Objective To investigate the early comprehensive intervention on neonatal hypoxic ischemic encephalopathy (HIE) effects and the biological mechanisms.Methods 120 cases of HIE were randomly divided into intervention group and control group.Under the basis of drug treatment,the intervention group were given the different perceptual stimuli,audiovisual stimulation,active and passive limb training early comprehensive intervention,the control group only to normal drug treatment.The mental development index(MDI) and psychomotor develo pmental index (PDI) were applied after 3,6,12,and 18 months.S100B protein levels were detected using enzyme immunoassay.Results MDI score in the intervention group with HIE,from the beginning of the 12 month,was higher than that in the control group,there was significant differences (12th month:(96.6±9.4)vs (86.8±9.5),P<0.01).PDI score from the beginning of the 6 month,was higher in the intervention group with HIE than that in the control group,there were significant differences (6th month:(91.6±9.2)vs (82.2±11.0),P<0.01).Serum S100B protein level has a tendency to fall for all HIE patients with the old growth.Born in two groups of serum S100B protein levels were higher in neonate period,but there was no difference(P>0.05).From the beginning of the 3rd month,serum S100B protein levels in the intervention group were reduced significandy,compared with the control group at each time point level(3rd month:(1.29±0.15)ng/L vs(1.40±0.14)ns/L;6th month:(1.06±0.21)ng/L vs(1.26±0.22)ng/L,P<0.01).Conclusion Early intervention can improve the mental and motor development of children with HIE,and serum S100B protein is involved in the mechanisms.

BACKGROUND:So far, inducible co-stimulator is the important costimulatory molecule family member. Inducible co-stimulator can promote the activation of T cel s proliferation and secretion, regulate Th1/Th2 cel polarization dependence, enhance B cel function which depend on the T cel s. So, blocking the inducible co-stimulator may result the inactivation and no reaction of cloning in T cel s, thus inducing the immune escape of tumor on the body.
OBJECTIVE:To build a plasmid expression of inducible co-stimulator Ig, in order to observe the expression in rat body.
METHODS:cDNA encoding the extracel ular domain of human inducible co-stimulator was prepared. The encode of the domain was fused with the gene of immunoglobulin IgG constant fragment (Ig) of encoding mouse, in order to build the inducible co-stimulator Ig fusion gene and the secreted eukaryotic expression vector pcDNA3-inducible co-stimulator Ig. Enzyme digestion of the recombinant and sequencing was performed, and then the positive liposome coated pcDNA3-inducible co-stimulator Ig was transferred into the muscle tissue of mouse right thigh. Western blot was used to detect the level of inducible co-stimulator Ig.
RESULTS AND CONCLUSION:The sequencing confirmed that the size of target gene fragment pcDNA3-inducible co-stimulator Ig plasmid was exactly the same with the sequence of inducible co-stimulator published on Genebank, which indicated the successful of plasmid construction. After transferred into the mouse for 7 days, the liposome coated pcDNA3-inducible co-stimulator Ig was positively expressed in the mice serum, which showed that pcDNA3-inducible co-stimulator Ig could be expressed in the rat muscle cel s. The results suggest that gene synthesis and recombinant technology can successful y construct the eukaryotic expression vector pcDNA3-inducible co-stimulator Ig.

Objective: To investigate the sensitization of physiological (10~(-9)mol/L) and pharmacological (10~(-5)mol/L) concentrations of melatonin on cell line MCF-7 for adriamycin and its mechanism. Methods: (1) MTT was applied to test the changes in inhibition ratio and IC_(50) of call line MCF-7 for adriamycin before and af-ter incubation with melatonin. (2) Flow cytometry was used to observe the effect of different concentrations of melatonin, adriamycin and melatonin plus adriamycin on cell apoptosis. (3) Western blot was employed to de-termine the expression of p53 and bcl-2 in MCF-7 cells incubated with melatonin, adriamycin and melatonin plus adriamycin. Results: (1) MTT method showed that adriamycin had inhibitive effect on the growth of MCF-7 cells in a dose- and time-dependent manner. The IC_(50) of cell line MCF-7 for adnamycin before treat-ment with melatonin was 0.62±0.07ug/mL (P>0.05). The IC50 of cell line MCF-7 for adriamycin incubated with physiological and pharmacological concentrations of melatonin was 0.59±0.09ug/mL and 0.42±0.02ug/mL, re-spectively, with a significant difference (P<0.01). (2) Flow cytometry method showed that adriamycin could promote apoptosis of MCF-7, and no changes in the apoptosis index were observed as the concentration of melatonin was changed (P>0.05). With the same concentration of adriamycin, the apoptosis index of cells treated with physiological concentration of melatonin plus adriamycin was not changed (P=>0.05), but the apop-tosis index of cells treated with pharmacological concentrations of melatonin plus addamycin was increased significantly. The concentration of adriamycin had no effect on the apoptosis index. (3) Western blot showed that P53 protein was expressed at a lower level and bcl-2 protein was highly expressed. Physiological concen-trations of melatonin increased the expression of p53 and decreased bcl-2 expression in a dose - dependent manner. The concentration of addamycin had no effect on the expression of p53 and bcl-2 proteins. Conclu-sion: (1) Physiological concentrations of melatonin had no effect on the anti-cancer effect of adriamycin. Phar-macological concentrations of melatonin showed sensitization of MCF-7 cells for adriamycin. (2) With a lower concentration of adriamycin, the promotion of apoptosis may be part of the mechanism of sensitization effect of melatonin. With the increase of adriamycin concentration, the cytotoxic mechanism of melotonin became more and more important. (3) Physiological concentration could increase the expression of p53 and decrease bcl-2 expression in ER~+ breast carcinoma cell line MCF-7 in a dose -dependent manner. The apoptosis involv-ing p53 and bcl-2 passway was part of the mechanism of sensitization effect of melatonin for addamycin.

