Mechanism of Yishen Tongluo Prescription in Inhibiting Endoplasmic Reticulum Stress and Improving Apoptosis of Renal Tubular Epithelial Cells Based on PERK/ATF4/CHOP / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Yishen Tongluo prescription （YSTLP） on apoptosis of renal tubular epithelial cells and explore the mechanism based on endoplasmic reticulum stress pathway of protein kinase R-like endoplasmic reticulum kinase （PERK）/activating transcription factor 4 （ATF4）/transcription factor C/EBP homologous protein （CHOP）. MethodThe db/db mice were randomly divided into model group， valsartan group （10 mg·kg-1）， and low， middle， high-dose YSTLP groups （1， 2.5， 5 g·kg-1）. Samples were collected after eight weeks of drug intervention. In addition， db/m mice in the same litter served as the control group. Human renal tubular epithelial cells （HK-2） were cultured in vitro and divided into the control group， advanced glycated end-product （AGE） group， and AGE + low， middle， and high-dose YSTLP groups （100， 200， 400 mg·L-1）. TdT-mediated dUTP nick end labeling （TUNEL） staining was used to detect the apoptosis rate of HK-2 cells. Methylthiazolyldiphenyl-tetrazolium bromide （MTT） assay was conducted to detect the viability of HK-2 cells. Calcium fluorescence probe staining and luciferase reporter gene method were adopted to detect the luciferase activity of folded protein response element （UPRE） and endoplasmic reticulum stress. Immunohistochemical （IHC） analysis was carried out to measure the protein expressions of phosphorylated PKR （p-PERK）， CHOP， and ATF4. Real-time polymerase chain reaction （Real-time PCR） was used to measure the mRNA expression levels of CHOP and X-box binding protein 1 （XBP1） in mouse kidney and HK-2 cells. Western blot was used to detect the protein expression level of p-PERK， PERK， CHOP， ATF4， B-cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax）， and cleaved Caspase-3 in mouse kidney and HK-2 cells. ResultIn the cellular assay， HK-2 cell viability was significantly reduced， and the apoptosis rate was elevated in the AGE group compared with the control group （P<0.01）. The mRNA and protein expression levels of apoptosis-related factor Bcl-2 were significantly reduced （P<0.01）， and those of Bax were significantly increased （P<0.01）. The protein expression level of cleaved Caspase-3 was significantly increased （P<0.01）. Compared with the AGE group， YSTLP administration treatment resulted in elevated cell viability and reduced apoptosis rate （P<0.01）. The mRNA and protein expression levels of Bcl-2 were significantly elevated in a time- and dose-dependent manner （P<0.01）， and those of Bax were significantly reduced in a time- and dose-dependent manner. The protein expression level of cleaved Caspase-3 was significantly reduced in a time- and dose-dependent manner （P<0.01）. The intracellular Ca2+ imbalance and UPRE luciferase fluorescence intensity were increased in the AGE group compared with the control group （P<0.01）. The mRNA levels of endoplasmic reticulum stress-related factors CHOP and XBP1 were significantly increased （P<0.01）， and the protein expression levels of p-PERK， CHOP， and ATF4 were significantly increased （P<0.05）. Compared with the AGE group， YSTLP effectively improved intracellular Ca2+ imbalance in HK-2 cells and decreased UPRE luciferase fluorescence intensity in a dose-dependent manner （P<0.01）. It reduced the mRNA levels of endoplasmic reticulum stress-related factors CHOP and XBP1 （P<0.01） and the protein expression levels of intracellular p-PERK， CHOP， and ATF4 in a dose- and time-dependent manner （P<0.01）. In animal experiments， the protein expression level of Bcl-2 was significantly reduced（P<0.01）， and that of cleaved Caspase-3 and Bax was significantly increased in the model group compared with the control group （P<0.05）. The protein expression level of Bcl-2 was dose-dependently elevated， and that of cleaved Caspase-3 and Bax was dose-dependently decreased in the YSTLP groups compared with the model group （P<0.01）. Compared with the control group， the mRNA expression levels of CHOP and XBP1 were significantly elevated in the model group （P<0.05， P<0.01）， and the protein expression levels of p-PERK， CHOP， and ATF4 were significantly increased （P<0.05）. Compared with the model group， YSTLP significantly decreased the mRNA expression levels of CHOP and XBP1 （P<0.01） and the protein expression levels of p-PERK， CHOP， and ATF4 （P<0.01）. ConclusionYSTLP can effectively inhibit endoplasmic reticulum stress and improve apoptosis of renal tubular epithelial cells， and its mechanism may be related to the regulation of the PERK/AFT4/CHOP pathway.

