Research progress on coping strategies of unreasonable drug use in the elderly / 中华老年医学杂志

Irrational drug use is common and inevitable in the elderly population, which leads to the occurrence of adverse drug reactions, the increase of hospital readmission rate and related mortality rate, and the increase of medical economic burden.Therefore, it is imperative to reduce irrational drug use, and the standardized drug prescription has become a new challenge for clinicians and pharmacists.Accurate detection method of irrational drug use, practical and effective drug use scheme, and intervention measures are the key to guide rational drug use in clinical practice.Mainly in terms of risk factors of irrational drug use, the status quo and its coping strategies, this paper reviews the research status at home and abroad in order to reduce irrational drug use in the elderly, reduce drug risk, and improve medication environment for the elderly.

Preclinical and early clinical studies of a novel compound SYHA1813 that efficiently crosses the blood-brain barrier and exhibits potent activity against glioblastoma

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults and is poorly controlled. Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression, and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment. Therefore, this study developed a novel and selective inhibitor of CSF1R and VEGFR, SYHA1813, possessing potent antitumor activity against GBM. SYHA1813 inhibited VEGFR and CSF1R kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo. SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models, including temozolomide (TMZ) insensitive tumors. Notably, SYHA1813 could penetrate the blood-brain barrier (BBB) and prolong the survival time of mice bearing intracranial GBM xenografts. Moreover, SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody. As a clinical proof of concept, SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial. The data of this study support the rationale for an ongoing phase I clinical study (ChiCTR2100045380).

Intravenous malposition of double J stent: a case report and literature review / 现代泌尿外科杂志

【Objective】 To investigate the causes of intravenous malposition of double J stent and treatment strategies, in order to improve clinicians’ awareness of this complication. 【Methods】 Clinical data of a patient with intravenous malposition of double J stent were analyzed and relevant literature was reviewed. 【Results】 A 51-year-old female was admitted with post-hysterectomy urinary fistula and diagnosed with right intravenous malposition of double J stent and ureterovaginal fistula. Da Vinci robot-assisted laparoscopic right double J stent removal and ureteral reimplantation were performed. 【Conclusion】 Intravenous malposition is a rare and life threatening complication of double J stent placement, which can migrate further. The surgical method should be selected according to the location of the stent and general condition of the patients. Minimally invasive surgery is the first choice of treatment.

Effects of plateau hypoxia on population pharmacokinetics and pharmacodynamics of metformin in patients with Type 2 diabetes / 中南大学学报(医学版)

OBJECTIVES@#Metformin is the basic drug for treating diabetes, and the plateau hypoxic environment is an important factor affecting the pharmacokinetics of metformin, but there have been no reports of metformin pharmacokinetic parameters in patients with diabetes mellitus type 2 (T2DM) in the high-altitude hypoxic environment. This study aims to investigate the effect of the hypoxic environment on the pharmacokinetics and assess the efficacy and safety of metformin administration in patients with Type 2 diabetes mellitus (T2DM).@*METHODS@#A total of 85 patients with T2DM taking metformin tablets in the plateau group (n=32, altitude: 1 500 m) and control group (n=53, altitude: 3 800 m) were enrolled according to the inclusion and exclusion criteria, and 172 blood samples were collected in the plateau group and the control Group. A ultra-performance liquid chromatography/tandem mass spectrometry (UFLC-MS/MS) method was established to determine the blood concentration of metformin, and Phoenix NLME software was used to establish a model of pharmacokinetics of metformin in the Chinese T2DM population. The efficacy and serious adverse effects of metformin were compared between the 2 groups.@*RESULTS@#The population pharmacokinetic modeling results showed that plateau hypoxia and age were the main covariates for model building, and the pharmacokinetic parameters were significantly different between the plateau and control groups (all P<0.05), including distribution volume (V), clearance (CL), elimination rate constant (Ke), half-life(T1/2), area under the curve (AUC), time to reach maximum concentration (Tmax). Compared with the control group, AUC was increased by 23.5%, Tmax and T1/2 were prolonged by 35.8% and 11.7%, respectively, and CL was decreased by 31.9% in the plateau group. The pharmacodynamic results showed that the hypoglycaemic effect of T2DM patients in the plateau group was similar to that in the control group, the concentration of lactic acid was higher in the plateau group than that in the control group, and the risk of lactic acidosis was increased after taking metformin in the plateau population.@*CONCLUSIONS@#Metformin metabolism is slowed down in T2DM patients in the hypoxic environment of the plateau; the glucose-lowering effect of the plateau is similar, and the attainment rate is low, the possibility of having serious adverse effects of lactic acidosis is higher in T2DM patients on the plateau than on the control one. It is probably suggested that patients with T2DM on the plateau can achieve glucose lowering effect by extending the interval between medication doses and enhancing medication education to improve patient compliance.

