OBJECTIVE:The main clinical manifestations of knee osteoarthritis are pain,swelling,stiffness,and limited activity,which have a serious impact on the life of patients.Exercise therapy can effectively improve the related symptoms of patients with knee osteoarthritis.This paper uses the method of network meta-analysis to compare the efficacy of different exercise types in the treatment of knee osteoarthritis. METHODS:CNKI,WanFang,PubMed,Embase,Cochrane Library,Web of Science,Scopus,Ebsco,SinoMed,and UpToDate were searched with Chinese search terms"knee osteoarthritis,exercise therapy"and English search terms"knee osteoarthritis,exercise".Randomized controlled trials on the application of different exercise types in patients with knee osteoarthritis from October 2013 to October 2023 were collected.The outcome measures included visual analog scale,Western Ontario and McMaster Universities Osteoarthritis Index score,Timed Up and Go test,and 36-item short form health survey.Literature quality analysis was performed using the Cochrane Manual recommended tool for risk assessment of bias in randomized controlled trials.Two researchers independently completed the data collection,collation,extraction and analysis.RevMan 5.4 and Stata 18.0 software were used to analyze and plot the obtained data. RESULTS:A total of 29 articles with acceptable quality were included,involving 1 633 patients with knee osteoarthritis.The studies involved four types of exercise:aerobic training,strength training,flexibility/skill training,and mindfulness relaxation training.(1)The results of network meta-analysis showed that compared with routine care/health education,aerobic training could significantly improve pain symptoms(SMD=-3.26,95%CI:-6.33 to-0.19,P<0.05);strength training(SMD=-0.79,95%CI:-1.34 to-0.23,P<0.05)and mindfulness relaxation training(SMD=-0.79,95%CI:-1.23 to-0.34,P<0.05)could significantly improve the function of patients.Aerobic training(SMD=-1.37,95%CI:-2.24 to-0.51,P<0.05)and mindfulness relaxation training(SMD=-0.41,95%CI:-0.80 to-0.02,P<0.05)could significantly improve the functional mobility of patients.Mindfulness relaxation training(SMD=0.70,95%CI:0.21-1.18,P<0.05)and strength training(SMD=0.42,95%CI:0.03-0.81,P<0.05)could significantly improve the quality of life of patients.(2)The cumulative probability ranking results were as follows:pain:aerobic training(86.6%)>flexibility/skill training(60.1%)>strength training(56.8%)>mindfulness relaxation training(34.7%)>routine care/health education(11.7%);Knee function:strength training(73.7%)>mindfulness relaxation training(73.1%)>flexibility/skill training(56.1%)>aerobic training(39.9%)>usual care/health education(7.6%);Functional mobility:aerobic training(94.7%)>mindfulness relaxation training(65.5%)>strength training(45.1%)>flexibility/skill training(41.6%)>routine care/health education(3.2%);Quality of life:mindfulness relaxation training(91.3%)>strength training(68.0%)>flexibility/skill training(44.3%)>aerobic training(34.0%)>usual care/health education(12.3%). CONCLUSION:(1)Exercise therapy is effective in the treatment of knee osteoarthritis,among which aerobic training has the best effect on relieving pain and improving functional mobility.Strength training and mindfulness relaxation training has the best effect on improving patients'function.Mindfulness relaxation training has the best effect on improving the quality of life of patients.(2)Limited by the quality and quantity of the included literature,more high-quality studies are needed to verify it.

