1.Shuangshen Ningxin Capsules Regulates Mitochondrial Fission and Fusion to Alleviate Myocardial Ischemia-reperfusion Injury in Rats
Gaojie XIN ; Yuanyuan CHEN ; Zixin LIU ; Yue YOU ; Ce CAO ; Aoao WANG ; Hongxu MENG ; Xiao HAN ; Jianxun LIU ; Lei LI ; Jianhua FU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(7):87-94
ObjectiveTo explore whether the mechanism of Shuangshen Ningxin capsules (SSNX) in alleviating myocardial ischemia-reperfusion injury (MIRI) in rats is related to the regulation of mitochondrial fission and fusion. MethodThis study focused on Sprague Dawley (SD) rats and ligated the left anterior descending branch of the coronary artery to construct a rat model of MIRI. The rats were divided into the sham operation group, model group, SSNX group (90 mg·kg-1) and trimetazidine group (5.4 mg·kg-1). The activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) were detected by micro method. Changes in mitochondrial membrane potential (△Ψm) and the degree of mitochondrial permeability transition pore (mPTP) opening were detected by the chemical fluorescence method. The intracellular adenosine triphosphate (ATP) level was detected by the luciferase assay. The messenger ribonucleic acid (mRNA) and protein expression levels of mitochondrial fission and fusion related factors dynamin-related protein 1 (DRP1), mitochondrial fission 1 protein (FIS1), optic atrophy protein 1 (OPA1), mitochondrial outer membrane fusion protein 1 (MFN1), and MFN2 were detected by real-time polymerase chain reaction (real-time PCR) and Western blot. ResultCompared with the sham operation group, the model group showed a decrease in serum SOD activity and an increase in MDA content. The opening level of mPTP, the level of △Ψm and ATP content decreased, the protein expressions of mitochondrial fission factors DRP1 and FIS1 increased, and the protein expressions and mRNA transcription levels of fusion related factors OPA1 and MFN1 decreased. Compared with the model group,SSNX significantly increased serum SOD activity, reduced MDA content, increased intracellular ATP level and △Ψm, reduced the opening level of mPTP, downregulated the protein expressions of mitochondrial fission factors DRP1 and FIS1, and increased the mRNA transcription levels and protein expressions of fusion related factors OPA1 and MFN1. ConclusionSSNX inhibits the expressions of mitochondrial fission factors DRP1 and FIS1, and increases the expressions of fusion related factors OPA1 and MFN1, inhibiting mitochondrial fission and increasing mitochondrial fusion, thereby alleviating MIRI.
2. Mechanism of Fufang Congrong Yizhi Capsules in treatment of mild cognitive impairment based on network pharmacology
Qin HAN ; Xiao-Yu XU ; Yi-Fei GENG ; Xiao-Bo SUN ; Yun LUO ; Jing-Jing LIU
Chinese Pharmacological Bulletin 2024;40(2):334-343
Aim To predict the mechanism of Fufang Congrong Yizhi Capsules (FCYC) in the treatment of mild cognitive impairment (MCI) by network pharmacology method, and further validate it in combination with cellular experiments. Methods TCMSP, Gene-Cards, OMIM and TTD databases, Chinese Pharmacopoeia and related literature were used to screen the active ingredients of FCYC and the targets of MCI treatment. The TCM-compound-target-disease network and PPI of intersection targets were constructed, and the GO and KEGG analysis were performed by the Ehamb bioinformation platform. GO and KEGG analysis were performed through Yihanbo biological information platform. Cell model of MCI was established by PC-12 injury induced by Aβ
3.Mechanism of salvianolic acid B protecting H9C2 from OGD/R injury based on mitochondrial fission and fusion
Zi-xin LIU ; Gao-jie XIN ; Yue YOU ; Yuan-yuan CHEN ; Jia-ming GAO ; Ling-mei LI ; Hong-xu MENG ; Xiao HAN ; Lei LI ; Ye-hao ZHANG ; Jian-hua FU ; Jian-xun LIU
Acta Pharmaceutica Sinica 2024;59(2):374-381
