Integrated care teams in primary care improve clinical outcomes and care processes in patients with non-communicable diseases

INTRODUCTION@#Primary care physicians face the increasing burden of managing multimorbidities in an ageing population. Implementing an integrated care team (ICT) with defined roles and accountability to share consultation tasks is an emerging care model to address this issue. This study compared outcomes with ICT versus usual care for patients with multimorbidities in primary care.@*METHODS@#Data was retrospectively extracted from the electronic medical records (EMRs) of consecutive adult Asian patients empanelled to ICT and those in UC at a typical primary care clinic (polyclinic) in eastern Singapore in 2018. The study population had hypertension, and/or hyperlipidaemia and/or type 2 diabetes mellitus (T2DM). Clinical outcomes included the proportion of patients (ICT vs. UC) who attained their treatment goals after 12 months. Process outcomes included the proportion of patients who completed annual diabetic eye and foot screenings, where applicable.@*RESULTS@#Data from 3,302 EMRs (ICT = 1,723, UC = 1,579) from January 2016 to September 2017 was analysed. The ICT cohort was more likely to achieve treatment goals for systolic blood pressure (SBP) (adjusted odds ratio [AOR] = 1.52, 95% confidence interval [CI] = 1.38-1.68), low-density lipoprotein cholesterol (AOR = 1.72, 95% CI = 1.49-1.99), and glycated haemoglobin (AOR = 1.28, 95% CI = 1.09-1.51). The ICT group had higher uptake of diabetic retinal screening (89.1% vs. 83.0%, P < 0.001) and foot screening (85.2% vs. 77.9%, P < 0.001).@*CONCLUSION@#The ICT model yielded better clinical and process outcomes than UC, with more patients attaining treatment goals.

Research progress on biomarkers of pseudoexfoliative glaucoma / 国际眼科杂志(Guoji Yanke Zazhi)

Pseudoexfoliative glaucoma(PEXG)is an eye disease that seriously endangers vision. It is more invasive than primary open-angle glaucoma(POAG), with more serious damage to the optic nerve, worse prognosis and higher resistance to treatment. Early diagnosis of PEXG can help to treat the disease in time and delay the progress of the disease, so it is important to determine appropriate biomarkers. In recent years, more and more people have begun to study the biomarkers of PEXG, hoping to understand the pathogenesis of the disease, find out the potential early diagnosis and treatment targets of PEXG, and provide some help to the disease through the research of genomics, transcriptomics, proteomics, metabolomics and lipomics markers. This article will review the progress of biomarkers of PEXG in recent years, some biomarkers may provide new ideas for early diagnosis of PEXG in the future.

Emodin Ameliorates High Glucose-Induced Podocyte Apoptosis via Regulating AMPK/mTOR-Mediated Autophagy Signaling Pathway / 中国结合医学杂志

OBJECTIVE@#To investigate the effect of emodin on high glucose (HG)-induced podocyte apoptosis and whether the potential anti-apoptotic mechanism of emodin is related to induction of adenosine-monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR)-mediated autophagy in podocytes (MPC5 cells) in vitro.@*METHODS@#MPC5 cells were treated with different concentrations of HG (2.5, 5, 10, 20, 40, 80 and 160 mmol/L), emodin (2, 4, 8 µ mol/L), or HG (40 mmol/L) and emodin (4 µ mol/L) with or without rapamycin (Rap, 100 nmol/L) and compound C (10 µ mol/L). The viability and apoptosis of MPC5 cells were detected using cell counting kit-8 (CCK-8) assay and flow cytometry analysis, respectively. The expression levels of cleaved caspase-3, autophagy marker light chain 3 (LC3) I/II, and AMPK/mTOR signaling pathway-related proteins were determined by Western blot. The changes of morphology and RFP-LC3 fluorescence were observed under microscopy.@*RESULTS@#HG at 20, 40, 80 and 160 mmol/L dose-dependently induced cell apoptosis in MPC5 cells, whereas emodin (4 µ mol/L) significantly ameliorated HG-induced cell apoptosis and caspase-3 cleavage (P<0.01). Emodin (4 µ mol/L) significantly increased LC3-II protein expression levels and induced RFP-LC3-containing punctate structures in MPC5 cells (P<0.01). Furthermore, the protective effects of emodin were mimicked by rapamycin (100 nmol/L). Moreover, emodin increased the phosphorylation of AMPK and suppressed the phosphorylation of mTOR. The AMPK inhibitor compound C (10 µ mol/L) reversed emodin-induced autophagy activation.@*CONCLUSION@#Emodin ameliorated HG-induced apoptosis of MPC5 cells in vitro that involved induction of autophagy through the AMPK/mTOR signaling pathway, which might provide a potential therapeutic option for diabetic nephropathy.

