The use of melittin to enhance transgene expression mediated by recombinant adeno-associated virus serotype 2 vectors both in vitro and in vivo / 中西医结合学报

OBJECTIVE@#Melittin, a cell-penetrating peptide, improves the efficiency of many non-viral gene delivery vectors, yet its application in viral vectors has not been well studied. The non-pathogenic recombinant adeno-associated virus (rAAV) vector is an ideal in vivo gene delivery vector. However, its full potential will only be achieved after improvement of its transduction efficiency. To improve the transduction efficiency of rAAV2 vectors, we attempted to develop a melittin-based rAAV2 vector delivery strategy.@*METHODS@#The melittin peptide was inserted into the rAAV2 capsid either in the loop VIII of all viral proteins (VPs) or at the N terminus of VP2. Various rAAV2-gfp or -fluc vectors were subjected to quantitative real-time polymerase chain reaction and Western blot assays to determine their titers and integrity of capsid proteins, respectively. Alternatively, the vectors based on wild-type capsid were pre-incubated with melittin, followed by transduction of cultured cells or tail vein administration of the mixture to C57BL/6 and BALB/c nude mice. In vivo bioluminescence imaging was performed to evaluate the transgene expression.@*RESULTS@#rAAV2 vectors with melittin peptide inserted in the loop VIII of VPs had low transduction efficiency, probably due to dramatically reduced ability to bind to the target cells. Fusing the melittin peptide at the N-terminus of VP2 produced vectors without the VP2 subunit. Interestingly, among the commonly used rAAV vectors, pre-incubation of rAAV2 and rAAV6 vectors with melittin significantly enhanced their transduction efficiency in HEK293 and Huh7 cells in vitro. Melittin also had the ability to increase the rAAV2-mediated transgene expression in mouse liver in vivo. Mechanistically, melittin did not change the vector-receptor interaction. Moreover, cell counting kit-8 assays of cultured cells and serum transaminase levels indicated melittin had little cytotoxicity.@*CONCLUSION@#Pre-incubation with melittin, but not insertion of melittin into the rAAV2 capsid, significantly enhanced rAAV2-mediated transgene expression. Although further in vivo evaluations are required, this research not only expands the pharmacological potential of melittin, but also provides a new strategy to improve gene therapy mediated by rAAV vectors.

Association of circulating levels of soluble PD-1, PD-1 gene polymorphisms with HBV infection and HBV infection-associated hepatocellular carcinoma / 中华预防医学杂志

Objective: To investigate the association of circulating sPD-1 level and PD-1 gene polymorphisms with HBV infection and HBV infection-associated hepatocellular carcinoma. Methods: A case-control study was conducted. A total of 237 chronic HBV infection cases and 138 HBV infection-associated hepatocellular carcinoma in the Department of Infectious Diseases of the First Hospital of Shanxi Medical University from 2018 to 2021 were selected as the case group. About 250 individuals who visited a hospital physical examination center for routine physical examination during the same period were selected as the control group. Plasma sPD-1 levels were measured by using an ELISA kit and genotyping was performed by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The association of sPD-1 levels and PD-1 polymorphisms with HBV infection as well as HBV infection-associated hepatocellular carcinoma was analyzed by using logistic regression models after adjusting for age, sex, alcohol consumption, smoking, ALT and AST levels. The sPD-1 level and PD-1 polymorphisms were independent variables, and HBV infection was the dependent variable. Results: The age of 237 chronic HBV infections, 138 HBV infection-related liver cancer case subjects and 250 control subjects in the study was (49.1±10.8), (51.9±12.7) and (50.7±11.9) years, respectively. Multivariate logistic regression model analysis showed that with a 1 pg/ml increase in sPD-1 level, the OR (95%CI) values for the risk of incident HBV infection cases and HBV hepatocellular carcinoma cases were 1.92 (1.68-2.19) and 2.02 (1.69-2.40). For rs2227981, compared with the CC genotype, the TT genotype had a lower risk of HBV infection and liver cancer associated with HBV infection, with OR (95%CI) values of 0.45 (0.22-0.91) and 0.35 (0.14-0.91). For rs2227982, compared with the CC genotype, the CT and TT genotypes also had a lower risk of HBV infection [OR (95%CI) values of 0.72 (0.53-0.97) and 0.57 (0.35-0.93)] and HBV infection-related liver cancer [OR (95%CI) values of 0.64 (0.45-0.92) and 0.52 (0.29-0.93)]. Conclusions: Plasma sPD-1 levels and PD-1 gene polymorphisms are associated with HBV infection and HBV infection-associated hepatocellular carcinoma.