This study aims to investigate the effect of salvianolic acid B (Sal B), the active ingredient of Salvia miltiorrhiza, on H9C2 cardiomyocytes injured by oxygen and glucose deprivation/reperfusion (OGD/R) through regulating mitochondrial fission and fusion. The process of myocardial ischemia-reperfusion injury was simulated by establishing OGD/R model. The cell proliferation and cytotoxicity detection kit (cell counting kit-8, CCK-8) was used to detect cell viability; the kit method was used to detect intracellular reactive oxygen species (ROS), total glutathione (t-GSH), nitric oxide (NO) content, protein expression levels of mitochondrial fission and fusion, apoptosis-related detection by Western blot. Mitochondrial permeability transition pore (MPTP) detection kit and Hoechst 33342 fluorescence was used to observe the opening level of MPTP, and molecular docking technology was used to determine the molecular target of Sal B. The results showed that relative to control group, OGD/R injury reduced cell viability, increased the content of ROS, decreased the content of t-GSH and NO. Furthermore, OGD/R injury increased the protein expression levels of dynamin-related protein 1 (Drp1), mitofusions 2 (Mfn2), Bcl-2 associated X protein (Bax) and cysteinyl aspartate specific proteinase 3 (caspase 3), and decreased the protein expression levels of Mfn1, increased MPTP opening level. Compared with the OGD/R group, it was observed that Sal B had a protective effect at concentrations ranging from 6.25 to 100 μmol·L-1. Sal B decreased the content of ROS, increased the content of t-GSH and NO, and Western blot showed that Sal B decreased the protein expression levels of Drp1, Mfn2, Bax and caspase 3, increased the protein expression level of Mfn1, and decreased the opening level of MPTP. In summary, Sal B may inhibit the opening of MPTP, reduce cell apoptosis and reduce OGD/R damage in H9C2 cells by regulating the balance of oxidation and anti-oxidation, mitochondrial fission and fusion, thereby providing a scientific basis for the use of Sal B in the treatment of myocardial ischemia reperfusion injury.
4.Analysis of the efficacy and prognosis of radiotherapy in acute leukemia with extramedullary infiltration
Wenbin LEI ; Hui LIU ; Yan ZHANG ; Yinghao LU ; Yi HUANG ; Ying CHEN ; Rui GAO ; Xiao CHAI ; Yun ZHAN ; Jie XIONG ; Lingyun WANG ; Lei LIU ; Jishi WANG ; Peng ZHAO
Chongqing Medicine 2024;53(4):547-554
Objective To investigate the clinical characteristics,treatment methods,and prognosis of a-cute leukemia patients with extramedullary infiltration.Methods The clinical characteristics and treatment methods of 47 acute leukemia patients with extramedullary infiltration admitted to the Affiliated Hospital of Guizhou Medical University from April 2014 to April 2023 were retrospectively analyzed.Subgroup analysis was performed according to whether there was extramedullary infiltration before transplantation,and whether there was isolated extramedullary recurrence after transplantation.Based on this analysis,the patients were di-vided into the pre-transplantation radiotherapy group and pre-transplantation non-radiotherapy group,the post-transplantation radiotherapy group and post-transplantation non-radiotherapy group.According to the treatment methods of central nervous system leukemia(CNSL),the patients were divided into the intrathecal injection group(n=12)and combination of intrathecal injection and radiotherapy group(n=13).The local remission situation,survival duration,and toxic and side effects of radiotherapy and chemotherapy were com-pared.Results For acute leukemia patients with extramedullary infiltration,the overall survival time(OS)in the radiotherapy group was better than that in the non-radiotherapy group(median OS:706 d vs.151 d,P=0.015).Subgroup analysis showed that the OS of the pre-transplantation radiotherapy group was better than that of the pre-transplantation non-radiotherapy group(median OS:592 d vs.386 d,P=0.035).For CNSL,the combination of intrathecal injection and radiotherapy group had a better OS than the intrathecal injection group(median OS:547 d vs.388 d,P=0.045).The event-free survival time(EFS)of the radiotherapy group was better than that of the non-radiotherapy group(median EFS:175 d vs.50 d,P=0.005).The COX pro-portional-hazards model showed that treatment with or without radiotherapy had a significant impact on the OS of acute leukemia patients with extramedullary infiltration.The risk of death in the pre-transplantation non-radiotherapy group was 2.231 times higher than that in the pre-transplantation radiotherapy group(HR=3.231,95%CI:1.021-10.227,P=0.046).Compared with the non-radiotherapy group,the radiother-apy group had a higher local remission and a lower risk of haematological toxicity,infection,and haemorrhage.Conclusion Radiotherapy can rapidly alleviate the local symptoms of acute leukemia complicated with extr-amedullary infiltration,prolong the survival time of these patients,and reduce the risk of hematologic toxicity,infection,and haemorrhage.
