OBJECTIVE:Repetitive transcranial magnetic stimulation and transcranial direct current stimulation have shown positive effects in improving gross motor function in children with cerebral palsy.A network meta-analysis was performed to analyze the clinical efficacy of repetitive transcranial magnetic stimulation and transcranial direct current stimulation on the improvement of lower limb motor function and gait in children with cerebral palsy.METHODS:Randomized controlled trials(RCT)about repetitive transcranial magnetic stimulation and transcranial direct current stimulation on lower limb motor function and gait in children with cerebral palsy were collected from CNKI,WanFang,VIP,SinoMed,PubMed,Web of Science,Medline.The search time limit was from the inception to October 5,2024.After screening literature,extracting data and evaluating the risk of bias of included studies,Stata 15.0 software was used for network meta-analysis,AND GRADE profiler was used for quality evaluation.RESULTS:A total of 19 studies were included,involving 4 treatment measures:conventional therapy,high-frequency repetitive transcranial magnetic stimulation,low-frequency repetitive transcranial magnetic stimulation and anodic transcranial direct current stimulation.The results of network meta-analysis showed that in terms of improving gross motor function,low-frequency repetitive transcranial magnetic stimulation[mean difference(MD)=9.48,95％confidence interval(CI)(6.61,12.34),P＜0.05]was the most effective.In terms of alleviating spasticity,high-frequency repetitive transcranial magnetic stimulation[MD=-0.63,95％CI(-1.72,0.45),P＜0.05]had the best efficacy.In terms of improving ankle joint range of motion and step speed,transcranial direct current stimulation[MD=2.27,95％CI(1.37,3.17),P＜0.05;MD=0.11,95％CI(0.05,0.17),P＜0.05]was the most effective.CONCLUSION:Existing clinical evidence suggests that low-frequency repetitive transcranial magnetic stimulation has the best therapeutic effect compared with other intervention measures in terms of improving lower limb gross motor function.In terms of reducing spasticity,high-frequency repetitive transcranial magnetic stimulation has a more significant effect.In terms of improving gait,transcranial direct current stimulation has more advantages.

OBJECTIVE:Repetitive transcranial magnetic stimulation and transcranial direct current stimulation have shown positive effects in improving gross motor function in children with cerebral palsy.A network meta-analysis was performed to analyze the clinical efficacy of repetitive transcranial magnetic stimulation and transcranial direct current stimulation on the improvement of lower limb motor function and gait in children with cerebral palsy.METHODS:Randomized controlled trials(RCT)about repetitive transcranial magnetic stimulation and transcranial direct current stimulation on lower limb motor function and gait in children with cerebral palsy were collected from CNKI,WanFang,VIP,SinoMed,PubMed,Web of Science,Medline.The search time limit was from the inception to October 5,2024.After screening literature,extracting data and evaluating the risk of bias of included studies,Stata 15.0 software was used for network meta-analysis,AND GRADE profiler was used for quality evaluation.RESULTS:A total of 19 studies were included,involving 4 treatment measures:conventional therapy,high-frequency repetitive transcranial magnetic stimulation,low-frequency repetitive transcranial magnetic stimulation and anodic transcranial direct current stimulation.The results of network meta-analysis showed that in terms of improving gross motor function,low-frequency repetitive transcranial magnetic stimulation[mean difference(MD)=9.48,95％confidence interval(CI)(6.61,12.34),P＜0.05]was the most effective.In terms of alleviating spasticity,high-frequency repetitive transcranial magnetic stimulation[MD=-0.63,95％CI(-1.72,0.45),P＜0.05]had the best efficacy.In terms of improving ankle joint range of motion and step speed,transcranial direct current stimulation[MD=2.27,95％CI(1.37,3.17),P＜0.05;MD=0.11,95％CI(0.05,0.17),P＜0.05]was the most effective.CONCLUSION:Existing clinical evidence suggests that low-frequency repetitive transcranial magnetic stimulation has the best therapeutic effect compared with other intervention measures in terms of improving lower limb gross motor function.In terms of reducing spasticity,high-frequency repetitive transcranial magnetic stimulation has a more significant effect.In terms of improving gait,transcranial direct current stimulation has more advantages.