ObjectiveTo explore the molecular mechanism of Sanhuang Xiexintang （SHXXT） in protecting stress gastric ulcer （SGU） in rats through network pharmacology， molecular docking， and animal experiments. MethodThe active ingredients and corresponding targets in SHXXT were collected and screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， Traditional Chinese Medicine Information Database （TCMID）， Bioinformation Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine （BATMAN-TCM）， and Swiss Target Prediction database. SGU-related targets were screened from the Online Mendelian Inheritance in Man （OMIM）， Therapeutic Target Database （TTD）， GeneCards database， and PharmGKB database. Herbal-ingredient-target （H-C-T） network was constructed by using Cytoscape 3.9.1 software. Protein-protein interaction （PPI） of drug and disease intersection targets was analyzed by using the Protein Interaction Platform （STRING） database. Gene ontology （GO） enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analysis were conducted through the Database for Annotation Visualization and Integrated Discovery （DAVID）. The active ingredients and key targets were validated using AutodockVina 1.2.2 molecular docking software， and the experimental results were further validated through animal experiments. ResultThe 55 active ingredients were screened， and 255 potential target genes for SHXXT treatment of SGU were predicted. The PPI analysis showed that protein kinase B （Akt）， phosphatase and tensin homolog deleted on chromosome ten （PTEN）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and cyclooxygenase-2 （COX-2） are the core targets of SHXXT for protecting SGU. GO and KEGG analyses showed that SHXXT may affect the development of SGU by regulating various biological processes such as the phosphoinositide 3-kinase （PI3K）/Akt signaling pathway and inflammatory processes. The molecular docking results showed that both the active ingredients and key targets had good binding ability. Animal experiments showed that compared with the blank group， the ulcer index （UI） of the model group was significantly increased （P<0.01）， and the serum levels of TNF-α and IL-1β significantly increased （P<0.01）. The phosphorylation level of PTEN in gastric mucosal tissue was significantly down-regulated （P<0.05）. The phosphorylation levels of PI3K， Akt， and nuclear factor kappa-B （NF-κB） were significantly up-regulated （P<0.05）. Compared with the model group， the UI of the treatment group was significantly reduced （P<0.01）， and the serum levels of TNF-α and IL-1β were significantly reduced （P<0.01）. The phosphorylation level of PTEN in gastric mucosal tissue was significantly up-regulated （P<0.01）， and the phosphorylation levels of PI3K， Akt， and NF-κB were significantly downregulated （P<0.01）. ConclusionThe application of network pharmacology prediction， molecular docking simulation， and animal experimental validation confirms that SHXXT regulates the PI3K/Akt/NF-κB signaling pathway to regulate the inflammatory response of rats and thus protects the gastric mucosa of SGU rats.

Objective We investigated the effects of Xueguan Ruanhua Pills(XGRHW) on ferroptosis in ApoE-/- atherosclerotic mice through the nuclear factor E2 related factor 2 (Nrf2)/xCT/glutathione peroxidase 4 (GPX4) signaling pathway.Methods Ten male C57BL/6J mice in the normal group were fed normal chow. Additionally, 50 ApoE-/- mice were fed high-fat chow for 12 weeks, and were divided into the following five groups (10 mice per group): the model group, the XGRHW low-dose (2.34g/kg) group, the XGRHW high-dose (4.68 g/kg) group, the XGRHW high-dose combined with the Nrf2 inhibitor ML385 (0.03 g/kg) group, and the ferrostatin-1 (1 mg/kg) group. Drugs were administered for 6 weeks. The blood levels of four types of lipids were detected by an automatic lipid analyzer, lipid deposition in the aorta was observed by Oil Red O staining, histomorphological changes in the aortic sinus were observed by HE staining, the serum levels of Fe2+, MDA, GSH, and SOD were determined by colorimetric assays, and the expression levels of FTH1 and FTL in the aortic sinus were observed by immunofluorescence. The protein levels of Nrf2, xCT, and GPX4 in mouse aortic tissues were detected by Western blotting. The ultrastructural changes of aortic mitochondria were observed by transmission electron microscopy.Results Compared with the normal group, mice in the model group showed obvious lipid plaque deposition in the aorta, severely calcified lesions in the aortic sinus, elevated serum levels of TC, TG, LDL-C, Fe2+, and MDA, decreased levels of HDL-C, SOD, and GSH (P<0.01), and decreased protein expressions of aortic Nrf2, xCT, and GPX4 as well as the iron storage proteins FTH1 and FTL (P<0.01), and serve damage to mitochondrial structure and morphology. Compared with the model group, the relative aortic plaque area was decreased, calcified lesions in the aortic sinus were decreased, serum levels of TC, TG, LDL-C, Fe2+, and MDA were decreased, and HDL-C, SOD, and GSH levels were increased in the XGRHW low-dose and high-dose and ferrostatin-1 groups (P<0.05 or P<0.01), and Nrf2, xCT, GPX4, and the iron storage proteins FTH1 and FTL were upregulated in aortic tissues (P<0.05 or P<0.01), and mitochondrial structure approaching normal. In the XGRHW high-dose+ML385 group, compared with the XGRHW high-dose group, the levels of blood lipids and lipid peroxidation were increased and the protein levels of Nrf2, xCT, and GPX4 in aortic tissue and the iron storage proteins FTH1 and FTL were decreased (P<0.01), and mitochondrial structure was damaged indicating that ML385 could inhibit the therapeutic effect of the XGRHW in atherosclerotic mice.Conclusion The XGRHW can improve blood lipid levels and reduce the degree of arterial plaque lesions in atherosclerotic mice, and its mechanism of action may be related to activation of the Nrf2/xCT/GPX4 pathway to inhibit ferroptosis.

