1.Mechanism of Qingrun Prescription-containing Serum Improving Insulin Resistance in HepG2 Cells via Branched-chain α-keto Acid Dehydrogenase Regulation of Branched-chain Amino Acids (BCAAs)/mTOR Pathway
Xiangwei BU ; Xiaohui HAO ; Runyun ZHANG ; Meizhen ZHANG ; Ze WANG ; Haoshuo WANG ; Jie WANG ; Qing NI ; Lan LIN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):90-98
ObjectiveTo investigate the effect of Qingrun prescription(QRP)-containing serum on improving insulin resistance in HepG2 cells and its potential mechanisms. MethodsAn insulin resistance model was established in HepG2 cells with 1×10-6 mol·L-1 insulin. Branched-chain α-keto acid dehydrogenase (BCKDH) gene silencing was achieved using siRNA, and the cells were divided into 8 groups: normal group, model group (1×10-6 mol·L-1 insulin), metformin group (1 mmol·L-1 metformin), high-, medium-, and low-dose QRP groups (20%, 10%, and 5% QRP-containing serum, respectively), QRP + siRNA-silenced BCKDH (si-BCKDH) group (10% QRP-containing serum + si-BCKDH), and QRP + si-NC group (10% QRP-containing serum + si-NC). Glucose levels in the supernatant were measured with a glucose assay kit, while glycogen content was assessed using a glycogen assay kit. Levels of branched-chain amino acids (BCAAs) and branched-chain keto acids (BCKAs) were determined using ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). mRNA transcription and protein expression levels of BCKDH, dishevelled, Egl-10, and pleckstrin (DEP) domain-containing mammalian target of rapamycin (mTOR)-interacting protein (DEPTOR), mTOR, and ribosomal protein S6 kinase 1 (S6K1) were detected using real-time quantitative polymerase chain reaction (Real-time PCR) and Western blot. ResultsCompared to the normal group, the model group exhibited significantly decreased glucose consumption and glycogen content, increased levels of BCAAs and BCKAs, downregulated expression of BCKDH and DEPTOR, and upregulated mTOR and S6K1 expression (P<0.01). In comparison to the model group, QRP treatment at all doses significantly enhanced glucose consumption and glycogen content while reducing BCAAs and BCKAs levels (P<0.01). The high- and medium-dose QRP groups demonstrated significant upregulation of BCKDH mRNA transcription and protein expression, as well as DEPTOR mRNA transcription. Moreover, the DEPTOR protein expression level was significantly increased in high-, medium-, and low-dose QRP groups, while mTOR and S6K1 mRNA and protein expression levels were markedly downregulated (P<0.05, P<0.01). Compared to the QRP + si-NC group, the QRP + si-BCKDH group exhibited increased BCAAs and BCKAs levels, significantly decreased BCKDH mRNA transcription and protein expression, downregulated DEPTOR mRNA and protein expression, and upregulated mTOR and S6K1 mRNA and protein expression (P<0.05, P<0.01). ConclusionQRP may improve insulin resistance by reprogramming BCAAs metabolism. This effect involves upregulating BCKDH, reducing BCAAs and BCKAs levels, and suppressing the mTOR pathway activation.
