Systematic evaluation of the efficacy and safety of intravenous human immunoglobulin combined with cyclophosphamide in the treatment of systemic lupus erythematosus / 中国药房

OBJECTIVE To systematically evaluate the safety and effectiveness of intravenous human immunoglobulin （IVIG） combined with cyclophosphamide in the treatment of systemic lupus erythematosus （SLE）， and to provide an evidence-based basis for clinical medication. METHODS Retrieved from PubMed， Embase， Cochrane Library， CBM， CNKI and Wanfang database， randomized controlled trials （RCTs） about IVIG combined with cyclophosphamide versus cyclophosphamide alone based on glucocorticoids were collected. The quality of the included literature was evaluated with Cochrane 5.1.0 risk of bias assessment tool after literature screening and data extraction， and meta-analysis was performed by using RevMan 5.4 software. RESULTS A total of 13 RCTs were included， involving 842 patients. Meta-analysis showed that compared with cyclophosphamide alone， IVIG combined with cyclophosphamide improved the overall response rate of systemic lupus erythematosus [RR＝1.23， 95%CI（1.15， 1.32）， P＜0.000 01]， lowered the systemic lupus erythematosus disease activity index [MD＝－2.05， 95%CI（－2.51， －1.60）， P＜0.000 01]， relieved 24 h proteinuria [MD＝－1.29， 95%CI（－1.57， －1.01）， P＜0.000 01]， reduced the inflammatory factor MCP-4 [MD＝－28.04， 95%CI（－32.72， －23.37， P＜0.000 01）]， IL-4 [MD＝－1.66， 95%CI（－1.96， －1.36）， P＜0.000 01]， and boosted immune complement C3 [SMD＝0.74，95%CI（0.34，1.14）， P＝0.000 3] and complement C4 [SMD＝0.99，95%CI （0.31，1.67）， P＝0.004]； it had similar incidence of adverse drug reactions to cyclophosphamide therapy alone [RR＝0.81， 95%CI （0.57， 1.17）， P＝0.26]. CONCLUSIONS Compared with cyclophosphamide alone， IVIG combined with cyclophosphamide has a positive role in improving the overall response rate of treating SLE， improving clinical symptoms， reducing inflammatory factors， improving immune function， but the results should be interpreted with caution.

Intraocular pressure distribution and reference interval of high-altitude eye health screening population from Xining, Qinghai / 中华实验眼科杂志

Objective:To investigate the distribution of intraocular pressure (IOP) in high-altitude population aged 18 years and over in Xining, Qinghai and establish the reference interval (RI) of IOP.Methods:A cross-sectional study was conducted in Xining, Qinghai Province at 2.271 km above sea level from September 2019 to May 2020.Ophthalmic examinations and IOP measurement were conducted among subjects from Physical Examination Center of Qinghai Provincial People's Hospital.The subjects who had been living in Xining without leaving for three months were enrolled.Ophthalmic examinations included vision examination, IOP measurement, slit-lamp microscopy, fundus photography, anterior and posterior segment optical coherence tomography.IOP was measured using Goldmann applanation tonometry under local anesthesia.Subjects with factors that could cause significant changes in IOP and affect the accuracy of IOP measurement, and those who were unable to receive IOP measurement were excluded.Subjects were grouped according to sex, age and ethnicity, and the distribution and RI of IOP were compared among all groups.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Beijing Tongren Hospital, Capital Medical University (No.TRECKY2017-024). Written informed consent was obtained from each subject.Results:A total of 6 120 subjects (6 120 eyes) aged 18-90 years old were enrolled, including 2 850 males and 3 270 females with average age of (45.54±13.85) years.The average IOP of high-altitude population in Xining, Qinghai Province was (14.32±1.93) mmHg (1 mmHg=0.133 kPa), with the RI of 10.54-18.10 mmHg.The average IOP was (14.42±1.98) mmHg in male with the RI of 10.54-18.30 mmHg, (14.23±1.88) mmHg in female with the RI of 10.55-17.91 mmHg.The IOP of male was higher than that of female ( t=3.71, P<0.001). The IOP of Han, Tibetan, Hui and other nationalities were (14.38±1.91), (13.93±2.06), (14.21±1.87), (13.94±1.95) mmHg, respectively, with a statistically significant overall difference ( F=6.73, P<0.001). The IOP of Han nationality was significantly higher than that of Tibetan, Hui and other nationalities, and the differences were statistically significant (all at P<0.05). Conclusions:RI of IOP in high-altitude population from Xining, Qinghai is lower compared with normal altitude area.