Effects of hypoxia on the expression and function of P-gp in Caco-2 cells / 中南大学学报(医学版)

OBJECTIVES@#Hypoxia can alter the oral bioavailability of drugs, including various substrates (drugs) of P-glycoprotein (P-gp), suggesting that hypoxia may affect the function of P-gp in intestinal epithelial cells. Currently, Caco-2 monolayer model is the classic model for studying the function of intestinal epithelial P-gp. This study combines the Caco-2 monolayer model with hypoxia to investigate the effects of hypoxia on the expression and function of P-gp in Caco-2 cells, which helps to elucidate the mechanism of changes in drug transport on intestinal epithelial cells in high-altitude hypoxia environment.@*METHODS@#Normally cultured Caco-2 cells were cultured in 1% oxygen concentration for 24, 48, and 72 h, respectively. After the extraction of the membrane proteins, the levels of P-gp were measured by Western blotting. The hypoxia time, with the most significant change of P-gp expression, was selected as the subsequent study condition. After culturing Caco-2 cells in transwell cells for 21 days and establishing a Caco-2 monolayer model, they were divided into a normoxic control group and a hypoxic group. The normoxic control group was continuously cultured in normal condition for 72 h, while the hypoxic group was incubated for 72 h in 1% oxygen concentration. The integrity and polarability of Caco-2 cells monolayer were evaluated by transepithelial electrical resistance (TEER), apparent permeability (Papp) of lucifer yellow, the activity of alkaline phosphatase (AKP), and microvilli morphology and tight junction structure under transmission electron microscope. Then, the Papp of rhodamine 123 (Rh123), a kind of P-gp specific substrate, was detected and the efflux rate was calculated. The Caco-2 cell monolayer, culturing at plastic flasks, was incubated for 72 h in 1% oxygen concentration, the expression level of P-gp was detected.@*RESULTS@#P-gp was decreased in Caco-2 cells with 1% oxygen concentration, especially the duration of 72 h (P<0.01). In hypoxic group, the TEER of monolayer was more than 400 Ω·cm2, the Papp of lucifer yellow was less than 5×10-7 cm/s, and the ratio of AKP activity between apical side and basal side was greater than 3. The establishment of Caco-2 monolayer model was successful, and hypoxia treatment did not affect the integrity and polarization state of the model. Compared with the normoxic control group, the efflux rate of Rh123 was significantly reduced in Caco-2 cell monolayer of the hypoxic group (P<0.01). Hypoxia reduced the expression of P-gp in Caco-2 cell monolayer (P<0.01).@*CONCLUSIONS@#Hypoxia inhibits P-gp function in Caco-2 cells, which may be related to the decreased P-gp level.

Progress on factors affecting gastrointestinal function and drug protection in high altitude hypoxia environment / 药学实践与服务

Due to factors such as low pressure, low oxygen and cold in the plateau environment, people who enter the plateau rapidly are susceptible to digestive system diseases, such as upper abdominal pain, loss of appetite, nausea and vomiting and other gastrointestinal dysfunction, which seriously affect the health and work ability of people who enter the plateau rapidly. The gastrointestinal dysfunction caused by the rapid advance to the plateau is mainly reflected in three aspects: gastrointestinal motility dysfunction, impaired mucosal barrier function, and intestinal flora imbalance. At present, the pathogenesis of gastrointestinal dysfunction is still not very clear, and there are fewer drugs for targeted prevention and treatment. Gastrointestinal hormones, oxygen free radicals, inflammatory factors, intestinal flora and other factors, as well as the protective effects of related drugs were reviewed in this paper to provide treatment options and theoretical basis for the prevention and treatment of the gastrointestinal emergency response caused by entering the plateau.