Outcomes of different types of pulmonary atresia in neonates treated by ductus arteriosus stenting / 中华儿科杂志

Objective: To summarize the outcomes of different types of pulmonary atresia in neonates treated by ductus arteriosus stenting. Methods: This study was a retrospective cohort study. A total of 19 neonates who had pulmonary atresia treated by ductus arteriosus stenting in Xinhua Hospital, Shanghai Jiao Tong University School of Medicine from April 2014 to June 2021 were included. They were divided into the intact ventricular septum (PA-IVS) group and the ventricular septal defect (PA-VSD) group. Ductus arteriosus stents were implanted by different approaches. These children were followed up regularly at the 1, 3, 6, and 12 months after the surgery and annually since then to evaluate the outcome. Independent sample t-test was used for the statistical analysis. Results: There were 12 children in PA-IVS group and 7 in PA-VSD group. All of them were full term in fants. The gestational age of the PA-IVS group and the PA-VSD group was (38.8±1.1) and (37.7±1.8) weeks, the birth weights were (3.2±0.4) and (3.4±1.1) kg, and the age at operation was (10±9) and (12±7) days, respectively, without significant difference (all P>0.05). Among the 12 children with PA-IVS, 9 had stents successfully implanted through the femoral artery and 3 through the femoral vein. Of the 7 children with PA-VSD, 2 had the stents successfully implanted via the femoral artery and 2 failed, and the remaining 3 had stents successfully implanted via the left carotid artery. There was no postoperative thromboembolism, arteriovenous fistula, pseudoaneurysm or other vascular complications. Five children with PA-VSD who had successful operations were followed up at 6 months of age. They all had the operation for pulmonary atresia, repair of the ventricular septal defect, removal of arterial duct stents, and ligation of the arterial duct. All children survived without any stent displacement or stenosis and biventricular circulation was achieved during the follow-up. Conclusions: Ductus arteriosous stenting can be the first-stage treatment for children with PA-IVS and PA-VSD. In addition to the traditional femoral vein and femoral artery approach, the carotid artery can be used as a route for stent placement.

FOXP4 promotes proliferation of human spermatogonial stem cells / 亚洲男科学杂志(英文版)

Continuous self-renewal and differentiation of spermatogonial stem cells (SSCs) is vital for maintenance of adult spermatogenesis. Although several spermatogonial stem cell regulators have been extensively investigated in rodents, regulatory mechanisms of human SSC self-renewal and differentiation have not been fully established. We analyzed single-cell sequencing data from the human testis and found that forkhead box P4 (FOXP4) expression gradually increased with development of SSCs. Further analysis of its expression patterns in human testicular tissues revealed that FOXP4 specifically marks a subset of spermatogonia with stem cell potential. Conditional inactivation of FOXP4 in human SSC lines suppressed SSC proliferation and significantly activated apoptosis. FOXP4 expressions were markedly suppressed in tissues with dysregulated spermatogenesis. These findings imply that FOXP4 is involved in human SSC proliferation, which will help elucidate on the mechanisms controlling the fate decisions in human SSCs.

Double-column Die-punch fractures of distal radius treated with butterfly plate fixation via Henry approach / 中国骨伤

OBJECTIVE@#To explore clinical effect of open reduction and internal fixation with Henry's approach butterfly plate in treating double-column Die-punch fractures of distal radius.@*METHODS@#From January 2018 to June 2021, 26 patients with double-column Die-column distal radius were treated with open reduction and internal fixation through Henry's surgical approach and using distal radius volar column plate(butterfly plate), including 14 males and 12 females, aged from 20 to 75 years old with an average age of (44.2±3.4) years old. Postopertaive complications were observed, Gartland-Werley score at 12 months after opertaion was used to evaluate wrist joint function.@*RESULTS@#All 26 patients were followed up from 10 to 18 months with an average of(13.4±0.8) months. All fractures were obtained fracture union, the time ranged from 8.5 to 15.8 weeks with an average of (11.4±0.5) weeks. All incisions healed at stageⅠwithout infection, nerve injury and internal fixation failure occurred. Postoperative Gartland-Werley score at 12 months was (3.65±0.36), and 16 patients got excellent result, 8 good and 2 moderate.@*CONCLUSION@#Open reduction and internal fixation with butterfly plate for the treatment of double-column Die-punch fractures of the distal radius through volar Henry approach could obtain satisfactory clinical outcomes.