Activation of HIF-1α/ACLY signaling axis promotes progression of clear cell renal cell carcinoma with VHL inactivation mutation / 中华病理学杂志

Objective: To explore the potential pathogenesis of clear cell renal cell carcinoma (ccRCC) based on the HIF-1α/ACLY signaling pathway, as well as to provide new ideas for the treatment of ccRCC. Methods: Seventy-eight ccRCC cases diagnosed at the First Affiliated Hospital of Soochow University, Suzhou, China were collected. The VHL mutation was examined using exon sequencing. The expression of HIF-1α/ACLY in VHL-mutated ccRCC was evaluated using immunohistochemical staining and further validated in VHL-mutated ccRCC cell lines (786-O, A498, UM-RC-2, SNU-333, and Caki-2) using Western blot. The mRNA and protein levels of ACLY were detected using real-time quantitative PCR and Western blot after overexpression or interference with HIF-1α in ccRCC cell lines. HeLa cells were treated with CoCl2 and hypoxia (1%O2) to activate HIF-1α and then subject to the detection of the ACLY mRNA and protein levels. The potential molecular mechanism of HIF-1α-induced ACLY activation was explored through JASPAR database combined with chromatin immunoprecipitation assay (ChIP) and luciferase reporter gene assay. The effect of HIF-1α/ACLY regulation axis on lipid accumulation was detected using BODIPY staining and other cell biological techniques. The expression of ACLY was compared between patients with ccRCC and those with benign lesions, and the feasibility of ACLY as a prognostic indicator for ccRCC was explored through survival analysis. Results: Exon sequencing revealed that 55 (70.5%) of the 78 ccRCC patients harbored a VHL inactivation mutation, and HIF-1α expression was associated with ACLY protein levels. The protein levels of ACLY and HIF-1α in ccRCC cell lines carrying VHL mutation were also correlated to various degrees. Overexpression of HIF-1α in A498 cells increased the mRNA and protein levels of ACLY, and knockdown of HIF-1α in Caki-2 cells inhibited the mRNA and protein levels of ACLY (P<0.001 for all). CoCl2 and hypoxia treatment significantly increased the mRNA and protein levels of ACLY by activating HIF-1α (P<0.001 for all). The quantification of transcriptional activity of luciferase reporter gene and ChIP-qPCR results suggested that HIF-1α could directly bind to ACLY promoter region to transcriptionally activate ACLY expression and increase ACLY protein level (P<0.001 for all). The results of BODIPY staining suggested that the content of free fatty acids in cell lines was associated with the levels of HIF-1α and ACLY. The depletion of HIF-1α could effectively reduce the accumulation of lipid in cells, while the overexpression of ACLY could reverse this process. At the same time, cell function experiments showed that the proliferation rate of ccRCC cells with HIF-1α knockdown was significantly decreased, and overexpression of ACLY could restore proliferation of these tumor cells (P<0.001). Survival analysis further showed that compared with the ccRCC patients with low ACLY expression, the ccRCC patients with high ACLY expression had a poorer prognosis and a shorter median survival (P<0.001). Conclusions: VHL mutation-mediated HIF-1α overexpression in ccRCC promotes lipid synthesis and tumor progression by activating ACLY. Targeting the HIF-1α/ACLY signaling axis may provide a theoretical basis for the clinical diagnosis and treatment of ccRCC.

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.