Preliminary estimation of lung cancer risk of radon exposure in a uranium mine using different corrections / 中国职业医学

Objective: To explore the correction factors of lung cancer caused by radon exposure in a uranium mine, and estimate the excess relative risk (ERR) coefficient of lung cancer caused by radon in the uranium miners. Methods: Male miners who worked in a uranium mine more than one year in Hunan Province from 1958 to 2018 were selected. This study preliminarily estimated the ERR coefficient of lung cancer caused by radon in the miners with different corrections using the Possion regression model. Results: This study cohort included 4 851 uranium miners, with 187 miners died with lung cancer from 1958 to 2018, and cumulative follow-up of 207 251 person-year. The ERR coefficient of lung cancer caused by radon without correction factors was estimated to be 0.21%/WLM (95%CI: 0.04%/WLM-0.27%/WLM). In the final model, the exponential correction factors of radon-induced lung cancer were time since exposure and exposure rate. In this model, if time since exposure was 45 years and the average exposure rate was 0.14 WL, the estimated ERR coefficient was 1.73%/WLM (95%CI: 0.36%/WLM-3.11%/WLM). The ERR decreases by about 60.00% for every 10 years since exposure, and increases by about 30.00% for every one WL increase exposure rate. Conclusion: The correction factors of lung cancer caused by radon in uranium miners in this mine were the time since exposure and exposure rate. It was preliminarily estimated that the ERR coefficient of lung cancer caused by radon in the occupational radon exposed population in this uranium mine was 1.73%/WLM (95%CI: 0.36%/WLM-3.11%/WLM).

Application of SpyGlass peroral choledochoscopy to the diagnosis and treatment of biliary stricture after liver transplantation / 中华消化内镜杂志

Objective:To explore the characteristics of biliary stricture after liver transplantation (LT) under SpyGlass peroral choledochoscopy and to investigate its treatment value for difficult stricture.Method:A total of 24 patients of biliary stricture after LT at the Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi'an Jiaotong University underwent SpyGlass examination from January 2019 to December 2020, 15.5 months (2-58 months) after surgery. The characteristics of different types of strictures and the selective guidewire placement results by SpyGlass were recorded and analyzed.Results:Of the 24 patients, 9 were anastomostic strictures (AS) and 15 others were non-anastomostic strictures (NAS). The main characteristic of 5 initial AS patients was scar constriction. Whether treated or not, all of the 15 NAS patients showed evident inflammatory hyperplasia in hilar bile duct under SpyGlass, 80% (12/15) of which were accompanied with intrahepatic biliary stones. The strictures disappeared with mild hyperplasia in 8 patients (4 AS and 4 NAS) whose biliary stents were extracted. Eleven patients (5 AS and 6 NAS) needed guidwire placement under SpyGlass, six (54.5%) of whom succeeded. The successful rate in AS patients was higher than that of NAS (4/5 VS 2/6).Conclusion:The main characteristic of AS is scar constriction and that of NAS is inflammatory hyperplasia. Selective guidewire placement can be achieved by SpyGlass peroral choledochoscopy with a satisfactory successful rate in the difficult AS.

Etiology and Pathogenesis of Hepatolenticular Degeneration Caused by Latent Toxin Blocking Collaterals / 中国实验方剂学杂志

Hepatolenticular degeneration（HLD），also known as Wilson disease （WD）， is a genetic disorder characterized by copper metabolism disorder caused by ATP7B gene mutation. Specifically， due to the ceruloplasmin synthesis disorder induced by gene mutation，copper cannot be excreted through bile，which results in pathological deposition of copper in various organs and damage to organs such as the brain and the liver. The incidence of WD in Chinese is significantly higher than that in the world. Copper chelating agents， such as D-penicillamine and dimercaptosuccinic acid， are used as the main therapeutic agents in western medicine. However， many clinical adverse events limit the application of these drugs. Traditional Chinese medicine （TCM） has its characteristics in the treatment of WD. As confirmed by long-term research on TCM clinical diagnosis and treatment，MD has become TCM dominant disease. In spite of many views about the etiology and pathogenesis of WD，a consensus has not been reached so far. Based on the theory of latent pathogen in TCM and the pathological mechanism of excessive deposition of copper ions in the body，this study proposed that latent toxin is the key etiology of WD，and further elaborated that the latent toxin of WD was inherited from parents and occurred in children and adolescents，which was hidden in the liver and the kidney and damaged the brain. The latent toxin， Yang in nature and dispersing in property， is prone to transform into dampness-heat to block Qi movement and produce phlegm leading to stasis. Furthermore， this study determined latent toxin blocking collaterals as the basic pathogenesis of WD and revealed the complex clinical manifestations of latent toxin blocking collaterals such as liver collaterals，brain collaterals，kidney collaterals，spleen collaterals，stomach collaterals，lung collaterals，heart collaterals， and uterus collaterals. Treatment should follow the basic therapeutic principles of resolving pathogens，removing toxins， and dredging collaterals. This study is expected to provide a theoretical basis for syndrome differentiation and treatment of WD in TCM.

