Effects of exercise training on glucose metabolism indicators and inflammatory markers in obese children and adolescents:A metaanalysis

BACKGROUND Obesity in children and adolescents is a serious problem,and the efficacy of exercise therapy for these patients is controversial.AIM To assess the efficacy of exercise training on overweight and obese children based on glucose metabolism indicators and inflammatory markers.METHODS The PubMed,Web of Science,and Embase databases were searched for randomized controlled trials related to exercise training and obese children until October 2023.The meta-analysis was conducted using RevMan 5.3 software to evaluate the efficacy of exercise therapy on glucose metabolism indicators and inflammatory markers in obese children.RESULTS In total,1010 patients from 28 studies were included.Exercise therapy reduced the levels of fasting blood glucose(FBG)[standardized mean difference(SMD):-0.78;95%confidence interval(CI):-1.24 to-0.32,P=0.0008],fasting insulin(FINS)(SMD:-1.55;95%CI:-2.12 to-0.98,P<0.00001),homeostatic model assessment for insulin resistance(HOMA-IR)(SMD:-1.58;95%CI:-2.20 to-0.97,P<0.00001),interleukin-6(IL-6)(SMD:-1.31;95%CI:-2.07 to-0.55,P=0.0007),C-reactive protein(CRP)(SMD:-0.64;95%CI:-1.21 to-0.08,P=0.03),and leptin(SMD:-3.43;95%CI:-5.82 to-1.05,P=0.005)in overweight and obese children.Exercise training increased adiponectin levels(SMD:1.24;95%CI:0.30 to 2.18,P=0.01)but did not improve tumor necrosis factor-alpha(TNF-α)levels(SMD:-0.80;95%CI:-1.77 to 0.18,P=0.11).CONCLUSION In summary,exercise therapy improves glucose metabolism by reducing levels of FBG,FINS,HOMA-IR,as well as improves inflammatory status by reducing levels of IL-6,CRP,leptin,and increasing levels of adiponectin in overweight and obese children.There was no statistically significant effect between exercise training and levels of TNF-α.Additional long-term trials should be conducted to explore this therapeutic perspective and confirm these results.

Using Tree Shrews (Tupaia belangeri)as a Novel Animal Model of Liver Transplantation

Liver transplantation (LT)is most effective and promising approach for end-stage liver disease.However,there remains room for further improvement and innovation,for example, to reduce ischemic reperfusion injury,transplant rejection and immune tolerance.A good animal model of LT is essential for such innovation in transplant research.Although rat LT model has been used since the last century,it has never been an ideal model because the results observed in rat may not be applied to human because these two species are genetically distinct from each other.In this study,we for the first time performed LT using the tree shrew (Tupaia belangeri),a species in the Order Scandentia which is closely related with primates,and evaluated the possibility to adopt this species as a new model of LT.We performed LT on 30 animals using the two-cuff technique, examining the success rate,the survival rate and the immunological reaction.The recipient operation time was 60 min averagely,and we limited the time of the anhepatic phase within 20 min.Twenty-seven (90%)of the animals survived for at least 3 days after the transplantation. Thirteen animals that did not receive any immunosuppressive drug died in 8 days mostly because of acute rejection effect (n=9),similar to the reaction in human but not in experimental rat.The rest 14 animals that were given rapamycin survived significantly longer (38 days)and half of them survived for 60 days until the end of the study.Our results suggest that performing LT in tree shrews can yield high success rate and high survival rate.More importantly,the tree shrews share similar immunological reaction with human.In addition,previous genomics study found that the tree shrews share more proteins with human.In sum,the tree shrews may outperform the experimental rats and could be used as a better and cost-effective animal model for LT.

Confocal laser endomicroscopy distinguishing benign and malignant gallbladder polyps during choledochoscopic gallbladderpreserving polypectomy:A case report

BACKGROUND In the last decade, confocal laser endomicroscopy (CLE) has emerged as a newendoscopic imaging modality for real-time in vivo histological examination at themicroscopic level. CLE has been shown to be useful for distinguishing benign andmalignant lesions and has been widely used in many digestive diseases. In ourstudy, we used CLE for the first time to examine the morphology of cholesterolpolyps as well as the different parts of normal gallbladder mucosa.CASE SUMMARY A 57-year-old woman was diagnosed by ultrasound with a polyp of 21 mm in thegallbladder wall. She consented to polyp removal by laparoscopic choledochoscopy.During laparoscopic cholecystectomy combined with choledochoscopicpolyp resection, CLE was used to observe the morphology of the polyp surfacecells. The appearance of the mucosa and microvessels in various parts of thegallbladder were also observed under CLE. Through comparison betweenpostoperative pathology and intraoperative CLE diagnosis, the reliability ofintraoperative CLE diagnosis was confirmed. CLE is a reliable method to examineliving cell pathology during cholecystectomy. Based on our practice, CLE shouldbe prioritized in the diagnosis of gallbladder polyps.CONCLUSION Compared with traditional histological examination, CLE has several advantages.We believe that CLE has great potential in this field.