5.Effect of pulmonary surfactant combined with budesonide in improving oxygenation and clinical outcomes in neonatal acute respiratory distress syndrome
Yi-Yang LIU ; Rong ZHANG ; Shuai ZHAO ; Lan KANG ; Xiao-Ping LEI ; Wen-Bin DONG
Medical Journal of Chinese People's Liberation Army 2024;49(3):259-264
Objective To explore the role of pulmonary surfactant(PS)combined with budesonide in improving oxygenation and clinical outcomes of neonatal acute respiratory distress syndrome(ARDS).Methods The present study is a historically controlled trial.Infants with ARDS requiring mechanical ventilation and PS replacement therapy were collected from the neonatal unit of Southwest Medical University.Those from January 2022 to November 2022 were set as intervention group(PS+ budesonid,n=35),treated with intratracheal instillation of a mixed suspension of budesonide(0.25 mg/kg)and PS(200 mg/kg),and continuous budesonide nebulization(0.25 mg/kg,twice per day)until withdrawal,then compared with a historical cohort,who just received intratracheal instillation of PS(200 mg/kg)(January 2020-December 2021,PS group,n=35).Baseline data such as gender,mode of delivery,1 min and 5 min Apgar score,birth weight,gestational age,time of onset,and cause of onset were recorded in both groups.The oxygenation and clinical outcomes of infants were compared between the two groups,including:(1)Arterial blood gas analysis indicators,such as partial pressure of oxygen(PaO2)and oxygenation index(OI)before treatment and at 6,12 and 24 hours of treatment;(2)Clinical observation and evaluation indicators,such as the time to withdrawal,duration of oxygen supplementation,length of stay,improvement of the radiological images of the lungs at 72 h of treatment,and repeated PS use;(3)Blood chemistry indicators,such as white blood cell(WBC),neutrocyte(NEU),procalcitonin(PCT)before treatment and at 3 and 7 days of treatment;and(4)Observation indicators of complications,weight growth,and mortality outcomes,such as the incidences of intracranial hemorrhage,gastrointestinal hemorrhage,neonatal necrotizing enterocolitis(NEC),and hyperglycemia,weight growth,and fatality rate.Results The differences in baseline data between the two groups were not statistically different(P>0.05).The levels of PaO2 of the two groups were increased after treatment for different time periods,while the levels of OI were decreased(P<0.001),and the levels of above indexes changed more significantly in PS+budesonide group than those in PS group(P<0.05).The time to withdrawal,duration of oxygen supplementation,and length of stay in PS+budesonide group were shorter than those in PS group;the radiological images of the lungs showed that the pulmonary inflammation absorption was significantly better in PS+ budesonide group than that in PS group,while no significant difference between the two groups of infants with repeated PS use.The NEU was significantly higher in PS+budesonide group than in PS group at 3 d and 7 d of treatment(P<0.001);and at 3 days of treatment,the PCT levels were significantly lower in PS+budesonide group than that in PS group(P<0.05).The incidences of intracranial hemorrhage,gastrointestinal hemorrhage,NEC,hyperglycemia,weight growth,and fatality rate were not significantly different between the two groups(P>0.05).Conclusion The use of budesonide in addition to surfactant may improve the oxygenation of neonates with ARDS,improve the inflammatory infiltrates in lungs,shorten the duration of mechanical ventilation and oxygen supplementation,and without short-term complications associated with budesonide use.
6.miR-375 Attenuates The Migration and Invasion of Osteosarcoma Cells by Targeting MMP13
Zhong LIU ; Lei HE ; Jian XIAO ; Qing-Mei ZHU ; Jun XIAO ; Yong-Ming YANG ; Yong-Jian LUO ; Zhong-Cheng MO ; Yi-Qun ZHANG ; Ming LI
Progress in Biochemistry and Biophysics 2024;51(5):1203-1214
ObjectiveTo explore whether miR-375 regulates the malignant characteristics of osteosarcoma (OS) by influencing the expression of MMP13. MethodsPlasmid DNAs and miRNAs were transfected into OS cells and HEK293 cells using Lipofectamine 3000 reagent. Real-time quantitative polymerase chain reaction was performed to measure the expression of miR-375 and MMP13 in OS patients and OS cells. Western blot was performed to analyze the MMP13 protein in the patients with OS and OS cells. The targeting relationship between miR-375 and MMP13 was analyzed by luciferase assay. Migration and invasion were analysed by heal wound and transwell assays, respectively. ResultsmiR-375 expression in OS tissues was lower than that in normal tissues. The expression of MMP13 was upregulated in OS tissues. MMP13 expression was negatively correlated withmiR-375 expression in patients with OS. Migration and invasion were significantly inhibited in OS cells with the miR-375 mimic compared with OS cells with the miRNA control. MMP13 partially reversed the inhibition of migration and invasion induced by miR-375 in the OS cells. ConclusionmiR-375 attenuates migration and invasion by downregulating the expression of MMP13 in OS cells.
