Toxicokinetics of MDMA and Its Metabolite MDA in Rats / 法医学杂志

Objective To investigate the toxicokinetic differences of 3,4-methylenedioxy-N-methylamphetamine(MDMA)and its metabolite 4,5-methylene dioxy amphetamine(MDA)in rats af-ter single and continuous administration of MDMA,providing reference data for the forensic identifica-tion of MDMA.Methods A total of 24 rats in the single administration group were randomly divided into 5,10 and 20 mg/kg experimental groups and the control group,with 6 rats in each group.The ex-perimental group was given intraperitoneal injection of MDMA,and the control group was given intraperi-toneal injection of the same volume of normal saline as the experimental group.The amount of 0.5 mL blood was collected from the medial canthus 5 min,30 min,1 h,1.5 h,2 h,4 h,6 h,8 h,10 h,12 h after administration.In the continuous administration group,24 rats were randomly divided into the experi-mental group(18 rats)and the control group(6 rats).The experimental group was given MDMA 7 d by continuous intraperitoneal injection in increments of 5,7,9,11,13,15,17 mg/kg per day,respectively,while the control group was given the same volume of normal saline as the experimental group by in-traperitoneal injection.On the eighth day,the experimental rats were randomly divided into 5,10 and 20 mg/kg dose groups,with 6 rats in each group.MDMA was injected intraperitoneally,and the con-trol group was injected intraperitoneally with the same volume of normal saline as the experimental group.On the eighth day,0.5 mL of blood was taken from the medial canthus 5 min,30 min,1 h,1.5 h,2 h,4 h,6 h,8 h,10 h,12 h after administration.Liquid chromatography-triple quadrupole tandem mass spectrometry was used to detect MDMA and MDA levels,and statistical software was employed for data analysis.Results In the single-administration group,peak concentrations of MDMA and MDA were reached at 5 min and 1 h after administration,respectively,with the largest detection time limit of 12 h.In the continuous administration group,peak concentrations were reached at 30 min and 1.5 h af-ter administration,respectively,with the largest detection time limit of 10 h.Nonlinear fitting equations for the concentration ratio of MDMA and MDA in plasma and administration time in the single-administration group and continuous administration group were as follows:T=10.362C-1.183,R2=0.974 6;T=7.397 3C-0.694,R2=0.961 5(T:injection time;C:concentration ratio of MDMA to MDA in plasma).Conclusions The toxicokinetic data of MDMA and its metabolite MDA in rats,obtained through single and continuous administration,including peak concentration,peak time,detection time limit,and the relationship between concentration ratio and administration time,provide a theoretical and data foundation for relevant forensic identification.

Preparation process for initiating extracorporeal cardiopulmonary resuscitation in hospital: best evidence summary / 中国实用护理杂志

Objective:To retrieve, evaluate and integrate the evidence related to the preparation process for initiating extracorporeal cardiopulmonary resuscitation in hospital, so as to provide reference for clinical implementation of extracorporeal cardiopulmonary resuscitation.Methods:According to the evidence-based nursing method and the 6S evidence model, guidelines, clinical decisions, expert consensus, systematic review and other literatures related to the preparation process for initiating extracorporeal cardiopulmonary resuscitation in hospital were searched from National Guideline Clearinghouse, Scottish Intercollegiate Guidelines Network, National Institute for Health and Care Excellence, and other websites, UpToDate, The Cochrane Library, PubMed, Embase, CNKI, Wanfang and other databases. The retrieval date limit was from the establishment of the database to May 20, 2023. Researchers assessed the quality of the included articles, and extracted and summarized the evidence that met the quality standards.Results:A total of 11 articles were included, including 2 guidelines, 6 expert consensuses, 1 systematic review and 2 quasi-experimental studies. A total of 18 pieces of evidences were summarized from 6 aspects, including medical conditions, team building, materials management, operation mechanism, pre-initiating treatment and initiating judgment.Conclusions:This study summarizes the evidence of preparation process for initiating extracorporeal cardiopulmonary resuscitation in hospital, which can provide reference for promoting the implementation of extracorporeal cardiopulmonary resuscitation. Future studies still need to focus on team building, personnel training and assessment, and optimisation of the management system, so as to improve the efficiency and readiness of treatment.