Macular thickness as a predictor of loss of visual sensitivity in ethambutol-induced optic neuropathy

Ethambutol is a common cause of drug-related optic neuropathy.Prediction of the onset of ethambutol-induced optic neuropathy and consequent drug withdrawal may be an effective method to stop visual loss.Previous studies have shown that structural injury to the optic nerve occurred earlier than the damage to visual function.Therefore,we decided to detect structural biomarkers marking visual field loss in early stage ethambutol-induced optic neuropathy.The thickness of peripapillary retinal nerve fiber layer,macular thickness and visual sensitivity loss would be observed in 11 ethambutol-induced optic neuropathy patients（22 eyes） using optical coherence tomography.Twenty-four healthy age-and sex-matched participants（48 eyes） were used as controls.Results demonstrated that the temporal peripapillary retinal nerve fiber layer thickness and average macular thickness were thinner in patients with ethambutol-induced optic neuropathy compared with healthy controls.The average macular thickness was strongly positively correlated with central visual sensitivity loss（r2=0.878,P=0.000）.These findings suggest that optical coherence tomography can be used to efficiently screen patients.Macular thickness loss could be a potential factor for predicting the onset of ethambutol-induced optic neuropathy.

Adrenocorticotropic hormone combined with magnesium sulfate therapy for infantile epileptic spasms syndrome:a real-world study

Background Infantile epileptic spasms syndrome(IESS)is a serious disease in infants,and it usually evolves to other epilepsy types or syndromes,especially refractory or super-refractory focal epilepsies.Although adrenocorticotropic hormone(ACTH)is one of the first-line and effective treatment plans for IESS,it has serious side effects and is not sufficiently effective.Methods A retrospective study of the clinical outcomes of ACTH combined with magnesium sulfate(MgSO4)therapy for IESS in two hospital centers was conducted.The major outcome of the single and combined treatment was evaluated by changes in seizure frequency and improvements in hypsarrhythmia electroencephalography(EEG).To reduce the confounding bias between the two groups,we used SPSS for the propensity score matching(PSM)analysis.Results We initially recruited 1205 IESS patients from two Chinese hospitals and treated them with ACTH combined with MgSO4 and ACTH alone.Only 1005 patients were enrolled in the treatment(ACTH combined with MgSO4:744,ACTH:261),and both treatment plans had a more than 55%response rate.However,compared to patients treated with ACTH alone,those patients treated with ACTH combined with MgSO4 had better performance in terms of the seizure frequency and hypsarrhythmia EEG.After PSM,the two groups also showed significant differences in responder rate[70.8%(95%confidence interval,CI)=66.7%–74.8%)vs.53.8%(95%CI=47.4%–60.2%),P<0.001],seizure frequency(P<0.001)and hypsarrhythmia EEG resolution(P<0.001).Notably,multivariate analysis revealed that the lead time to treatment and the number of antiseizure medications taken before treatment were two factors that may affect the clinical outcome.Patients with less than 3 months of lead time responded to the treatment much better than those with>3 months(P<0.05).In addition,the overall incidence of adverse reactions in the ACTH combined with MgSO4 group was much lower than that in the ACTH group(31.4%vs.63.1%,P<0.001).During the treatment,only infection(P=0.045)and hypertension(P=0.025)were significantly different between the two groups,and no baby died.Conclusion Our findings support that ACTH combined with MgSO4 is a more effective short-term treatment protocol for patients with IESS than ACTH alone,especially for those patients with short lead times to treatment.

Phase I clinical trial of intracerebral injection of lentiviral-ABCD1 for the treatment of cerebral adrenoleukodystrophy