Protective effect of heme chloride on hypoxia-induced tissue injury in mice / 中南大学学报(医学版)

Objective:Heme chloride(Hemin)is an in vitro purified form of natural heme and an important raw material for anti-anemia and antitumor drugs.This study aims to analyze the protective effect of Hemin on tissue damage in low-pressure oxygen chamber simulated plateau hypoxic mice,and explore its role in anti-plateau hypoxia. Methods:Thirty male BALB/c mice were randomly divided into a blank group,a positive drug group(acetazolomide,200 mg/kg),a Hemin low-dose group(15 mg/kg),a Hemin medium-dose group(30 mg/kg),and a Hemin high-dose group(60 mg/kg)with intraperitoneal injection.The anti-hypoxic activity of Hemin was explored by atmospheric closed hypoxia experiment and the optimal dose was screened.Thirty-six male BALB/c mice were randomly divided into a blank group,a hypoxia group,a positive drug group,and a Hemin high-dose group.The plasma inflammatory factor levels and oxidative stress indicators malondialdehyde(MDA),glutataione(GSH),and superoxide dismutase(SOD)levels of myocardium,brain,lung,and liver tissues were measured in different groups with hypoxia for 24 h.The degree of histopathological damage of mice was observed with HE staining.The degree of protection of Hemin against tissue hypoxia injury was detected with the hypoxia probe piperidazole. Results:Compared with the blank group,the survival time of mice in the positive drug group,the Hemin medium-dose group,and high-dose group was significantly extended(all P<0.05),with the highest prolongation rate in the Hemin high-dose group.Compared with the hypoxia group,mice in the Hemin high-dose group showed a significant increase in SOD level and GSH content of brain tissue,and a significant decrease in MDA content of lung tissue(all P<0.05).The results of HE staining and hypoxia probe showed that Hemin had a significant protective effect on the damage of liver,heart,brain and lung tissues of mice with hypoxia,and the most obvious effect on that of the brain tissue. Conclusion:Hemin has an effect of improvement on oxidative stress and inflammatory response caused by hypoxia,and has obvious protective effect on tissue damage caused by hypoxia.

Effects of plateau hypoxia on pharmacokinetic parameters and cerebral-blood distribution of levetiracetam in rats / 中南大学学报(医学版)

Objective:Plateau hypoxia exposure causes changes in pharmacokinetic parameters and cerebral-blood distribution of drugs,including many substrates of P-glycoprotein(P-gp).Levetiracetam,a kind of antiepileptic drugs,is a substrate of P-gp.Whether plateau hypoxia exposure changes its pharmacokinetic characteristics and cerebral-blood distribution remains unclear.This study aims to investigate the effects of plateau hypoxia on the pharmacokinetics and cerebra-blood distribution of levetiracetam. Methods:Wistar rats were divided into a low-altitude control group,a high-altitude group,a solvent group,and a P-gp induction group.After 24 h of exposure at altitude of 4 010 m,rats in the high-altitude group were given levetiracetam orally or intravenously.The plasma was respectively collected at 0.083,0.25,0.5,0.83,1.25,2,4,6,8,10,12,and 24 h after oral administration of the drug,while both plasma and brain were respectively collected at 5,45,60,120 and 240 min after intravenous injection.After 3 days administration of dexamethasone,plasma and brain of rats in the P-gp induction group were collected at 120 min after intravenously giving levetiracetam.Plasma and brain concentrations of the drug were determined by high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS).The expression of P-gp in blood-brain barrier was detected by Western blotting. Results:Compared with the low-altitude control group,the area under the curve(AUC)and mean residence time(MRT)of levetiracetam were respectively decreased by 14.69%(P<0.01)and 15.42%(P<0.01),while the clearance(CL)was increased by 16.67%(P<0.01)in the high-altitude group.The ratio of brain/blood plasma drug concentration was decreased by 22.82%(P<0.05),12.42%(P<0.05),17.40%(P<0.01),and 13.22%(P<0.01)at 5,45,120,and 240 min after injection,respectively.The expression of P-gp on the blood-brain barrier was increased by 86.3%(P<0.05).Compared with the solvent control group,the expression of P-gp on the blood-brain barrier in the P-gp induction group was increased by 56.3%(P<0.05),the ratio of brain/blood plasma drug concentration was decreased by 19.3%(P<0.05). Conclusion:After acute plateau hypoxia exposure,the pharmacokinetic of levetiracetam in rats are altered,and the cerebral-blood distribution of the drug in rats is decreased,which may be related to the up-regulation of P-gp expression on the blood-brain barrier.

