Efficacy and safety of glucokinase activators for type 2 diabetes mellitus therapy：a meta-analysis / 中国药房

OBJECTIVE To systematically evaluate the efficacy and safety of glucokinase activators in the treatment of type 2 diabetes mellitus. METHODS PubMed， Cochrane Library， Web of Science， Embase and CNKI databases were searched from the inception to March 2022. Randomized controlled trials about glucokinase activators versus placebo （or other oral hypoglycemic agents） in the treatment of type 2 diabetes were included， data were extracted and meta-analysis was analyzed using RevMan 5.4 software. RESULTS A total of 9 studies with 215 0 patients were included. In terms of hypoglycemic effect， compared with control group， glucokinase activators significantly reduced glycosylated hemoglobin （HbA1c） [MD＝－0.40， 95%CI（－0.53， －0.26）， P＜0.000 01]， fasting blood glucose[MD＝－0.53， 95%CI（－0.85， －0.20）， P＝0.001] and 2 h postprandial blood glucose [MD＝－2.28， 95%CI（－2.68， －1.88）， P＜0.000 01] in diabetic patients. In terms of safety， the incidence of hypoglycemia caused by glucokinase activators was higher than control group on the whole [RR＝1.55， 95%CI（1.20，2.01）， P＝ 0.000 8]. According to the subgroup analysis of organs activated by glucokinase activator， the incidence of hypoglycemia in the pancreas-liver dual activator group [RR＝1.44， 95%CI（1.11，1.89）， P＝0.007] and liver-selective activator group [RR＝2.26， 95%CI（1.02，5.03）， P＝0.05] was higher than that in the control group， the difference was statistically significant. CONCLUSIONS Glucokinase activators can effectively reduce HbA1c， fasting blood glucose and 2 h postprandial blood glucose in patients with type 2 diabetes， but the risk of hypoglycemia remains to be addressed.

Pharmacoeconomic evaluation of clopidogrel versus aspirin for secondary prevention of ischemic stroke / 中国药房

OBJECTIVE To evaluate the cost-effectiveness of clopidogrel versus aspirin monotherapy regimens for secondary prevention of ischemic stroke and to provide economic evidence and reference for clinical medication and decision-making. METHODS Based on the CAPRIE trial， a Markov model was constructed； the probabilities of risk events， health utility values， and costs of risk event management were obtained from relevant literature. The cycle length was 6 months， and the time horizon was 10 years. A discount rate of 5% per year was applied. The primary outcomes were total costs， quality-adjusted life-years （QALYs）， and incremental cost-effectiveness ratio （ICER）. Cost-utility analysis was performed for above 2 regimens by using TreeAge Pro software. The one-way sensitivity analysis， probabilistic sensitivity analysis and scenario analysis were conducted to validate the robustness of the analyses. RESULTS Compared with the aspirin regimen （325 mg/d of CAPRIE trial dose）， the ICER values of clopidogrel regimen for secondary stroke prevention for 10 years， 20 years and 30 years were 4 284.06， 4 201.20 and 3 986.78 yuan/QALY， respectively， which were E-mail：liuxiaoyanrj@sjtu.edu.cn all less than the willing-to-pay （WTP） threshold of one time 。 China’s per capita gross domestic product （GDP） in 2021. E-mail：scilwsjtu-wb@yahoo.com Compared with the aspirin regimen （clinically recommended dose in China， 100 mg/d）， the ICER values of clopidogrel regimen for stroke secondary prevention for 10 years， 20 years and 30 years were 58 238.27， 42 164.72 and 36 164.77 yuan/QALY， respectively， which were all less than WTP threshold. When comparing with aspirin regimen of 325 mg/d， results of one-way sensitivity analysis showed that the cost of clopidogrel and aspirin， probability of the first recurrence of ischemic stroke were sensitive factors of model. Results of probabilistic sensitivity analysis showed that when WTP was set at one time GDP per capita in China in 2021， clopidogrel had a probability of being cost- effective of about 66.5%. Results of scenario analysis showed that neither changing the time horizon to 10， 20 or 30 years nor using different doses of aspirin （50， 100， 150， 200 or 250 mg/d） would not alter any conclusions. CONCLUSIONS Compared with aspirin monotherapy， clopidogrel monotherapy is more cost-effective for secondary prevention of ischemic stroke.