Effect and mechanism of Zexie Decoction in promoting white adipose tissue browning/brown adipose tissue activation based on GLP-1R/cAMP/PKA/CREB pathway / 中国中药杂志

This study investigated the mechanism of Zexie Decoction(ZXD) in promoting white adipose tissue browning/brown adipose tissue activation based on the GLP-1R/cAMP/PKA/CREB pathway. A hyperlipidemia model was induced by a western diet(WD) in mice, and the mice were divided into a control group, a model group(WD), and low-, medium-, and high-dose ZXD groups. An adipogenesis model was induced in 3T3-L1 cells in vitro, and with forskolin(FSK) used as a positive control, low-, medium-, and high-dose ZXD groups were set up. Immunohistochemistry and immunofluorescence results showed that compared with the WD group, ZXD promoted the expression of UCP1 in white and brown adipose tissues, and also upregulated UCP1, CPT1β, PPARα, and other genes in the cells. Western blot analysis showed a dose-dependent increase in the protein expression of PGC-1α, UCP1, and PPARα with ZXD treatment, indicating that ZXD could promote the white adipose tissue browning/brown adipose tissue activation. Hematoxylin-eosin(HE) staining results showed that after ZXD treatment, white and brown adipocytes were significantly reduced in size, and the mRNA expression of ATGL, HSL, MGL, and PLIN1 was significantly upregulated as compared with the results in the WD group. Oil red O staining and biochemical assays indicated that ZXD improved lipid accumulation and promoted lipolysis. Immunohistochemistry and immunofluorescence staining for p-CREB revealed that ZXD reversed the decreased expression of p-CREB caused by WD. In vitro intervention with ZXD increased the protein expression of CREB, p-CREB, and p-PKA substrate, and increased the mRNA level of CREB. ELISA detected an increase in intracellular cAMP concentration with ZXD treatment. Molecular docking analysis showed that multiple active components in Alismatis Rhizoma and Atractylodis Macrocephalae Rhizoma could form stable hydrogen bond interactions with GLP-1R. In conclusion, ZXD promotes white adipose tissue browning/brown adipose tissue activation both in vivo and in vitro, and its mechanism of action may be related to the GLP-1R/cAMP/PKA/CREB pathway.

Effects of SARS-CoV-2 on male reproductive system and sexual health / 现代泌尿外科杂志

SARS-CoV-2 may have potential effects on the male reproductive system. Evidence has shown that SARS-CoV-2 is not likely to transmit through sexual intercouse. However, male infected with SARS-CoV-2 may experience sexual dysfunction, semen quality decline, testicular damage and abnormal sex hormones. The extent and duration of these damages are still unclear, and further multidimensional research is necessary.

Hemodynamic characteristics of proper hepatic artery and portal vein in patients after splenectomy and devascularization / 临床肝胆病杂志

Objective To investigate the characteristics of hemodynamics of proper hepatic artery and portal vein after splenectomy and devascularization. Methods The clinical data of 103 patients with portal hypertension who underwent splenectomy and devascularization in the Capital Medical University-Affiliated You'an Hospital from April 2014 to February 2019 were retrospectively analyzed. Their hemodynamics of the proper hepatic artery and portal vein were recorded before and 1 week-, and 1-, 3-, 6-, 12-, and 24-months after surgery and then statistically analyzed. Continuous data with normal distribution were compared using paired-samples t test. Results Compared with the before surgery data, the portal vein diameter, portal vein flow, maximum velocity, and average velocity of the portal vein were all significantly decreased 1-week-, 1-, 3-, 6-, 12-, and 24-months after splenectomy and devascularization (all P < 0.05). The blood flow and velocity of the proper hepatic artery was significantly increased 1 week and 1 month after surgery (all P < 0.05); however, there was no statistically significant difference at 3-, 6-, 12-, and 24-months after surgery. Conclusion The diameter, flow, and flow velocity of the portal vein after splenectomy and devascularization were significantly lower than those before surgery, whereas the proper hepatic artery flow and flow velocity were increased within 1 month after surgery and then returned back to the pre-surgery levels 3 months after surgery.