Research progress on proactive healthy lifestyle and disease immunoprevention / 中华预防医学杂志

The paradox of increasing health needs and limited health resources prompted a change in the traditional concept of disease prevention and control, and the concept of proactive health has emerged. Proactive health aimed to prevent and control disease and improve the body's immunity by using controlled methods and means to activate the body's self-healing ability and to identify foreign harmful substances as well as damage factors and tumor cells that the body itself may produce while giving full play to individual initiative. With the continuous development of science, people could maintain and improve their immune system from many aspects, which could be roughly divided into nonpharmaceutical interventions and pharmaceutical interventions. Nonpharmacological interventions included changing lifestyles and habits, adjusting the nutritional structure and intake of food, regulating mindsets and emotions, and improving the living and working environment, etc. This review systematically elaborated on the functions and molecular mechanisms of nutrition, exercise, sleep, and emotion in regulating immunity, to provide some scientific evidence and theoretical support for proactive health.

Assessing the impact of educational methods on influenza vaccine uptake and patient knowledge and attitudes: a randomised controlled trial

INTRODUCTION@#Although influenza vaccination reduces rates of pneumonia, hospitalisation and mortality, influenza vaccination uptake remains low in older patients. The primary aim was to compare individualised counselling with educational pamphlets alone in improving influenza vaccination uptake. The secondary aims were to evaluate knowledge and attitudes towards influenza vaccination and factors influencing uptake.@*METHODS@#A randomised controlled study was conducted in two government polyclinics with 160 participants per arm. Patients aged 65 years and above attending for doctor consultation were recruited. All participants received an educational pamphlet on influenza vaccination. The intervention group received additional face-to-face counselling. Participants filled a pre- and postintervention questionnaire assessing knowledge of influenza and attitudes towards the vaccine. Follow-up calls and verification of electronic records was done at three months to determine actual vaccine uptake.@*RESULTS@#At three months, 16 (10%) patients in the intervention group and 20 (12.5%) patients in the control group had completed influenza vaccination (P = 0.48). Factors positively associated with vaccine uptake were willingness to receive vaccination immediately after intervention (adjusted odds ratio [OR] 12.15, 95% confidence interval [CI] 4.42-33.38), and male gender (adjusted OR 2.96, 95% CI 1.23-7.12). Individualised counselling was more effective in improving knowledge (P < 0.01). Overall knowledge scores did not influence actual vaccine uptake rates. (adjusted OR 1.10 [0.90-1.3]).@*CONCLUSION@#Both arms of patient education increased uptake of influenza vaccination. Individualised counselling was not superior to pamphlets alone in improving uptake. Performing vaccination at the initial point of contact improves actual uptake rates.

Structural and Functional Neural Alterations in Internet Addiction: A Study Protocol for Systematic Review and Meta-Analysis

A growing number of neuroimaging studies have revealed abnormal brain structural and functional alterations in subjects with internet addiction (IA), however, with conflicting conclusions. We plan to conduct a systematic review and meta-analysis on the studies of voxelbased morphometry (VBM) and resting-state functional connectivity (rsFC), to reach a consolidated conclusion and point out the future direction in this field. A comprehensive search of rsFC and VBM studies of IA will be conducted in the PubMed, Cochrane Library, and Web of Science databases to retrieve studies published from the inception dates to August 2021. If the extracted data are feasible, activation likelihood estimation and seed-based d mapping methods will be used to meta-analyze the brain structural and functional changes in IA patients. This study will hopefully reach a consolidated conclusion on the impact of IA on human brain or point out the future direction in this field.

Retrospective analysis of strabismus surgery in adolescents and children in Yunnan province / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To analyze the strabismus surgery situation of adolescents and children in Yunnan province.METHODS: A retrospective analysis was conducted on medical records data of 3 068 adolescents and children who received strabismus surgery at Affiliated Hospital of Yunnan University from January 2017 to December 2021. The analysis included gender, constituent ratio of age, distribution of strabismus types and combination with other ocular diseases, etc.RESULTS: Among the included patients, 52.12% were males, and 47.88% were females. Preschool patients(1 to 6 years old)accounted for 32.89%, primary pupils(7 to 12 years old)accounted for 45.89% and high school students(13 to 18 years old)accounted for 21.22%. Exotropia accounted for 63.17% of the total strabismus, of which intermittent exotropia was the most common type. Esotropia accounted for 19.69%, and concomitant esotropia was the most common type. The special type of strabismus accounted for 17.14%, and A-V syndrome and dissociative vertical deviation(DVD)were the most common types. Strabismus combined with ametropia accounted for 61.02% and amblyopia accounted for 10.89%. A few patients also combined with other eye diseases.CONCLUSION: In Yunnan province, intermittent exotropia was the most common type of strabismus among adolescents and children. Some patients combined with other ocular diseases.