New trends and developments of functional training research in the field of health care / 中国组织工程研究

BACKGROUND:Functional training has been popular in recent years,but it is mainly applied in sports training field.There are still insufficient studies and applications in medical and health fields. OBJECTIVE:To provide a theoretical basis for relevant research in sports,medical and health fields,through a more comprehensive and in-depth exploration and analysis of the research hot spots,ideological trends,frontiers and development trends of international functional training in the field of medical and health care. METHODS:The 2 206 high-quality articles addressing health-related functional training during 2012-2022 were exported from the Web of Science Core Set Database as the object of analysis.Combined with research methods such as literature analysis,Citespace V analysis software was used for visual analysis of keywords,subject categories and highly cited literatures. RESULTS AND CONCLUSION:The number of articles published on functional training in the field of health is on the rise.There are more articles from the United States,with a larger impact.China also has a high volume of publications,but the impact and depth of research is lacking.Improving physical and mental health and cognitive ability of middle-aged and older people is the main focus,followed by preventing sports injuries and promoting recovery in athletes.In the future,more research will be conducted on teenagers,the disabled and other groups,and there will be a continued increase in injury prevention and recovery promotion for athletes.Chinese scholars have less research on the effects of functional training on the physical health of the general public,and more attention should be paid to improving the physical and mental health of the general public.

Design,synthesis and properties of oral composite resin monomers with different photoinitiators / 中国组织工程研究

BACKGROUND:At present,the dental composite resin filling material composed of resin matrix monomer is the first choice material for the filling treatment of dental defects,but with the increase of its use time in the oral environment,the dental tissue will develop secondary caries and the filling material will wear and break.The main cause of these problems is the polymerization shrinkage of the filling material and its mismatch with the mechanical properties of the dental tissue. OBJECTIVE:To synthesize a new type of dental composite resin monomer by adding initiators with different components,to improve the traditional double bond conversion rate of the system and further improve the mechanical properties of the material. METHODS:A new composite resin matrix system was prepared by adding different initiators to the monomer of 3,3′,5,5′-tetramethoxybiphenyl-4,4′-diol epoxy acrylate resin.In group A,camphorquinone with a mass fraction of 1.1%was added.In group B,1-phenyl-1,2-propanedione with a mass fraction of 2.1%was added.In group C,a mixture of camphorquinone and 1-phenyl-1,2-propanedione(a mass ratio of the two was 1:1)with a mass fraction of 3.1%was added.The double bond conversion,polymerization shrinkage and mechanical properties of the samples were determined. RESULTS AND CONCLUSION:(1)The double bond conversion rate of groups B and C was higher than that of group A(P<0.05).The polymerization shrinkage of group B was higher than that of group A(P<0.05),while that of group C was lower than that of group A(P<0.05).(2)The flexural strength,elastic modulus and compressive strength of groups B and C were higher than those of group A(P<0.05,P<0.01).Vickers hardness of group B was higher than that of group A(P<0.05),and the Vickers hardness of group C was lower than that of group A(P<0.01).(3)These findings suggest that 1-phenyl-1,2-propanedione is an initiator with ideal performance.The combined application of 1-phenyl-1,2-propanedione and camphorquinone can effectively improve the double bond conversion rate of the resin matrix system and further improve the mechanical property of the resin.

Mechanism of Yantiao Fang regulating the Rho/ROCK signaling pathway in apoptosis of intestinal epithelial cells in mice with acute gastrointestinal injury caused by sepsis / 中国比较医学杂志

Objective To investigate the effect of Yantiao Fang on apoptosis of intestinal epithelial cells in mice with acute gastrointestinal injury caused by sepsis by regulating the Rho/ROCK signaling pathway.Methods Seventy BALB/c mice were randomly divided into normal,sham,and model groups.Except for normal and sham groups,mice were subjected to cecal ligation and perforation to establish a mouse model of acute gastrointestinal injury caused by sepsis.The mouse models were randomly divided into model,Low,Medium,and High dose of Yantiao Fang,and ROCK inhibitor groups.Histopathological changes of the ileum were observed by HE staining.Serum levels of IL-1β,IL-6,TNF-α,and IL-10 were measured by ELISA.PCNA and Ki-67 expression was detected by immunohistochemistry.Cleaved caspase3 and Bax expression was detected by Western blot.ROCK and MLC mRNA expression in the ileum was measured by RT-qPCR.Results Compared with normal and sham groups,Chiu's pathological score,proinflammatory factor(IL-1β,IL-6,and TNF-α)levels,cleaved caspase3 and Bax protein expression,and ROCK and MLC mRNA levels were increased in the model group(P＜0.05).Moreover,anti-inflammatory mediator IL-10 and expression of PCNA and Ki-67 in the ileum were decreased in the model group(P＜0.05).Compared with the model group,histopathological changes of the ileum in all Yantiao Fang groups were improved by various degrees with the increase in dose.Chiu's pathological score,IL-1β,IL-6,and TNF-α serum levels,cleaved caspase3 and Bax protein expression,and ROCK and MLC mRNA levels were decreased in Yantian Fang groups(P＜0.05).The IL-10 level and expression of PCNA and Ki-67 in the ileum were increased in Yantian Fang groups(P＜0.05).Conclusions Yantiao Fang may inhibit apoptosis of intestinal epithelial cells in mice with acute gastrointestinal injury due to sepsis by regulating the Rho/ROCK signaling pathway,thereby alleviating intestinal tissue inflammation and ultimately preventing intestinal mucosal tissue injury.