Anti-tumor Mechanisms of Bruceine D： A Review / 中国实验方剂学杂志

Malignant tumors seriously threaten human life and health. Radiotherapy and chemotherapy are the conventional methods for the clinical treatment of advanced tumors. The prognosis and efficacy are still far from satisfactory due to the radiotherapy has serious adverse effects on the body and the chemotherapy often causes problems such as tumor resistance and cell proliferationinhibition. Therefore， the search for new， safe， and effective anti-tumor drugs and the elucidation of their molecular mechanisms are effective measures for clinical treatment of tumors and improvement of patients' quality of life. Active ingredients derived from Chinese herbal medicines and natural products have gradually become a hot spot in the research and development of anti-tumor drugs due to their multi-target and multi-channel anti-tumor pharmacological activity characteristics and their advantages such as less adverse reaction on the body. Bruceine D is a class of tetracyclic triterpenoids extracted from the fruit of the Chinese herbal medicine Bruceae Fructus， with anti-inflammatory， anti-malarial， anti-parasitic， and other pharmacological activities， and its anti-tumor activity is particularly significant. Pharmacological studies have found that bruceine D can regulate various cellular physiological activities such as proliferation， apoptosis， invasion， and migration of lung cancer， liver cancer， pancreatic cancer， intestinal cancer， and other cancer cells by targeting different signaling pathways. Bruceine D can be used in combination with other chemotherapeutic drugs to improve the sensitivity of tumor cells to chemotherapeutic drugs， thereby reducing the adverse effect of chemotherapy. Clinical application practice has shown that Bruceae Fructus oil emulsion injection containing bruceine D has significant advantages in the efficacy and safety of tumor treatment. Although there are many studies on the antitumor pharmacological activity of bruceine D and its clinical efficacy is significant， the specific antitumor molecular mechanism of bruceine D is still unclear， and there is a lack of systematic review on the existing antitumor mechanism of bruceine D. Therefore， based on the research on bruceine D in China and abroad in recent years， this paper reviewed the anti-tumor effect and related molecular mechanisms of bruceine D from six aspects， namely， tumor cell proliferation， apoptosis， metastasis and invasion， glucose metabolism process， autophagy， and chemotherapy sensitivity. This paper is expected to provide a pharmacological basis and scientific reference for the antitumor drug development and clinical application of bruceine D.

Association between triglyceride glucose index and impairment of renal function in community-dwelling middle-aged and elderly population / 中华全科医师杂志

Objective:To explore the relationship between the triglyceride glucose (TyG) index and impairment of renal function in community-dwelling middle-aged and elderly population.Methods:A total of 4 988 residents aged ≥45 years undergoing health check-up in Yongshun Health Service Center from January 2016 to December 2021 were enrolled and followed up. According to the quartile of the baseline TyG index, all subjects were divided into Q1, Q2, Q3 and Q4 groups. The medical history, physical examination and laboratory test results were documented. Participants were followed up through regular health check-up until March 31, 2023. The outcomes were rapid decline of estimated glomerular filtration rate (eGFR) (a loss in eGFR>3 ml·min -1·1.73 m -2 per year) and the new-onset of chronic kidney disease (CKD) during the follow-up period. Linear regression model, multivariate logistic regression model, restricted cubic spline fitting logistic regression model and ROC curve analysis were used to analyze the association between the TyG index and the impairment of renal function. Results:Among 4 988 residents, 1 396 (28.0%) were males and the age was (59.76±6.28) years. There were 1 247 participants in Q1, Q2, Q3 and Q4 groups, respectively. After 56 months of follow-up, the incidence of rapid eGFR decline and new-onset CKD was 21.9% (1 294/4 988) and 4.0% (200/4 988), respectively. Multivariate logistic regression model analysis showed that TyG index was correlated positively with rapid eGFR decline and new-onset of CKD ( OR=1.34, 95%CI: 1.17-1.52, P<0.001, and OR=1.57, 95%CI:1.19-2.06, P=0.001). Taking group Q1 as a reference, higher levels of TyG index ( Q2, Q3 and Q4 groups) was an independent risk factor for rapid eGFR decline ( P<0.05), which has a dose-response relationship (for trend P=0.002). Compared with the lowest quartile, the adjusted OR of new-onset CKD in the highest quartile was 1.85 ( 95%CI:1.13-3.03, P=0.014). The results of restricted cubic spline fitting logistic regression analysis showed a linear association between TyG index and both outcomes (both P>0.05). The area under ROC curve ( AUC) of the TyG index for predicting the two adverse outcomes were 0.536 ( 95%CI: 0.516-0.556, P<0.001) and 0.588 ( 95%CI:0.548-0.627, P<0.001), respectively. Conclusion:The elevated levels of TyG index may be used as an independent predictor of rapid eGFR decline and new-onset CKD.