Improved Glass Bead-Vortex Oscillation Method for DNA Extraction from Diatom / 法医学杂志

OBJECTIVES@#To examine the effect of improving diatom DNA extraction by glass bead - vortex oscillation method.@*METHODS@#The DNeasy PowerSoil Pro kit was used as control, two plant DNA extraction kits with different principles (New Plant genomic DNA extraction kit and Plant DNA Isolation kit) and one whole blood DNA extraction kit (whole blood genomic DNA extraction kit) were selected to extract diatom DNA from lung tissue and water sample of the same drowning case. The combination of mass ratio of glass beads with different sizes and vortex oscillation time was designed, and the optimal DNA extraction conditions were selected with the addition of glass beads oscillation. The extracted products of the conventional group and the modified group were directly electrophoretic and detected by diatom specific PCR. Finally, all the extracts were quantified by qPCR, and the Ct values of different groups were statistically analyzed.@*RESULTS@#When the frequency of vortex oscillation was 3 000 r/min, the optimal combination of DNA extraction was vortex oscillation for 4 min, and the mass ratio of large glass beads to small glass beads was 1∶1. The DNeasy PowerSoil Pro kit was used as a reference, and the Ct value of 10 mL water sample was greater than that of 0.5 g tissue. The Ct values of the other three kits used for plant DNA extraction decreased after the glass beads-vortex oscillation method was used, and the Ct values of the tissues before and after the improvement were statistically significant (P<0.05). The whole blood genomic DNA extraction kit used in this study could successfully extract diatom DNA, the extraction of water samples was close to DNeasy PowerSoil Pro kit, after the modified method was applied to tissue samples, the difference in Ct value was statistically significant (P<0.05). However, when the three kits were used to extract diatom DNA from water samples, Ct values before and after the improvement were only statistically significant in New Plant genomic DNA extraction kit group (P<0.05).@*CONCLUSIONS@#The improved glass bead-vortex oscillation method can improve the extraction efficiency of diatom DNA from forensic materials, especially from tissue samples, by plant and blood DNA extraction kits.

Correlation analysis between the judgment of medical damage liability disputes related to off-label drug use and evidence-based evidence / 中国药房

OBJECTIVE To explore wheth er there is a relationship between the judgment results of medical damage liability disputes related to off-label drug use and evidence-based evidence. METHODS By searching for medical damage liability disputes related to off-label drug use up to 2021 on pkulaw.cn ，documents were extracted to record objective factors ，subjective factors and judgment results ；whether there was evidence-based evidence was judged according to Off-label Drug Use List and Evidence-based Evaluation Standards for Off-label Drug Use of Guangdong Pharmaceutical Association ；univariate analysis was adopted to test the relationship between the judgment results and evidence-based evidence. RESULTS A total of 57 cases were included. Cases mainly occurred in the eastern China （63.2％）and tertiary hospitals （64.9％），the main appraisal agency was the appraisal center or institute（61.4％），and the most common type of off-label drug use was overdose drug use （45.6％）. Among the judgment results ， 23 cases（40.4％）of off-label drug use had a causal relationship with medical damage ，most of the responsibility of doctors was secondary responsibility （28.1％），and the actual compensation amount of the most cases were less than 100，000 yuan（54.4％）. There were 25 cases（43.9％）with evidence-based evidence. Univariate analysis found that for off-label drug use the claim amount of the case with evidence-based evidence was significantly higher than that of the case without evidence-based evidence （P＝ 0.040），and there was no significant correlation between evidence-based evidence and the actual compensation amount of the case （P＝0.741），causality determination （P＝0.256），liability type （P＝0.598）or appraisal agency （P≥0.260）. CONCLUSIONS There is no significant correlation between the judgment results of medical damage liability disputes related to off-label drug use and evidence-based evidence ，indicating that there may be certain differences between judicial trials and medical science. The off-label drug use should be regulated by establishing a complete off-label drug use management system and standardizing informed consent procedure for off-label drug use. 1610307322@pku.edu.cn

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.