2.Effect of foot progression angle on lower extremity kinetics of knee osteoarthritis patients of different ages:a systematic review and meta-analysis
Zeyi ZHANG ; Yimin YANG ; Wenyan LI ; Meizhen ZHANG
Chinese Journal of Tissue Engineering Research 2024;28(6):968-975
OBJECTIVE:Knee adduction moment and knee adduction angular impulse enlargement is the main biomechanical risk factor of knee osteoarthritis.According to the survey,a change in the foot progression angle could effectively change the motion mode of patients with knee osteoarthritis.However,the impact of toe-in and toe-out on knee adduction moment and knee adduction angular impulse in young and elderly patients did not reach a consensus.Therefore,this study comprehensively discussed the effect of foot progression angle on knee adduction moment and knee adduction angular impulse in different populations through meta-analysis and provided a reference for the treatment of knee osteoarthritis. METHODS:By June 2022,searches were conducted on Web of Science,EBSCO,PubMed and CNKI databases using"foot progression angle,knee adduction moment,knee adduction angular impulse,gait"as Chinese and English search terms.Self-controlled randomized controlled studies analyzing the effects of toe-in and toe-out on knee adduction moment bimodality and knee adduction angular impulse were included.The cochrane bias risk assessment tool was utilized to make a quality evaluation of the literature.Stata 15.1 software was used for subgroup analysis to determine the effect of foot progression angle on knee adduction moment and knee adduction angular impulse.Meta-regression analysis was used to further determine characteristics of outcome indicators(knee adduction moment,knee adduction angular impulse)changing with foot progression angle. RESULTS:(1)A total of 15 self-control trials and 2 randomized controlled trials(455 subjects)were included in the meta-analysis.All of the included articles were of medium to high quality.(2)The meta-analysis results showed that the toe-in gait could reduce the first peak of knee adduction moment(SMD=-0.380,95%CI:-0.710 to-0.060,P=0.022)and knee adduction angular impulse(SMD=-1.470,95%CI:-2.160 to-0.770,P<0.001)in young patients.The toe-out gait reduced the second peak of knee adduction moment(SMD=-0.720,95%CI:-1.010 to-1.440,P<0.001)in young patients.In addition,toe-in gait could reduce the first peak of knee adduction moment in elder patients(SMD=-0.550,95%CI:-0.800 to-0.300,P<0.001),but increase the second peak knee adduction moment of elderly(SMD=0.280,95%CI:-0.010 to 0.560,P=0.047).The toe-out gait could decrease the second peak knee adduction moment in this population(SMD=-0.510,95%CI:-0.830 to-0.190,P=0.002).(3)Meta-regression showed that the greater the toe-out in elderly patients,the lower the second peak knee adduction moment. CONCLUSION:(1)Toe-in reduced the first peak knee adduction moment and knee adduction angular impulse in young knee osteoarthritis patients aged 18 to 34 years.Since knee adduction moment and knee adduction angular impulse were associated with medial knee loading and knee osteoarthritis incidence,toe-in gait intervention may be a suitable rehabilitation strategy for young patients.(2)Toe-in increased the second peak of knee adduction moment in older knee osteoarthritis patients over 60 years of age,which may exacerbate knee osteoarthritis in this population.However,the second peak of knee adduction moment during walking in this population decreases as the toe-out increases,contributing to a reduction in medial knee loading,suggesting that older patients may consider using toe-out gait during walking.
3.Biomechanics characteristics during sitting up in knee osteoarthritis patients of different ages:a systematic review and meta-analysis
Ke WANG ; Zeyi ZHANG ; Liwen ZHANG ; Meizhen ZHANG
Chinese Journal of Tissue Engineering Research 2024;28(18):2939-2946
OBJECTIVE:There is no consensus on which sit-up strategy to adopt in knee osteoarthritis patients of different ages.Therefore,this study evaluated the biomechanical characteristics of sit-ups in knee osteoarthritis patients of different ages compared with healthy individuals by meta-analysis system and analyzed the sit-up movement patterns of patients of different ages to provide a reference for improving the sit-up function of patients. METHODS:By March 2023,observational studies of biomechanical characteristics of sitting up in patients with knee osteoarthritis and healthy population were retrieved on PubMed,Web of Science and CNKI.Subjects were required to be patients over 50 years of age with knee osteoarthritis who had Kellgren-Lawrence severity grading≥Ⅰ on knee imaging and who had regular knee pain.Subjects were analyzed by age(50-60 years vs.over 60 years)and severity(mild to moderate patients vs.severe patients)subgroups according to inclusion and exclusion criteria.Quality assessment was performed using the modified Down and black scale.Stata 16.0 software was used to perform subgroup analysis to