Role of Danggui Buxue Decoction for the prevention and treatment of cardiovascular and pulmonary diseases / 中南大学学报(医学版)

Cardiovascular and pulmonary diseases have become the major disease endangering people's physical and mental health because of its high morbidity and mortality.Danggui Buxue Decoction,a noteworthy classical prescription,is composed of astragali radix and angelicae sinensis radix at a ratio of 5∶1.It is a prescription for tonifying both vital energy and blood and has the effect of dredging collaterals.Its main active components,such as polysaccharides,saponins,flavonoids and volatile oils,have good effects on antioxidation,inflammation regulation,immune regulation and promotion of blood circulation.Danggui Buxue Decoction can improve myocardial ischemia-reperfusion injury and heart failure,relieve the symptoms of diabetic cardiomyopathy,inhibit pulmonary fibrosis,protect lung injury and fight against lung cancer and other cardiopulmonary diseases.Preclinical studies have showed that this prescription can inhibit inflammation and oxidative stress,regulate autophagy and enhance immune function through multi-target pathways.Reviewing the main effective components,pharmacological action and mechanism,and clinical application of Danggui Buxue Decoction are helpful to provide comprehensive information for the clinical application of Danggui Buxue Decoction in prevention and treatment of cardiovascular and pulmonary diseases.

Research progress in the prevention and treatment of insomnia with classical prescriptions / 中南大学学报(医学版)

Insomnia is a common disease and its impact on human health cannot be ignored.At present,there are 3 main clinical treatments for insomnia,including traditional Chinese medicine treatment,sedative hypnotic drug therapy,and cognitive behavioral therapy.Traditional Chinese medicine(TCM)treatment for insomnia is widely used due to its advantages of low side effects,good efficacy,and no drug dependence.This paper summarizes the pathogenesis of insomnia in the theories of traditional Chinese and Western medicine.Modern medical research generally believes that sleep-wake disorder is the main pathological mechanism of insomnia,involving many factors such as monoamine neurotransmitter disorder,cytokine imbalance and intestinal flora imbalance.TCM mainly divides the pathogenesis of insomnia into 9 kinds of syndrome types:Liver depression transforming into fire,hyperactivity of fire due to yin deficiency,phlegm-heat attacking internally,disharmony between heart and kidney,deficiency of both heart and spleen,qi deficiency of both heart and gallbaldder,stomach qi disharmony,exuberance of heart fire,and internal blockade of static blood.According to these 9 kinds of pathogenesis of insomnia,the corresponding classical prescriptions such as Longdanxiegan decoction,Suanzaoren decoction,Huanglian-Wendan decoction,Jiaotai pill and Guipi decoction were analyzed and summarized.There is evidence that traditional Chinese medicine could treat insomnia mainly by increasing the level of 5-hydroxytryptamine,reducing the levels of dopamine,noradrenaline,tumor necrosis factor α,and interlukin-6,decreasing the ratio of glutamic acid to γ-aminobutyric acid,and inhibiting the hypothalamic-pituitary-adrenal axis.

Analysis of the current situation of model research wards construction in Beijing / 中华医院管理杂志

Objective:To understand the construction status of research wards in the first model research wards in Beijing, and provide reference for promoting their high-quality development.Methods:From July to September 2022, a questionnaire survey was conducted on the setting mode, facility deployment, operational efficiency, and implementation of supportive policies of the research wards among the first batch of model research wards in Beijing. Descriptive analysis was used to analyze the questionnaire data.Results:The 8 hospitals surveyed had all set up specialized research wards; 5 of them had shared research wards, including 4 general hospitals and 1 specialized hospital. The number of research ward beds in each hospital ranged from 31 to 120, with only 1 hospital having research ward beds accounting for 11.3% of the hospital′s beds, while the other 7 hospitals were less than 10.0%. Compared with 2020, the number of clinical research projects carried out in the research wards of 8 hospitals in 2021 have increased by a total of 403, while the ethical review time was less than or equal to 14 working days, 2.5 working days shorter than 2020; 4 hospitals could complete the experimental project approval within 60 working days and the first visit within 22 working days, while 5 hospitals could complete the research conclusion within 14 working days. There were 2 hospitals that link the performance evaluation of research wards with salary distribution, and 3 hospitals link it with professional title evaluation and employment.Conclusions:The model research wards in Beijing have adopted different setting modes for the construction of research wards, all operating well. It is recommended to further improve such areas as selecting a research ward setting mode to fit the needs of the hospital, optimizing and integrating the resource allocation of research wards, improving operational efficiency to increase market competitiveness, and effectively implementing supportive policies related to human resource management. These practices can better promote the high-quality construction of research wards and comprehensively enhance the supportive role of clinical research in pharmaceutical and healthcare collaborative innovation.

