Network meta-analysis of five Chinese patent medicines in the treatment of coronary microvascular disease / 国际中医中药杂志

Objective:To evaluate the clinical efficacy rate, vascular endothelial relaxation factor NO and safety of five different Chinese patent medicines combined with western medicine in the treatment of coronary microvascular disease (CMVD).Methods:Randomized controlled trials (RCTs) of Shexiang Baoxin Pills, Tongxinluo Capsules, Compound Danshen Dripping Pills, Yindan Xinnaotong Soft Capsules, and Xinkeshu Tablets combined with conventional western medicine therapy in the treatment of CMVD were retrieved from China National Knowledge Infrastructure (CNKI), China Academic Journal Database (Wanfang Data), Chinese Science and Technology Journal Database (Chongqing VIP), China Biomedical Literature Service System (SinoMed), PubMed, Cochrance Library and Embase databases from the establishment of the database to June 2022. The literature was imported and screened by EndNote software, and the risk quality of literature bias was evaluated by Revman 5.4 software. StataSE16 (64-bit) software was used for reticular meta analysis to compare the differences in clinical efficacy and drug safety of five proprietary Chinese medicines combined with western medicine.Results:A total of 24 RCT studies were included, 24 of which were double-arm studies, and five kinds of proprietary Chinese medicine combined with western medicine were compared. The results of reticular meta analysis: in terms of improving the clinical effective rate, the order of the five proprietary Chinese medicine combination groups was as follows: Yindan Xinnaotong Soft Capsules group > Shexiang Baoxin Pills group > Tongxinluo Capsules group > Xinkeshu Tablets group > Compound Danshen Dripping Pills group. In terms of regulating vasodilation factor NO, the order of the four proprietary Chinese medicine combination groups is as follows: Yindan Xinnaotong Soft Capsules group > Compound Danshen Dripping Pills group > Tongxinluo Capsules group > Shexiang Baoxin Pills group. In terms of safety, there were 3 reports of adverse reactions in the research literature of the five proprietary Chinese medicines.Conclusions:The clinical efficacy rate of five kinds of proprietary Chinese medicine combined with western medicine routine regimen is better than that of western medicine routine regimen alone, and the combination group of four kinds of proprietary Chinese medicine is superior to western medicine in regulating vasodilation factor NO, and Yindan Xinnaotong Soft Capsules group is superior in clinical efficacy rate and regulation of vasodilation factor NO. However, the quality and samples of this study are different, and the comparison of the curative effect of the combined group of proprietary Chinese medicine still needs a large sample and high-quality RCT study to demonstrate.

Overview of systematic review on TCM for functional dyspepsia / 国际中医中药杂志

Objective:To re-evaluate the reliability of the conclusions of the systematic reviews (SR)/meta-analysis (MA) of Traditional Chinese Medicine (TCM) in the treatment of functional dyspepsia (FD).Methods:CNKI, CBM, WanFang Data, VIP, PubMed, Cochrane Library, and Embase were searched from the establishment of the database to March 30, 2022. Two researchers independently screened literature and extracted data, and included SRs/MAs in the treatment of FD with TCM. The AMSTAR 2 and GRADE tools were used to evaluate the included the study carried out methodological quality evaluation, outcome evidence quality grading, and descriptive analysis of the main outcome.Results:A total of 28 SRs/MAs were included, with 34 outcome indicators. According to the AMSTAR 2 evaluation results, 21 SRs/MAs were of medium quality, and 7 SRs/MAs were of low quality. The GRADE quality of evidence grading results showed that of the 100 evidence bodies, 13 were of high quality, 58 were of moderate quality, 24 were of low quality, and 5 were of very low quality.Conclusion:TCM in the treatment of FD can improve the clinical efficiency, improve the cure rate, reduce the recurrence rate, and improve the clinical symptoms, but the methodological quality and evidence quality of related SRs/MAs have certain defects, so this conclusion should be treated with caution.

Visualized Analysis of Advances and Hot Spots of Lianhua Qingwen in Recent 10 Years / 中国实验方剂学杂志

ObjectiveTo analyze relevant literature on Lianhua Qingwen preparations and clarify the research advances and hot spots in this field， so as to provide references for clinical rational application and further research. MethodLiterature related to Lianhua Qingwen preparations in the recent 10 years was retrieved from six databases， including China National Knowledge Infrastructure（CNKI）， VIP， Wanfang Data， PubMed， and Web of Science， followed by management and analysis by NoteExpress and CiteSpace. ResultFinally， 344 and 76 Chinese and English research articles were included， and the number of publications increased in recent years. The research articles were published in 162 Chinese and 48 English journals. Shijiazhuang Yiling Pharmaceutical Co.， Ltd. and Guangzhou Medical University were institutions with the largest number of Chinese and English publications， respectively. LIU Minyan was the author who had published the most articles. Keywords with high frequency included clinical efficacy， Lianhua Qingwen， inflammatory factors， traditional Chinese medicine， and coronavirus disease-2019（COVID-19）. Nineteen clusters， including clinical efficacy， Chinese medicine， Lianhua Qingwen， COVID-19， and influenza A virus， and 47 emergent keywords， including herpes zoster， pneumonia， inflammatory factors， influenza， and gut microbiota， were generated. ConclusionCooperation and exchanges in this field are insufficient. Research focuses on the clinical efficacy of Lianhua Qingwen in the treatment of COVID-19 and other diseases， pharmacological action and mechanism of antiviral drugs， and micro-mechanism research focuses on related pathways and target proteins， as well as the combination of Chinese and western medicines.