Intervention of Gandou Fumu Decoction on Liver Fibrosis in Mice with Wilson's Disease Through JNK Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo identify the protective effect and possible mechanism of Gandou Fumu decoction （GDFMD） on liver fibrosis in mice with Wilson's disease. MethodA total of 50 homozygous TXJ mice were randomly divided into five groups， with 10 mice in each group. Ten wild-type mice were selected as a normal group. The GDFMD high， medium， and low-dose groups were given 13.92， 6.96， 3.48 g·kg-1 of GDFMD， respectively. The penicillamine group were given 0.1 g·kg-1 of penicillamine. The model group and the normal group were given the same volume of 0.9% sodium chloride solution once a day for 4 consecutive weeks. The enzyme-linked immunosorbent assay （ELISA） method was performed to detect serum superoxide dismutase （SOD） activity and malondialdehyde （MDA） content. Corresponding kits were used to detect the mitochondrial adenine triphosphate （ATP） content and Na+-K+-ATPase activity in liver tissues. Hematoxylin-eosin （HE） and Masson staining were used to observe the pathological morphology of liver tissue， and transmission electron microscope was used to observe ultrastructural changes of liver tissues in mice. Western blot was used to detect the c-Jun N-terminal kinase， the phosphorylated protein， and the expressions of Caspase-3， B cell lymphoma-2 （Bcl-2）， and Bcl-2 associated X protein （Bax） in c-Jun N-terminal kinase （JNK） signaling pathway. ResultCompared with the normal group， MDA content increased and SOD activity decreased in the model group （P<0.05）. Compared with the model group， SOD activities in the GDFMD high-， medium-， and low-dose groups and the penicillamine group significantly increased （P<0.01）， and MDA content significantly decreased （P<0.05， P<0.01）. Compared with the normal group， ATP content and Na+-K+-ATPase activity significantly decrease in the model group （P<0.05）. Compared with the model group， ATP content and Na+-K+-ATPase activity in the GDFMD medium and high-dose groups and the penicillamine group significantly increased （P<0.05， P<0.01）. The results of the pathological morphology of liver tissue showed that a large number of liver cells degeneration and necrosis， inflammatory cell infiltration， unclear liver lobule structure， and collagen fiber deposition were observed in the model group. Transmission electron microscopy showed that the number of mitochondria in liver tissues significantly reduced， the mitochondria were locally damaged， and the cristae of mitochondria were broken even disappear in the model group. The pathological morphology of liver tissue and mitochondrial structure recovered to varying degrees after medicinal intervention. The results of Western blot suggested that， compared with the normal group， the expression levels of phosphorylation-JNK （p-JNK）， p-JNK/JNK， Caspase-3， and Bax in the liver tissues were up-regulated， while the expression of Bcl-2 was down-regulated in the model group （P<0.05）. The expression levels of p-JNK， p-JNK/JNK， Caspase-3 and Bax were down-regulated and the expression of Bcl-2 was up-regulated in the GDFMD high and medium-dose groups and the penicillamine group （P<0.01）. ConclusionGDFMD can alleviate oxidative stress damage and recover mitochondrial function of TXJ mice with liver fibrosis. The mechanism of GDFMD may be related to regulating the JNK signaling pathway and downstream factors and inhibiting cell apoptosis.

Analysis of the situation ，influential factors and their relationship of hospital pharmacy managers ’servant leadership behavior and hospital pharmacists ’job satisfaction / 中国药房

OBJECTIVE To investigate the situation ，influential factors and their re lationship of hospital pharmacy managers ’ servant leadership behavior and hospital pharmacists ’job satisfaction. METHODS The questionnaire survey method was adopted to stratified cluster sampling from primary ，secondary and tertiary hospitals ，five for each in Henan province. The personal basic data scale of pharmacists ，the hospital pharmaceutical service leadership behavior scale and the job satisfaction scale of pharmacists were used to conduct a questionnaire survey among hospital pharmacists. Excel 2019 and SPSS 23.0 software were used for statistical analysis. RESULTS A total of 956 questionnaires were distributed and 882 questionnaires were recovered ，including 841 valid questionnaires，with an effective recovery rate of 95.35％. The reliability coefficients Cronbach’s α of hospital pharmacy managers ’ servant leadership behavior scale and hospital pharmacists ’job satisfaction scale were 0.986 and 0.978，and the validity coefficients KMO were 0.908 and 0.977（P＜0.01）. The total score of hospital pharmacy managers ’servant leadership behavior was （110.73± 18.63）. The total score of hospital pharmacists ’job satisfaction was （126.33±17.79）. Hospital grade ，gender，age，professional title and highest education level all affected pharmacists ’recognition for managers ’servant leadership behavior （P＜0.05）. Hospital grade，age，professional title ，marital status ，highest education level and position all affected job satisfaction （P＜0.05）. The servant leadership behavior of hospital pharmacy managers was positively correlated with the job satisfaction of hospital pharmacists （correlation coefficient r was 0.521-0.698，all P＜0.01）. CONCLUSIONS The promotion and optimization the servant leadership behavior of hospital pharmacy managers can improve the job satisfaction of pharmacists ，stabilize the team of pharmacists ，and provide high-quality pharmaceutical care for patients ，so as to improve the core competitiveness of the hospital.