Pharmacodynamic of cilostazol for anti-altitude hypoxia / 中南大学学报(医学版)

OBJECTIVES@#The plateau environment is characterized by low oxygen partial pressure, leading to the reduction of oxygen carrying capacity in alveoli and the reduction of available oxygen in tissues, and thus causing tissue damage. Cilostazol is a phosphodiesterase III inhibitor that has been reported to increase the oxygen release of hemoglobin (Hb) in tissues. This study aims to explore the anti-hypoxic activity of cilostazol and its anti-hypoxic effect.@*METHODS@#A total of 40 male BALB/C mice were randomly divided into a low-dose cilostazol (6.5 mg/kg) group, a medium-dose (13 mg/kg) group, a high-dose (26 mg/kg) group, and a control group. The atmospheric airtight hypoxia experiment was used to investigate the anti-hypoxic activity of cilostazol and to screen the optimal dosage. Twenty-four male Wistar rats were randomly divided into a normoxia control group, a hypoxia model group, an acetazolamide (22.33 mg/kg) group, and a cilostazol (9 mg/kg) group. After 3 days of hypoxia in the 4 010 m high altitude, blood from the abdominal aorta was collected to determine blood gas indicators, the levels of IL-6 and TNF-α in plasma were determined by enzyme-linked immunosorbent assay, and the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutataione (GSH) were measured. The degree of pathological damage for rat tissues was observed with HE staining.@*RESULTS@#Compared with the control group, the survival time of mice in the low, medium, and high dose group of cilostazol was significantly prolonged, and the survival time of mice in the medium dose group was the longest, with an extension rate at 29.34%, so the medium dose was the best dose. Compared with the hypoxia model group, the P50 (oxygen partial pressure at Hb oxygen saturation of 50%) value of rats in the cilostazol group was significantly increased by 1.03%; Hb and Hct were significantly reduced by 8.46% and 8.43%, and the levels of IL-6 and TNF-α in plasma were reduced by 50.65% and 30.77%. The MDA contents in heart, brain, lung, liver, and kidney tissues were reduced by 37.12%, 29.55%, 25.00%, 39.34%, and 21.47%, respectively. The SOD activities were increased by 94.93%, 9.14%, 9.42%, 13.29%, and 20.80%, respectively. The GSH contents were increased by 95.24%, 28.62%, 28.57%, 20.80%, and 44.00%, respectively. The results of HE staining showed that compared with the hypoxia model group, cilostazol significantly improved the damage of heart, lung, and kidney tissues in rats after hypoxia.@*CONCLUSIONS@#Cilostazol can significantly improve the oxidative stress and inflammatory reaction caused by rapid altitude hypoxia, and it has a significant protective effect on tissue damage caused by hypoxia, suggesting that it has obvious anti-hypoxic activity.

Analysis of Risk Factors of Non-curative Resection of Endoscopic Submucosal Dissection for Early Colorectal Cancer and Precancerous Lesions / 胃肠病学

Background: The risk factors affecting the non ⁃ curative resection of endoscopic submucosal dissection (ESD) for early colorectal cancer and precancerous lesions were still lacking large scale studies in China. Aims: To analyze the efficacy of ESD for patients with early colorectal cancer and precancerous lesions, and explore the risk factors affecting the non⁃curative resection. Methods: A total of 229 patients with early colorectal cancer and precancerous lesions underwent ESD from September 2016 to September 2021 at Beijing Hospital were collected. The clinicopathological characteristics, efficacy of ESD were analyzed. Risk factors affecting the non ⁃ curative resection of ESD were analyzed by univariate analysis and Logistic multivariate regression analysis. Results: A total of 255 lesions were found. The en bloc resection rate was 90.2%, R0 resection rate was 87.8%, and curative resection rate was 83.5%. The total incidence of complications was 2.7%. Univariate analysis showed that detection rate of intraluminal protruding tumor (61.0% vs. 24.4%, P<0.05), rate of severe submucosal fibrosis (24.4% vs. 2.4%, P<0.05) were significantly increased in the non⁃curative resection group than in the curative resection group, and positive rate of lifting sign was significantly decreased (80.5% vs. 95.1%, P<0.05). Logistic multivariate regression analysis showed that intraluminal protruding tumor (OR=4.087, 95% CI: 1.523⁃10.968, P= 0.005) and severe submucosal fibrosis (OR=9.609, 95% CI: 1.107⁃83.439, P=0.04) were risk factors for ESD non⁃curative resection of early colorectal cancer and precancerous lesions. Conclusions: R0 resection rate and curative resection rate of ESD for early colorectal cancer and precancerous lesions are high, the incidence of surgical complications is low. Intraluminal protruding tumor, severe submucosal fibrosis are the independent risk factors of non⁃curative resection. Strict evaluation should be carried out before operation and reasonable treatment strategies should be formulated accordingly.