Research progress of biomimetic nano drug delivery system in nervous system disease / 药学学报

Brain delivery of drugs remains challenging due to the presence of the blood-brain barrier (BBB). With advances in nanotechnology and biotechnology, new possibilities for brain-targeted drug delivery have emerged. Biomimetic nano drug delivery systems with high brain-targeting and BBB-penetrating capabilities, along with good biocompatibility and safety, can enable 'invisible' drug delivery. In this review, five different types of biomimetic strategies are presented and their research progress in central nervous system disorders is reviewed. Finally, the challenges and future prospects for biomimetic nano drug delivery systems in intracerebral drug delivery are summarized.

Research progress of anti-tumor in situ gel delivery system / 药学学报

Cancer is the most important leading cause of death worldwide, with about 10 million deaths caused by cancer in 2020. In situ gel drug delivery systems have attracted much attention in the field of pharmacy and biotechnology due to their good histo-compatibility, excellent injectability, high drug delivery capacity, slow-release drug delivery, and less influence by the in vivo environment. Meanwhile, in situ gel can be combined with chemotherapy, photo-thermal therapy, chemokinetic therapy, immunotherapy and so on to deliver drugs into the tumor site in a less invasive way without surgical operation, forming a semi-solid gel reservoir in the tumor site to realize in situ tumor combined therapy. In this paper, the author summarized the research progress of anti-tumor in situ gel delivery system in the past 10 years, introduced its commonly used polymer materials, classification principles and specific application examples, and finally summarized and discussed the key issues, in order to provide reference for the development of new anti-tumor drug delivery system in the future.

Personalized neoantigen-specific T-cell adoptive immune: a long way to go / 中国肿瘤生物治疗杂志

@#[摘 要] 近年来，肿瘤新抗原掀开了个体化免疫治疗的新篇章，作为基于新抗原个体化免疫治疗的重要组成部分，新抗原特异性T细胞的过继输注（ACT）疗法备受瞩目。本文将首先从新抗原特异性T细胞ACT治疗应用策略及临床应用现状介绍新抗原特异性T细胞ACT治疗这一新兴的精准免疫治疗的发展现状，然后从新抗原的预测、新抗原特异性T细胞筛选及扩增等方面系统地总结新抗原T细胞ACT治疗所面临的阻碍和挑战，最后从优化新抗原预测、增加新抗原特异性T细胞数量和多样性、防止新抗原特异性T细胞过度分化或死亡、缩短生产周期和减少生产成本及探索联合治疗方式等五个方面对该领域的未来发展机遇和研究方向进行重点阐述。

Influence of sperm morphology on pregnancy outcome and offspring in / 亚洲男科学杂志(英文版)

Sperm morphology was once believed as one of the most predictive indicators of pregnancy outcome in assisted reproductive technology (ART). However, the impact of teratozoospermia on in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) outcomes and its offspring remains inconclusive. In order to evaluate the influence of teratozoospermia on pregnancy outcome and newborn status after IVF and ICSI, a retrospective study was conducted. This was a matched case-control study that included 2202 IVF cycles and 2574 ICSI cycles and was conducted at the Reproductive and Genetic Hospital of CITIC-Xiangya in Changsha, China, from June 2013 to June 2018. Patients were divided into two groups based on sperm morphology: teratozoospermia and normal sperm group. The pregnancy outcome and newborn outcome were analyzed. The results indicated that couples with teratozoospermia had a significantly lower optimal embryo rate compared to those with normal sperm morphology in IVF (P = 0.007), while there were no statistically significant differences between the two groups in terms of the fertilization rate, cleavage rate, implantation rate, and pregnancy rate (all P > 0.05). Additionally, teratozoospermia was associated with lower infant birth weight in multiple births after IVF. With regard to ICSI, there was no significant difference in both pregnancy outcome and newborn outcome between the teratozoospermia and normal groups (both P > 0.05). Furthermore, no increase in the risk of birth defects occurred in the teratozoospermia group after IVF/ICSI. Consequently, we believe that teratozoospermia has limited predictive value for pregnancy outcomes in IVF/ICSI, and has little impact on the resulting offspring if multiple pregnancy is avoided.