Animal experimentation constitutes a critical link between basic research and clinical application, making its research quality and translational efficiency paramount. Although considerable progress has been made in standardizing operational procedures and ethical guidelines, the standardization of outcome evaluation systems has significantly lagged, creating a key bottleneck that constrains the quality of biomedical research and evidence synthesis. This deficiency is manifested by pronounced heterogeneity in outcome selection across similar studies, incomplete methodological reporting, and disparate criteria for result interpretation, which severely impairs the comparability of findings and the evidence integration. To cope with this challenge, this paper systematically introduces a mature methodological tool from clinical research–the core outcome set (COS)–and explores its construction strategies and application potential in the field of animal experimentation. Given the extensive diversity of animal experiments, a pragmatic strategy of "focusing on key areas, implementing phased pilots, and promoting gradual expansion" should be adopted. This approach prioritizes the development of domain-specific COS for disease areas characterized by high research volume, urgent translational needs, and well-established animal models. A multi-source integration pathway for COS development is detailed, comprising systematic literature searches, methodological appraisals, and expert consensus, with the feasibility of leveraging artificial intelligence (AI) to enhance efficiency also being examined. The development and promotion of such COS are not intended to restrict scientific exploration; rather, they aim to establish a new, tiered evaluation paradigm consisting of "core outcomes" (mandatory), "recommended outcomes" (encouraged), and "exploratory outcomes" (optional). This framework is expected not only to enhance research quality through standardization and to adhere to the "3R" principles but also to accelerate the accumulation of high-quality evidence. This, in turn, provides a solid foundation for higher-level evidence synthesis, ultimately facilitating the effective translation of basic research findings into clinical practice and providing an essential methodological framework for scientific advancement in relevant disciplines.

OBJECTIVE To investigate the therapeutic effect and mechanism of Qiwei dongqingye powder （QDP） on bronchial asthma in mice. METHODS The mice were divided into blank group （normal saline）， model group （normal saline）， dexamethasone group （2 mg/kg）， and QDP low-， medium-， and high-dose groups （200， 400， 800 mg/kg）， with 14 mice in each group. Except for the blank group， mice in all other groups were given ovalbumin via intraperitoneal injection followed by aerosol inhalation to induce a bronchial asthma model. During the modeling process， mice in each group were administered corresponding drug solutions or normal saline intragastrically/intraperitoneally. After the last medication， the number of cells in the bronchoalveolar lavage fluid （BALF） of the mice was observed and counted； the pathological changes of the bronchus and lung tissue were observed； the levels of malondialdehyde （MDA）， nitric oxide （NO）， total superoxide dismutase （T-SOD）， and glutathione peroxidase （GSH-Px） in the lung tissue of the mice were determined， and the level of interleukin-17 （IL-17） in the BALF and serum was determined. Transcriptomics was employed to predict and validate the mechanism of action of QDP against bronchial asthma. RESULTS Compared with the model group， the total cell count， neutrophil count， lymphocyte count， and macrophage counts in the BALF of the QDP high-dose group were all significantly reduced （ P ＜0.05）； the levels of MDA and NO in the lung tissue， and the levels of IL-17 in the BALF and serum were all decreased significantly （ P ＜0.05）； the levels of T-SOD and GSH-Px were significantly increased （ P ＜0.05）； the arrangement of lung tissue cells tended to normalize， with reduced infiltration of inflammatory cells and decreased exfoliation of bronchial simple columnar epithelial cells. The transcriptomic results revealed that the differentially expressed genes were B-cell receptor signaling pathway， nuclear factor κB （NF-κB） signaling pathway， ferroptosis signaling pathway， and others. Further validation revealed that， compared with the model group， the expression levels of NF-κB p65 and chemokine ligand 20， as well as the phosphorylation level of NF-κB inhibitor protein α， were significantly decreased in the lung tissues of the mice in all QDP groups （ P ＜0.05）. Conversely， the protein expression of nuclear factor erythroid 2-related factor 2 （Nrf2） and heme oxygenase 1 （HO-1） were significantly increased （ P ＜0.05）. CONCLUSIONS QDP can effectively alleviate bronchial asthma by inhibiting the NF-κB signaling pathway， activating the Nrf2/HO-1 signaling pathway， regulating oxidative stress， and reducing inflammatory responses.