determine the biomechanical characteristics of sitting up in patients with knee osteoarthritis of different ages and severities. RESULTS:A total of 14 randomized controlled trials(824 subjects)were included in the meta-analysis.The mean quality score of all included literature was 76.2,with a range of 66.7 to 86.7,all of which were of medium to high quality and representative.The included studies were of moderate to high quality and representative.Meta-analysis results found that(1)compared to healthy individuals,patients with knee osteoarthritis had longer total sitting up time(SMD=0.92,95%CI:0.76-1.09),P<0.001)and longer extension phase time(SMD=0.46,95%CI:0.18-0.74,P=0.001).Compared to mild to moderate patients,the total duration increased more significantly in severe patients(P<0.001)and the duration of the extension phase increased more significantly in patients over 60 years of age than in patients 50-60 years of age(P=0.001).(2)Compared to healthy individuals,patients with knee osteoarthritis had greater sitting-up trunk flexion motion range(SMD=0.64,95%CI:0.37-0.91,P<0.001);knee flexion motion range(SMD=-0.47,95%CI:-0.70 to-0.24,P<0.001)and ankle dorsiflexion motion range(SMD=-0.32,95%CI:-0.56 to-0.08,P=0.01)were smaller.And knee flexion motion range decreased more significantly in patients over 60 years of age than in patients 50-60 years of age(P<0.001).(3)The peak hip flexion moment(SMD=-0.57,95%CI:-0.83 to-0.31,P<0.001)and peak knee extension moment(SMD=-0.83,95%CI:-1.08 to-0.59,P<0.001)were smaller in patients with knee osteoarthritis. CONCLUSION:(1)Patients with knee osteoarthritis over the age of 60 years have a longer sit-up cushion and extension phase than patients aged 50 to 60 years.The increase in total sit-up duration was also more pronounced in patients with higher severity grades.The increased length of sitting up in patients with advanced age and knee osteoarthritis severity may increase the duration of cartilage loading,exacerbate knee pain symptoms,and increase the difficulty of sitting up in this population.(2)Patients with knee osteoarthritis exhibit limited knee and ankle flexion motion range.Knee mobility is more limited in patients over 60 years of age.(3)Patients with knee osteoarthritis have reduced peak hip flexion and knee extension moments,which may be a compensatory strategy for pain relief.
4.Development and Verification of a Traditional Chinese Medicine Diagnostic Scale for Type 2 Diabetes Mellitus with Turbid-Toxin Accumulation Syndrome
Pai PANG ; Bin WANG ; Shentao WU ; Yuntao MA ; Cuijuan SHI ; Meizhen ZHANG
Journal of Traditional Chinese Medicine 2024;65(2):159-166
To develop a traditional Chinese medicine (TCM) diagnostic scale for type 2 diabetes mellitus with turbid-toxin accumulation syndrome and to validate the performance of the scale. A candidate pool was established through literature review and expert consultation, and a clinical case information collection form was developed accordingly. Patients with type 2 diabetes mellitus admitted to the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine from July 2021 to January 2022 were investigated, and 312 valid clinical case information collection forms were obtained, which were randomly divided into 235 cases in the study group and 77 cases in the validation group. Four statistical methods, namely, differentiation analysis, Cronbach's coefficient, correlation coefficient, and stepwise regression, were used to screen out the candidate items, and Logistic regression analysis and factor analysis were used to assign weights to the items, and the final diagnostic model was determined by the receiver operating characteristic (ROC) curve, and the diagnostic thresholds were calculated for the Yoden index. The final TCM diagnostic scale for type 2 diabetes mellitus was composed of 8 items: turbid dirt coating (with a weight value of 23, the same below), sticky stools (16), fullness in the epigastrium and abdomen (12), dark complexion (12), irritability (11), brown spots on the skin (11), heaviness of head (10), and chest stuffiness (5), and the degree score was 0, 0.5, 1.0, and 1.5 points corresponding to no, mild, moderate and severe symptoms, respectively. The total score was the sum of the degree score multiplied by the weighted value of each item, and when the total score reached 33 points, it is diagnosed as the turbid-toxin accumulation syndrome. The established scale was tested and evaluated in the study group and the validation group, and the results showed that the sensitivity of the study group and the validation group was 89.38% and 89.47%, with the specificity of 95.90% and 89.74%, the Yoden index of 0.85 and 0.79, the positive predictive value of 95.28% and 89.47%, the negative predictive value of 90.70% and 89.74%, the diagnostic advantage ratios of 198.18 and 72.67, and the Kappa values of 0.86 and 0.79, which indicated that the TCM diagnostic scale for turbid-toxin accumulation syndrome of type 2 diabetes mellitus showed good diagnostic ability.