Antidepressant mechanism of Shenling Kaixin Granules based on BDNF/TrkB/CREB pathway / 中国中药杂志

To investigate the antidepressant mechanism of Shenling Kaixin Granules(SLKX) in treating chronic unpredictable mild stress(CUMS) model rats. Ninety male SD rats were randomly divided into control group, model group, Shugan Jieyu Capsules(110 mg·kg~(-1)) group and SLKX low-(90 mg·kg~(-1)), medium-(180 mg·kg~(-1)), and high-dose(360 mg·kg~(-1)) groups. Depression rat model was replicated by CUMS method. After treatment, the behavioral changes of rats were evaluated by sugar preference, open field, elevated cross maze and forced swimming experiments. The contents of interleukin 1 beta(IL-1β), tumor necrosis factor α(TNF-α), brain-derived neurotrophic factor(BDNF) and 5-hydroxytryptamine(5-HT) in serum were determined by enzyme linked immunosorbent assay(ELISA), and the activities of superoxide dismutase(SOD) and catalase(CAT) in hippocampal CA1 region were also detected. Pathological changes in hippocampal CA1 region were detected by hematoxylin-eosin(HE) staining, and Western blot was used to determine the expression of nerve growth factor(NGF), BDNF, phospho-tyrosine kinase receptor(p-TrkB)/TrkB, phospho-cAMP-response element binding protein(p-CREB)/CREB, nuclear factor E2 related factor 2(Nrf2), heme oxygenase 1(HO-1), B-cell lymphoma-2(Bcl-2)/Bcl-2 associated X protein(Bax) and caspase-3 in hippocampal CA1 region. RESULTS:: showed that compared with the control group, the model group had decreased sugar preference, reduced number of entries and time spent in the center of open field and shortened total distance of movement, reduced number of entries and proportion of time spent in open arm, and increased number and time of immobility in forced swimming experiment. Additionally, the serum contents of IL-1β and TNF-α and the expression of caspase-3 were higher, while the contents of BDNF and 5-HT, the activities of SOD and CAT in hippocampal CA1 region, the expressions of NGF, BDNF, p-TrkB/TrkB, p-CREB/CREB, HO-1 and Bcl-2/Bax, and the Nrf2 nuclear translocation were lower in model group than in control group. Compared with the conditions in model group, the sugar preference, the number of entries and time spent in the center of open, total distance of movement, and the number of entries and proportion of time spent in open arm in treatment groups were increased while the number and time of immobility in forced swimming experiment were decreased; the serum contents of IL-1β and TNF-α and the expression of caspase-3 were down regulated, while the contents of BDNF and 5-HT, the activities of SOD and CAT in hippocampal CA1 region, the expressions of NGF, BDNF, p-TrkB/TrkB, p-CREB/CREB, HO-1, Bcl-2/Bax, and Nrf2 nuclear translocation were enhanced. In conclusion, SLKX might regulate the Nrf2 nucleus translocation by activating BDNF/TrkB/CREB pathway, lower oxidative stress damage in hippocampus, inhibit caspase-3 activity, and reduce apoptosis of hippocampal nerve cells, thereby playing an antidepressant role.

Chaihu Longgu Mulitang in Treatment of Coronary Heart Disease Complicated with Anxiety and Depression： A Review / 中国实验方剂学杂志

Coronary heart disease （CHD） with atherosclerosis is a common chronic disease worldwide， and anxiety and depression are potential and crucial risk factors for adverse prognosis in CHD. Chaihu Longgu Mulitang （CLMT）， first mentioned in the Shang Han Lun （《伤寒论》）， is a classic prescription for treating Shaoyang diseases combined with disturbance of the mind and spirit， with the effects of harmonizing Shaoyang and calming the mind. Current research on mechanisms has shown that CLMT can play a role in CHD complicated with anxiety and depression through multiple pathways， including regulating related signaling pathways， inhibiting the expression of inflammatory factors， improving oxidative stress damage， modulating neurotransmitter levels， suppressing the hypothalamic-pituitary-adrenal axis， promoting mobilization of mesenchymal stem cells from the bone marrow， and inhibiting platelet activation. Clinical studies have demonstrated that CLMT significantly improves symptoms such as angina and insomnia caused by CHD complicated with anxiety and depression， effectively reduces negative emotions， improves traditional Chinese medicine （TCM） syndrome scores， and decreases levels of inflammatory factors. Furthermore， it has fewer adverse reactions and higher safety than conventional western medicine treatments. This article provides a review of the mechanisms and clinical studies of CLMT in the treatment of CHD complicated with anxiety and depression based on a comprehensive analysis of literature from the China National Knowledge Infrastructure （CNKI）， Wanfang Data， VIP， PubMed， and other databases in the past 15 years， in order to provide references for further research on the use of CLMT in the management of CHD complicated with anxiety and depression.

