ObjectiveTo explore the mechanism by which Yizhi Qingxin prescription improves mitochondrial dysfunction in Alzheimer's disease （AD） through regulating mitochondrial Ca²⁺ homeostasis and kinetic balance based on the protein kinase A （PKA）/calcineurin （CaN） signaling pathway. MethodsSixty three-month-old amyloid precursor protein （APP）/presenilin 1 （PS1） double transgenic mice were randomly divided into a model group， a donepezil group（0.65 mg·kg^-1）， a low-dose Yizhi Qingxin prescription group （YQF-L，2.6 g·kg^-1）， a medium-dose Yizhi Qingxin prescription group （YQF-M，5.2 g·kg^-1）， and a high-dose Yizhi Qingxin prescription group （YQF-H，10.4 g·kg^-1）， with 12 mice in each group. Twelve C57BL/6J mice with the same genetic background served as a normal group. Each treatment group received gavage administration daily， with the model and normal groups receiving equal volume of physiological saline. Intervention continued for 12 consecutive weeks. The learning and memory abilities of the mice were assessed using the novel object recognition （NOR） and Morris water maze （MWM） tests. Hematoxylin-eosin （HE）/Nissl staining was used to observe histopathological changes in the hippocampus. Transmission electron microscopy （TEM） was used to observe mitochondrial ultrastructure. Fluo-4 acetoxymethyl ester （Fluo-4 AM） Ca²⁺ probe was used to measure intracellular Ca²⁺ concentration in brain tissue. Western blot was used to determine the protein expression of PKA， CaN， sodium/calcium/lithium exchanger （NCLX）， mitochondrial calcium uniporter （MCU）， calmodulin （CaM）， dynamin-related protein 1 （Drp1）， and phosphorylated dynamin-related protein 1 （serine 637 site） ［p-Drp1（S637）］ in the hippocampus. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to measure the expression of PKA， CaN， CaM， NCLX， MCU， and Drp1 mRNAs. ResultsCompared with those in the normal group， the recognition index （RI） of the model group decreased （P0.01）， and the number of crossings through the original platform area， the duration of stay in the target quadrant， and the distance were reduced （P0.01）. The protein expression of PKA， NCLX， and p-DRP1 （ser637） significantly decreased （P0.05）， and the mRNA expression of PKA and NCLX significantly decreased （P0.05）. The escape latency （EL） was prolonged （P0.05）， and the intracellular Ca²⁺ level significantly increased （P0.01）. The protein expression of CaN， CaM， MCU， and Drp1， as well as the mRNA expression of CaN， MCU， and Drp1， significantly increased （P0.05）. After intervention with Donepezil and Yizhi Qingxin prescription， compared with that in the model group， the RI of the treatment group significantly increased （P0.05）， and the number of crossings through the platform and the duration of stay in the target quadrant significantly increased （P0.05）. The protein expression of PKA， NCLX， and p-Drp1 （ser637） and the mRNA expression of PKA and NCLX significantly increased （P0.05）. On the 4th and 5th days， the EL was shortened （P0.05）， and the intracellular Ca²⁺ level decreased （P0.05）. The protein expression of CaN， CaM， MCU， and Drp1 and the mRNA expression of CaN， MCU， and Drp1 significantly decreased （P0.05）. ConclusionYizhi Qingxin prescription regulates the PKA/CaN pathway， upregulates the expression of PKA， NCLX， and p-Drp1 （ser637） proteins， reduces the expression of CaN， CaM， MCU， and Drp1 proteins， and regulates Ca²⁺ homeostasis and mitochondrial dynamic balance， thereby enhancing the spatial learning and memory abilities of AD mice.