OBJECTIVE To investigate the in vitro inhibitory mechanism of berberine on the proliferation of tumor stem cells and evaluate its in vivo safety. METHODS Flow cytometry was used to select tumor stem cells from mouse skin melanoma B16F10 cells； CD44， CD133， Nanog homologous box protein （NANOG） and octamer-binding transcription factor 4 （OCT4） were used as indicators to characterize tumor stem cells. Tumor stem cells were divided into control group， all-trans retinoic acid （ATRA） group， and berberine group， and the CCK-8 method was used to detect the effects of berberine on the viability of tumor stem cells； flow cytometry was adopted to detect cell apoptotic rate， the proportion of CD44+/CD133+ and the positive cell rate of sex determining region Y box protein 2 （SOX2）； the morphological changes of tumor balls were recorded after treatment with berberine； the morphology of cell pyroptosis in each group was recorded， and the release rate of lactate dehydrogenase （LDH） was detected； Western blot assay was adopted to detect the expressions of pyroptosis-related protein gasdermin E （GSDME）， GSDME- N， caspase-3 and cleaved caspase-3. Preliminary evaluation of in vivo safety of berberine was conducted by using zebrafish embryo toxicity experiments. RESULTS Compared with B16F10 cells， the proportion of CD44+/CD133+ cells in tumor stem cells and the fluorescence intensity of NANOG and OCT4 were significantly increased （P＜0.000 1）. The half-inhibitory concentration of berberine to tumor stem cells was 50.98 μmol/L. Compared with the control group， the apoptotic rate of cells in the berberine group was significantly increased， while the proportion of CD44+/CD133+ cells and the rate of SOX2 positive cells were reduced significantly （P＜0.000 1）； tumor stem cell spheroids were atrophied， with partial cell death. After treatment with berberine， tumor stem cells exhibited swelling in their outermost layer， the release rate of LDH of cells was significantly increased and the release rate of LDH increased with increasing dose； the protein expressions of GSDME-N and cleaved-caspase-3 of cells in berberine 20， 40 μmol/L groups were significantly increased， and the protein expressions of GSDME and caspase-3 were significantly reduced （except for berberine 20 μmol/L group， P＜0.05）. The embryonic development of zebrafish treated with berberine was almost unaffected， and the survival rate of embryo reached 100%， with no obvious abnormalities observed. CONCLUSIONS Berberine has good activity against the proliferation of tumor stem cells， and its mechanism of action may be related to activating GSDME and promoting cell pyroptosis； berberine has good in vivo safety.

Standards are the technical support for economic activities and social development. The construction and standardization of the pathogenic microorganism preservation standard system is an important technical foundation for the high-quality development of preservation work. Establishing a pathogenic microorganism resource standard system is also important to the national biosafety standards. Through the standardization of pathogenic microbial resource preservation, we can ensure the effective management and sustainable utilization of pathogenic microbial resources, promote the transformation of resources, and serve as an important new element of new productivity to assist the innovative development of biosafety science and technology. This article elaborates and analyzes the establishment background, construction framework, standardization process, and application effects of the standard system for preserving pathogenic microbial resources, providing stronger support for further improving the standard system and promoting the standardization of pathogenic microbial resource preservation.