Analysis on Quality Standard of Fraxini Cortex（Fraxinus chinensis） Dispensing Granules Based on Standard Decoction / 中国实验方剂学杂志

ObjectiveTo establish the quality standard for Fraxini Cortex（Fraxinus chinensis） dispensing granules based on standard decoction， and to provide a basis for the quality control of this dispensing granules. MethodHigh performance liquid chromatography（HPLC） specific chromatograms of 15 batches of Fraxini Cortex（F. chinensis） standard decoctions and 3 batches of Fraxini Cortex（F. chinensis） dispensing granules were established with the mobile phase of 0.1% phosphoric acid aqueous solution（A）-acetonitrile（B） for gradient elution（0-10 min， 12%-15%B； 10-30 min， 15%-32%B） and the detection wavelength of 220 nm. And similarity evaluation， cluster analysis and principal component analysis（PCA） were also carried out. HPLC quantitative analysis of multi-components by single marker（QAMS） was established to determine the contents of the main components in the standard decoctions and dispensing granules. The contents of the corresponding components in Fraxini Cortex（F. chinensis） decoction pieces were also detected， and the transfer rates from decoction pieces to standard decoctions and dispensing granules were calculated. ResultThe similarities between specific chromatograms of 15 batches of Fraxini Cortex（F. chinensis） standard decoctions and 3 batches of Fraxini Cortex（F. chinensis） dispensing granules were all>0.9， and 7 common peaks were identified. The results of cluster analysis and PCA showed that there was some differences in the composition of different batches of standard decoctions， but did not show aggregation of origin. As the standard decoctions， the extract rate was 6.18%-11.62%， the contents of esculin， syringin， fraxin， esculetin， fraxetin， calceolarioside B were 44.92-103.51， 1.36-11.87， 33.26-90.73， 4.63-29.75， 2.40-16.86， 2.49-17.35 mg·g-1， and the transfer rates from decoction pieces to standard decoction were 25.21%-42.54%， 52.57%-88.84%， 43.43%-79.45%， 49.15%-88.27%， 49.22%-72.69%， 27.66%-47.67%， respectively. The extract rates of Fraxini Cortex（F. chinensis） dispensing granules were 10.4%-10.7%， the transfer rates of the above six components from decoction pieces to dispensing granules were 42.76%-43.17%， 80.01%-80.90%， 59.59%-59.88%， 51.35%-52.67%， 60.50%-60.93%， 37.98%-38.37%， respectively， which were generally consistent with the transfer rates from decoction pieces to standard decoctions. ConclusionThe established quality control standard of Fraxini Cortex（F. chinensis） dispensing granules based on standard decoctions is reasonable and reliable， which can provide reference for the quality control and process research of this dispensing granules.

Efficacy of second session of endoscopic ultrasound-guided lauromacrogol ablation for pancreatic cystic neoplasms / 中华消化内镜杂志

Objective:To evaluate the efficacy and safety of the second session of endoscopic ultrasound-guided lauromacrogol ablation (EUS-LA) for pancreatic cystic neoplasms (PCNs).Methods:A total of 74 patients with suspected of PCNs who underwent EUS-LA in the First Medical Center of Chinese PLA General Hospital from April 2015 to December 2020 were enrolled in the study. Fifteen of them underwent the second ablation. The efficiency of EUS-LA was determined based on the change of lesion volume during the imaging follow-up, categorized into complete resolution (CR), partial resolution (PR) and stable disease (SD). The safety was determined by the complication incidence.Results:Among the 15 patients undergoing the second EUS-LA, there were 9 males and 6 females with age of 51.5±17.6 years. Thirteen patients completed imaging follow-up after the second EUS-LA, CR was achieved in 8 patients, PR in 2 patients and 3 in SD. The CR rate increased from 0 after the first ablation to 8/13 after the second ablation ( P=0.002). The median cyst diameter decreased from 22.0 mm before the second ablation to 15.0 mm after the second ablation ( Z=-2.666, P=0.008) and the median cyst volume reduced from 2 419.7 mm 3 to 1 099.5 mm 3 ( Z=-2.134, P=0.033). The complication incidence of the second ablation was 2/15, similar to that of the first ablation. Conclusion:The second ablation is effective and safe without increasing the complication incidence in patients without achieving CR after the first EUS-LA.