Effects of Mild Moxibustion on Proteins Expression of BDNF/TrkB Signaling Pathway in Hypothalamus of Primary Dysmenorrhea Rats with Cold and Dampness Stagnation Syndrome / 中国中医药信息杂志

Objective To observe the analgesic effects of mild moxibustion on primary dysmenorrhea(PD)rats with cold and dampness stagnation syndrome and its effect on BDNF/TrkB signaling pathway in hypothalamus;To explore its mechanism for the treatment of PD.Methods A total of 32 Wistar non-pregnant female rats were randomly divided into blank group,model group,Western medicine group and mild moxibustion group,with 8 rats in each group.Except for the blank group,the other groups received estradiol benzoate intraperitoneal injection combined with ice bath treatment + oxytocin intraperitoneal injection to establish PD with cold and dampness stagnation syndrome model.The mild moxibustion group received treatment at"Shenque"and"Guanyuan"from the eighth day of modeling for 10 min,and the Western medicine group was given ibuprofen solution intragastically for 4 days.The latency period of rats twisting was observed and the twisting score was calculated,Western blot and PCR were used to detect the expressions of c-fos,BDNF,TrkB protein and mRNA in hypothalamic tissue.Results Compared with the blank group,the model group showed a shortened latency period and an increased twisting score(P<0.01),the expressions of c-fos,BDNF,TrkB protein and mRNA in hypothalamic tissue increased(P<0.01,P<0.05).Compared with the model group,the mild moxibustion group had a longer latency period and lower twisting score(P<0.01),while the expressions of c-fos,BDNF,TrkB protein and mRNA in hypothalamic tissue increased(P<0.01,P<0.05).Conclusion Mild moxibustion may effectively improve the pain state of PD rats with cold and dampness stagnation syndrome.This mechanism may be related to downregulating c-fos expression,inhibiting BDNF/TrkB signaling pathway activation,thereby inhibiting pain signal transmission,regulating pain occurrence and maintenance.

XEN drainage tube implantation combined with mitomycin C for open angle glaucoma / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the clinical efficacy and safety of XEN drainage tube implantation combined with mitomycin C(MMC)for open angle glaucoma(OAG).METHODS:A total of 37 OAG patients(37 eyes)were retrospectively included, grouped by anti-glaucoma surgical treatment as the first choice or not, with 17 patients(17 eyes)in the group with primary surgical treatment, and 20 patients(20 eyes)in the group with the numerous surgeries. The intraocular pressure(IOP), kinds of IOP-lowering drugs, and complications were collected and analyzed in 1 a follow-up postoperatively.RESULTS:Upon the one-year follow-up, IOP had decreased from 27.56±9.94, 28.43±14.18 mmHg to 15.16±3.65, 17.18±5.83 mmHg in both groups, respectively, representing a reduction of 55.01% and 60.43%, respectively(t=4.863, P&#x003C;0.001; t=3.255, P=0.004). The IOP at various follow up points were lower than preoperative points in both groups(Ftime=6.876, Ptime&#x003C;0.001; Fintergroup=0.242, Pintergroup=0.626; Ftime×intergroup=0.959, Ptime×intergroup=0.458). The complete success rate was 47% and 45%, the qualified success rate was 76% and 75%(Z=-0.115, P=0.909), respectively, and there was no significant difference in the cumulative survival rate between two groups(χ2=0.042, P=0.838; χ2=0.004, P=0.949). At the last follow up, IOP-lowering drugs were reduced from 3(2, 3)to 1(0, 2)in both groups(Z=-3.289, -3.796, all P&#x003C;0.001), and no significant difference between groups(Z=-0.581, P=0.561). Hypotony is the most common short-term complications, anterior chamber haemorrhage followed, while, filtering bleb encapsulation is the most frequent long-term complication, no serious complications occurred, but with XEN drainage tube exposure in 1 eye and drop in 1 eye.CONCLUSION:Initial XEN drainage tube implantation combined with MMC and numerous glaucoma surgeries are both safe and effective treatment for OAG patients, while the incidence of filtering bleb encapsulation is high in those with numerous glaucoma surgeries.

