1.Core stability training reduces risk of anterior cruciate ligament injury in landing movements
Boshi XUE ; Changrui LIN ; Liangliang ZHENG ; Chen YANG ; Zhipeng ZHOU
Chinese Journal of Tissue Engineering Research 2024;28(16):2467-2472
BACKGROUND:Studies have shown that poor dynamic postural control may lead to abnormal movement patterns during exercise,which may increase the risk of lower limb joint and anterior cruciate ligament injury.The stability of the body core is the basis of good dynamic postural control. OBJECTIVE:To investigate the effects of core stability training on dynamic postural control and risk of injury in landing movements,and to compare the differences in training effects between genders. METHODS:Thirty-five college students(male=19,female=16)were recruited for 6 weeks of core stability training.The results of the Y balance test,trunk extensor endurance test,trunk flexor endurance test,lateral bridge endurance test,and landing error scoring system were analyzed before and after training. RESULTS AND CONCLUSION:The 6-week core stability training could improve trunk extensor endurance(P<0.001),flexor endurance(P<0.001),and lateral abdominal muscle endurance(P<0.001).Core stability training could improve forward distance(P=0.026),backward inward distance(P<0.001),backward outward distance(P=0.005)and comprehensive score(P<0.001)of Y balance test for male and female college students.Landing error scoring system scores of both male and female college students significantly decreased after 6 weeks of core stability training(P<0.001)while increasing knee(P<0.001)and hip flexion angles(P<0.001),decreasing knee valgus angle(P<0.001)at the moment of touchdown,and could increase the maximum knee flexion angle(P<0.001)and decrease the maximum knee valgus angle(P<0.001).It is concluded that core stability training improves dynamic postural control and improves landing movement patterns,suggesting that it may help reduce the risk of anterior cruciate ligament injury.There are no sex differences in core stability training in terms of increased trunk flexor endurance,lateral bridge muscle group endurance,improved dynamic postural control,and reduced risk of anterior cruciate ligament injury.
2.Hydralazine represses Fpn ubiquitination to rescue injured neurons via competitive binding to UBA52
Shengyou LI ; Xue GAO ; Yi ZHENG ; Yujie YANG ; Jianbo GAO ; Dan GENG ; Lingli GUO ; Teng MA ; Yiming HAO ; Bin WEI ; Liangliang HUANG ; Yitao WEI ; Bing XIA ; Zhuojing LUO ; Jinghui HUANG
Journal of Pharmaceutical Analysis 2024;14(1):86-99
A major impedance to neuronal regeneration after peripheral nerve injury(PNI)is the activation of various programmed cell death mechanisms in the dorsal root ganglion.Ferroptosis is a form of pro-grammed cell death distinguished by imbalance in iron and thiol metabolism,leading to lethal lipid peroxidation.However,the molecular mechanisms of ferroptosis in the context of PNI and nerve regeneration remain unclear.Ferroportin(Fpn),the only known mammalian nonheme iron export protein,plays a pivotal part in inhibiting ferroptosis by maintaining intracellular iron homeostasis.Here,we explored in vitro and in vivo the involvement of Fpn in neuronal ferroptosis.We first delineated that reactive oxygen species at the injury site induces neuronal ferroptosis by increasing intracellular iron via accelerated UBA52-driven ubiquitination and degradation of Fpn,and stimulation of lipid peroxidation.Early administration of the potent arterial vasodilator,hydralazine(HYD),decreases the ubiquitination of Fpn after PNI by binding to UBA52,leading to suppression of neuronal cell death and significant ac-celeration of axon regeneration and motor function recovery.HYD targeting of ferroptosis is a promising strategy for clinical management of PNI.
3.Effect of muscle energy technique on dynamic postural control and lumbar neuromuscular function in patients with non-specific low back pain:a randomized controlled trial
Jianbin ZHAO ; Yingce YAO ; Jing WU ; Boshi XUE ; Xiaowei YANG ; Zhipeng ZHOU ; Liangliang ZHENG
Chinese Journal of Rehabilitation Theory and Practice 2024;30(9):1092-1098
Objective To explore the effect of muscle energy technique(MET)on dynamic posture control and lumbar neuromuscu-lar function in patients with non-specific low back pain. Methods From March to June,2022,30 college students with non-specific low back pain from Shandong Sport Universi-ty were randomly divided into control group(n=15)and intervention group(n=15).The control group received health education,and the intervention group received MET,for four weeks.They were assessed with Visual Ana-logue Scale(VAS)of pain,Oswestry Disability Index(ODI),Y-balance test and trunk flexion-relaxation test be-fore and after intervention. Results VAS scores decreased in both groups after intervention(|t|>2.449,P<0.05),and it was less in the intervention group than in the control group(t=-5.068,P<0.001);while ODI score decreased in the intervention group(t=4.785,P<0.001),and it was less in the intervention group than in the control group(t=-2.895,P=0.007);the performance of Y-balance test increased(t=-3.662,P=0.003)in the intervention group,as well as flexion-re-laxation ratio of multifidus(t=-2.460,P=0.029). Conclusion MET is effective on alleviating pain and lumbar dysfunction,improving dynamic posture control and en-hancing the function of the multifidus during flexion in patients with non-specific low back pain.