Comparison of efficacy and safety of TACE and DEB-TACE in treatment of patients with unresectable hepatocellular carcinoma / 中华肝胆外科杂志

Objective:To compare the clinical efficacy and safety of conventional transcatheter arterial chemoembolization (TACE) with drug-eluting bead transcatheter arterial chemoembolization (DEB-TACE) in treatment of patients with unresectable hepatocellular carcinoma.Methods:The data of patients with unresectable hepatocellular carcinoma who underwent hepatic artery chemoembolization at General Hospital of Ningxia Medical University from July 2019 to April 2020 were retrospectively analyzed. Of 282 patients who were enrolled, there were 233 males and 49 females, aged (55.9±10.0) years. The groups were divided into the conventional TACE group ( n=179) and the DEB-TACE group ( n=103) based on the treatments. The efficacy of the two groups was compared according to the modified response evaluation criteria in solid tumors. Postoperative adverse effects and liver function between the two groups were compared. Results:The differences in comparing the preoperative and postoperative liver function indexes between the two groups were not statistically significant. Patients who died and were lost to follow-up at 6 months after surgery were excluded and 240 patients were excluded in the efficacy analysis, with 148 patients in the conventional TACE group and 92 patients in the DEB-TACE group. At 6 months after treatment in the conventional TACE group, there were 64 patients (43.2%) with complete remission, 18 patients (12.2%) with partial remission, 27 patients (18.2%) with stable disease, and 39 patients (26.4%) with disease progression. In the DEB-TACE group, the corresponding figures were 38 patients (41.3%), 17 patients (18.5%), 26 patients (28.3%), and 11 patients (12.0%), respectively. The efficacy of DEB-TACE was better than conventional TACE with statistically significant differences between the 2 groups (χ 2=8.96, P=0.030). The incidence of postoperative embolic syndrome was 53.1% (95/179) in the conventional TACE group, which was significantly higher than the 34.0% (35/103) in the DEB-TACE group (χ 2=7.34, P=0.007). Conclusion:The efficacy and safety of DEB-TACE for unresectable hepatocellular carcinoma were superior to those of the conventional TACE group.

Contrasting effects of DOM and lisuride on impul-sive decision-making in delay discounting task / 中国药理学与毒理学杂志