7.Application of optimized hippocampus-avoidance prophylactic cranial irradiation in limited-stage small cell lung cancer
Tianyou ZHAN ; Lei DENG ; Wenqing WANG ; Tao ZHANG ; Nan BI ; Jianyang WANG ; Xin WANG ; Wenyang LIU ; Yirui ZHAI ; Zefen XIAO ; Jima LYU ; Qinfu FENG ; Dongfu CHEN ; Ye-Xiong LI ; Zongmei ZHOU
Chinese Journal of Radiation Oncology 2024;33(3):205-211
Objective:To analyze the treatment efficacy, safety and dose parameters of optimized hippocampus-avoidance prophylactic cranial irradiation (HA-PCI) in limited-stage small cell lung cancer (LS-SCLC) and explore the corresponding dosimetric parameters under the condition of narrowing the hippocampus avoidance region as hippocampus region plus 2 mm in three dimensions.Methods:Clinical data of patients with LS-SCLC receiving HA-PCI (hippocampus avoidance region defined as hippocampus region plus 2 mm in three dimensions) in Cancer Hospital Chinese Academy of Medical Sciences from August 2014 to June 2020 were retrospectively analyzed. Dose parameters of HA-PCI and adverse events were analyzed using descriptive statistics analysis. Changes of neurocognitive function, such as mini-mental state examination (MMSE) and Hopkins verbal learning test-revised (HVLT-R) scores, were evaluated by analysis of variance and Kruskal-Wallis H test. Overall survival (OS), progression-free survival (PFS) and intracranial PFS (iPFS) were calculated using Kaplan-Meier method. The cumulative incidence of local-regional recurrence (LRR), extracranial distant metastases (EDM), and locoregional recurrence (LR) were investigated under competing risk analysis. Results:A total of 112 patients were included, the median follow-up time was 50 months (95% CI: 45.61-54.38). The median volume of hippocampus was 4.85 ml (range: 2.65-8.34 ml), with the average dose ≤9 Gy in 106 patients (94.6%), ≤8 Gy in 92 patients (82.1%). The median volume of hippocampus avoidance area was 15.00 ml (range: 8.61-28.06 ml), with the average dose ≤12 Gy in 109 patients (97.3%), ≤10 Gy in 101 patients (90.2%). The 2-year cumulative LRR, EDM, LR rates were 16.9%, 23.2% and 28.5%, respectively. The 5-year cumulative LRR, EDM, LR rates were 23.2%, 26.9% and 33.3%, respectively. The 2-year iPFS, PFS and OS rates were 66.1% (95% CI: 57.9%-75.4%), 53.6% (95% CI: 45.1%-63.7%) and 80.4% (95% CI: 73.3%-88.1%), respectively. The most common grade I-Ⅱ adverse events were nausea (33.9%) and dizziness (31.3%), and only 1 patient developed grade Ⅲ nausea and dizziness. MMSE ( n=57) and HVLT-R tests ( n=56) showed no significant decline. Conclusions:Optimized HA-PCI can achieve similar dose limitation with favorable efficacy and light toxicity. No significant decline is observed in short-term neurocognitive function in evaluable patients.
8.Trends and factors associated with overweight and obesity among primary and secondary school students in Tianjin from 2019 to 2023
Chinese Journal of School Health 2024;45(8):1176-1180
Objective:
To understand trends and related factors influencing overweight and obesity among primary and secondary school students in Tianjin, so as to provide a basis for formulating overweight and obesity prevention and control strategies.
Methods:
In September of each year from 2019 to 2023, a survey was conducted among 197 707 primary and secondary school students in 16 districts of Tianjin through a stratified random cluster sampling method. Physical examination was carried out in accordance with the Technical Standard for Physical examination for Student, and overweight and obesity survey was carried out. Basic information, smoking, drinking, diet, physical exercise, and sleep status were collected through questionnaire surveys.
Results:
The detection rates of overweight and obesity among primary and secondary school students in Tianjin from 2019 to 2023 were 39.07%, 43.33%, 41.54%, 43.92%, and 40.24%, respectively,showing an increasing trend(χ2trend=7.96,P<0.01). The detection rates of overweight increased in both vocational high schools and suburban counties (χ2trends=9.08, 47.18, P<0.01). The detection rates of obesity increased among both male and female students, in primary and vocational high schools and suburban counties (χ2trends=108.34, 15.99, 7.32, 10.95, 14.75, P<0.01). Multivariate Logistic regression analysis showed that smoking, drinking, unhealthful diet, and lack of proper physical exercise had a higher risk of obesity among primary and secondary school students (OR=1.26, 1.13, 1.08, 1.21, P<0.05). Stratified analysis showed that the risk of obesity was higher among boys with unhealthful and moderate lifestyle habits, as well as primary school students with unhealthful lifestyle habits (OR=1.15, 1.11, 1.27, P<0.05). Boys, girls and primary school students with unhealthful lifestyle habits, girls and ordinary high school students with moderate lifestyle habits had higher risk of being overweight (OR=1.14, 1.32, 1.21, 1.18, 1.40, P<0.05).