This was a single-arm,multicenter,open-label phase I trial.Lentiviral vectors(LV)carrying the ABCD1 gene(LV-ABCD1)was directly injected into the brain of patients with childhood cerebral adrenoleukodystrophy(CCALD),and multi-site injection was performed.The injection dose increased from 200 to 1600 lL(vector titer:1×10^(9) transduction units per mL(TU/mL)),and the average dose per kilogram body weight ranges from 8 to 63.6 lL/kg.The primary endpoint was safety,dose-exploration and immunogenicity and the secondary endpoint was initial evaluation of efficacy and the expression of ABCD1 protein.A total of 7 patients participated in this phase I study and were followed for 1 year.No injectionrelated serious adverse event or death occurred.Common adverse events associated with the injection were irritability(71%,5/7)and fever(37.2-38.5℃,57%,4/7).Adverse events were mild and selflimited,or resolved within 3 d of symptomatic treatment.The maximal tolerable dose is 1600 lL.In 5 cases(83.3%,5/6),no lentivirus associated antibodies were detected.The overall survival at 1-year was 100%.The ABCD1 protein expression was detected in neutrophils,monocytes and lymphocytes.This study suggests that the intracerebral injection of LV-ABCD1 for CCALD is safe and can achieve successful LV transduction in vivo;even the maximal dose did not increase the risk of adverse events.Furthermore,the direct LV-ABCD1 injection displayed low immunogenicity.In addition,the effectiveness of intracerebral LV-ABCD1 injection has been preliminarily demonstrated while further investigation is needed.This study has been registered in the Chinese Clinical Trial Registry(https://www.chictr.org.cn/,registration number:ChiCTR1900026649).

Sirolimus can promote the disappearance of renal angiomyolipoma associated with tuberous sclerosis complex:a prospective cohort study

Background Renal angiomyolipoma(RAML)is the most common kidney lesion in patients with tuberous sclerosis complex(TSC),affecting about 80%of patients.It is a benign tumor that grows over time,usually bilaterally,and can easily lead to kidney complications such as acute hemorrhage.Herein,we investigated the efficacy and safety of sirolimus in children with TSC-associated RAML and explored the factors affecting tumor disappearance under sirolimus treatment through subgroup analysis.Methods A prospective cohort study was conducted.Sirolimus was initiated at 1 mg/(m^(2)×day),and dose adjustments were made by a 2-week titration period to attain a trough blood concentration of 5-10 ng/mL.The disappearance of RAML in chil-dren after sirolimus treatment was observed,and Cox regression was used to screen the factors affecting tumor disappearance.Results One hundred and twenty-six patients who met the criteria were analyzed.After 3 months,6 months,12 months,and 24 months of follow-up,tumors disappeared in 18(14.3%),30(23.8%),39(31.0%),and 42(33.3%)children,respec-tively.Tumors disappeared in 50(39.7%)children by the last visit of each individual,and 30(60%)of them occurred within 6 months.The multivariate Cox regression analysis showed that patients with a smaller maximum tumor diameter at baseline had a higher tumor disappearance rate.Thirty-six(29%)patients had stomatitis during the entire treatment period,and no serious adversereactionswereobserved.Conclusions Sirolimus could promote the disappearance of TSC-related RAML.The disappearance rate was correlated with the maximum diameter at baseline,and the smaller the tumor was,the higher the disappearance rate.It is well tolerated in the treatment of RAML associated with TSC.

Clinical application and mechanism of traditional Chinese medicine in treatment of lung cancer

Lung cancer is a malignant tumor characterized by a rapid proliferation rate,less survivability,high mortality,and metastatic potential.This review focuses on updated research about the clinical application of traditional Chinese medicine(TCM)as an adjuvant therapy to lung cancer treatment and the mechanisms of TCM effect on lung cancer in vitro and in vivo.We summarized the recent 5 years of different research progress on clinical applications and antitumor mechanisms of TCM in the treatment of lung cancer.As a potent adjuvant therapy,TCM could enhance conventional treatments(chemotherapy,radiation therapy,and epidermal growth factor receptors[EGFRs]tyrosine kinase inhibitors[TKIs])effects as well as provide synergistic effects,enhance chemotherapy drugs chemosensitivity,reverse drug resistance,reduce adverse reactions and toxicity,relieve patients’pain and improve quality of life(QOL).After treating with TCM,lung cancer cells will induce apoptosis and/or autophagy,suppress metastasis,impact immune reaction,and therapeutic effect of EGFR-TKIs.Therefore,TCM is a promisingly potent adjuvant therapy in the treatment of lung cancer and its multiple mechanisms are worthy of an in-depth study.

Probiotics with anti-type 2 diabetes mellitus properties:targets of polysaccharides from traditional Chinese medicine

Traditional Chinese medicine polysaccharides is a biologically active ingredient that is not easy to be digested.It is fermented by intestinal microflora to promote qualitative and selective changes in the composition of the intestinal microbiome,which often result in beneficial effects on the health of the host.People call it“prebiotics”.In this review,we systematically summarized the anti-diabetic effect of traditional Chinese medicine polysaccharides.These polysaccharides regulate the metabolism of sugar and lipids by inter-influence with the intestinal microflora,and maintain human health,while improving type 2 diabetes-like symptoms such as high blood glucose,and abnormal glucose and lipid metabolism.