ObjectiveTo explore the mechanism by which Yizhi Qingxin prescription improves mitochondrial dysfunction in Alzheimer's disease （AD） through regulating mitochondrial Ca²⁺ homeostasis and kinetic balance based on the protein kinase A （PKA）/calcineurin （CaN） signaling pathway. MethodsSixty three-month-old amyloid precursor protein （APP）/presenilin 1 （PS1） double transgenic mice were randomly divided into a model group， a donepezil group（0.65 mg·kg^-1）， a low-dose Yizhi Qingxin prescription group （YQF-L，2.6 g·kg^-1）， a medium-dose Yizhi Qingxin prescription group （YQF-M，5.2 g·kg^-1）， and a high-dose Yizhi Qingxin prescription group （YQF-H，10.4 g·kg^-1）， with 12 mice in each group. Twelve C57BL/6J mice with the same genetic background served as a normal group. Each treatment group received gavage administration daily， with the model and normal groups receiving equal volume of physiological saline. Intervention continued for 12 consecutive weeks. The learning and memory abilities of the mice were assessed using the novel object recognition （NOR） and Morris water maze （MWM） tests. Hematoxylin-eosin （HE）/Nissl staining was used to observe histopathological changes in the hippocampus. Transmission electron microscopy （TEM） was used to observe mitochondrial ultrastructure. Fluo-4 acetoxymethyl ester （Fluo-4 AM） Ca²⁺ probe was used to measure intracellular Ca²⁺ concentration in brain tissue. Western blot was used to determine the protein expression of PKA， CaN， sodium/calcium/lithium exchanger （NCLX）， mitochondrial calcium uniporter （MCU）， calmodulin （CaM）， dynamin-related protein 1 （Drp1）， and phosphorylated dynamin-related protein 1 （serine 637 site） ［p-Drp1（S637）］ in the hippocampus. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to measure the expression of PKA， CaN， CaM， NCLX， MCU， and Drp1 mRNAs. ResultsCompared with those in the normal group， the recognition index （RI） of the model group decreased （P0.01）， and the number of crossings through the original platform area， the duration of stay in the target quadrant， and the distance were reduced （P0.01）. The protein expression of PKA， NCLX， and p-DRP1 （ser637） significantly decreased （P0.05）， and the mRNA expression of PKA and NCLX significantly decreased （P0.05）. The escape latency （EL） was prolonged （P0.05）， and the intracellular Ca²⁺ level significantly increased （P0.01）. The protein expression of CaN， CaM， MCU， and Drp1， as well as the mRNA expression of CaN， MCU， and Drp1， significantly increased （P0.05）. After intervention with Donepezil and Yizhi Qingxin prescription， compared with that in the model group， the RI of the treatment group significantly increased （P0.05）， and the number of crossings through the platform and the duration of stay in the target quadrant significantly increased （P0.05）. The protein expression of PKA， NCLX， and p-Drp1 （ser637） and the mRNA expression of PKA and NCLX significantly increased （P0.05）. On the 4th and 5th days， the EL was shortened （P0.05）， and the intracellular Ca²⁺ level decreased （P0.05）. The protein expression of CaN， CaM， MCU， and Drp1 and the mRNA expression of CaN， MCU， and Drp1 significantly decreased （P0.05）. ConclusionYizhi Qingxin prescription regulates the PKA/CaN pathway， upregulates the expression of PKA， NCLX， and p-Drp1 （ser637） proteins， reduces the expression of CaN， CaM， MCU， and Drp1 proteins， and regulates Ca²⁺ homeostasis and mitochondrial dynamic balance， thereby enhancing the spatial learning and memory abilities of AD mice.

Objective To observe the effects of Renshen Yimai Prescription on oxidative stress and vascular aging in ApoE-/-mice;To explore its mechanism of intervention in vascular aging.Methods Forty ApoE-/-mice were divided into model group,Western medicine group(rosuvastatin,2.6 mg/kg),TCM low-and high-dosage group(Renshen Yimai Prescription,4.29,8.58 g/kg),with 10 mice in each group.Another 10 C57BL/6J mice were set as normal group.A vascular aging model was established by ApoE-/-mice fed with a Western diet.Each medication group was given corresponding drugs by gavage for 12 consecutive weeks,the normal group and model group were given equivalent volume of pure water.HE staining and Masson staining were used to observe the morphological changes of aortic tissue,and ox-LDL content in serum was detected by ELISA,the contents of ROS,GSH,GPX and NAD+in serum were detected by colorimetric method,the expressions of SIRT1,p53,p21 and NOX4 protein in aortic tissue were detected by Western blot.Results Compared with the normal group,the model group mice showed significant fat deposition in the aorta,thickening of the intima and media,a significant decrease in elastic fibers,and an increase in collagen fibers;the serum contents of ox-LDL and ROS significantly increased(P<0.01),while the contents of GSH,GPX and NAD+significantly decreased(P<0.01);the expression of SIRT1 protein in the aortic tissue significantly decreased(P<0.05),the expressions of p21 and p53 protein significantly increased(P<0.01,P<0.05).Compared with the model group,a small amount of lipid deposition was observed in the intima of aorta in each medication group,with clearer membrane structures in each layer and reduced collagen fiber;the serum contents of ox-LDL and ROS in each medication group were significantly decreased(P<0.01),while the GSH content significantly increased(P<0.05,P<0.01),the NAD+content in TCM low-dosage group significantly increased(P<0.05);the expressions of p21 and NOX4 protein in aortic tissue of the TCM high-dosage group significantly increased(P<0.05,P<0.01).Compared with the Western medicine group,the TCM high-dosage group showed a significant decrease in ROS content(P<0.01)and a significant decrease in p53 protein expression(P<0.05).Compared with the TCM low-dosage group,the TCM high-dosage group showed a significant decrease in p21 protein expression(P<0.01)and a significant increase in NOX4 protein expression(P<0.01).Conclusion Renshen Yimai Prescription may reduce vascular endothelial damage by regulating oxidative stress levels and related protein expression,thereby playing a role in improving vascular aging.