Evodiamine inhibits high-fat diet-induced colitis-associated cancer in mice through regulating the gut microbiota / 中西医结合学报

OBJECTIVE@#High-fat diet is one of the main risk factors that disrupt the balance of gut microbiota, which eventually will induce colorectal cancer (CRC). Evodiamine (EVO) is a wildly used multifunctional traditional Chinese medicine extract. In this study, we investigated the role of gut microbiota in high-fat diet-propelled CRC and the potential of EVO for CRC chemoprevention.@*METHODS@#Gut microbiota, serum d-lactic acid and endotoxin from 38 patients with colon cancer and 18 healthy subjects were detected by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA). In addition, body mass index, phospho-signal transducer and activator of transcription 3 (p-STAT3) expression in cancer tissues and paracancerous tissues were detected by immunohistochemistry. A mouse intestinal inflammatory tumor model was established by azomethane/sodium dextran sulfate, followed by treatment with EVO and 5-aminosalicylic acid (ASA). Gut microbiota and inflammatory factors were detected by quantitative polymerase chain reaction, while serum d-lactic acid and endotoxin were detected by ELISA. Furthermore, cell proliferation, cell apoptosis, and interleukin (IL)-6/STAT3/P65 pathway were evaluated by 5-ethynyl-2'-deoxyuridine, terminal-deoxynucleotidyl transferase-mediated nick-end labeling, and Western blot assays.@*RESULTS@#In patients with colon cancer, the numbers of Enterococcus faecalis and Escherichia coli were increased, while those of Bifidobacterium, Campylobacter and Lactobacillus were decreased. Serum endotoxin and d-lactic acid levels and p-STAT3 levels were significantly increased. In the mouse model, both EVO and ASA inhibited tumor formation, decreased the proliferation of tumor cells, and induced apoptosis of tumor cells. Compared with the control group, the numbers of E. faecalis and E. coli were decreased, while Bifidobacterium, Campylobacter and Lactobacillus numbers were increased. In the EVO group, serum endotoxin and d-lactic acid levels and inflammatory factors were significantly decreased. Further, the IL6/STAT3/P65 signaling pathway was inhibited in the EVO group.@*CONCLUSION@#EVO may inhibit the occurrence of colon cancer by regulating gut microbiota and inhibiting intestinal inflammation. The potential mechanism involves inhibition of the IL6/STAT3/P65 signaling pathway, revealing its potential therapeutic significance in clinical applications.

Construction and Identification of Leukemia Cell Line Stably Expressing CD123 and CLL-1 / 中国实验血液学杂志

OBJECTIVE@#To construct an acute myeloid leukemia cell line stably expressing CD123-CLL1 so as to provide an "in vitro" model for studying the role of CD123 and CLL-1 in leukemia and the treatment targeting CD123 and CLL-1.@*METHODS@#The recombinant plasmid of lentivirus was constructed by synthesizing CD123 and CLL-1 sequences and PCR homologous recombination. The lentivirus vector was packaged by three-plasmid packaging system. After collecting the supernatant of lentivirus, the virus titer was determined by quantitative PCR. K562 leukemia cells were collected and transtected with virus supernatant. Leukemia cell line stably expressing the target gene were screened by purinomycin. The expression levels of CD123 and CLL-1 were detected by RT-PCR and flow cytometry.@*RESULTS@#The lentiviral vector was successfully constructed, and identified by agarose gel electrophoresis and gene sequencing, then the virus titer of the supernatant was up to 5.81×10@*CONCLUSION@#Lentiviral vector expressing CD123-CLL1 has been successfully constructed, and K562 leukemia cell line stably expressing CD123 and CLL-1 has been successfully obtained.

Improving native human sperm freezing protection by using a modified vitrification method / 亚洲男科学杂志(英文版)