Drugs and physical stimulation,including light,electricity,and magnetic fields,can be used to influence how neurons operate,among which chemogenetic and optogenetic technologies are most widely used.In recent years,magnetogenetic technology has also been developed that can acti-vate neurons in magnetic fields through magnetic sensitive actuators,leading to non-invasive and instanta-neous activation of specific brain regions.This article reviews the evolution of and problems with chemoge-netic and optogenetic techniques commonly used in brain science research.It also outlines the latest progress in magnetogenetic technologies,which are not full-fledged yet,as well as the role of transcra-nial electrical stimulation,transcranial magnetic stimulation,deep brain stimulation and transcranial ultra-sound stimulation technology in the functional regulation of brain diseases.Constant adjustment and improvement can make it possible for these technologies to be used more widely for the study of brain sciences and the treatment of brain diseases.

Purpose To evaluate the consistency and repeatability of cerebral blood flow(CBF)values measured by automatic segmentation of region of interest(ROI)and arterial spin labeling(ASL)functional image fusion in hippocampal sclerosis patients with medial temporal lobe epilepsy.Materials and Methods From January 2021 to October 2022,a total of 52 patients with medial temporal lobe epilepsy confirmed by MRI or pathology in General Hospital of Ningxia Medical University were retrospectively collected.All subjects were scanned on 3.0T MRI to obtain axial T1 weighted three-dimensional magnetization reserve gradient echo(3D-T1W1-MPGAGE)sequence and three-dimensional pseudo continuous ASL sequence.The 3D-T1W1-MPGAGE imaging were automatically segmented.Two physicians used the freeview visualization interface of freeSurfer software to fuse the ROI and ASL functional images of the hippocampal subregions and to measure the CBF values.The intra-observer and inter-observer consistency and repeatability were evaluated and analyzed.The consistency analysis and repeatability evaluation were performed via intraclass correlation coefficient(ICC),Bland-Altman diagram and Wilcoxon rank sum test.Results The ICC of CBF values measured by two physicians were all>0.750,with an average of 0.868±0.095.The ICC of left and right hippocampal subregions were as follows:subiculum(SUB):0.818/0.801,cornu ammonis(CA)1:0.920/0.907,CA2-3:0.759/0.978,CA4:0.757/0.758 and dentate gyrus(DG):0.990/0.991;The ICC delineated by the same physician's ROI were all>0.990 with an average of 0.994±0.002.The ICC of left and right hippocampal subregions were as follows:SUB:0.993/0.993,CA1:0.996/0.995,CA2-3:0.989/0.994,CA4:0.992/0.995 and DG:0.993/0.996.The Bland-Altman diagram showed the scatter distribution and consistency,and the coefficient of repeatability was obtained.The same observer had certain repeatability for the fusion measurement of automatic segmentation ROI and ASL functional images.Conclusion The CBF values measured by fusing ROI and ASL functional images of automatically segmented hippocampal subregion have higher consistency and repeatability.

Objective:To elucidate the primary elements pertaining to the perception of relapse risk and to in-vestigate the characteristics and alterations of perception of the risk of recurrence in patients with schizophrenia.Methods:By using the method of phenomenological study,semi-structured in-depth interviews were conducted among schizophrenic patients with first onset,first recurrence and multiple recurrences.Twenty-three 23 outpatient and inpatient cases that met the criteria of the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition(DSM-5)were included,and all patients had PANSS scores below 60.The interview data were collated and analyzed according to Colaizzi analysis.Results:The perception of recurrence risk in patients with schizophrenia en-compassed 4 major themes and 11 sub-themes,namely susceptibility(limited overall understanding,transition from optimism to objectivity),detection of early warning symptoms(dynamic escalation,assistance from family mem-bers in identification),understanding risk factors(lack of understanding,the relationship between psychosocial fac-tors and relapse,dynamic understanding of medication-relapse relationship),and apprehension of the consequences of recurrence(care burden and financial constraints,impaired social functioning and maladjustment,impact on pub-lic safety,personal health risks).Conclusion:The content of risk perception of recurrence in patients with schizo-phrenia is relatively substantial.The overall level of risk perception of recurrence in patients with schizophrenia is low.

