OBJECTIVE:To establish a method for the determination of ursolic acid in pedo-stomach-invigorating&digestion-promoting granule.METHODS:The determination was performed by TLC-scanning method in which chloro-form-acetone-glacial acetic acid(18∶2∶0.2)was used as developing solvent,and10%sulphuric acid ethanol solution was taken as developer,which were baked under110℃until limpid prunosus spots were occurred,the scanning method was dual wavelength reflection zigzag scanning with detection wavelength at520nm,reference wavelength at700nm,linearity parameter Sx=3and slit size at0.4mm?0.4mm.RESULTS:Ursolic acid has a good linear relation with peak area score when its sample size was within the range of2?g～10?g(r=0.9996),the average recovery is97.8%(RSD=1.4%).CONCLUSION:This me_ thod can be served as a quality control for pedo-stomach-invigorating&digestion-promoting granule.

0.05),while there was difference between length of hospital stay,expense of antibacterial for prevention and total expense of hospitalization(P

Aims To investigate the protective effects of noninvasive limb ischemic preconditioning (LIPC) on myocardial ischemia-reperfusion (I /R)injury,and to explore the mechanism.Methods Healthy male Wistar rats were divided randomly into I /R,I /R +LIPC,I /R +5-Hydroxydecanoate (5-HD)and I /R +LIPC +5-HD groups.The I /R +LIPC and I /R +LIPC-5-HD groups of rats were subjected to three cy-cles of LIPC induction per day with 5 min of reperfu-sion after occlusion for 5 min at the left hind limb for 3 days.All rats were subjected to myocardial I /R injury on the fourth day.The I /R +5-HD and I /R +LIPC-5-HD groups of rats were given the inhibitor of ATP-sen-sitive potassium channel 5-HD before and during myo-cardial I /R injury. Results Compared with I /R group,LIPC reduced myocardial infarct size (P <0.05),lowered cardiocyte apoptosis index and Fas, FasL positive cell number (P <0.01 ),increased the reduced nitric oxide (NO)/endothelin (ET)-1 ratio (P <0.05)in serum in I /R +LIPC group.5-HD a-bolished the protective effects induced by LIPC in I /R+LIPC-5-HD group.Compared with normal myocardi-al tissue,expression of mir-30a-3p was increased in I /R group (P <0.01 )and was decreased in LIPC group (P <0.01 ).Conclusion LIPC alleviates myocardial I /R injury and improves endothelial function. The mechanism may be related with the opening of ATP-sensitive potassium channel,regulating the balance be-tween NO and ET-1 and decreasing the expression of myocardial mir-30a-3p.

OBJECTIVE:To establish the method for the identification of impurities in succinylcholine chloride raw material. METHODS:Two-dimensional UPLC-QTOF-MS was adopted. One dimension chromatographic condition was Hypersil GOLD C18 column using buffer solution(22 mmol/L sodium pentanesulfonate+50 mmol/L sodium chloride+5 mmol/L sulphuric acid)as mobile phase A and acetonitrile as mobile phase B,volume ratio of mobile phase A to mobile phase B 95:5,column temperature of 40 ℃,flow rate of 1.0 mL/min,detection wavelength of 214 nm. Two-dimension chromatographic condition was ACQUITY UPLC BEH C18column using 0.1% ammonia as mobile phase A and acetonitrile as mobile phase B(gradient elution)with column temperature of 30 ℃ at flow rate of 0.4 mL/min. Ionization mode was ESI+ with capillary voltage of 2.5 kV,source temperature of 120 ℃,temperature of atomizing gas at 450 ℃,flow rate of atomizing gas at 900 L/h,acquisition mode of MSE. RESULTS:The succinic acid,succinyl chloride(intermediate),pyridine(reagent)and other impurities were detected in succinylcholine chloride by one dimensional method of HPLC. Other 4 obvious unknown impurities were named impurity 1,impurity 2,impurity 3 and impurity 4,among which the apparent content of impurity 2 was the highest. Two-dimensional method of HPLC-QTOF-MS deduced that the impurity 2 was dehydrogenate succinylcholine chloride and impurity 4 was succinylcholine chloride. The impurity 1 and impurity 3 were not detected in mass spectrum. CONCLUSIONS:Establish method for the identification of impurity in succinylcholine chloride raw material,and the results of research are used for the evaluation of the quality of the succinylcholine chloride raw material.