4.Cost-utility Analysis of PD-1/PD-L1 Inhibitor Combination Therapies as First-line Treatment for Advanced Non-small-cell Lung Cancer
HE Yimin ; NIAN Zilin ; LIU Wenbin ; YANG Lin ; DONG Liangliang ; ZHAO Qiuling
Chinese Journal of Modern Applied Pharmacy 2024;41(13):1820-1829
OBJECTIVE
To compare the cost-utility of eight programmed death 1(PD-1)/programmed cell death-ligand 1(PD-L1) inhibitor combination regimens for first-line treatment of advanced non-small cell lung cancer(NSCLC) from the perspective of Chinese healthcare system.
METHODS
Relevant data were derived from a published network meta-analysis and randomized controlled trails, a three-state Markov model was established to analyze the cost-utility of eight immunotherapy combinations. The robustness of results were validated through sensitivity analyses and a series of scenario analyses was also conducted.
RESULTS
The incremental cost-utility ratio(ICUR) of the sintilizumab plus chemotherapy group and the tislelizumab plus chemotherapy group were ¥125143.88/quality adjusted life year(QALY) and ¥189609.64/QALY, respectively, which were less than the willingness-to-pay(WTP) threshold of ¥257094/QALY, and all the ICURs of other PD-1/PD-L1 inhibitor combination regimens exceeded the WTP threshold and were not economical. Scenario analyses found that even if the medical insurance reimbursement ratio reached 80%, the different combinations of pembrolizumab, nivolumab and atezolizumab were not economical.
CONCLUSION
Compared with other PD-1/PD-L1 inhibitor combination regimens, sintilizumab plus chemotherapy and tislelizumab plus chemotherapy have cost-utility advantages in the first-line treatment of advanced NSCLC, which can provide a certain reference for selecting a reasonable treatment plan for NSCLC patients.
5.Relationship of parental anger expression and symptoms in children with oppositional defiant disorder
Feifei SI ; Ting HE ; Liangliang YANG ; Mengjie ZHAO ; Min DONG ; Lu LIU ; Xiuyun LIN
Chinese Mental Health Journal 2024;38(3):254-259
Objective:This study is to investigate the relationship of parental anger expression and symptoms in children with oppositional defiant disorder(ODD).Methods:Forty-six children with ODD and 46 age-gender-matched normal children participated.The Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition(DSM-5),guided the diagnoses.Parental anger expression and children's anger management were assessed using the State-Trait Anger Expression Inventory-2 and Children Emotion Management Scales.Results:ODD symptoms were directly predicted by maternal anger index(AI)(β=0.13,P<0.05)and anger expression-out(AX-O)(β=0.25,P<0.05).Children's anger cope(AC)played a mediating function to maternal AI through ODD symptoms,occupying 13%of the total effect;their AC and anger dysregulation(AD)played a mediating function to maternal AX-Othrough ODD symptoms,accounting for 29%and 18%of the total effect,respectively.Conclusion:It sug-gests that anger cope and anger dysregulation in children with oppositional defiant disordermay may play a media-ting role between maternal anger expression and oppositional defiant disorder symptoms.