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.

OBJECTIVE To provide reference and suggestions for dynamic adjustment of classification management lists for clinical use of antibiotics and the promotion of rational use of antibiotics. METHODS The latest version of provincial classification management lists for clinical use of antibiotics were aggregated into the “national list”， which was compared with 2021 WHO AWaRe classification list of antibiotics （hereinafter referred as to “AWaRe classification list”） to make a descriptive statistical analysis about the number of different classes of antibiotics in the two lists and their differences. RESULTS Based on the different classification principles， 262 kinds of antibiotic preparations in the national list were classified into non-restricted （84）， restricted （83） and highly-restricted classes （95）， and 258 kinds in the AWaRe classification list were classified into access （87）， watch （142） and reserve classes （29）； 182 kinds of antibiotic preparations were both included in the two lists. In the national list， among the non-restricted antibiotic preparations， 36 kinds belonged to access class， 30 belonged to watch class and 1 belonged to reserve class； among restricted antibiotic preparations， 7 belonged to access class， 46 kinds belonged to watch class and 3 belonged to reserve class； among highly-restricted antibiotic 82805019。E-mail：yyy211anne@163.com preparations， 9 belonged to access class， 35 belonged to watch class and 15 kinds belonged to reserve class. Among them， 91 kinds of antibiotic preparations were not recommended by WHO （20 kinds） or not included in the AWaRe classification list （71 kinds）. CONCLUSIONS The classification methods of two lists are different in classification principles and grading of some similar drugs. The classification management list of antibiotics is one of the key points of antibiotics management， more research is needed in the future to provide sufficient evidence for optimizing antibiotics classification management.

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.

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.

Objective To explore the influence of excessive PTEN expression to fibroblast cycle and collagen secretion induced by LPS.Methods Normal skin fibroblast in the patient with hyperplastic scar were cultured in vitro.When the primary culture was close to 80% fusion,the digestive passage was performed,cultured to the third generation.LPS(0.5 μg/mL) was adopted to stimulate the third generation of normal skin fibroblasts.Defective adenovirus carrying PTEN gene was transfected to the third passage fibroblasts after LPS stimulation.Flow cytometer was adopted to detect the cell cycle.ELISA method was adopted to detect the secreted collagen amont.Results Excessive PTEN expression could inhibit the increase of G2M cell cycle induced by LPS.LPS stimulation could increase the secretion of collagen in skin fibroblasts,yet excessive PTEN expression could inhibit the secretion of collagen induced by LPS.Conclusion LPS could increase the amont of fibroblasts on G2M cell cycle and secretion of collagen,yet excessive PTEN expression can inhibit the effect.

Humans ; Lymphoma ; diagnosis ; therapy ; Molecular Targeted Therapy

Objective To explore the application of nursing intervention model based on motivational stimulation in glaucoma patients.Methods A total of 120 glaucoma patients selected from January 2014 to December 201 4 in our hospital were randomly divided into experimental group and control group on average. Patients in experimental group received nursing intervention based on motivational stimulation,while patients in control group received routine nursing care.Treatment compliance after nursing,average intraocular pressure, cup-to-disc ratio of optic nerve,mean defect and quality of life were compared between two groups.Results The ratio of treatment compliance in experimental group was significantly higher than the ratio in control group (P <0.05).Average intraocular pressure,cup-to-disc ratio and mean defect in experimental group were significantly lower than those in control group (P <0.05).Quality of life score in experimental group (75.95 ±7.52)was higher than (65.77 ±8.52)in control group (P <0.05).Conclusions Nursing intervention model based on motivational stimulation could increase the ratio of treatment compliance so as to achieve better disease control and improve life quality in glaucoma patients.