OBJECTIVE To explore the effect of iron sulfur cluster binding protein 1(ISCA1)mag-netic field on calcium inflow.METHODS ① A plasmid containing the ISCA1、Magneto 2.0 gene sequence,and an empty plasmid was prepared for lentivirus packaging,with all the three plasmids carrying the mCherry gene.The infection efficiency of lentiviruses was assessed using fluorescence microscopy.② The immunoprecipitation technique was employed to ascertain the interactions between ISCA1 and cryptochrome(CRY1)as well as CRY2 proteins.③ The technique of live cell calcium imaging was used to detect the intracellular calcium influx in cells exhibiting high levels of ISCA1 or Magneto 2.0 expression under the influence of a magnetic field(40 mT,0.1Hz,90%duty cycle).RESULTS ① Red fluorescence was observed by fluorescence microscopy,indicating successful transfection of lentivirus.② The exogenous ISCA1 proteins exhibited no affinity towards the endogenous CRY1 or CRY2 proteins.③ The green fluorescence intensity of the Magneto 2.0 group increased by(1.8±0.5)times compared to the pre-magnetic addition level,indicating a significant influx of calcium ions.However,there was no significant difference in the green fluorescence intensity between the ISCA1 group and control group before and after magnetic addition.CONCLUSION Cells with exogenously high expres-sion of ISCA1 do not elicit calcium influx and exhibit no discernible magnetic induction following stimula-tion by this magnetic field.

Objective To explore the hippocampal(HC)microstructural changes in patients with unilateral temporal lobe epilepsy(TLE)by neurite orientation dispersion and density imaging(NODDI).Methods The NODDI indexes of the whole HC and HC subregions of temporal lobe epilepsy with hippocampal sclerosis(TLE-HS)patients,non-HS patients and healthy controls(control group)were calculated.The differences of NODDI indexes among and within the three groups were compared,and the correlation between the difference indexes and the clinical characteristics of the patients was analyzed.Results A total of 47 patients with TLE(27 cases of TLE-HS,20 cases of non-HS)and 22 cases of healthy controls were enrolled.In the TLE-HS group,the free-water isotropic vol-ume fraction(fiso)values of the HC and granular cell layer of dentate gyrus(GC-DG)subregions of the affected side were signifi-cantly higher than those of the contralateral side;the orientation dispersion index(ODI)values of the CA1 and CA4 subregions were significantly lower than those of the contralateral side;and the neurite density index(NDI)values of the HC,CA1,CA2-3,CA4 and GC-DG subregions of the affected side decreased significantly.There was no significant difference between the affected side and the contralateral side in the non-HS group.The fiso values of the HC and GC-DG subregions of the affected side in the TLE-HS group were significantly higher than those in the control group,the ODI values of the HC CA1 subregions of the affected side in the TLE-HS group were significantly lower than those in the control group and the non-HS group,the NDI values of the HC and subiculum(Sub),CA1,CA4 and GC-DG subregions of the affected side in the TLE-HS group were significantly lower than those in the con-trol group,and the NDI values of the HC and CA1,CA4 and GC-DG subregions of the affected side in the non-HS group were significantly lower than those in the control group.In the TLE-HS group,the NDI value of the HC CA4 subregion of the affected side was negatively correlated with the disease course,but there was no clear correlation between other subregion variables and disease course,onset frequency and duration of single onset.Conclusion NODDI technique has the ability to detect the microstructural changes of HC in patients with TLE,among which NDI is more likely to highlight neuronal damage and fiber reorganization in patients with TLE.