MiR-542-5p Inhibits Hyperglycemia and Hyperlipoidemia by Targeting FOXO1 in the Liver

Purpose@#This research was designed to investigate how miR-542-5p regulates the progression of hyperglycemia and hyperlipoidemia. @*Materials and Methods@#An in vivo model with diabetic db/db mice and an in vitro model with forskolin/dexamethasone (FSK/DEX)-induced primary hepatocytes and HepG2 cells were employed in the study. Bioinformatics analysis was conducted to identify the expression of candidate miRNAs in the liver tissues of diabetic and control mice. H&E staining revealed liver morphology in diabetic and control mice. Pyruvate tolerance tests, insulin tolerance tests, and intraperitoneal glucose tolerance test were utilized to assess insulin resistance. ELISA was conducted to evaluate blood glucose and insulin levels. Red oil O staining showed lipid deposition in liver tissues. Luciferase reporter assay was used to depict binding between miR-542-5p and forkhead box O1 (FOXO1). @*Results@#MiR-542-5p expression was under-expressed in the livers of db/db mice. Further in vitro experiments revealed that FSK/DEX, which mimics the effects of glucagon and glucocorticoids, induced cellular glucose production in HepG2 cells and in primaryhepatocytes cells. Notably, these changes were reversed by miR-542-5p. We found that transcription factor FOXO1 is a target of miR-542-5p. Further in vivo study indicated that miR-542-5p overexpression decreases FOXO1 expression, thereby reversing increases in blood glucose, blood lipids, and glucose-related enzymes in diabetic db/db mice. In contrast, anti-miR-542-5p exerted an adverse influence on blood glucose and blood lipid metabolism, and its stimulatory effects were significantly inhibited by sh-FOXO1 in normal control mice. @*Conclusion@#Collectively, our results indicated that miR-542-5p inhibits hyperglycemia and hyperlipoidemia by targeting FOXO1.

Application of abnormal cell-free DNA methylation in pancreatic juice in the early diagnosis of pancreatic cancer / 临床肝胆病杂志

Pancreatic cancer is a digestive system tumor with insidious onset, high malignancy, and difficult diagnosis, and early diagnosis is the key to improving the survival rate and prognosis of patients with pancreatic cancer. This article introduces the research advances in abnormal methylation of cell-free DNA in pancreatic juice and the early diagnosis of pancreatic cancer, and it is believed that the detection of cell-free DNA methylation in pancreatic juice may be an effective method for the early diagnosis of pancreatic cancer.

Chemistry, manufacturing and control considerations of rAAV-based gene therapy products / 药学学报

Recombinant adeno-associated virus (rAAV)-based vector has shown great promise for human gene therapy, due to its advantage in eliciting long-term transgene expression, absence of adverse effect, infection ability to both dividing and non-dividing cells, non-genomic integration, and low immunotoxity. To date, three AAV-based products have been authorized to enter European and American markets, and more than 200 rAAV-based candidates are in the process of clinic trails. Nevertheless, domestic industry is facing the challenge of manufacturing clinical grade rAAV vector, and regulatory agencies are lack of practical experience in assessing such products. Herein, this paper summarizes the latest research progress of rAAV-based gene therapy products, and discusses some quality assessment concerns in raw materials, manufacturing process and quality control, expecting to promote its clinical transformation and application.

Advance in Sarcopenia-related Dysphagia (review) / 中国康复理论与实践

Sarcopenia is an age-related syndrome of extensive, aggressive muscle mass loss and function reducing, which seriously affects the quality of life and social participation of the elderly. Dysphagia can increase the prevalence of sarcopenia, in another hand, sarcopenia can also implicate swallow related muscles, to increase the risk of malnutrition and aspiration. In recent years, the concept of sarcopenic dysphagia has been widely recognized in many researches. Sarcopenia is mainly screened with CT, MRI, ultrasound, and other auxiliary examination, as well as consensus guidelines. Interventions for it mainly include functional training, nutrition management and drug therapy. Early identification and intervention are important for the outcome and quality of life of patients.

Resveratrol extracted from Chinese herbal medicines: A novel therapeutic strategy for lung diseases / 中草药·英文版

Lung diseases and their related complications represent a critical source of morbidity and mortality globally and have become a research focus in recent years. There are plenty of hazards that threaten the health of lung by exposure to external environmental stimuli, such as dust, cigarette smoke, PM2.5, air pollution and pathogen infection. These risks lead to the impairment of lung function and subsequent lung diseases including pneumonia, chronic obstructive pulmonary disease (COPD), asthma and idiopathic pulmonary fibrosis (IPF). Compared with antibiotics and corticosteroids therapies, traditional Chinese medicine prescriptions are more effective with fewer side effects. A considerable variety of bioactive ingredients have been extracted and identified from Chinese herbal medicines and are used for the treatment of different lung diseases, including resveratrol. Increasing studies have reported promising therapeutic effects of resveratrol against lung diseases by inhibiting oxidative stress, inflammation, aging, fibrosis and cancer both in vitro and in vivo. In this review, the recent progress in the studies of lung-protective effects and underlying mechanisms of resveratrol and also highlight the potency of resveratrol and traditional Chinese prescriptions containing resveratrol as promising therapeutic options were summarized for the treatment of lung and respiratory diseases.