Diagnostic and prognostic valuation of CD64, heparin binding protein and procalcitonin in children with sepsis shock / 中国医师进修杂志

Objective:To investigate the value of serum CD64, heparin binding protein (HBP) and procalcitonin (PCT) in early diagnosis of septic shock and its prognostic value.Methods:The clinical data of 40 children with sepsis (sepsis group) and 40 children with septic shock (septic shock group) in Children′s Hospital of Xuzhou Medical University from January 2018 to November 2021 were retrospectively analyzed. PCT was detected by chemiluminescence, HBP was detected by enzyme-linked immunosorbent assay, and CD 64 was detected by flow cytometry. All children were followed up within 1 month after discharge, and the occurrence of poor prognosis (including multiple organ failure and death) was recorded. The receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of serum CD 64, HBP and PCT for septic shock. Multivariate Logistic regression was used to analyze the independent risk factors for poor prognosis in children with septic shock. Results:The serum CD 64, HBP and PCT in septic shock group were significantly higher than those in sepsis group: 0.667 ± 0.120 vs. 0.501 ± 0.115, (116.46 ± 11.41) μg/L vs. (87.34 ± 23.49) μg/L and (11.41 ± 1.25) μg/L vs. (9.29 ± 1.31) μg/L respectively, and there were statistical differences ( P<0.05). ROC curve analysis result showed that the area under curve (AUC) of serum CD 64, HBP and PCT for predicting septic shock were 0.837, 0.894 and 0.880 respectively, and the optimal cut-off values were 0.586, 106.2 μg/L and 11.28 μg/L respectively; the AUC of serum CD 64, HBP and PCT combined detection for predicting septic shock was 0.914, with a sensitivity of 75.7%, specificity of 96.0%, and accuracy of 71.7%. According to the optimal cut-off values of serum CD 64, HBP and PCT, 40 children with septic shock were divided into high expression group and low expression group. The prognosis was good in 25 cases and bad in 15 cases. The incidence of poor prognosis in CD 64 high expression group, HBP high expression group and PCT high expression group was significantly higher than that in corresponding CD 64 low expression group, HBP low expression group and PCT low expression group: 56.52% (13/23) vs. 2/17, 10/17 vs. 21.74% (5/23) and 11/18 vs. 18.18% (4/22), and there was statistical difference ( P<0.01 or <0.05). Multivariate Logistics regression analysis result showed that serum CD64, HBP and PCT were independent risk factors for poor prognosis in children with septic shock ( OR = 0.818, 1.204 and 3.633; 95% CI 0.674 to 0.994, 1.022 to 1.419 and 1.090 to 12.108; P = 0.043, 0.026 and 0.036). Conclusions:The serum levels of CD 64, HBP and PCT in children with septic shock are significantly increased, which play an important role in the occurrence and development of septic shock, and which have predictive value for septic shock. The combined detection of the 3 indexes could be used to evaluate the prognosis, with a higher predictive value.