5.Effects of Different Trunk-Restraint Squatting Postures on Human Lower Limb Kinematics and Dynamics
Letian HAO ; Jijun CHEN ; Yimin YANG ; Qi ZHAO ; Meng WANG ; Jingchen GAO ; Meizhen ZHANG
Journal of Medical Biomechanics 2024;39(1):118-124
Objective To investigate the effect of trunk control on the biomechanical characteristics of lower limb movements during Asian squats(AS)and Western squats(WS)in young adults to provide empirical support for the application and promotion of deep squat training.Methods Twenty-four healthy young male collegiate students performed AS and WS with and without bar control,and their lower limb kinematic and kinetic characteristics were collected using an infrared light-point motion capture system and a three-dimensional(3D)dynamometer.The 3D angles of the lower limbs were obtained using Cortex-642.6.2 software,based on the calculation of Euler angles,and the 3D moments were obtained by applying the inverse dynamics method.The effects of trunk control and deep squatting posture on the lower limb kinematic characteristics were examined using a two-factor analysis of variance with a 2×2 repeated design.Results There was no significant interaction between trunk control and the deep squatting posture for either kinematic or kinetic parameters(P>0.05).The WS group had a large knee flexion angle,peak patellofemoral contact force,and ratio of peak hip and knee extension moments,and small ankle dorsiflexion and hip flexion angles(P<0.05).The deep squat with a bar had a large ankle dorsiflexion angle,peak patellofemoral contact force,and hip flexion angle as well as a small knee flexion angle and ratio of peak hip and knee extension moments(P<0.05).Conclusions WS is helpful for training hip extension muscle groups,whereas AS is helpful for training knee extension muscle strength.The peak patellofemoral joint contact force of the WS is significantly greater than that of the AS;therefore,it is recommended that patients with patellofemoral joint pain use the AS.A squat with a bar can compensate for the body's balance;thus,people with limited ankle dorsiflexion range of motion or anterior tibial muscle weakness may consider trunk control training,such as a deep squat with a bar.This may help improve lower limb stability during squats.
6.Epidemiological and pathogenic analysis of an imported case of Y serogroup ST167 complex Neisseria meningitidis
Zhencui LI ; Rong LI ; Yanmei FANG ; Chang ZHANG ; Xiaoping SHAO ; Yingliang LIU ; Meizhen LIU
Chinese Journal of Microbiology and Immunology 2024;44(6):480-484
Objective:To detect the pathogen and clinically diagnose for a suspected case of Neisseria meningitidis with positive blood culture result, and assess the risk of disease transmission among the community. Methods:Blood sample was collected for Neisseria meningitidis isolation and culture. Pathogen identification and serogroup typing were conducted by colony morphology, Gram staining, biochemical tests, latex agglutination test, slide agglutination test, and nucleic acid testing. The susceptibility to 12 antibiotics was also tested. Epidemiological investigation was conducted on the case, and epidemic control measures were also implemented. Results:Through various detection, the suspected case was diagnosed as Neisseria meningitidis invasive infection. The isolated strain belonged to group Y serotype, type 767 (multilocus sequence typing), and the ST167 clonal complex. The strain was sensitive to nine antibiotics, including penicillin, ampicillin, and meropenem. It exhibited intermediate sensitivity to ciprofloxacin and levofloxacin, and resistance to methicillin/sulfamethoxazole. Close contacts of the case and environmental testing results were negative. Conclusions:The case is confirmed to be an invasive infection caused by group Y Neisseria meningitidis, the ST167 clonal complex. Epidemiological investigation shows a relatively low risk of epidemic transmission. Continuous monitoring and surveillance are necessary for further assessment.