[Objective] To estimate the effects of ginsenoside Rb1 on melanogenesis in human melanocytes and underlying mechanisms.[Methods] Epidermal melanocytes were obtained from circumcision specimens of children,and subjected to primary culture.After 2 to 5 passages,the melanocytes were treated with different concentrations of ginsenoside Rb1,dimethyl sulfoxide (DMSO,vehicle control),forskolin at 10 μmol/L(positive control) or remained untreated (blank control).After additional culture for 72 hours,methyl thiazolyl tetrazolium (MTT) assay and NaOH lysis method were used to evaluate cell viability and melanin content in melanocytes respectively,spectrophotometer to determine dopa oxidase activity of tyrosinase,Western blot to quantify the protein level of tyrosinase,microphthalmia-associated transcription factor (MITF),phosphorylated and total cAMP response element binding protein (p-CREB and t-CREB) in melanocytes.[Results] After treatment with ginsenoside Rbl of 25,50 and 100 μmol/L for 72 hours,the melanocytes experienced no significant changes in viability (P ＞ 0.05 ),but a significant dose-dependent increase in melanin content (112.4％± 5.7％,155.7％ + 6.3％,217.2％ ± 11.7％ vs.100％,P＜ 0.05 or 0.01) and tyrosinase activity(117.9％ ± 5.7％,158.2％ ± 9.6％,182.6％ ± 10.0％ vs.100％,P＜ 0.05 or 0.01 ) compared with the vehicle control melanocytes.The protein expressions of tyrosinase,MITF and p-CREB were statistically higher in melanocytes treated with ginsenoside Rb1 of 100 μmol/L for 72 hours than in the vehicle control melanocytes (225.4％ ± 12.8％ vs.100％ ± 7.9％,313.5％ ± 16.7％ vs.100％ ± 9.8％,322.5％ ± 21.1％ vs.100％ ± 9.1％,all P＜ 0.01).The increase in MITF protein expression was inapparent in melanocytes at 8 hours after the treatment with ginsenoside Rb1 of 100 μmol/L,but statistically significant at 24 hours compared with the melanocytes at baseline (P＜ 0.01).The pretreatment with H-89 (a 8elective inhibitor of PKA) at 10 μmol/L,significantly suppressed the ginsenoside Rb1 (100 μmol/L for 72 hours) -induced phosphorylation of CREB,increase in MITF,tyrosinase expression,as well as tyrosinase activity and melanin content in melanocytes (all P ＜ 0.01 ).[Conclusion]s Ginsenoside Rb1could enhance the melanogenesis and tyrosinase activity in normal human melanocytes.The PKA/CREB/MITF/ tyrosinase signaling pathway may contribute to the pro-melanogenic effect of ginsenoside Rb1.