Role of preoperative administration of tranexamic acid in the treatment of senile proximal humeral fracture with locking plate internal fixation / 中华创伤杂志

Objective:To explore the efficacy and safety of preoperative application of tranexamic acid (TXA) in the treatment of senile proximal humeral fracture (PHF) with locking plate internal fixation.Methods:A prospective randomized controlled analysis was performed on clinical data of 89 elderly patients with PHF admitted to First Affiliated Hospital of Chongqing Medical University from December 2018 to December 2021. All patients received open reduction and locking plate internal fixation. The patients were divided into TXA group and control group according to the equal probability randomization method. In TXA group, the patients were given 1 g of TXA intravenously at 30 minutes before operation. In control group, the patients were given the same amount of normal saline at the same time. The general data (sex, age, body mass index, bone mineral density, Neer classification, and time from injury to operation), operation time, hospitalization time, and postoperative complications were recorded and compared between the two groups. At 3 months after operation, American Shoulder and Elbow Surgeons (ASES) score, Constant-Murley score, and shoulder range of motion (ROM) were used to compare the recovery of shoulder joint function between the two groups. The total blood loss (TBL), visible blood loss (VBL), hidden blood loss (HBL), intraoperative blood loss (IBL), postoperative drainage volume, drainage tube removal time and blood transfusion rate were compared between the two groups.Results:There were 47 patients in TXA group and 42 patients in control group. There were no significant differences in general data between the two groups (all P>0.05). The operation time and incidence of deep vein thrombosis (DVT) showed no significant difference between the two groups (all P>0.05). The hospitalization time was (7.4±2.5)days in TXA group, significantly shorter than (10.9±3.1)days in control group ( P<0.05). The wounds were healed at stage I in the two groups, with no incision infection, pulmonary embolism, cerebral embolism or other critical complications. There were no significant differences in ASES score, Constant-Murley score and shoulder ROM between the two groups at 3 months postoperatively (all P>0.05). In TXA group, the TBL, VBL, HBL, postoperative drainage volume and drainage tube removal time were (341.1±31.2)ml, (198.7±20.2)ml, (142.5±23.8)ml, (38.9±12.9)ml, and (25.6±3.2)hours respectively, while in control group, the TBL, VBL, HBL, postoperative drainage volume and drainage tube removal time were (643.7±42.4)ml, (223.1±28.6)ml, (420.6±31.8)ml, (58.9±16.9)ml, and (37.3±5.3)hours respectively ( P<0.05 or 0.01). There were no significant differences in IBL or blood transfusion rate between the two groups (all P>0.05). Conclusions:For senile PHF treated with locking plate internal fixation, preoperative intravenous infusion of TXA can effectively shorten the hospital stay, without increasing the incidence of DVT or affecting shoulder joint function. Meanwhile, TXA results in reduced TBL, VBL, HBL and postoperative drainage volume and early drainage tube removal, which has good clinical effectiveness and safety.

Comprehensive minimally invasive treatment for biliary anastomotic stenosis after orthotopic liver transplantation: a single center analysis of 60 cases / 器官移植

Objective To evaluate the clinical efficacy of endoscopic retrograde cholangiopancreatography (ERCP)-based comprehensive minimally invasive treatment for biliary anastomotic stenosis (BAS) after liver transplantation. Methods Clinical data of 60 BAS recipients after liver transplantation were retrospectively analyzed, 54 male and 6 female, aged (48±10) years. ERCP was initially carried out. If it succeeded, plastic or metallic stents were placed into the biliary tract. If it failed, percutaneous transhepatic cholangial drainage (PTCD) or single-operator cholangioscopy (SpyGlass) was adopted to pass through the stenosis. If all these procedures failed, magnetic anastomosis or other special methods were delivered. The incidence and treatment of BAS after liver transplantation were summarized. The efficacy, stent removal and recurrence were observed. Results The median time of incidence of BAS after liver transplantation was 8 (4, 13) months. Within postoperative 1 year, 1-2 years and over 2 years, 39, 16 and 5 recipients were diagnosed with BAS, respectively. All 60 BAS recipients after liver transplantation were successfully treated, including 56 cases initially receiving ERCP, and 41 completing BAS treatment, with a success rate of 73%. The failure of guide wire was the main cause of ERCP failure. The success rates of PTCD, SpyGlass and magnetic anastomosis were 5/9, 5/7 and 7/8, respectively. Two recipients were successfully treated by percutaneous choledochoscope-assisted blunt guide wire technique and stent placement in the biliary and duodenal fistula. After 3 (3, 4) cycles of ERCP and 13 (8, 18) months of stent indwelling, 38 recipients reached the stent removal criteria, including 25 plastic stents and 13 metallic stents. The indwelling time of plastic stents was longer than that of metallic stents (P < 0.05). Six cases suffered from stenosis recurrence at 12 (8, 33) months after stent removal, and the recurrence rate was 16%. Six patients were treated with ERCP, and 5 of them did not recur after the stents were successfully removed. Multivariate analysis showed that delayed diagnosis of stenosis and frequent ERCP before stent removal were the independent risk factors for BAS recurrence (both P < 0.05). Conclusions ERCP-based comprehensive minimally invasive treatment may improve the success rate of BAS treatment after liver transplantation and yield satisfactory long-term efficacy. Delayed diagnosis of BAS and high frequent ERCP required for stent removal are the independent risk factors for BAS recurrence.