OBJECTIVE The 5-HT2A receptor is the major target of classic hallucinogens.Both DOM(2,5-dimethoxy-4-methylamphetamine)and lisuride act at 5-HT2A receptors,and lisuride shares comparable affinity with DOM and acts as a partial agonist at 5-HT2A recep-tors.However,not like DOM,lisuride lacks hallucinogenic properties.Impulsive decision-making refers to the prefer-ence for an immediate small reinforcer(SR)over a delayed large reinforcer(LR).The current study aims to compare the effects of DOM and lisuride on impulsive decision-making and further to investigate the possible receptor mechanisms responsible for the actions of the two drugs.METHODS Impulsive decision-making was evaluated in male Sprague-Dawley rats by the percent-age of choice for the LR in delay discounting task(DDT).Delay to the LR changed in an ascending order(0,4,8,16,and 32 s)across one session.RESULTS DOM(0.3 and 0.5 mg·kg-1)increased impulsive decision-making,and the effects of DOM(0.5 mg·kg-1)was blocked by the 5-HT2A receptor antagonist ketanserin(1.0 mg·kg-1)rather than the 5-HT2C receptor antagonist SB-242084(1.0 mg·kg-1).Contrarily,lisuride(0.1,0.3 and 0.5 mg·kg-1)decreased impulsive decision-making.The effects of lisu-ride(0.3 mg·kg-1)were not antagonized by ketanserin(1.0 mg·kg-1),selective 5-HT1A antagonist WAY-100635(1.0 mg·kg-1)or selective dopamine D4 receptor antagonist L-745870(1.0 mg·kg-1),but were attenuated by the selec-tive dopamine D2/D3 receptor antagonist tiapride(40 mg·kg-1).CONCLUSION DOM and lisuride have contrasting effects on impulsive decision-making via distinct recep-tors.DOM-induced increase of impulsivity is mediated by the 5-HT2A receptor,while lisuride-induced inhibition of impulsivity is regulated by the dopamine D2/D3 receptor.

Health benefits of exercise rehabilitation in older adults with sarcopenia: a systematic review of systematic reviews / 中国康复理论与实践

ObjectiveTo analyze the disease and functioning characteristics of older adults with sarcopenia, the main exercise rehabilitation interventions, and its health benefits. MethodsLiterature related to exercise rehabilitation for older adults with sarcopenia was searched in PubMed, Medline, Embase, Cochrane Library and CNKI, from 2013 to 2023. The quality of included systematic reviews were evaluated. ICD-11 and ICF classification systems, and PICO framework from PRISMA guideline were used to report characteristics of the disease and functioning of the population, the exercise rehabilitation interventions, and its health benefits. ResultsFinally, seven systematic reviews from Netherlands, Spain, China, Brazil and Mexico were included, covering 98 related randomized controlled trials, involving 19 794 participants. These systematic reviews mainly came from the journals in the fields of aging, rehabilitation, nutrition, public health and physical exercise, and were published between 2018 and 2023. Exercise rehabilitation for sarcopenia were categorized into three types: exercise rehabilitation, exercise rehabilitation combined with nutritional supplementation, and exercise rehabilitation combined with nursing care. Interventions primarily included aerobic training, resistance training, gait training, strength training, and balance and flexibility exercises. The intervention frequency was six to 150 minutes, one to five times a week, with intensities ranging from low to high, over a duration of six to 144 weeks. The health benefits for older adults with sarcopenia from exercise rehabilitation were reflected in improvement in physical function and structure, and enhancement in activity and participation. In terms of body function and structure, exercise rehabilitation improved muscle strength, control, coordination, gait, balance, leg extension, leg press, back strength and grip strength, and increased muscle quality. In terms of activity and participation, exercise rehabilitation improved physical activity performance, such as walking speed and time of five-repetition chair stand test. ConclusionExercise rehabilitation for sarcopenia includes exercise rehabilitation, exercise rehabilitation combined with nutritional supplementation, and exercise rehabilitation combined with nursing care. Exercise rehabilitation can improve the physical function and structure, and enhance activity and participation.

Effects of KCNQ1OT1 Gene Knockout Combined with Bruceine D on Proliferation, Migration, and Invasion of Breast Cancer MDA-MB-231 Cells / 肿瘤防治研究