Effects of slow intravenous infusion of low-dose mannitol on hemodynamics in patients after cardiac surgery under cardiopulmonary bypass / 中华胸心血管外科杂志

Objective:To investigate the effect of slow intravenous infusion of low-dose mannitol on the hemodynamics of patients after cardiopulmonary bypass.Methods:Prospective, continuous inclusion of 62 patients after cardiac surgery under cardiopulmonary bypass. By random number method, they were divided into normal treatment group(group C) with 29 cases and mannitol treatment group(group M) with 33 cases. Group C was treated according to the postoperative routine treatment measures. On the basis of conventional treatment, group M received intravenous infusion of 20% mannitol injection 0.25 g/kg at 1、8、24 hours after operation, and the intravenous infusion time was 60 minutes each time. According to the hemodynamic changes during the two groups of treatment, the effect of slow intravenous infusion of low-dose mannitol on patients after cardiopulmonary bypass under cardiopulmonary bypass was analyzed.Results:In group M, CI and SVI were significantly increased after use of mannitol than before, with statistical significance( P<0.01). SVRI showed a downward trend, and the changes were statistically significant after use of mannitol( P<0.01). PAWP increased first and then decreased after operation, and the changes were statistically significant after mannitol use than before( P<0.05). RAP and MPAP had no significant changes after the first use of mannitol, but the changes after the latter two use mannitol were statistically significant than before( P<0.05). Repeated-measurement data analysis of variance was performed on the hemodynamic parameters of each group, and the results were all P<0.01. Conclusion:Postoperative slow intravenous infusion of low-dose mannitol optimizes hemodynamic status, increases stroke volume, reduces cardiac preload, improves systemic and pulmonary circulation resistance, and promotes recovery of postoperative cardiopulmonary function.

Research progress of pharmacokinetic factors of metformin / 中国药房

Metformin is the most common first-line oral hypoglycemic drug ，but there are large individual differences in pharmacokinetic parameters and pharmacodynamics during clinical use. The dosage of some patients should be adjusted to achieve satisfactory therapeutic effect. Pharmacokinetic parameters of metformin are affected by many factors ，including respects of transporter gene polymorphism ，drug interaction ，intestinal flora ，plateau hypoxia and physiological function and so on. In order to guide the clinical individualized use of metformin ，this study reviews the research progress on the influencing factors of metformin pharmacokinetics.

Establishment of SLC6A4 gene silencing stable cell line in PC12 cells and the effect of SLC6A4 gene silencing on apoptosis of hypoxia PC12 cells / 药学实践与服务

Objective To construct SLC6A4-shRNA lentiviral vector, establish PC12 cells stable transformation cell line，and detect the effect of SLC6A4 gene silencing on hypoxia induced PC12 cells apoptosis. Methods Three specific targets sequence of SLC6A4 were designed and short hairpin RNA was synthesized, and then were recombined into shRNA expression vector GV248 plasmid, with non-homology shRNA sequence as negative control. The connection products were switched to competent cells. After dentification and sequencing, the vectors were co-transfected with the auxiliary vectors into 293T cells in order to produce recombinant shRNA lentiviral particles. Then, PC12 cells were infected with the recombinant lentiviral and screened by puromycin. The PC12 cells were divided into two groups: lentiviral negative control group (NC-shRNA) and SLC6A4-silenced group (SLC6A4-shRNA). The expression of SLC6A4 mRNA was detected by real-time fluorescence quantitative and the 5-HTT protein level was assayed by Western blot, The effect of SLC6A4 gene silencing on hypoxia induced apoptosis was detected by flow cytometry. Results The SLC6A4-shRNA lentiviral expression vector was constructed and the recombinant lentiviral particles by packaging the 293T cells were obtained, the stably infected PC12 cells were established after filtering. Compared with negative control group, the expression level of SLC6A4 gene and 5-HTT protein in SLC6A4-shRNA group was suppressed notably (P<0.01). It was confirmed that lentiviral vector could effectively silence SLC6A4 gene in PC12 cells and SLC6A4 gene silencing could decrease apoptosis rate of PC12 cells under hypoxia condition. Conclusion The SLC6A4 gene of PC12 cells could be effectively silenced by shRNA lentivirus vector，which could reverse hypoxia induced apoptosis.

Research progress of atorvastatin gene polymorphism / 药学实践与服务

Atorvastatin is a blood lipid-lowering drug widely used clinically. Long-term use can prevent and reduce the occurrence of atherosclerotic cardiovascular disease (ASCVD). However, the efficacy of atorvastatin has significant inter-individual differences. Some individuals failed to achieve the expected lipid-lowering target value or had serious adverse reactions, which were related to the genetic diversity between individuals. Genetic variation can lead to differences in drug configuration, clinical efficacy and adverse reactions. The drug metabolism enzymes, drug transporters, drug targets and genetic polymorphisms related to lipid metabolism were reviewed in this paper that affect the drug response of atorvastatin, and from the gene level to explore the reasons for the differences in the pharmacokinetics, pharmacodynamics and susceptibility to adverse reactions of different individuals using atorvastatin.