Type and management of biliary fistula after orthotopic liver transplantation / 中华消化内镜杂志

Objective:To discuss the type, treatment and results of different therapies of biliary fistula after orthotopic liver tansplantation(OLT).Methods:Data of 24 patients who developed biliary fistula after OLT in the First Affiliated Hospital of Xi′an Jiaotong University from January 2000 to March 2019 were retrospectively analyzed. Patients with biliary fistula were classified into 4 types according to presence or absence of stricture. All patients were treated by endoscopic retrograde cholangiopancreatography (ERCP) or interventional therapy, including endoscopic nasobiliary drainage (ENBD), endoscopic retrograde biliary drainage (ERBD) or percuteneous transhepatic cholangial drainage (PTCD). Main outcome measurements were the onset time of biliary fistula, the site of biliary fistula, the complications of ERCP or PTCD, the time of removing abdominal or biliary drainage tube, and the onset of new biliary stricture.Results:Biliary fistula was found in (46.5±36.6) days (6-122 days) after OLT. The numbers of patients in four types of biliary fistula were 6, 14, 2 and 2, respectively. Biliary fistula was cured in 22 patients, with clinical cure rate of 91.7%. All patients underwent ERCP first, and the technical success rate and clinical cure rate were 87.5% (21/24) and 85.7% (18/21), respectively. The clinical cure rates of ERCP forⅠ-Ⅳ biliary fistula were 6/6, 84.6%(11/13), 1/2, and 0, respectively. The clinical cure rates of ENBD and ERBD were 8/10 and 6/8, respectively. Five cases in whom ERCP failed, underwent PTCD, with technical success and clinical cure rates of 4/5 and 3/4 respectively. Eight patients(33.3%)developed cholangitis after treatment, and the incidence rate seemed higher in type Ⅱ biliary fistula than that in type Ⅰ [35.7% (5/14) VS 16.7% (1/6)]. Incidence of cholangitis was higher in patients with non-anastomotic stricture than those with anastomotic stricture [83.3%(5/6) VS 16.7%(3/18)].Conclusion:The first line treatment for biliary fistula after OLT is ERCP, followed by PTCD. The best procedures of biliary fistula typeⅠ-Ⅳ were ENBD, ENBD combined with ERBD, ENBD and PTCD, respectively.

Safety analysis of postoperative cyclophosphamide combined with taxane chemotherapy in patients with triple-negative breast cancer and chronic renal failure / 中华普通外科杂志

Objective:To explore the safety of cyclophosphamide combined with taxane chemotherapy in triple-negative breast cancer patients with chronic renal failure and the management strategy of complications.Methods:Data of 8 patients with triple-negative breast cancer and chronic renal failure admitted to our hospital from Jun 2016 to Dec 2019 were retrospectively analyzed.Results:Eight patients received standard cyclophosphamide combined with taxane (TC regimen) chemotherapy after operation, 5 of which received docetaxel 75 mg/m 2 + cyclophosphamide 600 mg/m 2, and 3 received albumin paclitaxel 260 mg/m 2+ cyclophosphamide 600 mg/m 2, during chemotherapy, only leukopenia, hair loss and gastrointestinal reactions occurred in grades 3 to 4, and the incidence was 25%, 25% and 12%, respectively. Four patients adjusted the dosage due to adverse reactions. One patient quit, the remaining patients successfully completed 4 cycles of chemotherapy. The average serum creatinine before chemotherapy was (498±63) μmol/L, and after chemotherapy, it was (518±61) μmol/L ( t=-2.335, P>0.05). Conclusions:Combined with chronic renal failure is not a contraindication to postoperative chemotherapy for patients with breast cancer. It is safe to choose standard TC regimen and adjust the dose of adjuvant chemotherapy for patients with triple-negative breast cancer.

Effect and Safety of Tongyan Spray () on Hyoid Motion in Patients with Dysphagia after Ischemic Stroke / 中国结合医学杂志

OBJECTIVE@#To observe the effects and safety of Tongyan Spray () on the range and time of hyoid motion in patients with ischemic post-stroke dysphagia.@*METHODS@#Seventy-two patients with ischemic post-stroke dysphagia were selected and randomly assigned to a treatment group (36 cases) and a control group (36 cases) by a random number table from January 2013 to October 2014. All patients swallowed 4 kinds of barium meals with different traits respectively, and each patient underwent video fluoroscopy (VF) examination twice. In the treatment group, Tongyan Spray was sprayed to the pharynx on both sides and the middle part once respectively. The spray was applied 30 min before the second examination. Purified water at room temperature was used as placebo in the control group. The changes in the range and time of hyoid motion in both groups were observed before and after treatment.@*RESULTS@#Six patients dropped out in each group, and 60 patients completed the study and were included in the final analysis. Significant improvement was observed in the range of superior hyoid excursion distance and the time of hyoid motion in the treatment group compared with the control group (P<0.05). There were no obvious adverse reactions observed in oral mucosa in both groups during the whole study.@*CONCLUSION@#Tongyan Spray was an effective and safe medicine for improving swallowing function in patients with ischemic post-stroke dysphagia.