Effects of different fluid replenishment methods on internal environment, body thermal regulation response and severe heatstroke of 5-km armed cross-country training soldiers / 中华危重病急救医学

To explore the effects of different fluid replenishment methods on the internal environment, body thermal regulatory response and severe heatstroke of 5-km armed cross-country training soldiers. Methods A Special Force officers and soldiers who participated in 5-km armed cross-country training (2-3 times a week, 25-30 minutes each time for 3 weeks) during summer training from June to July in 2018 were enrolled, and they were divided into three groups according to the random number table, with 300 trainees in each group. 200 mL of drinking fluids were given to each group 15 minutes before and after each 5-km armed cross-country training: A group with boiled water, B group with purified water, and C group with beverage prepared by pharmaceutical laboratory of the 990th Hospital of PLA Joint Logistics Support Force (100 mL containing 6 g carbohydrates, 42 mg sodium, and 11 mg potassium). The venous blood was collected before and after the last training or during the onset of severe heatstroke to do the following tests: serum cardiac troponin I (cTnI, chemiluminescence), MB isoenzyme of creatine kinase (CK-MB, immunosuppressive), serum creatinine (SCr, enzymatic method), urea nitrogen (BUN, enzymatic method), alanine aminotransferase (ALT, tryptase), aspartate transaminase (AST, tryptase), and Na+, K+, Cl- (electrode method). The heart rate (HR) and core temperature (Tc, anal temperature) were monitored at the same time. The amount of sweat in training and the occurrence of severe heatstroke were also recorded. Results There was no significant difference in heart, liver, kidney function, electrolyte and body heat regulation reaction among three groups of 5-km armed cross-country trainees before training. Compared with before training, the levels of serum cTnI, CK-MB, SCr, BUN, ALT, AST, HR and Tc were significantly increased after training or during the onset of severe heatstroke in three groups, while the contents of Na+, K+, Cl- were significantly decreased, but the increase or decrease of group C was relatively smaller compared with group A and group B [cTnI (μg/L): 0.9 (0.6, 1.4) vs. 1.1 (0.7, 2.8), 1.0 (0.6, 3.3); CK-MB (U/L): 7.0 (5.0, 11.0) vs. 9.0 (6.0, 14.5), 8.0 (6.0, 15.0); SCr (μmol/L): 92.09±18.64 vs. 102.78±18.77, 103.64±20.07; BUN (mmol/L): 7 (6, 9) vs. 9 (8, 11), 10 (8, 13); ALT (U/L): 27 (22, 34) vs. 36 (30, 43), 34 (27, 43); AST (U/L): 37 (31, 48) vs. 41 (34, 50), 39 (34, 51); HR (bpm):87.01±17.07 vs. 95.88±21.06, 96.59±22.04; Tc (℃): 37.73±0.81 vs. 38.03±1.05, 38.10±1.04; Na+ (mmol/L):150.14±3.86 vs. 144.18±8.89, 144.04±9.39; K+ (mmol/L): 4.32±0.57 vs. 4.15±0.62, 4.13±0.51; Cl- (mmol/L):100.43±3.71 vs. 98.42±4.24, 98.41±4.58; all P < 0.01]. The incidence of severe heatstroke in group C was significantly lower than that in group A and group B [1.67% (5/300) vs. 5.00% (15/300), 5.33% (16/300), χ2 = 6.424, P = 0.040]. There was no significant difference in sweating volume in groups A, B, C (g: 370.47±48.71, 370.85±50.66, 370.17±50.21, F = 0.014, P = 0.986). There was no significant difference in the above indexes between group A and group B (all P > 0.05). Bi-classification Logistic regression analysis showed that the increase of HR, Tc and excessive loss of Na+, K+, Cl- were risk factors for severe heatstroke [odds ratio (OR) was 0.848, 0.138, 1.565, 17.996 and 2.328 respectively, all P < 0.01]. Conclusions Timely supplementation of carbohydrate, sodium and potassium ions can effectively change the internal environment and body heat regulation reaction of 5-km armed cross-country trainees, so as to reduce the occurrence of severe heatstroke. The increases of HR, Tc and excessive loss of Na+, K+, Cl- are risk factors for severe heatstroke.

