. In patients with uncontrolled DM (≥4 measurements of FBG ≥7 mmol/L in five times of follow-up), the risk of secondary outcome was significantly lower with MUSKARDIA (5/83, 6.0%) than with placebo (15/91, 16.5%) (HR = 0.35, 95%CI: 0.13-0.95). CONCLUSION: As an add-on to standard therapy, MUSKARDIA shows a trend of reduced MACEs in patients with stable CAD and DM. Furthermore, MUSKARDIA may reduce the frequency of all-cause death, hospitalization, and coronary angioplasty in this population, especially in those with uncontrolled DM. TRIAL REGISTRATION ChiCTR.org.cn, ChiCTR-TRC-12003513.
Humans ; Coronary Artery Disease/complications* ; Diabetes Mellitus, Type 2/drug therapy* ; Myocardial Infarction/complications* ; Stroke/epidemiology*

ObjectiveTo study the mechanism of Mahuang Xixin Fuzitang （MXFT） against migraine. MethodTraditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， SiwssTargetPrediction and other databases were used to screen the active components and action targets of MXFT as well as migraine-related targets. The potential protein-protein interaction （PPI） network diagram was plotted for the intersection targets of MXFT and migraine using STRING 11.5. Metascape was used for Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis of potential intersection targets. The component-target-pathway network of MXFT was constructed by Cytoscape 3.7.1 to screen core targets with high degree value. Finally， the binding strength between core target and its mapping components was verified by molecular docking， and the core targets with desirable docking results were verified by animal experiments in vivo. Forty eight SD rats were selected， and except the blank group， the other rats were subcutaneously injected with nitroglycerin to prepare the migraine rat model. The modeled rats were randomly divided into model group， positive drug group and MXFT high-， medium- and low-dose groups. The positive drug group was given zolmitriptan tablets， and the MXFT high-， medium- and low-dose groups were given high， medium and low doses of MXFT， respectively. The changes of behavior and pain threshold of rats in each group were observed every other day after modeling. The levels of calcitonin gene-related peptide （CGRP）， extracellular signal-regulated kinase 2 （ERK2） and c-fos proto-oncogene （FOS） protein in plasma were detected by enzyme-linked immunosorbent assay （ELISA）. Immunohistochemical technique and Western blot were employed to determine the levels of extracellular signal-regulated kinase 1/2 （ERK1/2， also known as MAPK1/3） and protein kinase B 1 （Akt1）， protein kinase C α （PRKCA） in trigeminal nerve of SD rats. ResultThe network pharmacology showed that the core targets of MXFT in the treatment of migraine were MAPK1， MAPK3， Akt1， PRKCA， etc.， mainly involving neuroactive ligand-receptor interaction signaling pathway， calcium signaling pathway， MAPK signaling pathway， etc. The molecular docking demonstrated that MAPK1， MAPK3， Akt1， PRKCA， PRKCB and PRKCG had good binding ability with their mapping components. The animal experiments indicated that compared with the conditions in the blank group， the number of head scratching in the model group was increased （P<0.01）， and the pain threshold was decreased （P<0.01）. Compared with the conditions in the model group， the number of head scratching in each administration group was reduced （P<0.01）， and the pain threshold was increased （P<0.01）. In addition， the levels of CGRP， ERK2 and FOS proteins in plasma， and Akt1， ERK1/2 and PRKCA proteins in trigeminal ganglion of the model group were higher than those of the blank group （P<0.05， P<0.01）. The levels of CGRP， ERK2 and FOS proteins in plasma and Akt1， ERK1/2 and PRKCA proteins in trigeminal ganglion of each administration group were lower than those of the model group （P<0.05， P<0.01）. ConclusionMXFT had multi-component， multi-target and multi-pathway characteristics in the treatment of migraine， and the mechanism might be related to inhibiting vasodilation， reducing the release of inflammatory factors and inhibiting neuronal hyperactivity.