7.Vigabatrin-associated brain abnormalities on magnetic resonance imaging in the treatment of infantile spasms: a case report
Xiaoping YANG ; Huifen WANG ; Huifang WANG ; Yating ZHANG ; Qiong WANG ; Meizhen SUN ; Junhong GUO ; Yi YAO ; Xiaoping DU
Chinese Journal of Neurology 2023;56(4):438-441
Vigabatrin-associated brain abnormalities on magnetic resonance imaging (VABAM) is a relatively rare side effect of vigabatrin, most of which are asymptomatic. However, there will be extremely rare cases with hyperkinetic disorders, myoclonus, tremor, and acute encephalopathy under certain circumstances. VABAM is often underappreciated by physicians and its accurate incidence remains unclear. A female infant who was diagnosed with infantile spasms and required adrenocorticotropic hormone therapy accompanied by various antiseizure medicines was reported. Unfortunately, she became lethargic and her spasm deteriorated gradually after vigabatrin exposure. Her brain magnetic resonance imaging revealed abnormal signals bilaterally in the dorsal midbrain, thalamus, and rostral part of the pallidum. She had a seizure amelioration and became lively as a result of vigabatrin withdrawal. In the meanwhile, magnetic resonance imaging returned to normal. Attempts were made to discover the risk factors of VABAM and potential pathogenesis. Further understanding of the disease should contribute to decreasing misdiagnosis and making precise decisions.
8.Effects of Backpack Types on Kinematics and Plantar Pressure in College Students During Stairs Walking
Ke YAN ; Yihui LIU ; Zeyi ZHANG ; Meizhen ZHANG ; Xiaogang WU ; Weiy CHEN
Journal of Medical Biomechanics 2023;38(3):E580-E586
Objective To analyze the influence of different backpack types and loads on kinematics and plantar pressure of college students during stair climbing, so as to provide references for choosing the appropriate backpack and carrying mode. Methods The Nokov infrared light point motion capture system and Podome plantar pressure system were used to analyze the differences in the range of motion ( ROM) of the trunk and lower limb joints, the kinematic parameters at the peak time, the peak pressure of each plantar partition, the contact time, the maximum pressure of the whole foot, the average pressure and the maximum contact area for 15 male college students during the support period of stair climbing. Results The 5% BW and 10% BW backpack loads reduced ROM of trunk rotation, increased ROM of ankle flexion/ extension and varus / valgus. The 10% BW backpack loads increased the peak pressure of the 1st and 3rd metatarsals bones and the maximum pressure of the whole foot ( P < 0. 05). Single-shoulder bag and handbag reduced ROM of trunk tilting and rotation, and increased ROM of ankle flexion and extension, hip flexion angle, peak pressure of foot arch and medial heel (P<0. 05). The double-shoulder bag loads increased peak pressure in the toe area (P<0. 05). Conclusions During walking on the stairs, the 5% BW and 10% BW backpack loads limited trunk rotation and increased ankle ROM. The 10% BW loads also increased the load in metatarsal area. The unilateral weight-bearing mode would make the trunk tilt to the unload side and rotate to the weight-bearing side. The pressure in toe area was higher when carrying double-shoulder bag, while single-shoulder bag and handbag mainly increased the pressure of arch foot and medial heel. It is suggested that college students choose symmetrical backpack scheme, and wisely allocate back weight to avoid the injury of foot area.