Self-reported quality of life in patients with coronary heart disease and analysis of the associated factors / 中华内科杂志

Objective: To investigate the quality of life and associated factors in patients with coronary heart disease (CHD) in China. Methods: A cross-sectional study of 25 provinces and cities in China was performed from June to September 2020. A questionnaire was used to collect the socio-demographic and clinical information of patients with CHD, while the European Five-dimensional Quality of Life Scale (EQ-5D) was used to assess the quality of life. Multiple linear regression model was performed to analyze the associated factors. Results: The median age of the 1 075 responders was 60 (52, 67) years, and 797 (74.1%) were men. The EQ-5D and EQ-VAS indices were 0.7 (0.5, 0.8) and 60.0 (40.0, 80.0). Among the five dimensions in the quality of life scale, the frequency of anxiety/depression was the highest (59.8%), while problems in self-care was the lowest (35.8%). In the multiple linear regression model, female, increasing age, obesity, comorbidity(ies), anxiety/depression, social media channels, and receiving the CABG therapy were associated with the lower EQ-5D index (all P<0.05). In addition, increasing age, obesity, comorbidity (ies), depression, anxiety and depression, social media channels, and receiving the CABG therapy were associated with lower EQ-VAS index (all P<0.05). Conclusion: Over half of the patients with CHD in China have a low quality of life, which is related to gender, age, obesity, treatment pathway, the presence or absence of comorbidity (ies), and psychological state. In addition to managing the adverse effects of traditional socio-demographic factors on the quality of life, clinical practices should pay attention to the psychological state of patients. Moreover, establishing a WeChat group for doctor-patient communication could improve the quality of life of CHD patients.

Multidisciplinary team strategy for treatment of diabetic foot / 中华普通外科杂志

Objective:To explore the team construction and treatment strategy of the Diabetic Foot-Multidisciplinary Team.Methods:The clinical data of 19 patients with severe ischemic diabetic foot treated by our Diabetic Foot-Multidisciplinary Team Center from Apr 2021 to Mar 2022 were collected, and the overall amputation rate, above-ankle major amputation rate, minor amputation rate and mortality, Diabetic Foot-Multidisciplinary Team consultation discipline participation rate and treatment participation degree were retrospectively analyzed.Results:Nineteen patients (15 males and 4 females) were enrolled, aged 26 to 94 (68.6±14.2). All were with severe ischemic diabetic foot ulcer:Rutherford grade 5 or up and dysfunction in 2 or more organs. Complications included arteriosclerosis obliterans of the lower extremities in 18 cases, heart diseases in 18, hypertension in 15, and renal insufficiencies in 10. The overall amputation rate was 36.8%, major amputation rate in 21.1%, minor amputation rate in 15.8%, and mortality rate was 15.8%. A total of 16 disciplines participated in Diabetic Foot-Multidisciplinary Team; the main participating disciplines were vascular surgery (19 times), endocrinology (12 times), and cardiology (11 times). The main treatment disciplines were vascular surgery (14 times), plastic surgery (3 times), and cardiology (2 times).Conclusion:For the diagnosis and treatment of diabetic foot, it is necessary to set up a multidisciplinary team as early as possible to control the causes of diabetic foot ulcer, prevent the recurrence of diabetic foot ulcer, reduce the mortality and amputation rate, and improve the quality of life of patients.

Study on the risk and countermeasure of prescription drugs sold online by drug retail enterprises / 中国药房

OBJECTIVE To analyze the risks of prescription drugs sold online by drug retail enterprises， and to provide countermeasures and suggestions for risk prevention and control of prescription drugs sold online. METHODS The risk hierarchy structure model of prescription drugs sold online by drug retail enterprises was constructed by using analytic hierarchy process. Multiple rounds of risk research and judgment were carried out on 123 pairs of evaluation indicators by using Delphi expert survey method. The normalized weight calculation and consistency test of risk judgment matrix were carried out to perform fuzzy quantitative research. RESULTS The risk of prescription dispensing and review （6.48%）， the risk of drug first and prescription later （5.48%）， the risk of rational drug use guidance （4.99%）， the risk of buying drugs by abnormal channel （4.97%）， the risk of “first diagnosis， non-chronic disease and non-common disease” （4.43%）， and the quality and safety risk of returned drugs （4.34%） and the application risk of regulatory technology （4.06%） were high risks； the overall risk of drug retail enterprises （chain） selling prescription drugs online was 38.67%， and the overall risk of drug retail enterprises （individual） selling prescription drugs online was 61.33%， with a difference of 22.66% between them. CONCLUSIONS There were 7 high-risk indicators for prescription drugs sold online by drug retail enterprises. Among them， the risk of prescription dispensing and review， the risk of drug first and prescription later， and the risk of rational drug use guidance are the top three high-risk points. The risk of prescription drugs sold online by drug retail enterprises （individual） is higher than that of drug retail enterprises （chain）. It is recommended that regulatory authorities focus on and regulate the prescription drugs sold online by drug retail enterprises （individual）， and encourage drug retail enterprises （chain） to establish a systematic online sales process for prescription drugs； for high-risk points of prescription drugs sold online， it is recommended that regulatory authorities and drug retail enterprises focus on it and take effective risk prevention and control measures to ensure the safe use of prescription drugs by the general public.