Conclusions
The detection rates of overweight and obesity among primary and secondary school students in Tianjin shows an increasing trend. Comprehensive lifestyle should be implemented to better prevent and control the risk of overweight and obesity.
9.Assessment of the health situation of daily learning time for elementary school students in the context of Double Reduction policy
YANG Haoran, LI Jin, LIU Kaiqi, TU Ying, LI Suyun, YANG Xiao, LEI Suwen, LI Jing
Chinese Journal of School Health 2024;45(9):1354-1358
Objective:
To investigate the daily learning time status of elementary school students and understand the implementation of Health Requirements of Daily Learning Time for Secondary and Elementary School Students (GB/T 17223-2012) in schools, so as to provide a reference for strengthening and improving school health and health education in the new era.
Methods:
A stratified cluster random sampling method was used to select 7 776 primary school students in Shandong Province, and a survey questionnaire was designed based on the Health Requirements for Dayily Learning Time for Secondary and Elementary School Students(GB/T 17223-2012) standard to investigate their daily learning arrangements, sleep and physical activities, and breaks between classes. Comparison of intergroup differences were used by Chi square test and Kruskal-Wallis H test.
Results:
About 55.88 % of primary school students for daily learning time met the standard. There was a statistically significant difference in the daily learning time achievement rate among primary school students in three grades for first and second grade, third and fourth grade and fifth and sixth grade ( Z=1 629.47, P <0.01), and the fifth and sixth grade had the highest proportion of achieving the standard (85.92%). Specifically, the proportions of students whose class hours, class numbers and morning reading time meeting the standards were 30.07%, 10.20% and 42.19%, respectively. The sleep deficiency rate of primary school studnets was 58.69%, and the physical activity deficiency rate was 65.78%; and there was a statistically significant difference in the rate of insufficient sleep time and physical activity time among primary school students of different grades ( χ 2=56.39, 95.95, P <0.01), with sixth grade students showing the highest rates for both sleep and physical activity deficiencies (64.35%, 73.37%). Additionally, 49.78% of students had recess time below the standard requirements.
Conclusion
The health status of daily learning time among primary school students in Shandong Province is poor, with insufficient implementation of school standards, and the implementation of standards needs to be further strengthened.
10.Value of colored Doppler sound for differential diagnosis of benign and malignant thyroid nodules
Xingyue HUANG ; Xiao YUAN ; Yun XIA ; Lei WU ; Ti LIU
Chinese Journal of Radiological Health 2024;33(5):590-594
Objective To evaluate the efficiency of colored Doppler ultrasound for the differential diagnosis of benign and malignant thyroid nodules. Methods A total of 150 patients with thyroid nodules admitted to Wuwei Municipal People’s Hospital, Anhui Province, China during the period from July 2018 to December 2023 were enrolled. All patients underwent colored Doppler ultrasound of the thyroid gland and pathological examination of the thyroid nodules. The pathological examination of the thyroid nodules served as a gold standard to evaluate the value of colored Doppler ultrasound for the differential diagnosis of benign and malignant thyroid nodules. In addition, the value of different ultrasound image features for differential diagnosis of benign and malignant thyroid nodules was evaluated. Results With the pathological examination of the thyroid nodules as a gold standard, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the colored Doppler ultrasound were 100.00%, 95.87%, 85.29%, 95.87%, and 96.67% for the differential diagnosis of benign and malignant thyroid nodules. For differential diagnosis of benign and malignant thyroid nodules, a > 1 ratio of longitudinal to transverse diameters of thyroid nodules, irregular margin, and microcalcification showed a 100.00% sensitivity, irregular acoustic halos showed a 100.00% specificity, and microcalcification had the highest accuracy (98.00%). Conclusion Colored Doppler ultrasound has a high value for the differential diagnosis of benign and malignant thyroid nodules. A > 1 ratio of longitudinal to transverse diameters of thyroid nodules, irregular margin, and microcalcification provide valuable insights into the differentiation between benign and malignant thyroid nodules.


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