Effects of training burnout and sleep quality on heat regulation response and severe heatstroke in people performed 5-km armed cross-country training / 中华危重病急救医学

Objective To explore the relationship between training burnout, sleep quality and heat regulation response, severe heatstroke in people performed 5-km armed cross-country training. Methods 600 male officers and soldiers who participated in 5-km armed cross-country training in summer from 2017 to 2018 were enrolled. All trainees participated in 5-km armed cross-country training in environment with ambient temperature > 32 ℃ and (or) humidity > 65%. They were divided into two groups according to whether severe heatstroke occurred during 5-km armed cross-country training. The age, military age, body mass index (BMI), physical fitness score, external environment (such as ambient temperature, relative humidity, wind speed, heat index), training burnout score and Pittsburgh sleep quality index scale (PSQI) score, heart rate (HR), core temperature (Tc), sweating volume and serum Na+, K+, Cl- levels were compared between the groups. The risk factors of severe heatstroke during 5-km armed cross-country training were screened by binary multivariate Logistic regression analysis. Results There were 26 cases of severe heatstroke in 600 trainees who participated in 5-km armed cross-country training, with an incidence of 4.33%. There was no significant difference in age, military age, BMI, physical fitness score and external environment of 5-km armed cross-country training between people with or without severe heatstroke. Compared with those without severe heatstroke, the dimensions of training burnout and the total average scores of training burnout of severe heatstroke personnel before 5-km armed cross-country training were increased significantly (physical and mental exhaustion score: 12.4±2.5 vs. 9.4±3.5, training alienation score: 8.8±2.8 vs. 5.8±2.3, low sense of achievement score: 8.2±2.7 vs. 5.6±2.3, total score of training burnout: 9.8±3.2 vs. 6.9±3.2, all P < 0.01), all factors except daytime dysfunction (DD) of PSQI and total PSQI score were also increased significantly [sleep quality (SQ) score: 1.0 (1.0, 2.0) vs. 1.0 (1.0, 1.0), fall asleep time (SL) score: 2.0 (1.0, 3.0) vs. 1.0 (1.0, 1.0), sleep time (SH) score: 1.0 (0.8, 2.0) vs. 1.0 (0, 1.0), sleep efficiency (SE) score: 1.0 (0, 1.0) vs. 0 (0, 0.8), sleep disorder (SD) score: 2.0 (1.0, 3.0) vs. 1.0 (0, 2.0), total PSQI score: 1.0 (1.0, 2.0) vs. 1.0 (0, 1.0), all P < 0.01], HR was increased significantly at onset (bpm: 120.00±10.57 vs. 86.49±14.91, P < 0.01), Tc was increased significantly (℃: 41.46±0.57 vs. 37.97±0.83, P < 0.01), serum electrolyte contents were decreased significantly [Na+ (mmol/L): 130.54±5.97 vs. 143.15±10.56, K+ (mmol/L): 3.72±0.44 vs. 4.37±0.50, Cl- (mmol/L):97.58±4.80 vs. 102.10±2.39, all P < 0.01], and the amount of sweat during training was increased significantly (g: 395.81±16.16 vs. 371.88±40.76, P < 0.01). Binary multivariate Logistic regression analysis showed that total score of training burnout [odd ratio (OR) = 0.653, 95% confidence interval (95%CI) = 0.563-0.757], total PSQI score (OR =0.693, 95%CI = 0.525-0.916), HR (OR = 0.871, 95%CI = 0.838-0.908), Tc (OR = 0.088, 95%CI = 0.043-0.179), sweating volume (OR = 0.988, 95%CI = 0.979-0.997), Na+ (OR = 1.112, 95%CI = 1.069-1.158), K+ (OR = 13.900, 95%CI = 5.343-36.166), Cl- (OR = 1.393, 95%CI = 1.252-1.550) were independent risk factors for severe heatstroke during 5-km armed cross-country training (all P < 0.01). Conclusion Increase in training burnout, total PSQI score, excessive changes of body heat regulation response and excessive loss of Na+, K+, Cl- in serum are independent risk factors for severe heatstroke during 5-km armed cross-country training under the same conditions with high temperature and humidity environment.

Chemistry, manufacturing and controls regulatory considerations for marketing authorization application of therapeutic antibody in China / 药学学报

The marketing authorization application is a milestone of drug life cycle, which indicates a candidate has potential to become a commercial drug. As of now, there are only 12 domestic therapeutic antibodies approved in China. The chemistry, manufacturing and controls (CMC) development and evaluation of monoclonal antibody were more challenging for both industry and authority agency. As the result of domestic biopharmaceutical industry development and implement of priority review system, the marketing authorization application of domestic antibody biosimilar and imported antibodies had dramatic increased in recent years. Thus, the CMC evaluation of monoclonal antibody become the important task of biological product's marketing authorization registration management. In the article, the CMC regulatory considerations for marketing authorization application based on author's review experience was proposed, in order to accelerate development and registration of commercial antibody in China.