Objective To explore the effect of KCNQ1OT1 gene knockout combined with bruceine D on the proliferation, migration, and invasion of breast cancer MDA-MB-231 cells. Methods Cell Counting Kit-8, wound healing, and Transwell invasion assay were used to detect the effects of bruceine D and siKCNQ1OT1 on the viability, migration, and invasion of MDA-MB-231 cells. Effect of bruceine D and siKCNQ1OT1 on the expression of KCNQ1OT1 in MDA-MB-231 cells was detected by qRT-PCR. Western blot was used to detect the effect of bruceine D and siKCNQ1OT1 on the expression of EMT-related proteins and CDC42, p-MKK7, MKK7 proteins in MDA-MB-231 cells. Results Bruceine D and siKCNQ1OT1 could significantly inhibit the viability, migration, and invasion of MDA-MB-231 cells, and the inhibitory effect was enhanced when they were combined (all P < 0.05); bruceine D downregulated the expression of KCNQ1OT1 in MDA-MB-231 cells (all P < 0.05); bruceine D combined with siKCNQ1OT1 significantly decreased CDC42, p-MKK7, N-cadherin, and Vimentin expression in MDA-MB-231 cells and increased the expression of E-cadherin (all P < 0.05). Conclusion Bruceine D combined with siKCNQ1OT1 significantly inhibit the proliferation, migration, invasion, and EMT of human breast cancer MDA-MB-231 cells, and its molecular mechanism may be related to the blocking of CDC42/MKK7 signaling pathway.

Predicting Pathological Complete Response in Breast Cancer After Two Cycles of Neoadjuvant Chemotherapy by Tumor Reduction Rate: A Retrospective Case-Control Study / 한국유방암학회지

Purpose@#We aimed to identify effectiveness-associated indicators and evaluate the optimal tumor reduction rate (TRR) after two cycles of neoadjuvant chemotherapy (NAC) in patients with invasive breast cancer. @*Methods@#This retrospective case-control study included patients who underwent at least four cycles of NAC at the Department of Breast Surgery between February 2013 and February 2020. A regression nomogram model for predicting pathological responses was constructed based on potential indicators. @*Results@#A total of 784 patients were included, of whom 170 (21.68%) reported pathological complete response (pCR) after NAC and 614 (78.32%) had residual invasive tumors. The clinical T stage, clinical N stage, molecular subtype, and TRR were identified as independent predictors of pCR. Patients with a TRR > 35% were more likely to achieve pCR (odds ratio, 5.396; 95% confidence interval [CI], 3.299–8.825). The receiver operating characteristic (ROC) curve was plotted using the probability value, and the area under the ROC curve was 0.892 (95% CI, 0.863–0.922). @*Conclusion@#TRR > 35% is predictive of pCR after two cycles of NAC, and an early evaluation model using a nomogram based on five indicators, age, clinical T stage, clinical N stage, molecular subtype, and TRR, is applicable in patients with invasive breast cancer.

Effects of genistein supplementation on the characteristics of human sperm during liquid storage

Cryopreservation, the most popular way to preserve human sperm, led to a significant decline in sperm motility. Here, we tried to introduce a new method to store sperm without freezing. Different concentrations of genistein were added to liquid preserved sperm. We investigated the effects of supplementation on sperm total antioxidative capacity (T-AOC), glutathione(GSH), methane dicarboxylic aldehyde (MDA), acrosomal enzyme activity, and fertilization ability of sperm. The effects of liquid storage and cryopreservation on sperm parameters were also compared. IVF medium supplemented with genistein (20µmol L-1 ) maintained sperm motility for up to 11 days. The addition of genistein led to a decrease in reactive oxygen species (ROS) generation that demonstrated an effective improvement in sperm motility and decreased the MDA production and maintained the GSH content and enhanced the oxidative stress resistance ability of the sperm during liquid storage. The storage sperm were used for intracytoplasmic sperm injection(ICSI) into human oocytes and activated oocytes successfully. Sperm stored in liquid medium containing genistein was superior to sperm stored in liquid nitrogen in terms of antioxidant stress and fertilization ability. We confirmed that genistein could be used as an antioxidant for the liquid storage of sperm. Sperm stored in an IVF medium with genistein could avoid cryodamage, which may become an alternative option in assisted reproduction technology. (Afr J Reprod Health 2022; 26[7]: 72-82)