Analysis of antibiotic use and rationality for children in primary healthcare institutions from Beijing / 中国药房

OBJE CTIVE To inv estigate the antibiotic use and rationality for children in community health service institutions from Beijing ，and to provide reference for promoting rational use of antibiotics in primary healthcare institutions. METHODS All the prescriptions for children from primary healthcare institutions in 2019 were extracted from prescription review system of community health service institutions in Beijing. The use of antibiotics was described according to the related indicators of the World Health Organization/International Network for Rational Use of Drug （WHO/INRUD）. The structure of antibiotics use was analyzed according to the anatomical therapeutic chemical （ATC）classification as well as the WHO AWaRe classification and diagnosis. RESULTS A total of 288 primary healthcare institutions and 10 422 prescriptions for children were included. The number of institutions in high-income areas ，middle-income areas and low-income areas were 119，80 and 89 respectively，and the number of prescriptions involved were 2 430，2 163 and 5 829 respectively，including 1 447 prescriptions involving antibiotics （13.9％）. Among 1 447 prescriptions，the rate of prescriptions involving combined use of antibiotics was 1.4％（20 pieces）；the rate of prescriptions involving antibiotics injection was 9.7％（141 pieces）；4.8％ antibiotics prescriptions were rated as unreasonable （69 pieces）. The three most commonly used antibiotics were the macrolides （40.2％），the second-generation cephalosporins （26.5％） and the third-generati on cephalosporins （23.4％）. The proportion of antibioti cs prescriptions from groups of access ，caution， reserve and not recommended were 9.1％，92.1％，0.3％，and 0， respectively. The rate of antibiotics prescriptions fortonsillitis was the highest （31.9％ ）. Among 69 irrationalantibiotics prescriptions ，main of them were irrational drug use （56 pieces，81.2％）. CONCLUSIONS The rate of antibiotics prescriptions for children in primary healthcare institutions from Beijing is lower than the standard of WHO antibiotics prescription rate （20.0％-26.8％），but the use rate of antibiotics at caution grade is too high.

Comparative study on establishing an immune tolerance model for allergic conjunctivitis in mice with different methods / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To establish an immune tolerance model for allergic conjunctivitis in newborn mice with different methods and observe the impact of environmental factors on allergic conjunctivitis in early life.METHOD: A total of 50 Balb/c newborn mice were randomly divided into blank control group, ovalbumin(OVA)+subcutaneous injection group, OVA+nebulized inhalation group, OVA+gastric group, ragweed pollen(RW)+subcutaneous injection group, RW+nebulized inhalation group, RW+gastric group, house dust mite(HDM)+subcutaneous injection group, HDM+nebulized inhalation group, HDM+intragastric group(n=5 animals/group). Except for the blank control group, mice in each group were individually exposed to the corresponding antigens to induce immune tolerance early in life and stimulated with the corresponding antigens in adulthood. The ocular surface was visualized by anterior segment photography. The relative expression level of conjunctival RANTES and IL-17 mRNA was measured by RT-qPCR and serum IL-17 concentration was measured by ELISA.RESULTS: Compared with the blank control group, the relative expression level of conjunctiva IL-17 mRNA in RW+gastric group was the highest, and it was the lowest in RW+subcutaneous group(all P&#x003C;0.05). The relative expression level of conjunctiva RANTES mRNA was the highest in RW+gastric group(P&#x003C;0.001). Compared with the blank control group, the serum concentration of IL-17 was increased in all treatment groups except OVA+nebulizer group and RW+subcutaneous group(P&#x003C;0.05).CONCLUSION: The immune tolerance of allergic conjunctivitis induced by subcutaneous injection of antigen was the most suitable method in the early life of mice.