Investigation of Radix Achyranthis Bidentatae Phytochemistry and Pharmacology

Radix achyranthis bidentatae(RAB), a member of the Amaranthaceae family, has been widely used in Traditional Chinese Medicine for1000 s of years. Increasing interest in RAB-derived medicinal has led to the discovery of additional triterpenoid saponins, phytoecdysones,polysaccharides, and many other compounds, as well as investigations into their pharmacology. A large number of pharmacological studies have shown RAB and its active components possess a range of pharmacological activities, including anti-tumor, anti-fertility, anti-senile, and anti?inflammatory effects. This review is an up?to?date summary and synthesis of the uses of RAB from phytochemical and pharmacological perspectives.

The Fruits of Xanthium sibiricum Patr: A Review on Phytochemistry, Pharmacological Activities, and Toxicity

In recent years,drug development and research have gradually shifted from chemical synthesis to biopharmaceutical and natural drugs.Natural medicines,such as traditional Chinese medicine,have been among the first studied because of their long medicinal history,simplicity,and the relatively low cost of research.Among them,Xanthii Fructus(XF)is famous for the treatment of sinusitis.In this article,the achievements of research on XF from 1953 to 2020 are systematically reviewed,focusing on the aspects of chemical constituents,pharmacological effects,clinical applications,toxicity and side effects,and processing methods.To date,there have been significant advances in both the phytochemistry and pharmacology of XF.Some traditional uses have been validated and clarified in modern pharmacological studies.However,its mechanism of action in the treatment of allergic diseases has not been satisfactorily explained.Further in vitro and in vivo studies are required to rationally develop new drugs and to elucidate the therapeutic potential of XF.A comprehensive evaluation of XF and an understanding of network pharmacology are also needed.

Simultaneous Determination of Six Compounds in Rat Plasma by Ultra-Performance Liquid Chromatography with Tandem Mass Spectrometry: Application in the Pharmacokinetic Study of Qing Gan-Shu Yu-Fang

A rapid and high selective ultra-performance liquid chromatography(UPLC)with tandem mass spectrometry method for simultaneous determination of six compounds including albiflorin,paeoniflorin,picroside I,picroside II,saikosaponin A,and saikosaponin D in rat plasma was developed and validated using butyl p-hydroxybenzoate as an internal standard.One-step direct protein precipitation with acetonitrile was used to extract the compounds from the rat plasma samples.Chromatographic separation was achieved using an ACQUITY UPLC BEH C18 column(100 mm×2.1 mm,1.7μm)at a flow rate of 0.4 m L/min,using gradient mode containing 0.1%formic acid in water and acetonitrile were used as the Mobile phase A and B.Electrospray ionization in negative ion mode and multiple reaction monitoring were used to identify and quantify active components.Calibration curves showed good linearity(R^2>0.9908)over a wide concentration range for all compounds.The intra-and interday precision(relative standard deviation)ranged 2.4%–7.0%and 2.6%–8.0%,respectively.The accuracy(relative error)was from-13.0%to 13.2%at all quality control levels.The recovery ranged from 81.1%to 92.5%.The validated method was successfully applied to pharmacokinetic study in rats after oral administration of Qing Gan-Shu Yu-Fang.The results show that one can draw a conclusion that these six active ingredients can be quickly absorbed and play a pharmacodynamic role rapidly in vivo.

MONOSACCHARIDE COMPOSITION OF POLYSACCHARIDES THROUGH HILIC-UPLC-TQ-MS/MS

A simple,sensitive and direct method was developed for compositional analysis of plant polysaccharides using hydrophilic interaction ultra-performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry(HILIC-UPLC-TQ-MS/MS)in multiple-reaction monitoring(MRM).The effects of chromatographic columns,scan time,additive types,

Role of Substrate Roughness in ZnO Nanowire Arrays Growth by Hydrothermal Approach

The role of substrate roughness in ZnO nanowire（NW） arrays hydrothermal growth has been systematically studied.Six silicon substrates with different roughness by chemical etching have been selected to grow ZnO NW arrays hydrothermally after sputtering 5-nm-thick ZnO seed layer as catalyst.The as-grown samples reveal that average diameters and number densities of ZnO NW arrays are inversely proportional to the increasing substrate roughness observed by atomic-force microscopy and scanning electron microscopy.Furthermore,the theoretically derived equations based on nucleation with the Gibbs free energy to describe relations of substrate roughness versus average NW diameter and NW number density match well with experimental results.Research results in this paper can be used to control the number density and the average diameter of ZnO NW arrays by alternating substrate roughness.