Analysis of pathogenic genes in two cases of Sj?gren-Larsson syndrome / 中华皮肤科杂志

Objective:To detect pathogenic mutations in 2 patients with Sj?gren-Larsson syndrome.Methods:Clinical data were collected from 2 children with Sj?gren-Larsson syndrome, who were diagnosed and treated in Department of Dermatology, Capital Institute of Pediatrics, and genetic testing was performed to clarify their pathogenic mutations.Results:Both the 2 patients presented with typical ichthyosis-like skin manifestations, accompanied by a certain degree of intellectual disorder and growth, development and motor retardation. A previously reported homozygous mutation c.1157A>G was identified in the ALDH3A2 gene in case 1; compound heterozygous mutations c.1157A>G and c.1309A>T were identified in the ALDH3A2 gene in case 2, which were considered as novel pathogenic mutations.Conclusion:Genetic testing should be performed as early as possible in patients with suspected Sj?gren-Larsson syndrome, in order to facilitate early definite diagnosis.

Variability in reference for serum metabolomics profiles among healthy Han people in different regions of China / 中华内分泌代谢杂志

Objective:To establish the reference for serum metabolomics profiles among healthy Han adults in China, and explore the variation on metabolomics profiles by geographic regions, sex, and age.Methods:Cross-sectional data and serum samples were obtained from the China National Health Survey. A total of 1 039 male and 1 032 female healthy adults(≥30 years) were included in this study. Serum metabolomics analyses were conducted with ultra-performance liquid chromatography-mass spectrometry(UPLC-MS). Orthogonal partial least squares discriminant analysis(OPLS-DA) was performed to compare the differences of metabolomics among different region, sex, and age.Results:Significant differences on metabolomics profiles were identified among region, sex, and age. A total of 114 region-related metabolites were spotted, including 53 metabolites that involved in human metabolic pathways, mainly peptides(20 metabolites) and glycerophospholipid metabolism-related(14 metabolites). Fifty-nine metabolites were pinned down to be sex-related, among which cotinine was significant in all 7 provinces. Age-related metabolites were only found in Shaanxi and Hainan, with 22 metabolites were recognized.Conclusion:Serum metabolomics varies by geographic regions, sex, and age. When metabolomics is applied for diagnosis or biomarker screening in various studies, it shall take into consideration of setting tailored references.

The formula and medication rules of Chinese patent medicines for jaundice based on data mining / 国际中医中药杂志

Objective:To analyze the formula and medication rules based on the Chinese patent medicines database for treating jaundice, so as to provide reference for the treatment of jaundice.Methods:By using descriptive statistics and data mining methods to analyze the current condition of Chinese patent medicines treating jaundice, Chinese medicines that are frequently appeared and the Chinese medicine paris as well as the combination of mediicnes, and then by using complex network clustering and topology parameter analysis to screen the potential formulations and core Chinese medicines.Results:Seventy-nine Chinese patent medicines with the function of heat-clearing and detoxification were obtained, heat-clearing and removing dampness, and removing jaundice. A total of 233 Chinese medicines are involved, and the most frequently used are Artemisiae Scopariae Herba, Glycyrrhizae Radix et Rhizoma, Bupleuri Radix, Gardeniae Fructus, Scutellariae Radix, etc. The Chinese medicine pairs with high association rule support were Scutellariae Radix- Artemisiae Scopariae Herba, Gardeniae Fructus- Artemisiae Scopariae Herba, Glycyrrhizae Radix et Rhizoma- Artemisiae Scopariae Herba, etc. Based on the compatibility network, four clusters with close connection were obtained, including 23 Chinese medicines. According to the degree and closeness index, the core nodes of Artemisiae Scopariae Herba, Bovis Calculus, Carthami Flos, Glycyrrhizae Radix et Rhizoma, Aucklandiae Radix, Cyperi Rhizoma, Rhei Radix et Rhizoma, Bupleuri Radix, Salviae Miltiorrhizae Radix et Rhizoma were obtained. Conclusion:The combination of herbs and formula for treating icterus conforms to the TCM theory and clinical practice, which could provide reference for the treatment of icterus with TCM and related Chinese patent medicine research.