OBJECTIVE To investigate the effects of formononetin （FMN） on the apoptosis of intestinal epithelial cells in inflammatory bowel disease （IBD） rats and its possible mechanism. METHODS IBD rat model was constructed by using trinitrobenzene sulfonic acid （TNBS） induction. Forty-eight rats with successful modeling were divided into model group （normal saline）， low-dose and high-dose FMN groups （20 and 40 mg/kg FMN）， and high-dose FMN+YAP inhibitor Verteporfin （VTPF） group （40 mg/kg FMN+10 mg/kg VTPF）， with 12 rats in each group. Another 12 rats were set as the normal group （normal saline）. They were given drug/normal saline， once a day， for 7 consecutive days. After the last administration， the disease activity index （DAI） of rats was calculated， and the colon length of rats in each group was measured. The pathological changes in the colon tissue of rats were observed. The levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and IL-10 in serum were detected， and the apoptosis of intestinal epithelial cells was detected. The expressions of Yes associated protein （YAP）， cleaved cysteine-containing aspartate proteolytic enzyme 3 （cleaved-caspase-3）， B-cell lymphoma-2 （Bcl-2） and Bcl-2 associated X protein （Bax） were detected in colon tissue of rats. RESULTS Compared with the normal group， DAI score， the levels of TNF-α and IL- 6， the apoptotic rate of intestinal epithelial cells， and the expressions of cleaved-caspase-3 and Bax protein in the model group were increased greatly （P＜0.05）； the length of the colon was greatly decreased （P＜0.05）， and the serum level of IL-10 and the protein expressions of YAP and Bcl-2 were greatly reduced （P＜0.05）. The cell morphology of colon tissue was abnormal， with disordered arrangement and inflammatory cell infiltration. Compared with IBD group， the above indexes of rats were improved significantly in low-dose and high-dose FMN groups （P＜0.05）， in dose-dependent manner （P＜0.05）. VTPF significantly alleviated the effects of FMN on the above indexes of IBD rats （P＜0.05）. CONCLUSIONS FMN may promote the expression of YAP by inhibiting the Hippo/YAP signaling pathway， thereby inhibiting apoptosis of intestinal epithelial cells in IBD rats.

OBJECTIVE： To systematically evaluate the efficacy and safety of rivaroxaban versus low molecular weight heparin in the prevention of venous thromboembolism （VTE） in patients with hip fractures， and to provide evidence-based reference for clinical application. METHODS： Retrieved from Cochrane library， PubMed， Embase， CNKI， VIP and Wanfang database， randomized controlled trials （RCTs） about rivaroxaban （test group） versus low molecular weight heparin （control group） in the prevention of VTE in patients with hip fracture were collected during database establishment to Jun. 2018. After data extraction and quality evaluation with Cochrane system evaluator manual 5.1.0， Meta-analysis was performed by using Rev Man 5.3 statistical software for the incidence of  deep venous thrombosis （DVT）， postoperative discharge， activated partial thromboplastin time （APTT）， prothrombin time （PT） and the incidence of ADR. RESULTS： Totally 8 RCTs were included， involving 949 patients. Results of Meta-analysis showed that compared with low molecular weight heparin， rivaroxaban could significantly decreased the incidence of DVT [RR＝0.55， 95％CI （0.36， 0.83）， P＝0.004]. There was no statistical significance in postoperative discharge [MD＝－0.24， 95％CI （－5.27， 4.8）， P＝0.93]， APTT [MD=0.56， 95％CI （－0.75， 1.86）， P＝0.40]， PT [MD＝0.04， 95％CI（－0.03， 0.11）， P＝0.25] or the incidence of ADR [RR=1.73，95％CI（0.15，20.48）， P＝0.66] between 2 groups. CONCLUSIONS： Rivaroxaban has a better preventive effect on VTE in patients with hip fracture than low molecular weight heparin， and has a similar safety as low molecular weight heparin.