OBJECTIVE:To observe clinical efficacy and safety of exenatide combined with clomiphene citrate in the treatment of polycystic ovary syndrome with insulin resistance. METHODS:98 patients with polycystic ovary syndrome complicated with in-sulin resistance were randomly divided into control group (49 cases) and observation group (49 cases). Control group was given Clomiphene citrate capsule 50 mg orally,once a day,for 5 d+Metformin enteric-coated tablet with initial dose of 0.25 g orally, twice a day,adjusted to 0.50-0.75 g orally,twice a day,for 3 menstrual cycles. Observation group was given Clomiphene citrate capsule(usage and dosage same as control group)+Exenatide injection 5 μg subcutaneously,twice a day,adjusted to 10 μg subcu-taneously,twice a day,for 2 months. Clinical efficacies of 2 groups were observed as well as the levels of LH,FSH,LH/FSH and IR before and after treatment,ovulation and pregnancy of infertility patients after treatment. The occurrence of ADR was record-ed. RESULTS:Total response rate,ovulation rate and pregnancy rate of observation group were significantly higher than that of con-trol group,with statistical significance(P<0.05). Before treatment,there was no statistical significance in the levels of LH,FSH, LH/FSH and IR between 2 groups (P>0.05). After treatment,the levels of LH,LH/FSH and IR in 2 groups were significantly lower than before,and the observation group was significantly lower than the control group,the levels of FSH in 2 groups was sig-nificantly higher than before,and the observation group was significantly higher than the control group,with statistical significance (P<0.05). There was no statistical significance in incidence of ADR between 2 groups(P>0.05). CONCUSIONS:Exenatide com-bined with clomiphene citrate shows significant therapeutic efficacy for polycystic ovary syndrome complicated with insulin resis-tance and can increase ovulation rate and pregnancy rate through improving insulin resistance,but doesn't increase the occurrence of ADR.

Lung cancer is currently one of the most common malignant tumors in the world. The occurrence and development of lung cancer, especially non-small cell lung cancer (NSCLC), are closely related to the abnormal expression of long non-coding RNA (lncRNA). lncRNA with a transcript of more than 200 nucleotides is involved in chromatin modification, transcription activation, transcription interference and other regulatory processes, and has varying degrees of regulation on the proliferation, migration, and invasion of tumor cells. It is characterized by up-regulation or down-regulation of expression. At present, there are a large number of studies on lncRNA, because lncRNA has considerable application prospects in the diagnosis, clinical treatment, drug resistance research and prognosis evaluation of NSCLC. In this paper, the overview of lncRNA, the up-regulation or down-regulation of NSCLC-related lncRNA expression, NSCLC clinical treatment and drug-resistant lncRNA were summarized.

Objective:To explore the role of individualized teaching method based on failure mode and effect analysis (FMEA) in the teaching of rotation interns in operating room.Methods:Twenty-three operating room rotation interns received by Zhongnan Hospital, Wuhan University from February 2019 to September 2019 were selected as the control group, and another 23 operating room rotation interns received from October 2019 to May 2020 were selected as the research group. The control group adopted the conventional teaching method, while the research group adopted the individualized teaching method based on FMEA. The theoretical knowledge and practical operation examination results before and after teaching, self-directed learning ability before and after teaching and teaching satisfaction of interns after teaching were compared between the two groups. SPSS 25.0 was used for t test, chi-square test and rank sum test. Results:After teaching, the scores of theoretical knowledge [(91.13±6.35) vs. (84.26±5.94)] and practical operation [(89.39±5.45) vs. (79.78±5.65)], self-directed learning ability of each dimension and total scores [(280.63±23.39) vs. (248.17±20.68)] of the two groups were higher than those before teaching, and the scores of theoretical knowledge and practical operation, self-directed learning ability of each dimension and total score of the research group were higher than those of the control group ( P<0.05). After teaching, the satisfaction scores on the professional quality of the teachers, the rationality of the teaching mode and the effectiveness of the teaching mode of the interns in the research group were higher than those in the control group ( P<0.05). Conclusion:In the teaching of rotation interns in operating room, the individualized teaching method based on FMEA can not only improve the examination results of interns, enhance their self-directed learning ability, but also improve their teaching satisfaction.

Objective:To investigate the role of TRIZ theory in clinical teaching in orthopedic operating room.Methods:A total of 43 interns in the orthopedic operating room of our hospital from October 2019 to July 2020 were selected as control group, and 46 interns in the orthopedic operating room of our hospital from August 2020 to May 2021 were selected as observation group. The interns in the control group received traditional teaching, and those in the observation group received teaching based on TRIZ theory. The two groups were compared in terms of professional assessment results, self-evaluation, satisfaction score, and qualification of aseptic operation in orthopedic operating room. SPSS 22.0 was used to perform the t-test and the chi-square test. Results:Compared with the control group, the observation group had significantly higher theoretical knowledge score, practical skill score, and weighted total score ( t=14.90, 11.82, and 13.23, all P?0.001). Compared with the control group, the observation group also had significantly higher scores of analysis and problem-solving ability, clinical thinking, doctor-patient communication, psychological quality, clinical case analysis, self-study ability, and teaching satisfaction ( t=7.88, 11.78, 15.26, 7.94, 12.93, 9.83, and 13.22, all P?0.001). Compared with the control group, the observation group had significantly higher qualified rates of surgical hand-washing, wearing sterile surgical gowns, non-contact glove wearing; and bacteriological testing ( χ 2=4.22, 6.02, 4.92, and 7.59, P=0.040, 0.014, 0.027, and 0.006). Conclusion:TRIZ theory has a certain value in clinical teaching in orthopedic operating room and can significantly improve the scores of theoretical knowledge and practical skills, strengthen aseptic operation abilities in orthopedic operating room, and enhance the satisfaction with teaching among interns.