HBcAg-specific Th9 cells in patients with HBV infection / 中华微生物学和免疫学杂志

Objective:To investigate the changes of non-specific and HBV core antigen (HBcAg)-specific Th9 cells, and intereleukin-9 (IL-9) in HBV-infected patients, and to assess the influence of Th9 cells on CD8 + T cell function. Methods:Twelve patients with acute hepatitis B (AHB) and 58 with chronic hepatitis B (CHB), who were hospitalized in the First Affiliated Hospital of Xinxiang Medical University between January 2018 and January 2019, were enrolled in this study. Twenty healthy subjects negative for HBsAg were selected as controls. Peripheral blood mononuclear cells (PBMCs) and plasma samples were isolated. Non-specific Th9 cells (CD3 + CD4 + IL-9 + ) and HBcAg-specific Th9 cells were analyzed by flow cytometry. Plasma IL-9 level was measured by enzyme linked immunosorbent assay. CHB patients received tenofovir disoproxil fumarate (TDF) antiviral therapy. The changes of non-specific Th9 cells, HBcAg-specific Th9 cells and plasma IL-9 level were assessed 48 weeks after TDF therapy. CD4 + CCR4 -CCR6 -CXCR3 -(Th9) cells and CD8 + T cells were isolated from 12 HLA-A2 restricted CHB patients and co-cultured with HepG2.2.15 cells with the presence of anti-IL-9 neutralizing antibody. The percentage of dead HepG2.2.15 cells and the levels of IFN-γ and TNF-α were detected. Student′s t test, one-way analysis of variance or SNK- q test was used for statistical comparison between groups. Results:There were no significant differences in non-specific Th9 cells or plasma IL-9 level among AHB patients, CHB patients and healthy controls ( P>0.05). HBcAg-specific Th9 cells was down-regulated in CHB patients when compared with AHB patients [(2.49±0.61)% vs (3.19±0.62)%, P<0.001]. The percentage of HBcAg-specific Th9 cells was negatively correlated with HBV DNA ( r=-0.385, P=0.003), but not correlated with ALT ( P>0.05) in CHB patients. TDF therapy for 48 weeks remarkably elevated the HBcAg-specific Th9 cells [(2.94±0.48)%, P<0.001], however, did not affect non-specific Th9 cells or plasma IL-9 level ( P>0.05) in CHB patients. The cytotoxicity of HBcAg-specific Th9 cells was low in CHB patients. However, HBcAg-specific Th9 cells could induce enhanced cytotoxicity of CD8 + T cells to HepG2.2.15 cells, which manifested as increased percentage of dead HepG2.2.15 cells and higher levels of IFN-γ and TNF-α. Anti-IL-9 neutralizing antibody reduced the enhancement of CD8 + T cell cytotoxicity by HBcAg-specific Th9 cells ( P<0.001). Conclusions:Chronic HBV infection might suppress the level and function of HBcAg-specific Th9 cells, resulting in persistent infection.

Application of pueumatic tourniquet in the operation of lower tibiofibular fracture / 中国骨伤

OBJECTIVE@#To investigate the complications of tourniquet in the clinical application of lower tibiofibular fracture.@*METHODS@#From June 2018 to September 2019, 33 cases of closed lower tibiofibular fractures (AO type 43A) were treated with plates and screws and were divided into two groups according to whether pueumatic tourniquet was used:16 cases in the observation group, 13 males and 3 females, aged 18 to 69 (38.8±17.0) years, the operation time after injury was (6.9±1.7) days, and tourniquet was not used during operation. There were 17 cases in the control group, 13 males and 4 females, aged from 21 to 71 (43.8±12.4) years, the operation time after injury was (6.5±1.0) days, automatic pneumatic tourniquetwas routinely used in the operation. The operation time, blood loss, postoperative swelling, pain and other complications were compared between two groups.@*RESULTS@#Total of 33 patients were followed up for an average of 15 months. There was no significant difference in operation time and blood loss between two groups (@*CONCLUSION@#The fracture of lower tibiofibular segment is superficial and easy to be exposed and fixed during operation. In order to avoid tourniquet complications, it is not recommended to use air bag tourniquet routinely or minimize the application time of tourniquet.