ObjectiveTo explore the possible mechanism of Tongbian Decoction （通便汤， TD） in treating slow transit constipation （STC）. MethodsTwenty-four SD rats were randomly divided into normal group， model group， TD group， and mosapride group， with 6 rats per group. Except for the normal group， STC models were established by intragastric administration of loperamide hydrochloride combined with normal saline. On the day following successful model establishment， rats in the TD group received 18.63 g·kg⁻¹ of TD by gavage， while those in the mosapride group received 1.605 mg·d⁻¹ of mosapride， and those in the normal group and the model group received 10 ml·kg⁻¹ of normal saline by gavage. All treatments were administered once daily for 7 consecutive days. Twenty-four hours after the last administration， fecal pellet number and fecal water content were measured. After intragastric administration of a 10% activated charcoal suspension， the small intestinal transit rate was calculated 30 minutes later. Serum levels of gastrin （GAS） and motilin （MTL） were measured by ELISA. Colonic histopathology was observed by HE staining， and mucus secretion by Alcian blue-periodic acid-Schiff （AB-PAS） staining. Ultrastructure of colon tissue was examined using transmission electron microscopy. Protein expression levels of C-kit， stem cell factor （SCF）， autophagy-related protein 5 （ATG5）， Beclin1， vesicle-associated membrane protein B （VAPB）， and protein tyrosine phosphatase interacting protein 51 （VAPB-PTPIP51） were measured by Western Blot， and the mRNA levels were detected by real-time PCR. Immunohistochemistry was used to detect SCF， C-kit， Beclin1， and ATG5 expression. The calcium content in colon tissue was determined by ELISA. ResultsCompared to the normal group， rats in the model group showed significantly reduced fecal pellet number， fecal water content， small intestinal transit rate， and serum GAS and MTL levels （P＜0.01）； the number of goblet cells decreased， and the mucosal and muscular layers of the colon became thinner； mRNA and protein expression levels of ATG5 and Beclin1 in colon tissue significantly increased， while calcium content decreased （P＜0.05 or P＜0.01）； and electron microscopy revealed vacuolar degeneration and increased autophagosomes in colonic cells. Compared to the model group， both TD group and mosapride group showed increased fecal pellet number， fecal water content， small intestinal transit rate， serum GAS and MTL levels， and colonic calcium content， along with decreased Beclin1 and ATG5 protein levels （P＜0.05 or P＜0.01）； the mucosal thickness and goblet cell number increased significantly， and autophagosomes decreased； in the TD group， ATG5 and Beclin1 mRNA levels decreased； in the mosapride group， SCF， VAPB， and PTPIP51 mRNA levels increased， while Beclin1 mRNA decreased （P＜0.05 or P＜0.01）. Compared to the mosapride group， the TD group showed higher fecal pellet number， fecal water content， serum GAS levels， colonic calcium content， and C-kit expression， along with lower ATG5 and Beclin1 levels （P＜0.05 or P＜0.01）. ConclusionTD may improve constipation symptoms by upregulating the VAPB-PTPIP51 complex during mitochondria-endoplasmic reticulum interactions， reducing autophagy of interstitial cells of Cajal， and promoting intestinal motility.

ObjectiveTo explore the possible mechanism of Tongbian Decoction （通便汤， TD） in treating slow transit constipation （STC）. MethodsTwenty-four SD rats were randomly divided into normal group， model group， TD group， and mosapride group， with 6 rats per group. Except for the normal group， STC models were established by intragastric administration of loperamide hydrochloride combined with normal saline. On the day following successful model establishment， rats in the TD group received 18.63 g·kg⁻¹ of TD by gavage， while those in the mosapride group received 1.605 mg·d⁻¹ of mosapride， and those in the normal group and the model group received 10 ml·kg⁻¹ of normal saline by gavage. All treatments were administered once daily for 7 consecutive days. Twenty-four hours after the last administration， fecal pellet number and fecal water content were measured. After intragastric administration of a 10% activated charcoal suspension， the small intestinal transit rate was calculated 30 minutes later. Serum levels of gastrin （GAS） and motilin （MTL） were measured by ELISA. Colonic histopathology was observed by HE staining， and mucus secretion by Alcian blue-periodic acid-Schiff （AB-PAS） staining. Ultrastructure of colon tissue was examined using transmission electron microscopy. Protein expression levels of C-kit， stem cell factor （SCF）， autophagy-related protein 5 （ATG5）， Beclin1， vesicle-associated membrane protein B （VAPB）， and protein tyrosine phosphatase interacting protein 51 （VAPB-PTPIP51） were measured by Western Blot， and the mRNA levels were detected by real-time PCR. Immunohistochemistry was used to detect SCF， C-kit， Beclin1， and ATG5 expression. The calcium content in colon tissue was determined by ELISA. ResultsCompared to the normal group， rats in the model group showed significantly reduced fecal pellet number， fecal water content， small intestinal transit rate， and serum GAS and MTL levels （P＜0.01）； the number of goblet cells decreased， and the mucosal and muscular layers of the colon became thinner； mRNA and protein expression levels of ATG5 and Beclin1 in colon tissue significantly increased， while calcium content decreased （P＜0.05 or P＜0.01）； and electron microscopy revealed vacuolar degeneration and increased autophagosomes in colonic cells. Compared to the model group， both TD group and mosapride group showed increased fecal pellet number， fecal water content， small intestinal transit rate， serum GAS and MTL levels， and colonic calcium content， along with decreased Beclin1 and ATG5 protein levels （P＜0.05 or P＜0.01）； the mucosal thickness and goblet cell number increased significantly， and autophagosomes decreased； in the TD group， ATG5 and Beclin1 mRNA levels decreased； in the mosapride group， SCF， VAPB， and PTPIP51 mRNA levels increased， while Beclin1 mRNA decreased （P＜0.05 or P＜0.01）. Compared to the mosapride group， the TD group showed higher fecal pellet number， fecal water content， serum GAS levels， colonic calcium content， and C-kit expression， along with lower ATG5 and Beclin1 levels （P＜0.05 or P＜0.01）. ConclusionTD may improve constipation symptoms by upregulating the VAPB-PTPIP51 complex during mitochondria-endoplasmic reticulum interactions， reducing autophagy of interstitial cells of Cajal， and promoting intestinal motility.