OBJECTIVE To evaluate the rationality of clinical application of polymyxin B in the inpatients of a third grade class A hospital，so as to provide evidence for the optimization of clinical scheme of the drug. METHODS A retrospective method was conducted on the electronic medical records of inpatients treated with Polymyxin B sulfate for injection from January 2020 to March 2022 to collect the basic information of patients， inpatient departments and time， infection diagnosis， results of pathogenic bacteria test， laboratory test indicators， usage and dosage， and combined medication，etc. Based on the drug instructions， according to relevant guidelines and consensus， the rationality， efficacy and safety of polymyxin B in inpatient were evaluated. RESULTS & CONCLUSIONS A total of 101 inpatients were included， respiratory system infection was the main cause （62.4%）. All patients had received the etiological examination， and the pathogen with the highest detection rate was carbapenem‑resistant Acinetobacter baumannii （40.6%）. One hundred patients were treated by intravenous drip， and 4 patients were treated by combination of aerosol inhalation or intrathecal injection； 99 patients were given the dose of 500 thousand units by continuous intravenous infusion， q12 h. Totally 51.5% of patients were treated for 7-14 days； and 77 patients were treated with other anti-Gram-negative drugs. There were unreasonable phenomena including too short time of medication （29.7%）， no combination of medication （23.8%）， and no indication of medication （17.8%）. The clinical effective rate of 101 patients treated with polymyxin B was 49.5%， and 16 patients （15.8%） had acute kidney injury during the treatment. Clinical pharmacists should actively participate in the clinical treatment of polymyxin B， formulate individualized treatment plans according to the guidelines/consensus and in combination with the patient’s condition and infection status to improve the rationality of clinical medication.

ObjectiveTo investigate the potential machanism of Xiaozhong Zhitong Mixture （消肿止痛合剂， XZM） in the treatment of diabetes foot ulcer （DFU）. MethodsFifty SD rats were randomly divided into blank group， model group， XZM group， inhibitor group， XZM plus inhibitor group （combination group）， with 10 rats in each group. Except for the blank group， rats were fed with high-sugar， high-fat， high-cholesterol diet， intraperitoneally injected with streptozotocin， and subjected to skin defect to establish DFU model. After successful modeling， the XZM group and the combination group were given 1 ml/（100 g·d）of XZM by gavage， while the blank group， model group， and inhibitor group were all given an equal volume of 0.9% sodium chloride injection by gavage. Thirty minutes later， the inhibitor group and the combination group were intraperitoneally injected with 5 mg/（kg·d） of Notch1 inhibitor DAPT. All groups were treated once a day. After 14 days of administration， the skin tissue from the dorsal foot of the blank group rats and wound tissue from the other groups were collected. The pathological changes of granulation tissue in the wound were detected using hematoxylin eosin （HE） staining. The microvascular density （MVD） in wounds was detected through immunohistochemical staining. Real time fluorescence quantitative polymerase chain reaction （RT-PCR） and western blotting were used to detect the mRNA and protein levels of Notch1 homolog （Notch1）， Delta-like ligand 4 （Dll4）， Delta-like ligand 4 （VEGF）， and angiopoietin 2 （Ang-2）， respectively. ResultsHistological results showed that the epidermal structure in the dorsal foot skin tissue of the rats in the blank group was intact. In the wound tissue of the model group， the epidermis exhibited excessive keratinization， vacuolar cytoplasm， and a large number of inflammatory cells infiltrating the tissue， while in the XZM group， a large amount of scab formation was observed in the epidermis， with no significant inflammatory cell infiltration and a noticeable increase in fibroblasts. In the combination group and the inhibitor group， partial epidermal scab formation was observed in the wound tissue with a small amount of inflammatory cell infiltration. Compared to those in the blank group， the MVD in the wound tissue increased in the model group， as well as the mRNA expression and protein levels of Notch1 and Dll4， while VEGFA and Ang-2 mRNA expression and protein levels significantly decreased （P＜0.05 or P＜0.01）. Compared to those in the model group， the MVD in the wound tissue of all medication groups significantly increased， and the mRNA and protein levels of Notch1 and Dll4 decreased， while VEGFA and Ang-2 mRNA expression and protein levels increased （P＜0.05 or P＜0.01）. Compared to the XZM group， the inhibitor group and the combination group showed decreased MVD in wound tissue， increased Notch1 and Dll4 mRNA and protein levels， and decreased expression of VEGFA and Ang-2 mRNA and proteins （P＜0.05 or P＜0.01）. ConclusionXZM can effectively promote wound healing in DFU rats， and its mechanism of action may be related to the inhibition of Dll4/Notch1 signaling pathway in the wound tissue， therey promoting angiogenesis.