Slow freezing is the most commonly used technique for the cryopreservation of spermatozoa in clinical practice. However, it has been shown to have a negative impact on sperm function and structure. Vitrification as a successful alternative method has been proved to have better protective effects on human embryos, but vitrification of spermatozoa is still subject to low recovery rates. In this study, a modified vitrification method for native spermatozoa was developed. A total of 28 semen samples were included; each sample was divided into three equal parts and assigned to fresh, slow freezing, and vitrification groups. Sperm vitality, motility, morphology, DNA integrity, and acrosome reaction were assessed for each of the groups. The results showed that vitrification achieves better results for several sperm protection parameters than slow freezing; vitrification achieves a higher recovery rate (P < 0.05), motility (P <0.05), morphology (P <0.05), and curve line velocity (P <0.05) than slow freezing. Furthermore, DNA fragmentation was decreased (P <0.05) and better acrosome protection (P <0.05) was exhibited in the spermatozoa after vitrification. Principal component analysis of all sperm parameters revealed that the vitrification cluster was closer to the fresh cluster, indicating that spermatozoa are better preserved through vitrification. In conclusion, while both slow freezing and vitrification have negative effects on sperm function and structure, the vitrification protocol described here had a relatively better recovery rate (65.8%) and showed improved preservation of several sperm quality parameters compared with slow freezing.

Comparison on short-term safety outcomes between off-pump and on-pump coronary artery bypass grafting by experienced surgeons: a single center study with 31 075 cases / 中华心血管病杂志

Objective: To compare the short-term outcomes between off-pump and on-pump coronary artery bypass graft (CABG) by experienced surgeons with similar surgical team in a single large-volume cardiac surgery center. Methods: A total of 31 075 patients with multivessel coronary disease who underwent isolated off-pump or on-pump CABG between January 1, 2009 and December 31, 2019 by experienced surgeons in Fuwai hospital were enrolled in this retrospective study. Patients was divided into on-pump CABG group and on-pump CABG group on an intention-to treat basis. Short term safety endpoints, including 30 days mortality, composite endpoint of major morbidity or mortality, prolonged postoperative length of stay (PLOS), and prolonged ICU length of stay (PICULOS), and distal anastomosis were compared between the two groups. Mortality was evaluated on 30 days post operation, other endpoints were collected before discharge. After 1∶1 propensity-score matching of baseline characteristics for on-pump and off-pump CABG, postoperative endpoints were compared with use of McNemar's test and further adjusted with the use of a logistic regression model. Results: After propensity-score matching, 10 243 matched pairs of patients were included in the final analysis, there were 4 605(22.5%) females and mean age was (60.7±8.6) years. The standardized differences were less than 5% for all baseline variables in matched cohort. Univariate analysis indicated lower risk of 30 days mortality (0.2% vs. 0.7%, P<0.001), major morbidity or mortality (5.7% vs. 8.8%, P<0.001), PLOS (3.2% vs. 4.9%, P<0.001), PICULOS (9.4% vs. 12.2, P<0.001), and lower number of distal anastomosis ((3.3±0.8) vs. (3.6±0.8), P<0.001) in off-pump CABG group than in on-pump CABG group. After adjustment of cofounders, multivariate analysis showed that off-pump CABG was still associated with a lower risk of 30 days mortality (OR=0.29, 95%CI: 0.09-0.87, P=0.027), composite endpoint of major morbidity or mortality (OR=0.60, 95%CI: 0.53-0.68, P<0.001), PLOS (OR=0.64, 95%CI 0.54-0.75, P<0.001), PICULOS (OR=0.76, 95%CI: 0.69-0.84, P<0.001). Conclusions: Off-pump CABG is related with superior short-term safety outcomes than on-pump CABG by experienced surgeons in our center.

The use of miR122 and its target sequence in adeno-associated virus-mediated trichosanthin gene therapy / 中西医结合学报

OBJECTIVE@#Plant-derived cytotoxic transgene expression, such as trichosanthin (tcs), regulated by recombinant adeno-associated virus (rAAV) vector is a promising cancer gene therapy. However, the cytotoxic transgene can hamper the vector production in the rAAV producer cell line, human embryonic kidney (HEK293) cells. Here, we explored microRNA-122 (miR122) and its target sequence to limit the expression of the cytotoxic gene in the rAAV producer cells.@*METHODS@#A miR122 target (122T) sequence was incorporated into the 3' untranslated region of the tcs cDNA sequence. The firefly luciferase (fluc) transgene was used as an appropriate control. Cell line HEK293-mir122 was generated by the lentiviral vector-mediated genome integration of the mir122 gene in parental HEK293 cells. The effects of miR122 overexpression on cell growth, transgene expression, and rAAV production were determined.@*RESULTS@#The presence of 122T sequence significantly reduced transgene expression in the miR122-enriched Huh7 cell line (in vitro), fresh human hepatocytes (ex vivo), and mouse liver (in vivo). Also, the normal liver physiology was unaffected by delivery of 122T sequence by rAAV vectors. Compared with the parental cells, the miR122-overexpressing HEK293-mir122 cell line showed similar cell growth rate and expression of transgene without 122T, as well as the ability to produce liver-targeting rAAV vectors. Fascinatingly, the yield of rAAV vectors carrying the tcs-122T gene was increased by 77.7-fold in HEK293-mir122 cells. Moreover, the tcs-122T-containing rAAV vectors significantly reduced the proliferation of hepatocellular carcinoma cells without affecting the normal liver cells.@*CONCLUSION@#HEK293-mir122 cells along with the 122T sequence provide a potential tool to attenuate the cytotoxic transgene expression, such as tcs, during rAAV vector production.