Roles of NG2 Glia in Cerebral Small Vessel Disease / 神经科学通报·英文版

Cerebral small vessel disease (CSVD) is one of the most prevalent pathologic processes affecting 5% of people over 50 years of age and contributing to 45% of dementia cases. Increasing evidence has demonstrated the pathological roles of chronic hypoperfusion, impaired cerebral vascular reactivity, and leakage of the blood-brain barrier in CSVD. However, the pathogenesis of CSVD remains elusive thus far, and no radical treatment has been developed. NG2 glia, also known as oligodendrocyte precursor cells, are the fourth type of glial cell in addition to astrocytes, microglia, and oligodendrocytes in the mammalian central nervous system. Many novel functions for NG2 glia in physiological and pathological states have recently been revealed. In this review, we discuss the role of NG2 glia in CSVD and the underlying mechanisms.

Research advances on polyglycine diseases / 中华神经科杂志

Nucleotide repeat expansion is one of the common causes for neurodegenerative disorders. Polyglycine diseases are a newly defined neuro- and muscle- degenerative disease spectrum characterized by CGG trinucleotide repeat expansions, generation and aggregation of aberrant polyglycine protein, and formation of intranuclear inclusions. To date, the aggregation of pathogenic polyglycine protein has been proved in fragile X-associated tremor/ataxia syndrome and neuronal intranuclear inclusion disease. In recent years, the case load of these diseases grows rapidly with the increasing awareness and developing genetic testing technologies. This article aims to systematically review the recent progress in polyglycine diseases, and probe into their pathogenic mechanisms as well as clinical concerns.

Communication obstacles between contracted family doctor team and the disabled / 中华全科医师杂志

Objective:To investigate the status quo of communication between contracted family doctor team and the disabled.Methods:Using convenience sampling, family doctor team members of 80 community health centers (CHCs) in Beijing were selected to participate in a questionnaire survey from April to June 2022. The questionnaire included the basic information of team members, the choice of communication methods and targets, the acquisition of communication knowledge and skills and so on.Results:A total of 365 team members participated in the survey. The most common type of disability was physical disability (78.08%,285/365). All participants met communication obstacles with disabled people in contracted health service, and hearing and speech disabilities were the most common (70.14%, 256/365). Only 13.42% (49/365) chose to directly communicate with the disabled themselves; 84.93% (310/365) used "increase the volume and slow down" method when communicating with the disabled, and 38.63% (141/365) chose "write and convey multiple messages at the same time". Most of participants (84.38%, 308/365) indicated the need for professional training in communication with persons with disabilities.Conclusion:There are communication obstacles between family doctor team members and the disabled during contracted services. More relevant professional training are urgently needed for contracted family doctor team to improve the abilities to communicate with the disabled.

Analysis of consecutive patient visits in a community health service station in Beijing / 中华全科医师杂志

Objective:To analyze consecutive patients visits in a community health service station in Beijing.Methods:The basic information and behavior of the patients who visited Sanliheerqu Health Service Station in Beijing Xicheng district from January 1, 2015 to December 31, 2019 were retrieved from the electronic health records. The visiting situation, the stratification of the number of visits, and the correlation between the basic information and the consecutive visit was analyzed.Results:A total of 4 696 patients visited 202 560 times during 2015 to 2019, of whom 1 162 were consecutive patients (24.7%) with a total of 100 083 visits (49.4%).The annual number of visits, the total number of visits and the number of consecutive visits all showed an upward trend during the five years.The top 5 reasons for consecutive visit were all chronic diseases (hypertension, type 2 diabetes, dyslipidemia, coronary heart disease, and stroke) with median annual visits of 11 to 18, and it was increasing with the year. The rates of incidental visits (1-3/year, 66/1 162, 5.7%) and continuous visits (4-26/year, 1 020/1 162, 87.8%) in 2015 were higher than those in other years; while the rates of frequent visits (27-52/year, 71/1 162, 6.1%) and very frequent visits (>52/year, 5/1 162, 0.4%) were lower. The rates of frequent visits (181/1 162, 15.6%) and very frequent visits (78/1 162, 6.7%) in 2019 were higher than those in other years (χ 2=182.40, P<0.001).Compared with the non-consecutive visit group, the proportion of women (38.1%,735/1 930) and overweight/obesity (39.6%, 777/1 960) in the consecutive visit group was higher (χ 2=36.09, 69.69, P <0.001). Conclusion:The consecutive visit rate of residents in this institution needs to be improved. The utilization rate of primary medical resources for patients with consecutive visit is high and the number of medical visits is on the rise. Gender and BMI of patients may be related to consecutive visit.