Research progress on effects of high altitude hypoxia environment on antiepileptic drugs / 中国药理学通报

Hie high altitude hypoxic environment affects the pharmacokinetic process of rlnjgs by changing the body's gastrointestinal emptying rate, organ blood flow, drug plasma protein binding rate, dnjg metabolizing enzymes and transporter expression.Epilepsy is a brain disease that requires long-term medication.Most anti-epileptic drugs have a low therapeutic index and a narrow range of effective blood drug concentrations.'Ilierapeu- tic dnjg monitoring (TDM) is commonly used clinically to find the best individualized medication method for antiepileptic dnjgs.rI1iis article summarizes the commonly used anti-epileptic dnjgs and their treatment windows in clinical practice, and analyzes the influence of the pharmacokinetics of anti-epileptic dnjgs in the high altitude hypoxic environment, so as to provide reference for the clinical use of anti-epileptic drugs at high altitude.

Effects of altitude hypoxia on cerebral blood distribution of sodium valproate in mice / 中国药理学通报

Aim To investigate the effects of altitude hypoxia on serum sodium valproate eoncentration and eerebral blood distribution.Methods Male mice were divided into control group and plateau group.Each group was given sodium valproate orally and intrave¬nously, respectively.UFLC-MS/MS was used to deter¬mine the concentration of sodium valproate in plasma and brain, and Western blot was used to detect the ex¬pression of P-gp in BBB.Results Compared with the control group, the ratio of brain/blood drug concentra¬tion in plateau group was up-regulated by 44.0% , 57.9% , 176.8% and 184.5% at 10, 30, 60 and 120 min, respectively.The ratio of brain/blood drug con-centration increased by 33.9% , 50.6% and 125.6% at 60 min, 120 min and 240 min in plateau group, re¬spectively.Compared with the control group, the ex¬pression of P-gp protein in BBB of mice in altitude group was significantly down-regulated by 58.46% (P < 0.05 ).Conclusions Compared with the control group, the brain/blood drug concentration ratio of val¬proic acid increases in high altitude hypoxia environ¬ment.Meanwhile, it is found that P-gp expression lev-el decreased in the brain mierovessels of mice under high altitude hypoxia environment, and the cerebral and blood distribution of valproic acid in mic increases in high altitude hypoxia environment.

Exosomes Derived from Hydroquinone-transformed Human Bronchial Epithelial Cells Inhibited Recipient Cell Apoptosis by transferring miR-221 / 生物医学与环境科学（英文）

Objective@#Although benzene is a confirmed environmental carcinogen, the mechanism of its carcinogenicity remains largely unclear. The suggested oncogene, miR-221, is elevated and plays important roles in various tumors, but its role in benzene-induced carcinogenesis remains unknown.@*Methods@#In the present study, we constructed hydroquinone (HQ, a representative metabolite of benzene with biological activity)-transformed malignant cell line (16HBE-t) and analyzed the level of miR-221 in it with qRT-PCR. Exosomes from 16HBE-t cells incubated with or without an miR-221 inhibitor were isolated by ultracentrifugation, characterized by transmission electron microscopy and laser scanning confocal microscope, and then transfected into 16HBE cells. The effects of exosomal miR-221 on apoptosis induced by HQ in recipient cells were determined using flow cytometry.@*Results@#The amount of miR-221 in 16HBE-t was significantly increased compared with controls. When recipient cells ingested exosomes derived from 16HBE-t, miR-221 was increased, and apoptosis induced by HQ was inhibited. Blocking miR-221 in 16HBE-t using an inhibitor did not significantly alter miR-221 or apoptosis in recipient cells.@*Conclusion@#Exosomal miR-221 secreted by 16HBE-t inhibits apoptosis induced by HQ in normal recipient cells.