Advances in Kawasaki disease combined with giant coronary aneurysm / 国际儿科学杂志

Kawasaki disease coronary artery lesions have become one of the common acquired cardiovascular diseases in children in some countries and regions.Giant coronary artery aneurysms are a severe type of Kawasaki disease coronary artery lesion with less likelihood of complete recovery at a later stage, and their cardiovascular event rate and mortality are significantly higher than those of other children with Kawasaki disease.Children with giant coronary aneurysms are at higher risk of cardiovascular disease in adulthood and are closely associated with sudden cardiac death in young adulthood and the development of coronary atherosclerosis in adulthood, with serious implications for the long-term prognosis and quality of life of the child.This article reviews the clinical features and prognosis of Kawasaki disease combined with giant coronary aneurysms.

Epidemiology, pathogenesis and early identification of coronary artery lesions in Kawasaki disease / 国际儿科学杂志

Coronary artery lesions are the most serious complications of Kawasaki disease.The incidence of Kawasaki disease is still on the rise in recent years, and the proportion of children with coronary artery dilatation increased in parallel with the incidence of Kawasaki disease.But the incidence of severe coronary artery lesions, such as giant coronary aneurysms, coronary artery stenosis and even occlusion is stable or declining.The pathological changes of coronary artery disease are different with the severity and duration of the disease.Early recognition of coronary artery lesions should not be limited to the observation of luminal dimensions, but also should be explored in depth about the changes of coronary artery structure and function.

The Dilemma and Consideration about the Construction of the Subject Protection System / 中国医学伦理学

Relying only on the ethics committee to protect subjects is not enough, and the construction of the subject protection system is an inevitable trend for the protection of subjects’ rights. This paper elaborated on the current situation of Chinese subject protection system from four aspects: the lack of laws and regulations and administrative supervision, the insufficient attention of hospitals, poor construction of the subject protection system, and the absence of responsibilities of relevant personnel. Then this paper put forward countermeasures from three aspects: improving laws and regulations and strengthening supervision, mobilizing relevant departments to participate, and strengthening relevant training, in order to standardize the construction of the subject protection system and promote the development of the subject protection work.

Characteristics and associated factors of visual and motor integration in children with developmental dyslexia and attention deficit hyperactivity disorder / 中国学校卫生

Objective@#To investigate the characteristics of visual motor integration in children with developmental dyslexia and ADHD, and to provide a reference for the diagnosis and treatment of these children.@*Methods@#During July to November of 2020，students from grade 3 to grade 5 of 7 primary schools in Xinjiang were selected by using random cluster sampling method. A total of 56 dyslexia group (group DD), attention deficit hyperactivity disorder group (group ADHD), comorbidity group and normal control group were selected and compared the differences of their visual motor integration ability and related factors ability. Multiple linear regression analysis was used to explore the predictive effects of related factors on visual motor integration ability.@*Results@#The scores of visual integration ability and visual perception in comorbidity group (95.05±14.01, 12.71±7.40) were lower than those in DD group (104.77±17.19，23.04±11.48), ADHD group (104.00±14.11，25.70±10.74) and normal control group (129.80±12.91, 44.05±16.56) ( F/Z =58.24,110.49, P <0.05). The visual working memory score of the comorbidity group ( 73.64 ±5.36) was lower than the normal control group (78.96±4.68) ( P <0.05)，and there was no significant difference between the DD group (74.48±7.06) and the ADHD group (75.98±7.36) ( P >0.05). The results of multiple regression showed that visual perception, age, IQ and visual working memory were associated with visual and motor integration ability of dyslexia children with ADHD ( R 2=0.32，0.17，0.11， 0.04 ， P <0.05).@*Conclusion@#Visual motor integration and visual perception among children with DD combined ADHD are more severely impaired than those with ADHD and DD alone. Visual perception, age, IQ and visual working memory could help predict the development of visual and motor integration ability in children with DD combined ADHD.