A qualitative study on the feasibility of contracted nursing services for disabled persons / 中华全科医师杂志

Objective:To investigate the feasibility of contracted nursing services for disabled persons.Methods:A qualitative study on the feasibility of contracted nursing services for disabled persons was conducted from August 2020 to October 2020 with the phenomenological method. Community nurses were selected with the purpose of sampling method from Yuetan and Baizhifang Community Health Service Centers in Beijing Xicheng District for semi-constructed interviews, and 12 community nurses were finally interviewed according to the principle of information saturation. The research team took field notes, audio recordings and transcriptions of the interviews, coded to refine the themes, and fed back with the respondents to confirm the accuracy of the themes.Results:All the interviewed nurses thought that the contents of basic medical and public health required by the Guidance manual of contracted services of family doctors for disabled persons (the manual) including basic documentation, appointments, pre-diagnosis and post-diagnosis services, home care, rehabilitation nursing guidance, referral services and extended nursing services for the disabled and their families could be completed. All interviewees said that the manual had a guiding role in contracted services for disabled persons. Eight interviewed nurses believed that the manual involved referral services and rehabilitation care, but the technical guidance content did not meet the actual work needs and it should be supplemented and improved; 9 interviewees pointed out that there was a lack of communication with various types of disabled people in service practice, especially for those with vision, hearing, mental disabilities and disabled children; 7 interviewees said that it the free home care for the disabled was not sustainable. Conclusion:The contracted nursing services for disabled persons are feasible and the manual has a guiding role for the practice,and some contents need to be added in the manual to further improve service capacity for disabled people.

Influencing factors of visits of residents to contracted family doctors in a Beijing community / 中华全科医师杂志

Objective:To analyze the influencing factors related to visiting rate of residents to contracted family doctors in a community health service center in Beijing.Methods:One thousand patients with contracted family doctor services who visited our center from January 2019 to December 2019 were selected for retrospective analysis. According to the corresponding visiting rate of contracted family doctors,patients were divided into low corresponding visiting rate, medium corresponding visiting rate and high corresponding visiting rate, and the influencing factors were analyzed.Results:Among the 1 000 patients, 481 (48.1%) were in the high corresponding visiting rate group, 342 (34.2%) in the middle corresponding visiting rate group, and 177 (17.7%) in the low corresponding visiting rate group. Univariate analysis showed that the corresponding visit rate was significantly associated with the age, marital status and educational level of patients, history of hypertension, the number of family doctor visits, the total visiting time and the consultation time per year (χ 2=12.55, 12.42, 7.69, 21.69, 253.97, 49.54, 9.07, all P<0.05). Multivariate logistic regression analysis showed that compared with the high corresponding visiting rate group, fewer of family doctor visits ( OR=0.68, 95 %CI: 0.58-0.78), lower education level( OR=0.65, 95 %CI: 0.46-0.92), history of hypertension ( OR=0.09, 95 %CI: 0.02-0.49), and 18-65 years old( OR=1.80, 95 %CI: 1.27-2.55) were the influencing factors for the low corresponding family doctor visiting rate(all P<0.05); while fewer of family doctor visits( OR=0.91, 95 %CI: 0.83-0.99),lower education level ( OR=0.74, 95 %CI: 0.55-0.98)and history of hypertension( OR=0.09, 95 %CI: 0.02-0.44)were the related factors of the medium corresponding visiting rate(all P<0.05). Conclusions:The visiting rate of patients to the contracted family doctor needs to be improved. The number of consultations of the contracted family doctor, educational background, history of hypertension, and age are the influencing factors of the corresponding visiting rate.

Protective Effect of Guilu Erxianjiao on Reproductive Injury in Diabetic Rats and Its Mechanism / 中国实验方剂学杂志