Dendrobium officinale Kimura et Migo and American ginseng mixture: A Chinese herbal formulation for gut microbiota modulation / 中国天然药物

Dendrobium officinale Kimura et Migo (D. officinale) is a famous traditional Chinese medicine (TCM). A mixture of D. officinale and American ginseng has been shown to enhance cell-mediated immunity, humoral immunity, and monocyte/macrophage functions in mice. Here, the effects of a D. officinale and American ginseng mixture on the structure of gut microbial community in dogs were examined using high-throughput 16S rRNA gene amplicon sequencing. The data revealed that while the mixture did not change the diversity of gut microbial community significantly, differences among individuals were significantly reduced. Furthermore, the mixture-responsive operational taxonomic units (OTUs) exhibited a phase-dependent expression pattern. Fifty-five OTUs were found to exhibit a mixture-induced expression pattern, among which one third were short-chain fatty acid (SCFA)-producing genera and the others were probiotic genera included Lactobacillus spp., Sutterella, Alistipes, Anaerovorax, Bilophila, Coprococcus, Gordonibacter, Oscillibacter, among others. By contrast, 36% of the OTUs exhibiting a mixture-repressed expression pattern were disease-associated microorganisms, and six genera, namely Actinomyces, Escherichia/Shigella, Fusobacterium, Slackia, Streptococcus and Solobacterium, were associated with cancer. In addition, five genera were closely associated with diabetes, namely Collinsella, Rothia, Howardella, Slackia and Intestinibacter. Our results indicate that this D. officinale and American ginseng mixture may be used as a prebiotic agent to enhance SCFA-producing genera and prevent gut dysbiosis.

Role of T-type Calcium Channels in Generating Hyperexcitatory Behaviors during Emergence from Sevoflurane Anesthesia in Neonatal Rats / 神经科学通报·英文版

In the current study, we sought to investigate whether T-type Ca channels (TCCs) in the brain are involved in generating post-anesthetic hyperexcitatory behaviors (PAHBs). We found that younger rat pups (postnatal days 9-11) had a higher incidence of PAHBs and higher PAHB scores than older pups (postnatal days 16-18) during emergence from sevoflurane anesthesia. The power spectrum of the theta oscillations (4 Hz-8 Hz) in the prefrontal cortex was significantly enhanced in younger pups when PAHBs occurred, while there were no significant changes in older pups. Both the power of theta oscillations and the level of PAHBs were significantly reduced by the administration of TCC inhibitors. Moreover, the sensitivity of TCCs in the medial dorsal thalamic nucleus to sevoflurane was found to increase with age by investigating the kinetic properties of TCCs in vitro. TCCs were activated by potentiated GABAergic depolarization with a sub-anesthetic dose of sevoflurane (1%). These data suggest that (1) TCCs in the brain contribute to the generation of PAHBs and the concomitant electroencephalographic changes; (2) the stronger inhibitory effect of sevoflurane contributes to the lack of PAHBs in older rats; and (3) the contribution of TCCs to PAHBs is not mediated by a direct effect of sevoflurane on TCCs.