Grouping Effects and Its Additivity in Multiple Object Tracking / 生物化学与生物物理进展

Reducing the consumption of attentional resources and improving human performance in dynamic visual sustained attention tasks is a key issue in sustained attention research. The multiple object tracking (MOT) task is a widely used paradigm for studying individual sustained attention. In a classic MOT paradigm, observers need to maintain their attention on specific targets among a set of distractors and track their movement. To further utilize attentional resources and improve tracking performance, researchers have proposed studying the additivity problem of grouping effects in attention tracking. Grouping effects during MOT is the phenomenon that moving items can be perceived into larger moving units based on featural cues of themselves or task requirements. This article reviewed previous studies about attention resources, classification, additivity, and neural mechanisms of grouping effects in MOT. Based on previous research, we concluded that grouping effects in MOT can be classified into three categories, i.e., spatiotemporal-based grouping, object-based grouping, and feature-based grouping, according to different grouping cues (spatiotemporal continuity, global perception and organization of objects, and surface featural similarity). Grouping based on multiple cues will produce greater effects compared with one cue, this is the additive effect. The study of additivity is important for understanding the cognitive mechanisms of different grouping effects, the attentional mechanisms, and resource allocation in individual dynamic visual tracking. This study summarized previous behavioral and neuroimaging research and systematically explored the non-additivity based on different surface features and the additivity based on surface features and specific spatiotemporal features. Exploring the mechanism of additivity effects provides us with new insight into understanding grouping effects. For future studies, researchers need to thoroughly investigate the neural mechanisms of different kinds of groupings. This can not only provide explanations for the additivity of groupings but also provide substantial evidence for the classification of groupings.

Relationship between severity of preoperative brain injury and postoperative delirium in elderly patients: a latent class analysis of markers of brain injury / 中华麻醉学杂志

Objective:To evaluate the relationship between the severity of preoperative brain injury and postoperative delirium (POD) in elderly patients using latent class analysis based on markers of brain injury.Methods:One hundred and thirty-one American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ patients, aged 65-84 yr, with a body mass index of 18-28 kg/m 2, scheduled for elective unilateral total hip arthroplasty in our hospital, were selected. Cognitive function was assessed using the Mini-Mental State Examination before surgery. Arterial blood samples were collected before anesthesia to measure the plasma concentrations of brain-derived neurotrophic factor, inducible nitric oxide synthase, prostaglandin E2, central nervous system-specific protein (S100β), glial fibrillary acidic protein, neurofilament light chain, matrix metalloproteinase-9, fibroblast growth factor 23, complement 3, complement 3a, complement 5a and irisin using enzyme-linked immunosorbent assay. POD was evaluated using the Confusion Assessment Method within 3 days after operation, and the patients were divided into POD group and non-POD group. The patients were divided into different injury severity subtypes based on the levels of brain injury markers using latent class analysis, and logistic multivariate regression was used to analyze the independent risk factors for POD. Results:Compared with non-POD group, the concentrations of neurofilament light chain, glial fibrillary acidic protein, S100β and prostaglandin E2 were significantly different in POD group ( P<0.05). Using these four brain injury markers for latent class analysis, patients were divided into a high severity of brain injury group (91.51%) and a low severity of brain injury group (8.49%). The results of logistic multivariate regression analysis showed that subtypes of brain injury ( OR=8.31, 95% confidence interval [ CI] 1.77-38.90, P=0.007), age ( OR=1.14, 95% CI 1.03-1.24, P=0.007), and plasma irisin concentrations ( OR=0.99, 95% CI 0.98-0.99, P=0.027) were independent risk factors for POD. Conclusions:Higher severity of preoperative brain injury is an independent risk factor for POD in elderly patients.

Research on Patients’ Trust Risk Points and Promotion Path from the Perspective of Online Health Community / 中国医学伦理学

Online health community is a new medical treatment mode combining the Internet and medical treatment. Patients can get medical services through the network. However, it cannot be ignored that patients’ trust will be affected by the uncertainty of online medical information, the unsafe factors of patients’ private information, the insufficient standardization of the diagnosis and treatment process, and other issue in the process of using this new medical treatment mode. By taking measures such as improving the information quality in online health community, enhancing patients’ cognitive ability of health information, perfecting privacy protection measures in online health community, advancing patients’ participation in online health community and ensuring the standardization of diagnosis and treatment process, patients’ trust can be improved.

Research progress on vagus nerve stimulation affecting organ function / 临床麻醉学杂志

Vagus nerve is the main undertaker of the parasympathetic nervous system,participating in the regulation of inflammatory response and playing the role of organ function protection.Stimulation such as perioperative operation and anesthesia can often lead to a relative decrease in vagus nerve tension and in-crease in perioperative circulation,respiration,digestion,nerve,and other system-related complications.This article mainly reviews the effects of reduced vagal tone on perioperative multiple organ functions and va-gus nerve stimulation in organ function,aiming to provide new ideas for reducing various perioperative com-plications.