ObjectiveTo explore the effect of Guilu Erxianjiao on improving reproductive injury in diabetic rats and its possible mechanism. MethodFifty-three SD male rats were randomly divided into 5 groups， with 1 group as the normal group and the other 4 groups as the modeling groups. Rats in the modeling groups were fed with a high-fat diet combined with 30 mg·kg-1 streptozotocin （STZ） intraperitoneal injection to induce diabetes， with the random blood glucose >16.7 mmol·L-1 for 3 consecutive times as the criteria for inclusion in the model of diabetic reproductive injury. The rats with diabetic reproductive injury were then randomly divided into a model group， a Guilu Erxianjiao group （2 g·kg-1）， a Vitamin E group （0.03 g·kg-1）， and a Wuzi Yanzong pill group （0.6 g·kg-1） according to the blood glucose level. The rats were given the corresponding drug dose intragastric administration， once a day for 4 weeks， and their body weight and blood glucose were measured weekly. After 4 weeks， samples were collected for index determination. Morphological changes in testis and epididymis were observed by hematoxylin-eosin （HE） staining， and apoptosis of testis cells was observed by in situ end labeling （TUNEL） staining. Sperm concentration and motility were detected by the semen analyzer. Serum levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， and testosterone （T） were determined by enzyme-linked immunosorbent assay （ELISA）. The content of superoxide dismutase （SOD）， propylene glycol （MDA）， reactive oxygen species （ROS）， and glutathione peroxidase （GSH-Px） in the testicular tissue was determined by ELISA. The expressions of nuclear respiratory factor-2 （Nrf2）， heme oxygenase 1 （HO-1）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2 associated X protein （Bax） in the testicular tissue were detected by Western blot. ResultAs compared with the normal group， testicular tissue atrophy， decreased spermatogenic tubules， epididymal wall hyperplasia， and lumen stenosis were observed in the model group. Sperm concentration and motility decreased （P<0.01）， and serum levels of T， FSH， and LH decreased （P<0.01） in the model group. The content of ROS and MDA in the testis increased （P<0.01）， while that of SOD and GSH-Px decreased （P<0.01） in the model group. The expression of Bax increased （P<0.01）， and the expressions of Nrf2， HO-1， and Bcl-2 decreased （P<0.01） in the model group. As compared with the model group， the pathological changes in the testis and epididymis in the Guilu Erxianjiao group were improved to some extent. Sperm concentration and motility increased （P<0.05， P<0.01）. In the Guilu Erxianjiao group， serum levels of T and LH increased （P<0.05， P<0.01）， while FSH levels showed no significant difference. The content of ROS and MDA in the testis decreased （P<0.01）， while that of SOD and GSH-Px increased （P<0.01） in the Guilu Erxianjiao group. The expression of Bax decreased （P<0.01）， and the expressions of Nrf2， HO-1， and Bcl-2 increased （P<0.05， P<0.01） in the Guilu Erxianjiao group. ConclusionGuilu Erxianjiao improves the reproductive injury and sperm quality of diabetic rats to a certain extent， and the mechanism may be related to the improvement of oxidative stress and anti-apoptosis.

Protective Effect of Guilu Erxianjiao on Reproductive Injury in Diabetic Rats and Its Mechanism / 中国实验方剂学杂志

ObjectiveTo explore the effect of Guilu Erxianjiao on improving reproductive injury in diabetic rats and its possible mechanism. MethodFifty-three SD male rats were randomly divided into 5 groups， with 1 group as the normal group and the other 4 groups as the modeling groups. Rats in the modeling groups were fed with a high-fat diet combined with 30 mg·kg-1 streptozotocin （STZ） intraperitoneal injection to induce diabetes， with the random blood glucose >16.7 mmol·L-1 for 3 consecutive times as the criteria for inclusion in the model of diabetic reproductive injury. The rats with diabetic reproductive injury were then randomly divided into a model group， a Guilu Erxianjiao group （2 g·kg-1）， a Vitamin E group （0.03 g·kg-1）， and a Wuzi Yanzong pill group （0.6 g·kg-1） according to the blood glucose level. The rats were given the corresponding drug dose intragastric administration， once a day for 4 weeks， and their body weight and blood glucose were measured weekly. After 4 weeks， samples were collected for index determination. Morphological changes in testis and epididymis were observed by hematoxylin-eosin （HE） staining， and apoptosis of testis cells was observed by in situ end labeling （TUNEL） staining. Sperm concentration and motility were detected by the semen analyzer. Serum levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， and testosterone （T） were determined by enzyme-linked immunosorbent assay （ELISA）. The content of superoxide dismutase （SOD）， propylene glycol （MDA）， reactive oxygen species （ROS）， and glutathione peroxidase （GSH-Px） in the testicular tissue was determined by ELISA. The expressions of nuclear respiratory factor-2 （Nrf2）， heme oxygenase 1 （HO-1）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2 associated X protein （Bax） in the testicular tissue were detected by Western blot. ResultAs compared with the normal group， testicular tissue atrophy， decreased spermatogenic tubules， epididymal wall hyperplasia， and lumen stenosis were observed in the model group. Sperm concentration and motility decreased （P<0.01）， and serum levels of T， FSH， and LH decreased （P<0.01） in the model group. The content of ROS and MDA in the testis increased （P<0.01）， while that of SOD and GSH-Px decreased （P<0.01） in the model group. The expression of Bax increased （P<0.01）， and the expressions of Nrf2， HO-1， and Bcl-2 decreased （P<0.01） in the model group. As compared with the model group， the pathological changes in the testis and epididymis in the Guilu Erxianjiao group were improved to some extent. Sperm concentration and motility increased （P<0.05， P<0.01）. In the Guilu Erxianjiao group， serum levels of T and LH increased （P<0.05， P<0.01）， while FSH levels showed no significant difference. The content of ROS and MDA in the testis decreased （P<0.01）， while that of SOD and GSH-Px increased （P<0.01） in the Guilu Erxianjiao group. The expression of Bax decreased （P<0.01）， and the expressions of Nrf2， HO-1， and Bcl-2 increased （P<0.05， P<0.01） in the Guilu Erxianjiao group. ConclusionGuilu Erxianjiao improves the reproductive injury and sperm quality of diabetic rats to a certain extent， and the mechanism may be related to the improvement of oxidative stress and anti-apoptosis.