Crosstalk between CYP2E1 and PPARα substrates and agonists modulate adipose browning and obesity

Although the functions of metabolic enzymes and nuclear receptors in controlling physiological homeostasis have been established, their crosstalk in modulating metabolic disease has not been explored. Genetic ablation of the xenobiotic-metabolizing cytochrome P450 enzyme CYP2E1 in mice markedly induced adipose browning and increased energy expenditure to improve obesity. CYP2E1 deficiency activated the expression of hepatic peroxisome proliferator-activated receptor alpha (PPARα) target genes, including fibroblast growth factor (FGF) 21, that upon release from the liver, enhanced adipose browning and energy expenditure to decrease obesity. Nineteen metabolites were increased in Cyp2e1-null mice as revealed by global untargeted metabolomics, among which four compounds, lysophosphatidylcholine and three polyunsaturated fatty acids were found to be directly metabolized by CYP2E1 and to serve as PPARα agonists, thus explaining how CYP2E1 deficiency causes hepatic PPARα activation through increasing cellular levels of endogenous PPARα agonists. Translationally, a CYP2E1 inhibitor was found to activate the PPARα-FGF21-beige adipose axis and decrease obesity in wild-type mice, but not in liver-specific Ppara-null mice. The present results establish a metabolic crosstalk between PPARα and CYP2E1 that supports the potential for a novel anti-obesity strategy of activating adipose tissue browning by targeting the CYP2E1 to modulate endogenous metabolites beyond its canonical role in xenobiotic-metabolism.

Determination of a reasonable threshold of total bilirubin for the diagnosis of hepatitis B virus-associated acute-on-chronic liver failure / 临床肝胆病杂志

Objective To investigate a reasonable threshold of total bilirubin for the diagnosis of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF), and to realize accurate early diagnosis. Methods A retrospective analysis was performed for the clinical data of 1232 patients with HBV-ACLF who were admitted to The Fifth Medical Center of Chinese PLA General Hospital from September 2008 to September 2018, and according to the baseline serum level of total bilirubin (TBil), the patients were divided into group A (TBil 15%) in patients with acute-on-chronic liver failure (ACLF). Although there was a difference in long-term mortality rate between the two groups, there was no significant increase in transplant-free mortality rate after 90 days in either group. Conclusion Under the premise of international normalized ratio ≥1.5, it is not recommended to increase the threshold of TBil to 205.2 μmol/L in the diagnostic criteria for HBV-ACLF, so as to ensure the early diagnosis of more ACLF patients and bring more opportunities for treatment and cure.

Comparison of evaluation system for clinical value of antineoplastic agents at home and abroad / 中国药房

OBJECTI VE To introduce the evaluation system for clinical value of antineoplastic agents at home and abroad ，and to provide reference for continuous improvement of clinical value-oriented antineoplastic agents development and research guideline in China. METHODS The suggestions were put forward to improve the evaluation system for clinical value of antineoplastic agents in China by consulting the relevant data of evaluation system for clinical value of antineoplastic agents at home and abroad and domestic antineoplastic agents R&D and management policies ，sort outing and analyzing comparatively their dimensions ， perspectives，target audiences ，application scope ，advantages and disadvantages. RESULTS & CONCLUSIONS Seven foreign value evaluation systems （value assessment framework of American Society of Clinical Oncology ，clinical benefit scale of European Society of Clinical Oncology ，value evaluation framework of American Institute of Clinical and Economic Evaluation ， etc.）had their own characteristics and unique advantages under different settings ；several value evaluation systems differed in the criteria for defining value ，depending on the perspective and population they focus on. The value dimensions were constantly changing dynamically in response to scientific values and social needs ，including not only safety ，efficacy and cost-effectiveness ， but also innovation ，fairness，quality of life attributes. Some evaluation systems adopted value assessment tools that followed the trend of the information age in the presentation form and assessment mode ，which promoted shared decision-making between doctors and patients. Combining the characteristics of foreign value evaluation system and the current situation of development and application of antineoplastic agents in China ，we can have a deeper understanding of drug efficacy ，safety，quality of life ，research and development cost and pricing in the future. Antineoplastic 2021-10-28） agents will have a more reasonable position to solve the unmet needs of patients from the perspectives of drug research and development， clinical application ， drug accessibility and fairness.