Efficacy and mechanism of electroacupuncture on insulin resistant polycystic ovary syndrome / 中国针灸

OBJECTIVE@#To explore the therapeutic effect and partial mechanism of electroacupuncture (EA) for patients with insulin resistance (IR) polycystic ovary syndrome (PCOS).@*METHODS@#Seventy patients with IR-PCOS were randomly divided into an EA group (36 cases, 5 cases dropped off) and a medication group (34 cases, 4 cases dropped off). The patients in the medication group were treated with oral administration of metformin hydrochloride, 500 mg each time, twice a day. The patients in the EA group were treated with EA (continuous wave, 2 Hz of frequency) at Zusanli (ST 36), Zhongwan (CV 12), Qihai (CV 6), Yishu (EX-B 3), Shenshu (BL 23), Pishu (BL 20), Ciliao (BL 32) for 30 min, three times a week. One menstrual cycle or 4 weeks were taken as a course of treatment, and 3 continuous courses were given. The follow-up was 3 months. The lipid metabolism indexes of triacylglycerol (TG), total cholesterol (TC), high-density lipoprotein (HDL) and low-density lipoprotein (LDL), homeostasis model assessment-insulin resistance index (HOMA-IR) and testosterone (T) in serum were compared before and after treatment, and the clinical effects of the two groups were evaluated during the follow-up.@*RESULTS@#The total effective rate was 67.7% (21/31) in the EA group and 60.0% (18/30) in the medication group, with no significant difference between the two groups (>0.05). After treatment, the levels of serum T, HOMA-IR, LDL, TG and TC were decreased significantly in the two groups (<0.01, <0.05), and HDL was increased significantly (<0.01); the levels of TC in the EA group after treatment was lower than that in the medication group (<0.05).@*CONCLUSION@#EA may adjust some dyslipidemia in patients to correct IR and improve endocrine disorder of PCOS, which had superior/similar effects to metformin.

Correlation between serum dipeptidyl peptidase 4 activity and abnormal lipid metabolism / 中华内分泌代谢杂志

Objective:Dipeptidyl peptidase 4 (DPP4) is an incretin lyase, while DPP4 inhibitors have been used clinically as hypoglycemic drugs. Serum DPP4 is related to metabolic diseases such as cardiovascular disease and obesity, and lipid metabolic disorder is an important part of metabolic syndrome. This study was designed to explore the relationship between DPP4 and lipid metabolic disorder.Methods:There were 3644 participants from Chengqiao Town, Chongming District, Shanghai. All of the subjects recruited were residents between 40-70 years old, who have not diagnosed as diabetes mellitus (DM) and who have never used any lipid-lowering drugs. Glucose, insulin, lipid level, DPP4 activity and liver enzymes in serum of all participants were tested. In addition, height, weight and blood pressure were also recorded.Results:Participants were divided into four groups (Q1-Q4) according to the quartile value of serum DPP4 activities. Along with the increase of serum DPP4 activity, triglyceride, total cholesterol, and blood glucose levels increased, and triglyceride increased from (1.23 ± 0.70) mmol/L to (2.31 ± 1.89) mmol/L. Compared with cholesterol levels, the triglyceride was more closely related to DPP4 activity [the correlation coefficients of triglyceride, total cholesterol, low-density lipoprotein-cholesterol (LDL-C), and high-density lipoprotein-cholesterol (HDL-C) were 0.424, 0.281, 0.142, and 0.027, respectively]. After adjusting for confounding factors (age, gender, BMI), the result was similar. With the increase of DPP4 enzyme activity, the Q4 group had a higher risk of developing hyperglyceridemia ( OR=5.25) than the Q1 group, and the result was almost unchanged after adjusting for confounding factors and blood glucose levels ( OR=4.90). Conclusion:Serum DPP4 activity is independently related to blood lipid levels, and is particularly closely related to blood TG levels.

Effects of lifestyle intervention on diet, physical activities and health outcomes of obese children and adolescents / 中华临床营养杂志