Efficacy Analysis of Gonadotropin-Releasing Hormone Agonist Protocol and Gonadotropin-Releasing Hormone Antagonist Protocol in POSEIDON Group 1 / 实用妇产科杂志

Objective:To evaluate the effect of gonadotropin-releasing hormone agonist(GnRH-a)protocol and gonadotropin-releasing hormone antagonist(GnRH-ant)protocol in POSEIDON group 1.Methods:From January 2019 to December 2020,399 patients in POSEIDON group 1 who underwent assisted reproductive technology in the Center of Reproductive Medicine,Affiliated Hospital of Nantong University were retrospectively analyzed.Cohorts with similar baseline characteristics were screened by 1 ∶1 propensity score matching(PSM),and base-line data,clinical and laboratory parameters,and clinical outcomes were compared between GnRH-a and Gn-RH-ant groups.Results:①100 patients from GnRH-a group and 100 patients from GnRH-ant group were matched.②The total dose and total use time of gonadotropin(Gn)in GnRH-a group were higher than those in GnRH-ant group(P<0.001,P =0.048),and the hormone levels of luteinizing hormone,estradiol and progester-one on the day of HCG injection were lower than those in GnRH-ant group(P<0.001,P =0.011,P<0.001).There was no statistical difference in the number of follicles between the two groups(P>0.05),the number of oocytes retrieved,mature oocytes,normal fertilized oocytes,high-quality embryos and available embryos were lower in GnRH-a group than those in GnRH-ant group(P<0.01).③In GnRH-a group,the time to live birth(TTLB)was higher than GnRH-ant group(P =0.005),and the cumulative live birth rate(CLBR)was lower than GnRH-ant group(P =0.048),and there was no statistical difference in the number of transplants(P =0.536)and cumulative pregnancy rates(P =0.084)between the two groups.④The economic cost to live birth of GnRH-a group was higher than that of GnRH-ant group(P =0.02).Conclusions:Compared with GnRH-a group,Gn-RH-ant group could improve the cumulative live birth rate of a single ovulation induction cycle in patients in PO-SEIDON group 1,shorten the time to live birth and reduce the treatment cost of patients,and was the preferred protocol for patients in POSEIDON group 1.

Research progress on pharmacological mechanism of polygona-polysaccharose / 国际中医中药杂志

Polygona-polysaccharose is an important indicator to measure the quality of Polygonati Rhizoma. The polygona-polysaccharose has the effect of lowering blood sugar, regulating blood lipid, anti-fatigue, improving learning and memory ability. The Polygonati Rhizoma, as a Chinese herbal medicine with homology of medicine and food, has a good prospect and application value in the development of food and health products.

Relationship between blood uric acid level and plasma atherogenic index in patients with type 2 diabetes / 中国综合临床

Objective:To explore the correlation between serum uric acid level and atherogenic index of plama (AIP) in patients with type 2 diabetes mellitus (T2DM).Methods:A retrospective analysis of 485 T2DM patients hospitalized in the First Hospital of Qin Huangdao was performed in August 2019 to August 2021. They were divided into atherogenic phenotype group (the case group, AIP≥0.06, n=326) and non atherogenic phenotype group (the control group, AIP<0.06, n=159) with AIP=0.06 as the cut-off point. The age, sex, body mass index, uric acid, triglyceride, total cholesterol, high density lipoprotein-cholesterol, low density lipoprotein-cholesterol, glycosylated hemoglobin, smoking history and coronary heart disease history were compared between the two groups. The data processing using sample t-test and chi-square test. Pearson correlation analysis and multivariate logistic regression analysis were performed. Results:Body mass index (27.7±3.6) kg/m 2, systolic pressure (138.4±17.5) mmHg, uric acid (351.6±93.0) μmol/L, triglyceride (3.0±3.4) mmol/L and the proportion of men (61.6%(201/326)), coronary heart disease history (24.3%(79/326)) and smoking history (33.5%(109/326)) in case group were higher than those in control group (25.8±3.5) kg/m 2, (132.2±17.7) mmHg, (291.6±73.8) μmol/L, (1.0±0.3) mmol/L, (51.6%(82/159)), (15.7%(25/159)), (19.5%(31/159)) and the level of high density lipoprotein-cholesterol (1.1±0.3) mmol/L was lower than that in control group (1.3±0.3) mmol/L,with all statistically significant differences ( t=5.43, P<0.001; t=3.64, P<0.001; t=7.70, P=0.001; t=10.40, P<0.001; χ 2=4.47, P=0.034;χ 2=4.60, P=0.032;χ 2=10.11, P=0.001; t=5.18, P<0.001). The prevalence of hyperuricemia in case group (21.5%(70/326)) was 4.3 times higher than that in control group (5.0%(8/159)). AIP was positively correlated with body mass index ( r=0.300, P<0.001), uric acid ( r=0.343, P<0.001), systolic pressure ( r=0.117, P=0.010), diastolic pressure (r=0.119, P=0.009), triglyceride ( r=0.724, P<0.001), total cholesterol ( r=0.226, P<0.001), while that was negatively correlated with high density lipoprotein-cholesterol ( r=-0.185, P<0.001). Logistic regression analysis showed that after excluding the interference of other factors, uric acid was still related to AIP ( OR=3.727, 95% CI=1.702-8.158, P=0.001), and the risk of AIP increase increased with the increase of uric acid level. Conclusion:The level of serum uric acid in T2DM patients is related to AIP, and high uric acid is an independent risk factor for AIP in T2DM patients.