9.Discussion on mechanism and experimental validation of Bupiwei Xieyinhuo Shengyang Prescription in treatment of gastroesophageal reflux disease based on network pharmacology
Yalin LIANG ; Meizhen HUANG ; Yunyan ZHANG ; Maoguang HUANG ; Liqun LI ; Zhenyi LUO ; Huaying MENG ; Sheng XIE
International Journal of Traditional Chinese Medicine 2023;45(3):315-322
Objective:To explore the possible mechanism of Bupiwei Xieyinhuo Shengyang Prescription on gastroesophageal reflux disease (GERD) based on network pharmacology and molecular docking technology.Methods:The main active components and target information of Bupiwei Xieyinhuo Shengyang Prescription were screened by TCMSP database, and targets were identified by GeneCards, OMIM, TTD and PharmGKB databases. The intersection of active ingredient components and disease targets was selected to construct PPI network by STRING. Cytoscape CytoNCA plug-in was used to extract core targets for analysis. GO function enrichment and KEGG pathway enrichment analysis were performed using Metascape. Cytoscape 3.7.2 was used to construct the "component-target-signal pathway" network, and Autodock was used to complete molecular docking verification. Animal experiments were further used for verification. SPF SD male rats were selected and GERD model was established by esophageal stent implantation. After 14 days of intervention, serum TNF-α and COX-2 levels of rats in each group were detected for verification.Results:A total of 215 effective compounds were screened from Bupiwei Xieyinhuo Shengyang Prescription. The main targets of GERD were TNF, IL6, CASP3, TP53 and PTGS2, which mainly focused on cancer pathway, AGE-RAGE signaling pathway, calcium signaling pathway and NF-κB signaling pathway. The results of molecular docking showed that the binding potential and activity of the key active components of Bupiwei Xieyinhuo Shengyang Prescription and the core target were better. Compared with the model group, Bupiwei Xieyinhuo Shengyang Prescription could reduce the serum expression levels of TNF-α and COX-2 ( P<0.01). Conclusions:By regulating TNF, IL6, CASP3, TP53, PTGS2 and other core targets, Bupiwei Xieyinhuo Shengyang Prescription can regulate NF-κB signaling pathway, calcium signaling pathway and other signaling pathways to play a role in the treatment of GERD.
10.Treatment of thyroid nodules based on Chaihu constitution
Peiyu SHI ; Xiaohui HAO ; Meizhen ZHANG ; Xufei LIU ; Qing NI
International Journal of Traditional Chinese Medicine 2023;45(6):663-666
Thyroid nodule is a common endocrine system disease in clinic. Its onset is mostly related to affect-mind internal damage. The core pathogenesis is dysfunction of the liver and liver-qi stagnation, and the main pathological changes are qi stagnation, phlegm turbidity and blood stasis. Constitution is inherited from the natural factors and nourished from the postnatal factors, which is closely related to the occurrence of diseases, the transformation of syndromes and the transmission of diseases. Chaihu constitution refers to the type of constitution suitable for long-term use of Bupleuri Radix and prescriptions about Bupleuri Radix. The characteristics of patients with Chaihu constitution are similar to those of patients with thyroid nodules in clinic, and the risk of developing thyroid nodules is higher. Chaihu constitution is the internal basis of thyroid nodules. When treating thyroid nodule patients with Chaihu constitution, the dominant position of Bupleuri Radix should be highlighted, and Bupleuri Radix and prescriptions about Bupleuri Radix should be used flexibly. The dosage of Bupleuri Radix is mostly between 6-15 g, and according to the change of pathogenesis, it is often combined with Chinese materia medica with the efficacy of soothing liver and promoting qi, resolving phlegm and removing turbidity, promoting blood circulation and removing blood stasis, in order to prevent the occurrence and development of thyroid nodules.

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