6.Analysis of Molecular Mechanism of Angong Niuhuangwan in Alleviating Traumatic Brain Injury Based on Single Cell Sequencing
Zhiru YIN ; Liangliang TIAN ; Guangzhao CAO ; Jingjing ZHANG ; Hongjun YANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(23):35-45
ObjectiveTo reveal the molecular mechanism of Angong Niuhuangwan(AGNH) in improving traumatic brain injury(TBI) based on single cell sequencing. MethodSeventy-five male SD rats were randomly divided into the sham group, model group, piracetam group(3.6 g·kg-1), AGNH low- and high-dose groups(0.09, 0.27 g·kg-1), with 15 rats in each group. In addition to the sham group, the other 4 groups used the modified Feeney free-fall impact method to prepare TBI model, and the drugs were administered by gavage immediately after modeling, 24 hours later, the modified neurological deficit score(mNSS) was performed, and brain tissue was isolated to determine the degree of cerebral edema. Hematoxylin-eosin(HE) staining was used to observe the injury degree in the cortex, CA1 region and CA3 region of brain tissue. The expression levels of cyclooxygenase-2(COX-2), interferon regulatory factor 1(IRF1), Janus kinase 2(JAK2) and suppressor of cytokine signaling 3(SOCS3) were observed by immunofluorescence(IF) staining. The levels of interleukin(IL)-6, IL-18, IL-1β, IL-17A, tumor necrosis factor-α(TNF-α), Caspase-1 and nucleotide binding oligomerization domain(NOD)-like receptor heat protein domain associated protein 3(NLRP3) inflammasome were determined by enzyme-linked immunosorbent assay(ELISA). The regulation of AGNH on each cell population was analyzed by single cell sequencing, and differentially expressed genes were analyzed by Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG), which led to construct microglia differentially expressed gene network to search for the key targets, and validated by ELISA and IF. ResultCompared with the sham group, the mNSS and brain water content were significantly increased in the model group(P<0.01). Compared with the model group, mNSS and brain water content in the low and high dose AGNH groups were decreased(P<0.05,P<0.01). HE staining results showed that compared with the sham group, the cells in the cerebral cortex and hippocampus of rats in the model group were seriously lost, and the cells were arranged loosely(P<0.01). Compared with the model group, AGNH could significantly increase the density of neurons in the CA1 and CA3 regions of the cerebral cortex and hippocampus, making the arrangement more compact, as well as improved cell morphology(P<0.05,P<0.01). ELISA and IF staining showed that AGNH could reduce the levels of Caspase-1, IL-17A, TNF-α, NLRP3 and COX-2 in brain tissue of TBI rats(P<0.05, P<0.01). A total of 13 cell subsets were identified by single cell sequencing, among which microglia played an important role in neuroimmunity. The results of GO enrichment analysis of differentially expressed genes in microglia showed that AGNH improved TBI in response to inflammation and TNF-α. KEGG enriched IL-17 signaling pathway, TNF signaling pathway, Toll-like receptor signaling pathway, etc. The results of network analysis showed that the key targets of AGNH in regulating TBI might be IL-6, IL-1β, JAK2, SOCS3, IRF1. IF and ELISA verification results showed that compared with the sham group, SOCS3 expression in microglia was decreased in the model group, and the expressions of IL-6, IL-1β, JAK2 and IRF1 were increased(P<0.01). Compared with the model group, AGNH could increase the expression of SOCS3, decrease the expression of IL-6, IL-1β, JAK2, IRF1 (P<0.05, P<0.01). ConclusionAGNH can reduce the degree of brain edema and brain injury, decrease the expression of inflammatory factors, and inhibit the expression of NLRP3 and its downstream Caspase-1 in TBI rats, which may act on the targets of IL-6, IL-1β, JAK2, IRF1 and SOCS3 in microglia.
7.Clinical and genetic analysis of a Chinese pedigree affected with Familial focal epilepsy with variable foci due to variant of NPRL3 gene
Yongli LI ; Yifan YANG ; Jigang QIU ; Liangliang LU
Chinese Journal of Medical Genetics 2024;41(10):1213-1217
Objective:To explore the clinical manifestations and genetic etiology of a Chinese pedigree affected with Familial focal epilepsy with variable foci (FFEVF).Methods:A FFEVF pedigree presented at the Department of Medical Genetics of Linyi Maternal and Child Health Care Hospital on March 14, 2023 was selected as the study subject. The proband was subjected to whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing of the proband and other affected members and bioinformatic analysis. This study was approved by Medical Ethics Committee of the Linyi Maternal and Child Health Care Hospital (Ethics No. QTL-YXLL-2023048).Results:WES revealed that the proband has harbored a heterozygous c. 1642C>T (p.Arg548Cys) missense variant in exon 15 of the NPRL3 gene. Sanger sequencing confirmed that the variant was inherited from the proband′s father, and multiple members of the pedigree had also harbored the same variant. Based on guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as variant of unknown significance (PM2_supporting + PP3). Conclusion:The clinical phenotype of FFEVF patients caused by variants of NPRL3 gene is extensive, and the patients may present with neurological abnormality of autism spectrum disorder in addition to seizures.
