Inflammatory brain lesions preceding primary central nervous system lymphoma: a case report and genetic analysis.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) is an aggressive extranodal lymphoma exclusively occurring within the central nervous system. Inflammatory brain lesions as "sentinel lesions" of PCNSL are very rare. We present a rare case of PCNSL with preceding inflammatory lesions in an immunocompetent patient who underwent two biopsies, one craniotomy and two genetic testing. CASE REPORT: A 66-year-old male patient presented with left limb weakness and ataxia. Brain magnetic resonance imaging showed a contrast-enhancing lesion with perifocal brain edema in the near midline of right frontal lobe. Histological examination of a brain biopsy specimen revealed inflammatory lesion characteristics with infiltration of T-cell dominant lymphocytes and few B-cell. Given that the patient developed cerebral hematoma after biopsy, lesion resection by craniotomy was performed. An excised sample demonstrated mixed T-cell and B-cell infiltrating inflammatory lesions. Four months after total resection of the right frontal lobe lesion, another lesion appeared in the left frontal parietal lobe, which was diagnosed as diffuse large B-cell lymphoma by biopsy. In addition, genetic testing of the lesions at two different locations was performed, and the results showed that the inflammatory lesions had the same three gene (RELN, PCLO, and CREBBP) mutations as PCNSL. Interestingly, the three mutated genes are associated with tumor. CONCLUSION: Our present case is the first to demonstrate inflammatory brain lesions heralding PCNSL from genetic and pathological perspectives. This may help clinicians to select new auxiliary diagnostic methods for timely diagnosis of patients with suspected PCNSL.

Chinese expert consensus on diagnosis and management of gastroesophageal reflux disease in the elderly (2023).

Gastroesophageal reflux disease (GERD) in the elderly is characterized by atypical symptoms, relatively severe esophageal injury, and more complications, and when GERD is treated, it is also necessary to fully consider the general health condition of the elderly patients. This consensus summarized the epidemiology, pathogenesis, clinical manifestations, and diagnosis and treatment characteristics of GERD in the elderly, and provided relevant recommendations, providing guidance for medical personnel to correctly understand and standardize the diagnosis and treatment of GERD in the elderly.

Identification of a 5-gene-based signature to predict prognosis and correlate immunomodulators for rectal cancer.

BACKGROUND: Specific tumor markers have yet to be identified in rectal cancer. This study aims to identify a novel genetic signature in rectal cancer to provide clues for survival and immunotherapy. METHODS: DEGs were obtained from two GEO datasets of rectal cancer. By using data from TCGA and GSE133057, two cohorts of rectal cancer were applied to establish and evaluate the signature. A nomogram was constructed for training and validation. We integrated the risk-score with clinicopathological features and assessed its interplay with immune cells and molecules. Finally, our study performed functional annotations, gene-targeted miRNAs, and single-cell analysis. RESULTS: A total of 468 DEGs were identified, and a signature consisting of 5 genes (CLIC5, ENTPD8, PACSIN3, HGD, and GNG7) was selected to calculate the risk-score. The model exhibited high performance in time-dependent ROC and a nomogram. Further results showed that overall survival was significantly worse in the high-risk group. As an independent prognostic factor, the risk-score was associated with vascular invasion. There was a dramatic difference in nonregulatory CD4+ and CD8+ T cells between the high and low-risk groups, and the 5 genes were correlated with immune inhibitors. There was a considerable difference in autophagy, immune, cell cycle, infection, and apoptosis-associated terms and pathways in GO and KEGG. The functional states of differentiation, apoptosis, and quiescence were closely related to the 5-gene signature in single-cell analysis. CONCLUSION: Our results suggest that the signature could serve as a novel prognostic biomarker in rectal cancer, which might benefit decision-making regarding immunotherapy.

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.

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.

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.

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.

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.

Diffusion Kurtosis as an in vivo Imaging Marker of Early Radiation-Induced Changes in Radiation-Induced Temporal Lobe Necrosis in Nasopharyngeal Carcinoma Patients.

PURPOSE: Diffusion kurtosis imaging (DKI), an extension of the popular diffusion tensor imaging (DTI) model, has been applied in clinical studies of brain tissue changes. We explored the value of DKI for the early detection of radiation-induced changes in temporal lobe necrosis (TLN) after radiotherapy (RT) for nasopharyngeal carcinoma (NPC). METHODS: A total of 400 patients with NPC were retrospectively enrolled; all participants underwent MRI scans 0-7 days before RT, at 4 weeks during RT, and 1 month after completing RT. DKI-derived kurtosis parameters (mean kurtosis [MK], axial kurtosis [Ka], radial kurtosis [Kr]), and DKI-derived diffusion parameters (fractional anisotropy [FA], mean diffusivity [MD], axial diffusivity [λa], radial diffusivity [λr]) were assessed in temporal lobe white matter. RESULTS: Analysis was performed for 20 patients with temporal lobe necrosis following long-term follow-up. No brain abnormalities were visible on conventional MRI in any patient at 4 weeks during RT and 1 month after RT. Of all DKI-derived parameters, MK was significantly lower at 1 month after RT than before RT (P < 0.05). CONCLUSION: This study indicates DKI can detect the early presence of relatively subtle RT-induced brain abnormalities before TLN in patients with NPC and may provide a sensitive imaging technique for temporal white matter microstructural abnormalities that are silent on conventional modalities but precede TLN after RT.

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.

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.

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).

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.

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.

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.

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.

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.