The discussion on a proposed quality similarity assessment criteria of rituximab biosimilar / 药学学报

Recently, biosimilar antibodies have become a mainstream component of the biopharmaceutical industry in China. The principle requirements for the development and evaluation of biosimilars are based on proving similarity in product quality (analytical similarity) between a proposed biosimilar candidate and the originator reference drug. However, because the quality of a reference drug often varies during the life cycle and not all reference drug samples are able to collected by a biosimilar sponsor, it has not been practical to accurately determine the critical quality attributes as well as an accurate control range through the characterization of the limited number of reference drug lots that are typically collected. Therefore, the development and evaluation of biosimilars has been challenging both for industry and regulatory agencies. In this article, The Chemistry, Manufacturing and Control (CMC) dossier of the rituximab originator company and the dossiers of 18 biosimilar companieswere retrospectively analyzed. Furthermore, the assessment criteria to determine quality similarity of rituximab biosimilar candidates have been proposed, which criteria have been used by reviewing the physicochemical and biological properties data obtained from 123 lots of the reference drug. Moreover, some case studies have been provided that illustrate the application of the proposed analytical similarity criteria in the practice of drug evaluation.

Research progress, chemistry, manufacturing and controlsconsiderations of mesenchymal stem cell products / 药学学报

The number of clinical trials for mesenchymal stem cell (MSC) products ranked the top among all stem cell products, with more than 900 trials ongoing or completed by 2018. In China, many MSC clinical trials have started as "the third type of medical technique" and the dossiers of MSC products have been submitted to National Medical Products Administration (NMPA). The biological function and therapeutic effect of MSCs are constantly being recognized in scientific communities. However, the observed functions of MSCs in vitro are not fully reproduced in the living microenvironment in vivo. There are substantial variations among tissue origins, cellular phenotypes and biological functions. Different formulations, delivery methods, manufacture processes or doses all greatly affect the clinical efficacy. It is difficult for MSCs to maintain the naive state due to the differences between in vitro culture conditions and in vivo microenvironment. Meanwhile, there is no widely accepted scientific definition for MSCs until now, due to the complexity of manufacturing process and variable sources. Consequently, the regulation of MSC products is a challenge for drug administrative agencies. In this article, we review the research progress of MSC products around the world, and summarize the considerations in evaluating the chemistry, manufacturing and controls (CMC) section of MSC product applications, with respect to raw materials, manufacture processes and quality control. We hope that the information summarized here will provide insights for the development and evaluation of MSC products.

Effects of Soyasaponin on inflammatory factor level, antioxidant activity in severe heat stroke rats / 中国中西医结合急救杂志

Objective To observe the effects of Soyasaponins on inflammatory factors, antioxidant activity and exercise ability in rats with severe heat stroke. Methods Eighty male Sprague-Dawley (SD) rats were randomly divided into normal control group, heat shock model group, saline control group and Soyasaponin group, The rats that died during the experiment or with a low rectal temperature (< 41℃) were excluded, and finally 54 rats were included, 18 rats remaining in each group. The rats in the heat shock model group were placed in the simulated hot climate animal cabin at 30 ℃, and the temperature within 30 minutes was raised to 39 ℃ in the cabin with 65% humidity; in the mean time, the rat models of heat shock were replicated under the following situations: let the rats exercise on a treadmill with running speed set at 15 m/min, slope degree 0°, once running for 8 minutes, interval 2 minutes and the heat shock time was 90 minutes, the rats in the normal control group were fed in an environment with temperature ranging from 23-25 ℃ and relative humidity ranging from 50%-70%. After the establishment of models, the saline control group and Soyasaponin group were given daily saline and Soyasaponin (10 mg/kg) respectively by gavage for 3 consecutive months, while the heat shock model group was not given any treatment. The femoral artery blood was collected 24 hours after the rats left the cabin. The serum levels of interleukins (IL-6, IL-1β), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), malonaldehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) were measured by enzyme-linked immunosorbent (ELISA) and the contents of serum hemoglobin (Hb), serum urea (BUN), lactate dehydrogenase (LDH) and blood lactic acid (Lac) were measured by automatie biochemical analyzer. Results The levels of IL-6, IL-1β, TNF-α, IFN-γ, MDA, Hb, BUN, LDH, Lac in heat shock model group were significantly higher than those of the normal control group [IL-6 (ng/L): 86.17±4.82 vs. 12.60±3.49, IL-1β (ng/L): 83.00±5.98 vs. 15.70±3.64, TNF-α (ng/L): 72.22±6.93 vs. 13.75±2.69, IFN-γ (ng/L): 36.22±3.02 vs. 7.35±1.60, MDA (nmol/mg): 19.78±4.56 vs. 6.40±1.35, Hb (g/L): 136.22±1.93 vs. 126.75±5.84, BUN (mmol/L):21.06±3.44 vs. 5.65±1.35, LDH (μmoL·s-1·L-1): 9.65±0.83 vs. 2.12±0.17, Lac (mmol/L): 552.56±78.33 vs. 1.32±0.18, all P ＜ 0.05], SOD and GSH-Px were significantly lower than those in normal control group [SOD (kU/L):97.89±10.57 vs. 126.65±11.35, GSH-Px (kU/L): 19.22±2.58 vs. 43.45±4.02]; however, the levels of IL-6, IL-1β, TNF-α, IFN-γ, MDA, BUN, LDH and Lac in Soyasaponin group were significantly lower than those in heat shock model group [IL-6 (ng/L): 45.28±3.54 vs. 86.17±4.82, IL-1β (ng/L): 41.61±2.93 vs. 83.00±5.98, TNF-α (ng/L):37.22±2.46 vs. 72.22±6.93, IFN-γ (ng/L): 19.22±2.60 vs. 36.22±3.02, MDA (nmol/mg): 11.28±1.74 vs. 19.78±4.56, BUN (mmol/L): 11.78±2.13 vs. 21.06±3.44, LDH (μmoL·s-1·L-1): 3.70±0.26 vs. 9.65±0.83, Lac (mmol/L): 274.56±59.08 vs. 552.56±78.33, all P < 0.01], SOD, GSH-Px and Hb were significantly higher than those of heat shock model group [SOD (kU/L): 116.11±11.28 vs. 97.89±10.57, GSH-Px (kU/L): 31.17±2.90 vs. 19.22±2.58, Hb (g/L): 141.33±3.79 vs. 136.22±1.93, all P < 0.01]; there were no significant statistical differences in above indexes between heat shock model group and saline control group (all P > 0.05). Conclusion After heat shock and exercise management, the production and release of inflammatory factors are increased, and the level of lipid peroxidation was elevated in rats. The Soyasaponin can improve the ability to withstand heat shock and strong exercise by reducing the production and release of inflammatory factors and lipid peroxidation in the rats with severe heatstroke.