Objective:To investigate the mechanism of excessive iodine-induced apoptosis of chorionic trophoblast cells associated with missed early miscarriage.Methods:Patients with unexplained missed early miscarriage ≤12 weeks of gestation (MA group, n = 43) and normal pregnant women (control group, n = 64) who were treated at Tianjin Central Obstetrics and Gynecology Hospital from September 2019 to September 2022 were selected as the study subjects, and villous tissues were collected for proliferating cell nuclear agtigen Ki67 immunohistochemistry and apoptosis assay, while urine samples were collected for urinary iodine content assay. Different doses of iodine were used to stimulate the cultivation of human chorionic trophoblast cell line (HTR8/SVneo) for 24 h. Cell proliferation viability was detected using cell counting kit 8 (CCK8), and apoptosis was detected using flow cytometry. Results:(1) Urinary iodine values were 159.70 (114.21, 218.73) μg/L in the control group and 210.80 (143.10, 336.70) μg/L in the MA group, the difference between the two groups was statistically significant ( Z = 2.26, P = 0.024). (2) The proportion of positive and strong positive Ki67 immunohistochemical staining of the villous tissues in the MA group was significantly lower than that in the control group (χ 2 = 37.00, P < 0.001). (3) The apoptosis rate of villous tissue in the MA group was significantly higher than that in the control group [(26.24 ± 1.06)% vs (2.96 ± 1.97)%, t = 92.23, P < 0.001]. (4) The cell proliferation rates of HTR8/SVneo in the 50, 100, 300 and 500 μg iodine groups were significantly lower than that in the 0 μg iodine group ( P < 0.05), with the 500 μg iodine group below the median lethal dose (LD 50). (5) The apoptosis rates of 0, 50 and 500 μg iodine groups were (8.79 ± 0.12)%, (9.56 ± 0.08)% and (19.86 ± 0.05)%, respectively, and the differences among the three groups were statistically significant ( F = 7.32, P = 0.007); in which the 50 and 500 μg iodine groups were higher than that of the 0 μg iodine group, and the 500 μg iodine group was higher than that of the 50 μg iodine group ( P < 0.05). Conclusions:Urine iodine content significantly increases in patients with missed early miscarriage. Excessive iodine intake may lead to a decrease in the proliferation viability and an increase in cell apoptosis of chorionic trophoblast cells.

Objective To systematically evaluate the efficacy of β-blocker in pediatric patients with congestive heart failure and congenital heart disease,and to provide evidence for clinician.Methods Before-and-after self-control study and randomized controlled trials were retrieved from PubMed,EMbase,the Cochrane Library,CNKI,WanFang,VIP databases,and the search time was from the establishment of the database to October 31,2023.All outcomes included left ventricular ejection fraction(LVEF),left ventricular fraction shortening,LVFS),left ventricular end-diastolic dimension(LVDD),Left ventricular end-systolic dimension(LVSD),N-terminal proB brain natriuretic peptide(NT-proBNP),heart rate,blood pressure and cardiac function improvement.Results A total of 20 trials involving 1 068 children with heart failure(dilated cardiomyopathy and endocardial fibroelastosis were included.Meta-analysis results showed that the addition of β-blockers(metoprolol succinate,bisoprolol and carvedilol)on the basis of conventional drug therapy for heart failure had significant effects on LVEF[MD=13.06,95%CI(11.67,14.45),P<0.001],LVFS[MD=6.96,95%CI(6.54,7.37),P<0.001],LVDD[MD=-6.43,95%CI(-7.58,-5.28),P<0.001]and LVSD[MD=-8.30,95%CI(-8.83,-7.76),P<0.001]were significantly improved.In addition,blood pressure,heart rate,NT-proBNP and cardiac function could also be improved.Conclusion The combination regimen of β-blockers on the basis of conventional drug therapy for heart failure can improve cardiac function and symptoms of heart failure in children with congestive heart failure.Therefore,it is recommended that β-blockers should be actively used in the conventional treatment regimen for children with congestive heart failure.