Objective:To investigate the relationship between dietary behavior and sarcopenia in older adults aged ≥65 years in longevity areas of China based on latent class analysis.Methods:A total of 4 358 older adults aged ≥65 years were selected from the 2021 Healthy Aging and Biomarkers Cohort Study. The information about their demographic characteristics, lifestyles, and chronic disease histories were collected. A simplified food frequency questionnaire was used to collect information about their dietary intake in the last month. The food intake frequency and food category score were calculated, and the higher the food category score, the richer the dietary intake. Latent class analysis was used to identify the latent classes of the dietary behavior. Sarcopenia was diagnosed using the SARC-CalF. Multivariate logistic regression model was used to analyze the association of food category scores and different latent classes of the dietary behavior with the risk for sarcopenia.Results:In 4 358 older adults, 1 841 (42.24%) had sarcopenia. The frequencies of intakes of cereals and potatoes, vegetable and fruit, meat and bean products were lower in the sarcopenia group than in the non-sarcopenia group. The risk for sarcopenia decreased with the increase of food category score in older adults ( OR=0.850, 95% CI: 0.796-0.907). Latent class analysis identified 4 latent classes of the dietary behavior. Compared with those with class 1 (frequency of intake of all 5 food species was higher probability in T3 group), those with class 2 (frequency of intake of vegetables and fruits and energy-only foods were less likely to be in the T3 group) and class 3 (frequency of intake of all 5 food species was lower probability in T3 group) had significantly increased risk for sarcopenia ( OR=1.377, 95% CI: 1.131-1.676) and ( OR=1.354, 95% CI: 1.091-1.680), 37.7% and 35.4% increased risk for sarcopenia, respectively. Conclusion:Increasing dietary intake category and sufficient intake of various foods for a balanced dietary pattern can reduce the risk of sarcopenia in older adults.

Objective To investigate the expression levels of serum hemoglobin β(HBB)in hepatocellular carcinoma(HCC)patients and its correlation with topoisomeraseⅡα(TOP2A)gene.Methods A total of 48 HCC patients visited the Second Affiliated Hospital of Nantong University from August 2023 to September 2024 were selected as the HCC group,and 32 healthy individuals who underwent physical examination during the same period were selected as the healthy control group.Their blood samples were collected,and the ex-pression levels of serum HBB and TOP2A genes were detected by real-time fluorescence quantitative polymerase chain reaction(qRT-PCR).Then,the relationship between the expression of HBB gene and clinicopathological parameters of the patients was ana-lyzed.The Kaplan-Meier Plotter database was used to evaluate the relationship between the expression of HBB gene and the prognosis of HCC.The diagnostic value of the expressions of serum HBB and TOP2A genes for HCC was assessed by the receiver operating charac-teristic(ROC)curve.Spearman rank correlation analysis was used to evaluate the correlation between the expressions of serum HBB and TOP2A genes in HCC patients.The regulatory effect of HBB gene on TOP2A gene was verified by the cell experiment.Results The expression levels of serum HBB gene in HCC patients(0.097[0.055,0.155])were significantly lower than that in healthy controls(1.029[0.625,1.434],U=19,P＜0.001).The expression levels of serum TOP2A gene in HCC patients(1.810[0.825,3.623])were significantly higher than that in healthy controls(1.047[0.604,1.364],U=495,P=0.007).The expression level of serum HBB gene in HCC patients was significantly negatively correlated with that of TOP2A gene(ρ=-0.384,P=0.007).The analysis results of clinicopathological parameters showed that the expression level of HBB gene was only related to tumor size(χ2=4.090,P＜0.05).The Kaplan-Meier survival analysis showed that the 5-year overall survival rate of the patients with low expression of HBB gene was signifi-cantly lower than that with high expression(HR=0.680,95%CI:0.470-0.970,P＜0.05).The analysis of the ROC curve showed that the area under the ROC curve(AUCROC)of HBB gene in diagnosing HCC was 0.987(95%CI:0.963-1.000).When the cut-off value was 0.228,its sensitivity was 100%and specificity was 97%.The AUCROC of TOP2A gene for the diagnosis of HCC was 0.677(95%CI:0.559-0.797).When the cut-off value was 1.285,its sensitivity was 65%and specificity was 75%.The combined detection of HBB and TOP2A genes for the diagnosis of HCC had an AUCROC of 0.988(95%CI:0.965-1.000).When the cut-off value was 0.657,its sensitivity was 100%and specificity was 97%.The cell experiment results showed that the overexpression of HBB gene could inhibit the expression of TOP2A gene,while the knockout of HBB gene had the opposite effect.Conclusion HBB gene is lowly expressed in the serum of HCC patients and is significantly negatively correlated with the expression of TOP2A gene.