Influence of shared medical appointments on health-related quality of life and quality of sleep in patients after liver transplantation / 中华健康管理学杂志

Objective:To observe the influence of shared medical appointments on health-related quality of life and quality of sleep in patients after liver transplantation.Methods:By randomized controlled study, a total of 124 patients after liver transplantation were included from our hospital from January 2018 to January 2019, and according to the lottery method, all subjects were divided into the routine management group ( n=64) who received routine outpatient intervention and the shared medical management group ( n=60) who received shared medical appointments management. The health-related quality of life and quality of sleep were investigated and compared by post-liver transplant quality of life questionnaire (pLTQ) and Pittsburgh sleep quality index (PSQI) before intervention (the day of discharge) and after intervention (the end of the last shared outpatient service). Results:After intervention, the dimension scores of worry, economics, body function, emotional function, health service, complication and total score of pLTQ were improved in tow groups than before intervention [the routine management group: (41.90±7.61), (18.13±4.22), (22.22±5.10), (14.92±3.28), (20.39±4.87), (14.63±3.99), and (132.19±37.09) vs (32.25±5.55), (12.77±3.47), (17.58±4.72), (9.23±1.38), (15.17±4.81), (10.89±1.51) and (98.00±29.03) score, t=8.20, 7.85, 3.58, 12.79, 6.10, 7.01, 5.81, all P<0.001; shared medical management group: (46.12±7.92), (24.16±5.34), (25.55±5.42), (17.90±3.60), (24.81±5.12), (17.93±3.60) and (155.47±41.00) vs (32.57±5.69), (12.81±3.82), (17.00±4.70), (9.60±1.39), (15.39±4.84), (11.00±3.52) and (98.37±28.96) score, t=10.76, 13.39, 9.23, 16.66, 10.36, 10.66, 8.81, all P<0.001], and those in the shared medical management group were higher than those in routine management group ( t=3.03, 6.95, 3.53, 4.82, 4.93, 4.83, 3.32, all P<0.05). After intervention, the total score of PSQI scale were lower than before intervention in the routine management group [(10.48±2.14) vs (11.89±2.45) score, t=3.47, P=0.001], and the dimensions score of sleep quality, full-sleep time, sleep time, sleep efficiency, sleep disorders, daytime function, hypnotic and total score of PSQI were lower than before intervention in the shared medical management group [(1.41±0.32), (0.54±0.13), (1.17±0.26), (1.11±0.35), (1.21±0.27), (1.30±0.33), (1.08±0.21) and (8.05±1.75) vs (1.88±0.53), (0.86±0.37), (1.84±0.41), (2.05±0.56), (1.39±0.33), (1.47±0.43), (1.22±0.32) and (11.71±2.43) score, t=-5.88, -6.32, -10.69, -11.03, -3.27, -2.43, -3.65, -9.47, all P<0.05], and those in the shared medical management group were lower than those in routine management group ( t=-6.68, -6.39, -10.43, -10.97, -2.62, -2.12, -3.54, -6.90, all P<0.05). Conclusion:Shared medical appointments model can improve the health-related quality of life and quality of sleep in patients after liver transplantation, and improve the effectiveness of outpatient intervention.

Molecular mechanism of Cigu Xiaozhi formula interfering with HSC-T6 cell activation by regulating HIF-1α signaling pathway based on computer aided drug design / 药学学报