Objective:To explore the protective effect of Gegen Qinliantang on the intestinal mucosal epithelial barrier function of ulcerative colitis （UC） mice， and to explore its mechanism of action in the treatment of ulcerative colitis via matrix metallopeptidase-9 （MMP-9）/p38 mitogen-activated protein kinase （p38 MAPK） signaling pathway. Method:The 48 female C57BL/6 mice were randomly divided into normal group， model group， sulfasalazine group （0.3 g·kg^-1） and Gegen Qinliantang high， medium and low dose groups （2.84，1.42，0.71 g·kg^-1）. The UC murine model was established by 3% dextran sulfate sodium （DSS）. Gegen Qinliantang and sulfasalazine were intragastrically administered on the 8^th day after the model was established for 7 days， and the normal group was treated with the same amount of normal saline. Colon tissues were collected after the last administration， and the pathological changes of colon tissues were detected by hematoxylin-eosin （HE） staining. The expression of tight junction （TJ） proteins such as Occludin and zonula occludens-1（ZO-1） in colon tissues was detected by immunohistochemistry （IHC）， and the expression levels of tumor necrosis factor-alpha （TNF-α）， interleukin-1β （IL-1β）， and MMP-9 mRNA in colon tissues were detected by Real-time polymerase chain reaction （Real-time PCR）. The expression of phosphorylated p38 MAPK （p-p38 MAPK）， p38 MAPK and MMP-9 protein in colon tissues was detected by Western blot. Result:Compared with normal group， the body weight of mice decreased （P<0.01） and disease activity index （DAI） score increased significantly （P<0.01） in model group， the colon tissues of the model group were damaged more obviously， the expression of occludin and ZO-1 proteins in model group was significantly reduced （P<0.01）， and the relative expression levels of TNF-α， IL-1β， and MMP-9 mRNA in model group were significantly increased （P<0.01）， the expression of p-p38 MAPK and MMP-9 in model group was significantly increased （P<0.01）. Compared with model group， the body mass and DAI score of the sulfasalazine group and Gegen Qinliantang group were significantly improved （P<0.05，P<0.01）， the colonic tissues damage were significantly improved， and the expression of Occludin and ZO-1 protein was significantly increased （P<0.05，P<0.01）， the relative expression levels of TNF-α， IL-1β， and MMP-9 mRNA were significantly decreased （P<0.01）， and the expression of p-p38 MAPK and MMP-9 was significantly decreased （P<0.01）. The changes in the middle dose group were the most obvious among the various dose groups of Gegen Qinliantang. Conclusion:Gegen Qinliantang repairs the intestinal mucosal barrier function by inhibiting the expressions of MMP-9 and inflammatory cytokines such as TNF-α and IL-1β， blocking the activation of the p38 MAPK signaling pathway， and increasing the expressions of tight junction protein.

Objective:To investigate the therapeutic effect of polydatin on ulcerative colitis （UC） in mice and its regulation of protein kinase Cθ（PKCθ）/signal transducer and activator of transcription 3（STAT3） signaling on T helper cell 17（Th17） and its mechanism in the treatment of UC. Method:The 32 male C57BL/6 mice were randomly divided into normal group， model group， polydatin group （0.045 g·kg^-1） and sulfasalazine group （0.5 g·kg^-1）. The UC model was established by giving 3% dextran sodium sulfate （DSS） solution to free drinking water in mice. Polydatin and sulfasalazine groups were given by gavage 0.5 h before modeling for 7 days. The normal group and model group were given the same amount of normal saline. After the last administration， the colonic tissue was taken and hematoxylin-eosin （HE） was used to observe the pathological changes of colonic tissue. Flow cytometry was used to detect the proportion of Th17 in the lamina propria of colonic mucosa. The expression of interleukin-17A （IL-17A） in serum was detected by enzyme-linked immunosorbent assay （ELISA）. Polydatin was added to CD4⁺ T cells purified from spleen of C57BL/6 mice by magnetic-activated cell sorting （MACS） under the stimulation of cell stimulation cocktail in vitro in order to detect its impact on PKCθ and STAT3 phosphorylation. Result:Compared with normal group， the body weight was significantly decreased， and disease activity index （DAI） scores of the model group was significantly increased （P<0.01）， the colonic mucosal epithelium was damaged and inflammatory cells infiltration in the mucosa and submucosa was obvious， the proportion of Th17 in the lamina propria of colonic mucosa was significantly increased （P<0.01）， and the content of serum IL-17A was significantly increased （P<0.01）. Compared with the model group， the weight and DAI score of polydatin and sulfasalazine groups were significantly improved （P<0.01）， the degree of colon tissue damage was significantly improved， the proportion of Th17 in colon mucosa lamina propria was significantly decreased （P<0.01）， and the content of IL-17A in serum was significantly decreased （P<0.01）. In vitro experiments showed that polydatin could significantly inhibit the phosphorylation of PKCθ and STAT3 in Th17 （P<0.01） as well as IL-17A secretion. Conclusion:Polydatin can improve the ulcerative colitis in mice via inhibiting the phosphorylation of PKCθ and STAT3 to preclude IL-17A secreting in Th17.