Expression and clinical significance of receptor-interacting protein kinase-3 levels in children with mycoplasma pneumoniae pneumonia and their relationship with inflammatory factors / 中国综合临床

Objective:To explore the level of expression, clinical significance of receptor-interacting protein kinase-3(RIPK3) in the bronchoalveolar alveolar lavage fluid (BALF) of mycoplasma pneumoniae pneumonia(MPP) in children and the relationship between RIPK3 and various cytokines.Methods:Using a case-control study, 30 refractory mycoplasma pneumoniae pneumonia children treated in Children′s Hospital of Xuzhou Medical University from February 2019 to February 2021 were selected as the MRPP group, 35 mycoplasma pneumoniae pneumonia children as the RPP group.Meanwhile, 20 sex- and age-matched hospitalized children with bronchial foreign body were selected as the case-control group.In all subjects, protein levels of RIPK3 and mixed lineage kinase domain-like protein(MLKL) were determined by Western Blot.Meanwhile, levels of IL-6, IL-1β and TNF-α were determined by enzyme linked immuno sorbent assay(ELISA). Compare levels of different parameters between the three groups and analyze the correlation between levels of RIPK3 and MLKL, L-6, IL-1β, TNF-α in the BALF of MPP children using Spearman rank correlation analysis.Results:There were statistically significant differences in the levels of RIPK3, MLKL, IL-6, IL-1β and TNF-α in BALF between RMPP group, MPP group and control group (all P<0.001). Pairwise comparisons also showed statistical differences, and the RMPP group was the highest, followed by MPP group, and the control group was the lowest.The level of RIPK3 in BALF of MPP children was positively correlated with MLKL, IL-6, IL-1β and TNF-α ( r=0.711, 0.676, 0.725, 0.651, P<0.001). Linear regression analysis shows: MLKL=0.432×RIPK3. Conclusion:RIPK3 may be involved in the occurrence and development of MPP in children, and is closely related to cytokines such as IL-6, IL-1β and TNF-α.

Serum miR-195 and miR-599 predict the outcome of patients with acute ischemic stroke / 国际脑血管病杂志

Objective:To investigate the predicting value of serum miR-195 and miR-599 for the outcome of patients with acute ischemic stroke (AIS).Methods:Patients with AIS admitted to Danzhou People's Hospital from January 2018 to July 2020 were enrolled prospectively. The modified Rankin Scale was used to evaluate the outcome of patients at 14 d after onset or when they were discharged from the hospital. A score of 0-2 was defined as a good outcome and a score of >2 were defined as a poor outcome. Multivariate logistic regression analysis was used to determine the independent risk factors for poor outcome of patients with AIS. Receiver operating characteristic (ROC) curve analysis was used to determine the predictive value of serum miR-195 and miR-599 for the poor outcome of patients with AIS. Results:A total of 158 patients with AIS were enrolled. Their age was (65.80±12.36) years old, 105 were males (66.46); 95 patients (60.1%) had a good outcome, and 63 patients (39.9%) had a poor outcome. The age, total cholesterol, triglycerides, low-density lipoprotein cholesterol, baseline National Institutes of Health Stroke Scale (NIHSS) score, serum miR-195 and miR-599 levels in the poor outcome group were significantly higher than those of the good outcome group ( P<0.05). Multivariate logistic regression analysis showed that age (odds ratio [ OR] 1.984, 95% confidence interval [ CI] 1.315-3.617; P=0.036), low-density lipoprotein cholesterol ( OR 2.108, 95% CI 1.406-4.103; P=0.013), baseline NIHSS score ( OR 2.584, 95% CI 1.675-4.505; P=0.005), serum miR-195 ( OR 3.927, 95% CI 2.615-8.227; P<0.001) and miR-599 ( OR 2.952, 95% CI 1.973-6.114; P<0.001) were the independent risk factors for the poor outcome of patients with AIS. ROC curve analysis showed that the area under the curve (0.938, 95% CI 0.882-0.997) of serum miR-195 combined with miR-599 for predicting poor outcome was significantly higher than that predicted alone, and its predictive sensitivity and specificity were 97.0% and 87.4% respectively. Conclusions:The higher levels of serum miR-195 and miR-599 are associated with the poor outcome of patients with AIS. The combination of the both had good predictive value for the poor outcome of patients with AIS.