Content determination of four kinds of alkaloids in Uncaria by HPLC-MS-AIS / 四川精神卫生

ObjectiveTo determine the contents of four kinds of indole alkaloids （rhynchophylline， isorhynchophylline， corynoxeine， isocorynoxeine） in Uncaria by high-performance liquid chromatography-mass spectrometry-automatic internal standard （HPLC-MS-AIS）. MethodsChromatographic separation was performed using C18 column （3.0 mm×50 mm， 3.3 μm）， and the mobile phase， comprising 0.1% formic acid aqueous solution-acetonitrile （82∶18， V/V）， was eluted at a flow rate of 0.5 mL/min and column temperature of 30℃. Mass spectrometric detection was performed using an electrospray ionization source and positive multiple-reaction monitoring mode at a voltage capillary of 4 000 V. The mass-to-charge ratio （m/z） transition was 385.25/160.10 for rhynchophylline， 385.30/160.10 for isorhynchophylline， 383.25/160.15 for corynoxeine and 383.25/160.15 for isocorynoxeine， respectively. The injection volume was kept constant at 2 μL. ResultsThe linear concentration ranges of rhynchophylline， isorhynchophylline， corynoxeine and isocorynoxeine were 2.30~600.00 ng/mL （r=0.999 3）， 2.30~600.00 ng/mL （r=0.999 2）， 2.47~650.00 ng/mL （r=0.999 4） and 2.47~650.00 ng/mL （r=0.999 2）， respectively. The relative standard deviation （RSD） of precision and stability were all lower than 5.00%， the accuracy ranged from 92.40% to 104.10%， and the average recovery was 95.90%~104.60%. ConclusionHPLC-MS-AIS method is simple and accurate for the determination of four kinds of alkaloids in Uncaria， and can be used as a new method for quality control of Uncaria.

Development of a 2D-HPLC for simultaneous determination of rhynchophylline， isorhynchophylline， corynoxeine and isocorynoxeine / 四川精神卫生

ObjectiveTo develop a two-dimensional high-performance liquid chromatography （2D-HPLC） for simultaneous determination of the contents of four kinds of Uncaria alkaloids： rhynchophylline， isorhynchophylline， corynoxeine and isocorynoxeine. MethodsThe 2D-HPLC apparatus was comprised of a first chromatographic column in version Aston SC2 （3.5 mm×25 mm， 5 μm）， an intermediate column in version Aston SH C18 （3.5 mm×10 mm， 5 μm）， and an analytical column in version Aston SCB （4.6 mm×125 mm， 5 μm）. The mobile phase of the first and second liquid chromatography system were CAA-1 and mixed mobile phase （V BPI-1 basic mobile phase ∶ V MPI-1 mobile phase ∶ V OPI-1 organic mobile phase = 45∶14∶41）. The chromatographic parameters included a flow rate of 1.0 mL/min， a column temperature of 40℃， a wavelength of 254 nm， an injection volume of 500 μL and a detection time of 9.5 min. ResultsThe linear ranges of rhynchophylline， isorhynchophylline， corynoxeine and isocorynoxeine were 9.77~10 000.00 ng/mL （r=0.999 6）， 10.74~11 000.00 ng/mL （r=0.999 7）， 10.74~11 000.00 ng/mL （r=0.999 7）， 10.74~11 000.00 ng/mL（r=0.999 6）， respectively. The relative standard deviation （RSD） of precision， stability and repeatability were all less than 5.00%. The accuracy was 95.20%~104.01%， and the recovery rate was 93.63%~101.38%. ConclusionThe 2D-HPLC developed for simultaneous determination of four kinds of alkaloids in Uncaria is simple and accurate， which can be used as a new method for quality control of Uncaria.