8.Effects of Muscle Electrical Stimulation Combined with Muscle Strength Training on Biomechanical Characteristics of Knee Joint in Patients with Patellofemoral Pain
Yingce YAO ; Jianbin ZHAO ; Xiaowei YANG ; Jing WU ; Boshi XUE ; Xia WANG ; Chen YANG ; Liangliang ZHENG ; Zhipeng ZHOU
Journal of Medical Biomechanics 2024;39(4):677-684
Objective To investigate the effects of electrical stimulation combined with muscle strength training on knee joint biomechanical characteristics in patients with patellofemoral pain(PFP).Methods Forty-six patients with PFP were recruited and randomly assigned to the muscle strength training(MST)and electrical muscle stimulation with strength training(EMS)groups.The intervention was performed three times a week for six weeks.The anterior knee pain scale(AKPS)was used to measure the knee pain degree.Knee kinematics,dynamics,and surface electromyography(sEMG)data were collected using an infrared motion capture system,force platform,and sEMG system during drop jumps before and after the intervention.Two-way analysis of variance with repeated measures was applied to determine the differences between the dependent variables of the two groups before and after the intervention.Results Compared with pre-intervention,the AKPS score,vastus medialis oblique(VMO)activation,VMO/vastus lateralis(VMO/VL)activation,maximum knee flexion angle,and peak knee extension moment increased significantly in the EMS group;the maximum knee abduction,external rotation angle,and peak knee external rotation moment decreased significantly in the EMS group after intervention.Compared with pre-intervention,the AKPS score,maximum knee flexion angle,and peak knee extension moment increased significantly in the MST group after intervention,the peak knee abduction and external rotation moment significantly decreased in the MST group after intervention.Post-hoc comparisons indicated that compared with the MST group,the AKPS score,VMO activation,VMO/VL activation were significantly higher and the maximum knee abduction angle was significantly lower in the EMS group.Conclusions EMS contributes to the better balance muscle activation of the VMO and VL and corrects the excessive knee abduction angle during jump landing,which may be helpful in relieving pain and improving lower limb function in patients with PFP.
9.Expression of miR-33a-5p and SIRT6 in the serum of esophageal cancer patients and their relationship with clinical pathological characteristics
Cuiying YANG ; Zheng ZHAO ; Liangliang ZHANG ; Zhao JIN
Journal of Clinical Surgery 2024;32(11):1147-1151
Objective To investigate the expression levels of serum microRNA-33a-5p(miR-33a-5p)and Sirtuin6(SIRT6)in patients with esophageal cancer,and their relationship with clinical pathological characteristics and prognosis.Methods From March 2018 to March 2020,123 newly diagnosed patients with esophageal cancer(esophageal cancer group)and 94 patients with esophagitis(benign lesion group)admitted to our hospital were collected as the research subjects,another 72 healthy individuals who underwent physical examination were regarded as the health control group;the clinical and pathological characteristics of esophageal cancer patients were collected.Real-time fluorescence quantitative PCR method was applied to detect the expression of miR-33a-5p and SIRT6 mRNA in three groups of serum,the relationship between the expression levels of serum miR-33a-5p and SIRT6 mRNA in esophageal cancer patients and clinical pathological characteristics was analyzed;TargetScanHuman website was applied to predict the targeting relationship between miR-33a-5p and SIRT6;Pearson method was applied to analyze the correlation between serum miR-33a-5p and SIRT6 mRNA expression levels in esophageal cancer patients;Kaplan-Meier method was applied to analyze the relationship between the expression levels of serum miR-33a-5p and SIRT6 mRNA in esophageal cancer patients and their prognosis;Cox regression was applied to analyze the prognostic factors of esophageal cancer patients.Results The expression level of serum miR-33a-5p in the esophageal cancer group was greatly higher than that in the benign lesion group and healthy control group(P<0.05),the expression level of serum SIRT6 mRNA was greatly lower than that of the benign lesion group and healthy control group(P<0.05);TargetScanHuman website predicts that there was a targeted binding site between miR-33a-5p and SIRT6,and there was a negative correlation between serum miR-33a-5p and SIRT6 mRNA expression levels in esophageal cancer patients(r=-0.468,P<0.05);the expression levels of serum miR-33a-5p and SIRT6 mRNA in esophageal cancer patients were related to TNM staging,lymph node metastasis,and degree of differentiation;the 3-year survival rate of esophageal cancer patients with low expression of serum miR-33a-5p and high expression of SIRT6 mRNA was greatly higher than that of esophageal cancer patients with high expression of miR-33a-5p and low expression of SIRT6 mRNA(P<0.05);Cox regression analysis showed that high expression of miR-33a-5p and low expression of SIRT6 mRNA were independent risk factors for death in esophageal cancer patients(P<0.05).Conclusion The expression level of serum miR-33a-5p in esophageal cancer patients is greatly increased,while the expression level of SIRT6 mRNA is greatly reduced;the expression levels of both are closely related to the clinical pathological characteristics and prognosis of esophageal cancer patients.
10.Clinical Efficiency and Safety of Hypofractionated Thoracic Radiotherapy Combined with EP Chemotherapy on Patients with Limited-stage Small-cell Lung Cancer
Yisheng HE ; Liangliang BAO ; Jiawen YU ; Yang LYU
Cancer Research on Prevention and Treatment 2023;50(2):170-174
Objective To investigate the efficacy and safety of hypofractionated thoracic radiotherapy combined with EP chemotherapy in the treatment of limited-stage small-cell lung cancer (LS-SCLC). Methods A total of 117 patients with LS-SCLC were enrolled and randomly divided into test group (


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