Practical exploration on the Online Four-step Teaching of Encouraging and Sharing during COVID-19 period / 生理学报

The "Four-step Teaching of Encouraging and Sharing" is a learner-centered teaching method that advocates teamwork and gives full play to the role of the teacher in guiding learning. It is an innovative teaching approach to realize students' self-transcendence by stimulating students' internal motivation for independent learning, applying group task-driven learning, and giving teachers' feedback to students' sharing. It consists of four steps: teachers' guiding, students' self-regulated learning, team learning and practice, experience sharing. We have applied this method to the teaching practice of physiology and experimental physiological science with a significant impact on teaching effects. This teaching method has also been implemented to other courses in other majors. To solve the problems of reduced communication and interaction, low learning enthusiasm and motivation in online teaching course during COVID-19 pandemic, we recruited 21 undergraduates from different schools and majors. Using the "Tencent Meeting" platform, the authors tried to apply the whole process of the "Four-step Teaching of Encouraging and Sharing" to the online teaching of physiology. Group tests and questionnaires were used to evaluate teaching effects. The results showed that the implementation of the "Online Four-step Teaching of Encouraging and Sharing (OFST)" was feasible and effective, and to a certain extent alleviated the problems of loneliness and low learning motivation of students during online learning caused by home quarantine, which was particularly helpful for long-distance inter-school and inter-discipline team learning.

Mechanisms of bupivacaine inhibition of glutamate-induced intracellular calcium elevation in primary cultured rat hippocampal astrocytes / 药学学报

This research investigated the mechanism by which bupivacaine inhibits glutamate-induced intracellular free Ca2+ increases in primary cultured hippocampal astrocytes. Immunofluorescence was used to demonstrate the expression of metabotropic glutamate receptor (mGluR5 receptor) on neurons and astrocytes. Calcium imaging was used to measure the alteration of intracellular free Ca2+ ([Ca2+]i) in primary cultured rat hippocampal neurons and astrocytes. The animal experiments were approved by the Animal Experiments Ethical Committee of Hebei Medical University. The results showed that mGluR5 receptor was abundantly expressed in the primary cultured rat neurons and astrocytes. Bupivacaine (300 μmol·L-1) significantly inhibited 1 mmol·L-1 glutamate-induced [Ca2+]i increase in astrocytes (P < 0.01). 2-Methyl-6-(2-phenylethynyl)-pyridine (MPEP) (10 μmol·L-1) completely abolished the increase of [Ca2+]i induced by 1 mmol·L-1 glutamate in the astrocytes (P < 0.01), while the inhibitory effect on neurons was only 10%-20%. Bupivacaine (300 μmol·L-1) completely inhibited the [Ca2+]i increase induced by mGluR5 receptor agonists (RS)-3,5-dihydroxyphenylglycine (DHPG) (50 μmol·L-1) and (RS)-2-chloro-5-hydroxyphenylglycine sodium salt (CHPG) (1 mmol·L-1) in astrocytes (P < 0.01). In addition, bupivacaine inhibited the CHPG-induced [Ca2+]i increase in a dose-dependent manner in astrocytes with an IC50 of 100 μmol·L-1. The results from this study indicate that bupivacaine inhibits glutamate-induced [Ca2+]i elevation by acting on the mGluR5 receptor in primary cultured hippocampal astrocytes.

Systemic lupus erythematosus: year in review 2019 / 中华医学杂志(英文版)

Systemic lupus erythematosus (SLE) is an autoimmune disease with extreme heterogeneity and potentially involvement of any organ or system. Numerous unanswered questions and challenges in SLE always prompt further exploration. In 2019, great progress in various aspects of SLE emerged. Both the classification criteria and management recommendation for SLE were updated. New promising medications have been widely developed and tested, although subsequent clinical studies are warranted. As an emerging number of most notable studies in SLE were published in both clinical area and basic research in 2019, we aim to summarize the highest quality data on SLE regarding novel insights of pathogenesis, updated recommendations, hot-spot issues on clinical manifestations, new understanding of disease prognosis, and most importantly, the therapeutic advances in SLE in this review.

Analysis of diagnosis of 5 children with suspected neuronal ceroid lipofuscinosis / 中国实用儿科杂志

OBJECTIVE: To investigate diagnosis of children's neuronal ceroid lipofuscinosis(NCL),especially the significance of gene diagnosis. METHODS: The clinical data of 5 cases of suspected NCL in our hospital from January 2013 to January 2017 were retrospectively analyzed. There were 3 boys and 2 girls,2 of whom were sister and brother. The age of onset ranged from 3 years and 4 months to 8 years and 1 month,averaged 5 years and 9 months. The first visit to our hospital ranged from 3 years and 6 months to 14 years,with an average of 8 years and 1 month. DNA of peripheral blood was extracted from 4 children with abnormal imaging and their parents and brothers,and the related genes were detected.RESULTS: Four cases of children were diagnosed with NCL,and 1 case was diagnosed with hysteria;gene detection showed:case 1:TPP1 gene c.887-17 A>G was a shearing variant,and c.646 G>A was a missense mutation;case 2:TPP1 gene c.1015＿1016 del was frameshift mutation,and c.640 C>T was nonsense mutation;the nucleotide of case 3:CLN6 gene changed to c.158 T>C(p.L53 P)and c.889 C>T(p.P297 S). The parents of the 3 cases only carried one of the heterozygous variants,and the brother of case 3 had no mutation. Heterozygous mutation existed in case 4:CLN3 gene,c.1160＿1169 delCAGCCTACGTinsGC,which was not detected in the mother,and there was the deletion of the paternal sample;there was loss of heterozygosity in the exon E3-E8 of the CLN3 gene,which was the true missing from mother.Five cases were followed up for 15-60 months and there was no death. CONCLUSION: Suspected NCL patients should be checked head MRI,electroencephalogram and gene. The gene mutation leads to NCL,such as TPP1(c.887-17 A>G,c.1015＿1016 del),CLN3(c.1160＿1169 delCAGCCTACGTinsGC),CLN6[(c.158 T>C(p.L53 P) and c.889 C>T(p.P297 S)],are reported for the first time. Genotype is very important for NCL classification and prognosis.