In this study, we investigated the effect of Cigu Xiaozhi formula on HSC-T6 activity in hypoxic microenvironment based on network pharmacology and computer-aided drug design, and predicted and verified its possible targets and related signaling pathways. The potential active components and targets of Cigu Xiaozhi formula were screened by searching Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Encyclopaedia of Traditional Chinese Medicine (ETCM) and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM) databases, and the liver fibrosis related targets retrieved from Gene Cards and Pharm GK database were integrated to obtain the potential targets of Cigu Xiaozhi formula in the treatment of liver fibrosis. GO enrichment analysis and KEGG signaling pathway enrichment analysis were performed on Omic Share platform, and Cytoscape software was used to construct the "potential active ingredient-key target-pathway" network. The active components and target proteins were subjected to molecular docking analysis by Auto Dock software. According to the results of molecular dynamics simulation and binding free energy calculation, the top 5 active components with degree were scored. The active components stigmasterol and β-sitosterol were subjected to molecular docking. CoCl2 was used to induce HSC-T6 cells to construct hypoxia model in vitro. The cell viability was detected by CCK-8 assay, and the optimal time and concentration of hypoxia model of HSC-T6 cells was determined to be 100 µmol·L-1 CoCl2 for 24 h. Under hypoxia condition, HSC-T6 cells were activated, the wound healing rate was significantly increased, and the fluorescence signal of activation marker protein α-smooth muscle actin (α-SMA) was significantly enhanced. However, 6% drug-containing serum could inhibit the activation of HSC-T6 cells, and the wound healing rate was significantly decreased, and the fluorescence signal of α-SMA was significantly weakened. Further studies showed that the expressions of hypoxia-inducible factor-1α (HIF-1α), α-SMA and key proteins of Hedgehog (Hh) signaling pathway in HSC-T6 cells were up-regulated under hypoxia, while the expressions of HIF-1α, α-SMA, Patched-1 (Ptch-1) and glioma related oncogene homology-1 (Gli-1) were down-regulated in 6% drug-containing serum group, the YC-1 group and the cyclopamine group. These results indicated that HIF-1α and Hh signaling pathways were involved in the activation of HSC-T6 cells, and the traditional Chinese medicine Cigu Xiaozhi formula could inhibit the activation of HSC-T6 cells, and the mechanism may be related to the inhibition of HIF-1α expression and the blocking of Hh signaling pathway. In conclusion, Cigu Xiaozhi formula can inhibit the activation of HSC-T6 cells by directly acting on HIF-1α and Hh signaling pathway, and exert an anti-hepatic fibrosis effect. The animal experimental protocol has been reviewed and approved by Laboratory Animal Ethics Committee of Gansu University of Chinese Medicine, in compliance with the Institutional Animal Care Guidelines.

A nested case-control study on the association of neonatal cord blood selenium, iron and copper with congenital heart disease / 中华预防医学杂志

Objective: To investigate the relationship between the levels of selenium, iron and copper in cord blood of neonates and the risk of congenital heart disease (CHD), and analyze their interaction effects. Methods: The subjects were obtained from the birth cohort in Lanzhou area established from 2010 to 2012. A baseline survey was conducted in the first trimester, and the follow-up was conducted in the second trimester, third trimester and 42 days after delivery. The umbilical vein blood was collected from newborns at delivery, and information on their birth outcomes was extracted from medical records. A nested case-control study was used to select 97 neonates with CHD newly diagnosed by echocardiography as the case group, and 194 neonates were selected as the control group by 1∶2 matching according to their mother's age, block and CHD onset time. Inductively coupled ion mass spectrometry was used to detect the concentrations of selenium, iron and copper in neonatal cord blood. The element exposure was categorized into three groups, the low, medium and high concentrations, according to the quartiles Q1 and Q3 of selenium, iron and copper concentrations in the control group. The association between cord blood selenium, iron and copper concentrations and CHD was analyzed by conditional logistic regression model using medium concentration as the reference standard. The association of their interactions with CHD was analyzed by a phase multiplication model. Results: The M (Q1, Q3) concentration of neonatal cord blood copper was 746.12 (467.48, 759.74) μg/L in the case group and 535.69 (425.21, 587.79) μg/L in the control group, with a statistically significant difference between the two groups (P<0.05). After adjustment for confounders, logistic regression models showed that the risk of CHD development was increased in neonates with either high copper in cord blood (OR=4.062, 95%CI: 2.013-8.199) or high copper combined with high iron (OR=3.226, 95%CI: 1.343-7.750). No correlation was observed between selenium and iron concentrations and the development of CHD in neonates. There was a multiplicative interaction between copper and iron in cord blood on the risk of developing CHD (OR=1.303, 95%CI: 1.056-1.608). Conclusion: There is a multiplicative interaction between iron and copper elements. The high copper and the high copper combined with high iron in umbilical cord blood are risk factors for neonatal CHD.

T cell immunotherapy mediated by dual-affinity aptamer targeted liposome / 药学学报

Redirecting immune cells to the tumor cells and enhancing its anti-tumor immune response is a very promising cancer treatment strategy. AS1411 aptamers have high affinity for malignant tumors with high nucleolin expression, and cytotoxic T lymphocyte associated protein 4 (CTLA-4) aptamers can specifically bind to CTLA-4, which is expressed by T cells. In this study, a dual-affinity aptamer targeted liposome (Dat. Lipo) was constructed based on AS1411 aptamer and CTLA-4 aptamer, and its immunotherapeutic effect on T cells was studied. After the aptamer was modified with cholesterol, Dat. Lipo was prepared by instillation method; its effect of redirecting T cells was determined by confocal micrographs; its T cell immunotherapy effect was evaluated by cell counting kit-8 (CCK8) and T cell penetration was evaluated by tumor spheroids. The results showed that compared with liposomes loaded with one type aptamer, Dat. Lipo could effectively promote the redirection of T cells to tumor cells; Dat. Lipo had good biosafety and immunotherapeutic effect on MCF-7 and HepG2 cells in a concentration-dependent manner; Dat. Lipo could also promote T cells to infiltrate into the tumor spheroids and enhance the immunotherapy effect of T cells in different dimensions. In summary, Dat. Lipo can use the high affinity of aptamers to redirect T cells to tumor cells, enhance the effect of immunotherapy, and has a promising application prospect in tumor therapy. This study was approved by the Examination Committee of Cancer Hospital of Xiangya School of Medicine, Central South University, Hunan Cancer Hospital.