Objective To sort,summarize,and introduce key terms related to guideline reporting,evaluation,dissemination,implementation,and updating.Methods We systematically searched guideline de-velopment manuals and methodological literature from database inception to October 25,2024.Terms related to guideline reporting,updating,evaluation,and implementation were extracted,standardized,and finalized through a structured consensus process.Results A total of 13 guideline manuals and 32 methodological articles were included,yielding 14 core terms with standardized definitions.Conclusions This article introduces key terms such as reporting standards,external review,and research gaps across guideline development phases to promote concept application and deepen readers'understanding of guideline development.

Objective:To analyze the short-term hospital-based transmission characteristics and gene variation of Carbapenem-Resistant Klebsiella pneumoniae (CRKP) by genome-wide technique to provide evidence for transmission control. Methods:The experimental strain was derived from all the CRKP isolated in Affiliated Hospital of North China University of Science and Technology from October 2022 to December 2023. Strain identification and drug susceptibility were tested with VITEK 2-Compact automatic bacterial identification drug susceptibility analyzer or disk method, and the results were interpreted through whole genome sequencing. The ST type, carbapenem resistance gene, virulence factor, and O serotype of the collected strains were analyzed.Results:Among the 115 strains of CRKP, 94 strains were isolated from the intensive care unit (ICU), accounting for 81.7%, and 21 strains were isolated from the non-intensive care unit (NICU), accounting for 18.3%. The 115 strains of CRKP can be divided into 11 ST types, of which ST11 type was the most (54.8%, 63/115), followed by ST15 type (22.6%, 26/115) and ST5492 type (15.7%, 18/115). Type ST5492 was a new clonal group in the region. The 115 strains of CRKP could be divided into 7 O serotypes, most of which were O2a type(32.2%,37/115), followed by O5 type(30.4%,35/115) and O1 type(27.8%,32/115). The resistance genes of carbapenem antibiotics showed that there were 107 strains carrying the blaKPC-2 gene, one strain with the blaNDM-1 gene, and one strain with both the blaKPC-2 and blaNDM-13 genes. Virulence genes were detected in 55 CRKP strains (47.8%, 55/115), among which six strains detected peg-344, iucA, iroB, rmpA, and rmpA2 virulence genes (5.2%, 6/115). Four virulence genes ( peg-344, iucA, rmpA, and rmpA2) were detected in 34 strains (29.6%, 34/115). Three virulence genes ( iucA, iroB and rmpA) were detected in two strains (1.7%, 2/115). Three virulence genes ( peg-344, iucA and rmpA) were detected in one strain (0.8%, 1/115). IucA and rmpA virulence genes were detected in 12 strains (10.4%, 12/115). KPC-2_ST11_O2a, KPC-2_ST15_O1 and KPC-2_ST5492_O5 were dominant clones, and their distribution was mainly in the intensive care unit. The whole genome sequence analysis showed that there were three dominant clones, among which ST11 clones were subdivided into three dominant O serotypes, all of which were mainly in the intensive care unit. Conclusion:The popular strain in the hospital of CRKP is a KPC-2_ST11 clone group carrying iucA, rmpA/rmpA2, with cross-department transmission and mutation. ST5492 is a newly-launched clone type. The intensive care unit of hvKP carrying five virulence genes, including peg-344, should be alert to the epidemic risk of CR-hvKP outbreak.