Optimization of Extraction Technology of Flavonoids in Glycyrrhiza uralensis by Single Factor Experiment Combined with Box-Behnken Design-response Surface Methodology / 中国药房

OBJECTIVE： To optimize the extraction technology of the flavonoids from Glycyrrhiza uralensis. METHODS： Using total contents of four flavonoids， liquiritinapioside， glycyrrhizin， isoliquiritin apioside and formononetin as indexes， types and volume fractions of extraction solvents （water， ethanol）， volume of addition and extraction time as factors， based on single factor experiment， Box-Behnken design-response surface method was used to optimize the extraction technology of flavonoids from G. uralensis. Validation test was also conducted. RESULTS： The optimal extraction technology was 50 mL 50％ ethanol as extraction solvent， 0.200 g G. uralensis， ultrasonic extraction for 50 min. In validation test， the extraction amounts of liquiritinapioside， glycyrrhizin， isoliquiritin apioside and formononetin were 10.733 0， 27.784 9， 3.441 9， 0.429 1 mg/g， respectively （all RSDs＜3.0％， n＝3）. The average total extraction amount of four flavonoids was obtained was 42.388 9 mg/g， the relative error of which to predicted value （42.173 2 mg/g） was 0.52％ （n＝3）. CONCLUSIONS： The optimized extraction technology is simple， rapid and stable， and can be used for the extraction of flavonoids from G. uralensis.

Design, methodology, and preliminary results of the follow-up of a population-based cohort study in rural area of northern China: Handan Eye Study / 中华医学杂志(英文版)

Background@#Handan Eye Study (HES), a large population-based cohort study in rural area of northern China, was one of the few studies focusing on the major eye diseases of rural Chinese population. The aim of this study was to introduce the design, methodology and to assess the data quality of the follow-up phase of HES.@*Methods@#All participants were recruited in Yongnian county of Handan city between 2012 and 2013. Main outcomes were measured by visual quality scales and ocular examinations. We performed the Chi-square test to make comparison of categorical data among groups, One-way analysis of variance and Kruskal-Wallis test was applied to make comparison of continuous data among groups, a post-hoc test was done to make further pairwise comparison. Inter-class correlation coefficients (ICCs) and Kappa coefficients were used to evaluate the consistency between different operators. Logistic regression was used to explore the influence factors of death, odds ratio (OR) and 95% confidence interval (CI) were used to estimate the effect size of each influence factor.@*Results@#The follow-up rate was 85.3%. Subjects were classified into three groups: the follow-up group (n = 5394), the loss to follow-up group (n = 929), and the dead group (n = 507), comparison of their baseline information was done. Compared with the other two groups, age of the dead group (66.52 ± 10.31 years) was the oldest (Z = 651.293, P < 0.001), male proportion was the highest (59.0%) (χ2 = 42.351, P < 0.001), only 65.9% of the dead finished middle school education (Z = 205.354, P < 0.001). The marriage percentage, body mass index (BMI), best-corrected visual acuity (BCVA), and intra-ocular pressure of the dead group was the lowest either. Spherical equivalent error (SER) of the dead group was the highest. Besides, history of smoking, hypertension, diabetes, and heart disease were more common in the dead group. Multivariate analysis showed that age (OR = 1.901, 95% CI: 1.074–1.108), gender (OR = 0.317, 95% CI: 0.224–0.448), and BCVA (OR = 0.282, 95% CI: 0.158–0.503) were associated with death. While between the follow-up group and the loss to follow-up group, there was only difference on age, gender, BMI, systolic blood pressure and SER. The Cronbach coefficients of all scales used in the follow-up were ≥0.63 and the cumulative variances were ≥0.61, indicating good reliability and validity. The ICCs and Kappa coefficients between different operators were ≥0.69.@*Conclusions@#HES has a high follow-up rate and a low risk of loss to follow-up bias. Age, gender, and BCVA are influence factors of death. Specifically, male subjects are at a higher risk of death than female, age is a risk factor of death while BCVA is a protective factor for death.