Aim To investigate the effects of combined administration of loganin and berberine on bone structure and metabolism in diabetic mice and its potential mechanism.Methods The diabetic ICR mouse model was induced by high fat diet(HFD).After 10 weeks of combined intervention, the effects of loganin and berberine on body weight, body fat rate, blood glucose, blood lipid and serum oxidative stress levels were observed.Bone microstructure was scanned by micro-CT.Biomechanical characteristics of bone were measured by three-point bending test, and material properties were detected by fourier transform infrared(FTIR).The pathological changes were observed by HE and TRAP staining.Protein expressions involved in advanced glycation end products(AGEs)and their receptors(RAGE)/nuclear factor-κB(NF-κB)signaling pathway were detected by immunohistochemistry.Results The combined administration of loganin and berberine could significantly inhibit the weight gain, reduce the levels of blood glucose, blood lipid and oxidative stress, as well as improve glucose tolerance.In addition, combined intervention also decreased the expression levels of the proteins involved in AGEs/RAGE/NF-κB signaling pathway, and improved bone microstructure, finally contributing to increasing bone quality in diabetic mice.Conclusions The combination of loganin and berberine could improve bone metabolism in diabetic mice, which may be related to AGEs/RAGE/NF-κB signaling pathway.

OBJECTIVE: To analyze clinical feature and information of medication to explore the risk signals of preparations containing Psoraleae Fructus (BGZP) related with hepatobiliary adverse drug reactions (ADR), in order to reinforce pharmacovigilance. METHODS: A retrospective study was conducted based on hepatobiliary ADR related with BGZP from the China Adverse Drug Reaction Monitoring System in years from January 2012 to December 2016. Serious and general ADRs were analyzed and assessed. RESULTS: There were 355 cases of hepatobiliary ADR related to BGZP. Both the amount of cases and the proportion of serious ADR showed an increasing growth by years (P<0.05). It was found that 10.43% of 355 cases may be involved with irrational drug use, including overdose, repeated medication, and combination of multiple drugs. There were 190 cases which used BGZP (non-combination), and they were mainly for common in diseases caused by abnormal immune activation (accounting for 40.53% of the total cases). Especially at the age group with the most cases with age of 41-50 years, the cases associated with immunological diseases of female were obviously more than that of male (P<0.05). The latency of hepatobiliary ADR related to BGZP ranged from 1 to 386 days, and the median latency was 27.5 days, along with the range of cumulative dose (0.45-520.02 g) as well as the daily dose (0.09-2.64 g/d) after the conversion. CONCLUSIONS Cases of hepatobiliary ADR related to BGZP showed significant individual differences, and there was no correlation between drug usage duration and dosage and the occurrence of hepatobiliary ADR. It may be similar with idiosyncratic drug-induced liver injury, and recommended that BGZP should be used with more caution under monitoring liver function, especially in female patients with immunological diseases.
Adult ; Adverse Drug Reaction Reporting Systems ; Chemical and Drug Induced Liver Injury/etiology* ; Drug-Related Side Effects and Adverse Reactions ; Female ; Humans ; Male ; Middle Aged ; Pharmacovigilance ; Retrospective Studies

BACKGROUND: The Shexiang Baoxin Pill (MUSKARDIA) has been used for treating coronary artery disease (CAD) and angina for more than 30 years in China. Nevertheless, methodologically sound trials on the use of MUSKARDIA in CAD patients are scarce. The aim of the study is to determine the effects of MUSKARDIA as an add-on to optimal medical therapy (OMT) in patients with stable CAD. METHODS: A total of 2674 participants with stable CAD from 97 hospitals in China were randomized 1:1 to a MUSKARDIA or placebo group for 24 months. Both groups received OMT according to local tertiary hospital protocols. The primary outcome was the occurrence of a major adverse cardiovascular event (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction (MI), or non-fatal stroke. Secondary outcomes included all-cause mortality, non-fatal MI, non-fatal stroke, hospitalization for unstable angina or heart failure, peripheral revascularization, angina stability and angina frequency. RESULTS: In all, 99.7% of the patients were treated with aspirin and 93.0% with statin. After 2 years of treatment, the occurrence of MACEs was reduced by 26.9% in the MUSKARDIA group (MUSKARDIA: 1.9% vs. placebo: 2.6%; odds ratio = 0.80; 95% confidence interval: 0.45-1.07; P  = 0.2869). Angina frequency was significantly reduced in the MUSKARDIA group at 18 months (P = 0.0362). Other secondary endpoints were similar between the two groups. The rates of adverse events were also similar between the two groups (MUSKARDIA: 17.7% vs. placebo: 17.4%, P = 0.8785). CONCLUSIONS: As an add-on to OMT, MUSKARDIA is safe and significantly reduces angina frequency in patients with stable CAD. Moreover, the use of MUSKARDIA is associated with a trend toward reduced MACEs in patients with stable CAD. The results suggest that MUSKARDIA can be used to manage patients with CAD. TRIAL REGISTRATION chictr.org.cn, No. ChiCTR-TRC-12003513.
Angina Pectoris ; China ; Coronary Artery Disease/drug therapy* ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Humans