Objective:To observe the effects of lifestyle intervention on diet, physical activities and health outcomes in obese children and adolescents during one year of follow up.Methods:A total of 153 obese children and adolescents with body mass index more than 95th percentage of the same age and sex were recruited consecutively from June 2015 to June 2017 in our hospital whose parents had signed the informed consent forms. The children were followed-up once every three months and their diet and physical activities, anthropometric measurement and metabolic indicators were assessed on research scheme, which lasted for one year.Results:A total of 52 obese children completed four visits plan in 12 months (34.0%, one year group), 101 children (66.0%) dropped from 3 to 9 months (66.0%, less than one year group). The intake of total energy [(8 524.5±2 068.6)kJ vs (6 464.0±1 586.9)kJ, P<0.05], dietary protein [(75.5±20.7)g vs (64.2±16.8)g, P<0.05], fat [(79.0±18.8)g vs (60.3±14.2)g, P<0.05], carbohydrates [(257.1±83.6)g vs (188.9±63.8)g, P<0.05] decreased after one year intervention in one year group. Moreover, the numbers of physical activity of medium to high intensity increased in obese children (0 vs 32.7%, P<0.05). BMI-SDS [(3.15±0.85) vs (2.46±0.81), P<0.05], WHtR [(0.60±0.04) vs (0.56±0.06), P<0.05] and FM% [(39.9±5.4) vs (33.0±7.4), P<0.05] were reduced, while SMM% [(32.1±3.2) vs (36.0±4.3), P<0.05] increased significantly in one year group. The detection rate of insulin resistance, dyslipidemia and nonalcoholic fatty liver disease (NAFLD) were reduced in one year group at the end of follow up ( P<0.05). The decrease of body fat and the increase of skeletal muscle were more obvious in one-year follow up group( P<0.05). Conclusion:Children and adolescent have less energy intake, more physical activities, good clinical outcomes and less complications of obesity through lifestyle intervention and follow up for one year, so it is worthy of being promoted.

Clinical characteristics of insulin resistance and its relationship with metabolic complications in obese children and adolescents / 中华实用儿科临床杂志

Objective:To study the clinical characteristics of growth development and metabolic disorders in obese children and adolescents with insulin resistance (IR).Methods:Normal weight or obese children and adolescents who hospitalized at the Department of Children′s Health Care of Children′s Hospital Affiliated to Nanjing Medical University from September 2015 to April 2018 were recruited.Children′s height, body weight and waist circumference were measured, and waist-to-height ratio (WHtR) and body mass index (BMI) were calculated.Puberty process was determined by Tanner stage.Blood glucose, blood lipid and insulin were measured in fasting state, and homeostasis model assessment of insulin resistance (HOMA-IR) was calculated based on fasting blood glucose and insulin levels.IR was considered when HOMA-IR was over 2.69.Non-alcoholic fatty liver (NAFLD) was diagnosed by abdominal ultrasound.Results:(1) A total of 691 subjects were included, including 183 cases with the age of (9.73±2.38) years in the normal weight group/normal group, and 508 cases with the age of (10.24±2.05) years old in the obese group.The rate of IR was higher in obese group than that in normal group (55.71% vs. 10.38%), and the difference was statistically significant ( P<0.001). (2)HOMA-IR was positively correlated with age ( r=0.256, P<0.001), BMI ( r=0.426, P<0.001), waist circumference ( r=0.454, P<0.001), and WHtR ( r=0.321, P<0.001). After the adjustment for age, sex, and puberty stage, HOMA-IR was also positively correlated with BMI ( r=0.418, P<0.001), waist circumference ( r=0.419, P<0.001) and WHtR ( r=0.375, P<0.001). (3) During puberty, HOMA-IR in both of obese group and normal group was increased, and HOMA-IR in obese group was more particularly serious compared to normal group[TannerⅠ: 2.60(1.49, 3.94) vs.1.28(0.80, 1.90); Tanner Ⅱ: 3.07(1.75, 5.17) vs.1.80(1.16, 2.96); Tanner Ⅲ: 4.33(2.80, 6.57) vs.2.47(1.41, 3.68); Tanner Ⅳ-Ⅴ: 3.49(1.04, 5.78) vs.1.91(0.54, 2.60)], and the differences were all statistically significant(all P<0.05). (4)Compared with the obese objects without IR, obese children and adolescents with IR had higher systolic blood pressure[112(104, 124) mmHg vs.109(98, 121) mmHg, 1 mmHg=0.133 kPa], triglyceride level [1.27(0.95, 1.81) mmol/L vs.1.09(0.79, 1.61) mmol/L], fas-ting blood glucose level [4.80(4.46, 5.01) mmol/L vs.4.48(4.16, 4.76) mmol/L] and fasting insulin level [21.27(16.21, 28.56) mmol/L vs.7.62(4.43, 10.83) mmol/L], and the differences were all statistically significant(all P<0.05). IR was a risk factor for NAFLD in obese children( OR=1.536, 95% CI: 1.049-2.247, P<0.05). Conclusions:Serious and abdominal obesity in children and adolescents is a major risk factor for the development of IR.HOMA-IR of obese children and adolescents is particularly serious during puberty.The obese children with IR are more likely to have metabolic disorders in blood glucose, serum lipid and blood pressure, and have the risk of NAFLD development.