Advance in clinical research of subcortical U fiber / 中华神经科杂志

Subcortical U fibers, also known as arcuate fiber, are kind of short connective fibers connecting adjacent brain gyrus. They located in the outermost layer of white matter, adjacent to the cortex. With the development of imaging, more and more attention has been paid to the differential diagnosis of subcortical U fibers in different white matter lesions. In this article, subcortical U fibers are reviewed from the aspects of definition, anatomy and physiology.

Effectiveness，Safety and Economy of Evolocumab in the Treatment of Hypercholesterolemia ：A Rapid Health Technology Assessment / 中国药房

OBJECTIVE：To rapidly evaluate the effectiveness ，safety and economy of evolocumab in the treatment of hypercholesterolemia so as to provide evidence-based reference for clinical drug selection and decision. METHODS ：Retrieved from PubMed，Cochrane Library ，CNKI，Wanfang database and HTA relative official website ，HTA reports ，systematic evaluation/ Meta-analysis and pharmacoeconomic studies about evolocumab alone or combined with standard plan versus standard plan or placebo or ezetimibe in the treatment of hypercholesterolemia were collected during the inception to Jan. 2020. Based on literature screening and data extraction ，HTA checklist ，system evaluation measurement tool AMSTAR- 2 scale，comprehensive healthy economic evaluation report standard scale were used to evaluate the quality of included HTA reports ，systematic evaluation/ Meta-analysis and pharmacoeconomic literatures. Quantitative description was performed for effectiveness and safety results ，and qualitative description was performed for economic evaluation results. RESULTS ：A total of 13 literatures were included ，involving 6 Meta-analysis and 7 economic studies. The quality of Meta-analysis literatures was low ，and the quality of economic research was good. In terms of effectiveness ，compared with placebo or ezetimibe ，evolocumab significantly reduced the levels of LDL-C ，TC， TG and VLDL-C ，the incidence of cardiovascular events ，myocardial infarction ，coronary ischemia and stroke ，while increased the level of HDL-C （P＜0.05）. There was no statisti cal significance in the risk of hospitalizatio n，cardiac mortality or cardiovascular disease mortality in patients with unstable angina pectoris between placebo and evolocumab （P＞0.05）. In terms ofsafety，there was no significant difference in the incidence of 6237545。E-mail：zhangxu1130@163.com any adverse events ，any treatment emergency adverse events and back pain ，musculoskeletal and connective tissue diseases between evolocumab and placebo （P＞0.05）. In terms of economy，additional use of evolocumab ，based on standard plan ，had a cost-effectiveness advantage for patients with high-risk atherosclerotic cardiovascular disease （ASCVD）whose blood lipids were still not up to standard. CONCLUSIONS ：Evolocumab has good effectiveness and safety in the treatment of hypercholesterolemia. For high-risk patients with ASCVD whose blood lipids are still not up to standard after standard plan ，evolocumab has certain economy and can be used as an alternative.

Combining scalp acupuncture with hyperbaric oxygen therapy improves functional recovery after cerebral infarction / 中华物理医学与康复杂志

Objective:To observe the effect of combining scalp acupuncture with hyperbaric oxygen on serum homocysteine and highly-sensitive c-reactive protein levels and functional recovery after cerebral infarction.Methods:A total of 101 survivors of cerebral infarction were divided randomly into a scalp acupuncture group ( n=33), a hyperbaric oxygen group ( n=34) and a combined treatment group ( n=34). All received routine treatment plus the appropriate supplementary treatment once a day for 10 days. The subjects were evaluated before the experiment as well as 10 and 90 days afterward. The National Institutes of Health′s stroke scale (NIHSS) was used to quantify neurological deficits and the Barthel Index quantified ability in the activities of daily living. Ninety days after the treatment, modified Rankin scale scores were also assigned. The levels of serum homocysteine (Hcy) and highly-sensitive c-reactive protein (hs-CRP) before and after 10 days of treatment were also compared among the 3 groups. Results:The average NIHSS and Barthel Index scores of all three groups had improved significantly after 10 days of treatment and the improvements persisted at the follow-up 3 months later. Both results were significantly better in the combined treatment group than in the scalp acupuncture group at the 90-day follow-up evaluation. The average Rankin score of the combined treatment group was lower at the last follow-up. Compared with before the intervention, the average Hcy of the scalp acupuncture group, the average hs-CRP of the hyperbaric oxygen group, as well as the average Hcy and hs-CRP of the combined treatment group were significantly lower after 10 days of treatment. Compared with the scalp acupuncture group, the average Hcy [(11.68±2.6) μmol/L] of the combined treatment group was significantly lower after the 10 days of treatment.Conclusions:Supplementing scalp acupuncture with hyperbaric oxygen therapy improves the long-term outcomes of cerebral infarction, reducing the level of serum Hcy.