Systematic Review of Health and Economic Burden Caused by Antibiotic Resistance in China / 中国药房

OBJECTIVE：To provide scientific basis for evaluating the burden caused by antibiotic resistance （AbR）and reference for policy making on crubing AbR in China. METHODS ：Databases including CNKI ，Wanfang database ，VIP，PubMed， Scopus，Medline and EconoLite from Jan. 1st 2016 to Aug. 10th 2020 were searched to collect studies on burden caused by AbR in China . After independent literature screening anddata extraction ，Newcastle-Ottawa scale （NOS）was used to evaluate the literature quality ，and a descriptive analysis was conduced to evaluate the health and economic burden caused by AbR. RESULTS ：A total of 27 Chinese and English literatures were included. The NOS scores of i ncluded literatures were 4-6，and all of them were retrospective case-control study ； the patients were divided into case group （resistance infection ） and control group （susceptible infection or non-infection ）； mortality，length of stay and medical expenditure were commonly applied as the measurement indexes. In the included studies ，the mortality of patients infected with AbR bacteria was 0.7-12.0 times that of patients infected with susceptible bacteria ；the mean or medium value of total length of stay was 0.9-2.5 times that of patients infected with susceptible bacteria ；the mean or medium of total medical expenditure was 1.0-2.7 times that of patients with susceptible bacteria infection. The differences in these indicators were greater between patients infected with AbR infections and those without becterial infections. CONCLUSIONS ：Bacterial drug resistance could increase the health and economic burden. However ，the existing relevant studies were mainly single center researches，the sample representation was insufficient ；the research design did not adjust for time-dependent bias ；the repeatability was low ，and the perspective of evalution was limited. It is urgent to carry out multicenter studies with higher quality to comprehensively evaluate the health and economic burden caused by AbR in China.

Discussing tuina for atlantoaxial subluxation in adults based on the theory of 'tendon-bone balance' / 针灸推拿医学（英文版）

According to Chinese medicine, the atlantoaxial joint is a composite joint composed of tendons and bones, and the stability of the joint depends on the 'tendon-bone balance' involving tendons, ligaments, atlas and axis. Multiple causes of 'tendon off-position, joint subluxation' will lead to joint 'tendon-bone imbalance', which will evolve into atlantoaxial subluxation (AAS), endangering human health. Chinese therapeutic massage (tuina) is a very effective treatment for AAS in adults, but conventional manipulations are prone to ineffectiveness or accidents due to neglect of the causal relationship of the 'tendon-bone imbalance' and inappropriate manipulations. Compared with conventional manipulations, the rational choice of modified manipulations under the guidance of 'tendon-bone balance' theory is more effective and less risky, and more worthy of clinical promotion. From the 'tendon-bone balance' theory, we considered the shortcomings of conventional manipulations, and introduced several modified manipulations that have their own strengths in 'tendon smoothing' and 'bone setting', in order to provide new ideas for treatment of AAS in adults.

Analysis of Provincial Antibiotic Classification Management Lists in China / 中国药房

OBJECTIVE：To provide re ference for scientific management and rational use of antibiotics. METHODS ：Provincial antibiotic classification management lists were retrieved from official websites of provincial health administrative departments ， CNKI and other search engines from Apr. 2012 to Mar. 2020. The difference and adjustment of those lists were analyzed descriptively. RESULTS & CONCLUSIONS ： Since April 2012， 30 provinces released provincial antibiotic classification management lists ，among which only 10 provinces updated the lists. In the provincial classification management lists ，the list of Jiangsu included the most antibiotics （208 kinds），that of Xinjiang involved the least （101 kinds）. Among the 253 antibiotics included in the provincial lists ，134 antibiotics had two management levels ，and 19 antibiotics had three management levels. The 10 antibiotics with the most times of adjustment in the provincial lists mainly include nitimidazoles ，β-lautam compound preparations and quinolones. There was the phenomenon that the same antibiotics were simultaneously included or withdrawn from the lists ，and the grading management level was increased or decreased in the provincial adjustment. Provincial classification management lists updated slowly in China ，and the quantity and classification of drugs selected in the list were quite different. It is suggested that provincial health administrative departments should continuously optimizeand improve classification management list of antibiotics ， and form a long-term mechanism of dynamic adjustment of list and inter-provincial evidence sharing ，so as to promote the rational clinical use of antibiotics ，and curb bacterial resistance.