Immune regulation mechanism of Saposhnikoviae Radix polysaccharide based on zebrafish model / 中国中药杂志

The immunomodulatory effect of Saposhnikoviae Radix polysaccharide(SRP) was evaluated based on the zebrafish mo-del, and its mechanism was explored by transcriptome sequencing and real-time fluorescence-based quantitative PCR(RT-qPCR). The immune-compromised model was induced by navelbine in the immunofluorescence-labeled transgenic zebrafish Tg(lyz: DsRed), and the effect of SRP on the density and distribution of macrophages in zebrafish was evaluated. The effect of SRP on the numbers of macrophages and neutrophils in wild-type AB zebrafish was detected by neutral red and Sudan black B staining. The content of NO in zebrafish was detected by DAF-FM DA fluorescence probe. The content of IL-1β and IL-6 in zebrafish was detected by ELISA. The differentially expressed genes(DEGs) of zebrafish in the blank control group, the model group, and the SRP treatment group were analyzed by transcriptome sequencing. The immune regulation mechanism was analyzed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment, and the expression levels of key genes were verified by RT-qPCR. The results showed that SRP could significantly increase the density of immune cells in zebrafish, increase the number of macrophages and neutrophils, and reduce the content of NO, IL-1β, and IL-6 in immune-compromised zebrafish. The results of transcriptome sequencing analysis showed that SRP could affect the expression level of immune-related genes on Toll-like receptor pathway and herpes simplex infection pathway to affect the release of downstream cytokines and interferon, thereby completing the activation process of T cells and playing a role in regulating the immune activity of the body.

Effect of Liangfang Wenjing Decoction on expression of key glycolytic enzymes in uterus and ovaries of rats with coagulating cold and blood stasis syndrome / 中国中药杂志

This study aimed to investigate the relationship between coagulating cold and blood stasis syndrome and glycolysis, and observe the intervention effect of Liangfang Wenjing Decoction(LFWJD) on the expression of key glycolytic enzymes in the uterus and ovaries of rats with coagulating cold and blood stasis. The rat model of coagulating cold and blood stasis syndrome was established by ice-water bath. After modeling, the quantitative scoring of symptoms were performed, and according to the scoring results, the rats were randomly divided into a model group and LFWJD low-, medium-and high-dose groups(4.7, 9.4, 18.8 g·kg~(-1)·d~(-1)), with 10 in each group. Another 10 rats were selected as the blank group. After 4 weeks of continuous administration by gavage, the quantitative scoring of symptoms was repeated. Laser speckle flowgraphy was used to detect the changes of microcirculation in the ears and uterus of rats in each group. Hematoxylin-eosin(HE) staining was used to observe the pathological morphology of uterus and ovaries of rats in each group. The mRNA and protein expressions of pyruvate dehydrogenase kinase 1(PDK1), hexokinase 2(HK2) and lactate dehydrogenase A(LDHA) in the uterus and ovaries of rats were examined by real-time quantitative polymerase chain reaction(RT-qPCR) and Western blot, respectively. The rats in the model group showed signs of coagulating cold and blood stasis syndrome, such as curl-up, less movement, thickened veins under the tongue, and reduced blood perfusion in the microcirculation of the ears and uterus, and HE staining revealed a thinning of the endometrium with disorganized arrangement of epithelial cells and a decrease in the number of ovarian follicles. Compared with the model group, the treatment groups had alleviated coagulating cold and blood stasis, which was manifested as red tongue, reduced nail swelling, no blood stasis at the tail end as well as increased blood perfusion of the microcirculation in the ears and uterus(P<0.05 or P<0.01). Among the groups, the LFWJD medium-and high-dose groups had the most significant improvement in coagulating cold and blood stasis, with neatly arranged columnar epithelial cells in uterus, and the number of ovarian follicles was higher than that in the model group, especially mature follicles. The mRNA and protein expressions of PDK1, HK2, LDHA in uterus and ovaries were up-regulated in the model group(P<0.05 or P<0.01), while down-regulated in LFWJD medium-and high-dose groups(P<0.05 or P<0.01). The LFWJD low-dose group presented a decrease in the mRNA expressions of PDK1, HK2 and LDHA in uterus and ovaries as well as in the protein expressions of HK2 and LDHA in uterus and HK2 and PDK1 in ovaries(P<0.05 or P<0.01). The therapeutic mechanism of LFWJD against coagulating cold and blood stasis syndrome is related to the down-regulation of key glycolytic enzymes PDK1, HK2 and LDHA, and the inhibition of glycolytic activities in uterus and ovaries.