Observation of gastric injury induced by single large dose electron beam irradiation in Sprague-Dawly rats / 中华放射肿瘤学杂志

Objective To observe the gastric changes in adult male Sprague-Dawly (SD) rats irradiated by the single large dose electron beam,providing animal experimental evidence for intraoperative radiotherapy for gastric cancer.Methods Thirty-eight SD rats were randomly divided into the control and experimental groups.The stomach of the rats in the experimental group were subject to single 6 MeV 20 Gy irridiation by using the patent technology of Accurate Irradiation Experiment Table for Small Animal Radiation.The general conditions,gastric injury and body weight change were observed at different days following irradiation.Results The most severe gastric damage of rats was observed on the 14th d after irradiation.The gastric injury was gradually repaired accompanied with glandular atrophy at 28 d postirradiation,and the gastric injury was manifested as cellulose fibrinous repair on the 56th d after irradiation.Within 1 week post-irradiation,weight loss was noted in the experimental group,which significantly differed from the rats in the control group (P＜0.05).During the 2nd week,the body weight was increased in the experimental group,significantly lower compared with the rats in the control group (P＜ 0.05).The body weight of rats did not significantly differ between two groups at 6 weeks after irradiation (P＞ 0.05).Conclusions The most severe gastric injury is observed at 2 weeks after the single-dose 6 MeV electron beam 20 Gy irradiation,whereas no gastric perforation occurs.The gastric injury can be restored to normal status within 8 weeks following irradiation.

Treatment of Sanders type III fracture of the caIcaneus with poIymethyImethacryIate bone cement: a biomechanicaI study / 中国组织工程研究

BACKGROUND: Polymethylmethacrylate (PMMA), commonly known as bone cement, has been widely used in the orthopedic surgery. It ensures the immediate stability of prosthesis and the minimal micromotion at the cement-bone interface, allowing early weight-bearing after surgery. OBJECTIVE: To investigate the biomechanical performance of Sanders type III fracture of the calcaneus by using PMMA bone cement as a treatment. METHODS: Eight adult cadaveric ankle and calcaneus specimens were selected and served as normal controls after detection of biomechanical properties. Another eight specimens were collected and randomized into experimental group and control group to make a model of Sanders type III fracture in the calcaneus. In the experimental group, PMMA bone cement was injected into the defect area. In the control group, the artificial bone was implanted in the defect area and a steel plate was used to fix the lateral calcaneus. Biomechanical properties of the specimens in the experimental and control group were detected. RESULTS AND CONCLUSION: (1) Strain and stress of the calcaneus: The stress distribution of the calcaneus in the normal control group was consistent with that in the experimental group, and there was no significant difference between the two groups. The stress of the calcaneus in the experimental group was similar to that in the control group with no significant difference. (2) Displacement and axial stiffness of the calcaneus: Compared with the normal control group, the calcaneal displacement in the experimental group only decreased slightly, and there was no significant difference between the two groups, and likewise, the calcaneal displacement in the control group increased slightly. In the experimental group, the axial compression strength was (21.98±1.88) MPa and the axial compression stiffness was (1 633±150) N/mm. Therefore, there was no significant difference between the experimental group and the normal control group (P > 0.05). (3) Contact strength of the subtalar joint: Fractures basically recovered with good outcomes after PMMA bone cement injection. To conclude, by using PMMA bone cement in the treatment of calcaneus fractures, the scientific validity and clinical utility can be ensured.