ObjectiveTo investigate the effect of different exercise interventions on metabolism and liver parameters in patients with metabolic dysfunction-associated fatty liver disease （MAFLD）， and to provide evidence-based recommendations for clinical exercise rehabilitation. MethodsThis study was conducted according to the PRISMA guidelines， and the protocol was registered on the PROSPERO platform， with a registration number of CRD42025641717. PubMed， Web of Science， Scopus， Wiley Online Library， CNKI， Wanfang Data， and VIP were searched for related articles published up to September 2024. The Cochrane tool for assessing risk of bias was used to assess the quality of articles， and Stata MP 17.0 was used to perform the network meta-analysis. ResultsA total of 57 articles were included， involving 2 648 patients. The results showed that aerobic exercise combined with resistance exercise had the best effect in improving body mass index （mean difference ［WMD］=-0.97， 95% confidence interval ［CI］： -1.66 to -0.28］， P<0.05， surface under the cumulative ranking curve ［SUCRA］=85.4） and triglycerides （WMD=-29.6， 95%CI： -46.66 to 12.54， P<0.05， SUCRA=87.3）； resistance exercise was the optimal intervention method for improving total cholesterol （WMD=-15.99， 95%CI： -24.19 to -7.79， P<0.05， SUCRA=79.9） and glutamine transaminase （WMD=-8.08， 95%CI： -12.13 to -4.02， P<0.05， SUCRA=87.3）； low-intensity aerobic exercise had the best effect in improving aspartate aminotransferase （WMD=-4.3， 95%CI： -8.45 to -0.15， P<0.05， SUCRA=73.5）， gamma-glutamyl transpeptidase （GGT） （WMD=-3.26， 95%CI： -7.79 to 1.27， P>0.05， SUCRA=82.3）， and glycated hemoglobin （HbA1c） （WMD=-0.6， 95%CI： -2.02 to 0.82， P>0.05， SUCRA=78.8）； moderate-intensity aerobic exercise was the optimal intervention modality to improve Homeostasis Model Assessment of Insulin Resistance （WMD=-0.92， 95%CI： -1.51 to -0.33， P<0.05， SUCRA=69.4）. It should be noted that there were no significant differences in HbA1c and GGT across different exercise interventions （all P>0.05）， suggesting that there was currently no sufficient statistical evidence to support that exercise could improve these two indicators. ConclusionBased on the comprehensive league table and cumulative probability ranking， aerobic exercise combined with resistance exercise， resistance exercise， and low- and moderate-intensity aerobic exercise may be the best exercise modality for improving key indicators in MAFLD patients， and targeted exercise modalities should be selected for intervention against different indicators； however， due to limitations of the original studies， further studies are needed for validation and exploration.

Psoriasis is an incurable chronic inflammatory disease that requires new interventions. Here, we found that fibroblasts exacerbate psoriasis progression by promoting macrophage recruitment via CCL2 secretion by single-cell multi-omics analysis. The natural small molecule celastrol was screened to interfere with the secretion of CCL2 by fibroblasts and improve the psoriasis-like symptoms in both murine and cynomolgus monkey models. Mechanistically, celastrol directly bound to the low-density lipoprotein receptor-related protein 1 (LRP1) β-chain and abolished its binding to the transcription factor c-Jun in the nucleus, which in turn inhibited CCL2 production by skin fibroblasts, blocked fibroblast-macrophage crosstalk, and ameliorated psoriasis progression. Notably, fibroblast-specific LRP1 knockout mice exhibited a significant reduction in psoriasis like inflammation. Taken together, from clinical samples and combined with various mouse models, we revealed the pathogenesis of psoriasis from the perspective of fibroblast-macrophage crosstalk, and provided a foundation for LRP1 as a novel potential target for psoriasis treatment.

OBJECTIVES: To investigate the protective effect of Yiqi Yangyin Huazhuo Tongluo Formula (YYHT) against high glucose-induced injury in mouse renal podocytes (MPC5 cells) and the possible mechanism. METHODS: Adult Wistar rats were treated with 19, 38, and 76 g/kg YYHT or saline via gavage for 7 days to prepare YYHT-medicated or blank sera for treatment of MPC5 cells cultured in high glucose (30 mmol/L) prior to transfection with a miR-21a-5p inhibitor or a miR-21a-5p mimic. The changes in miR-21a-5p expressions and the mRNA levels of FoxO1, PINK1, and Parkin in the treated cells were detected with qRT-PCR, and the protein levels of nephrin, podocin, FoxO1, PINK1, and Parkin were detected with Western blotting. Autophagic activity in the cells were evaluated with MDC staining. The effect of miR-21a-5p mimic on FoxO1 transcription and the binding of miR-21a-5p to FoxO1 were examined with luciferase reporter gene assay and radioimmunoprecipitation assay. RESULTS: MPC5 cells exposed to high glucose showed significantly increased miR-21a-5p expression, lowered expressions of FoxO1, PINK1, and Parkin1 mRNAs, and reduced levels of FoxO1, PINK1, parkin, nephrin, and podocin proteins and autophagic activity. Treatment of the exposed cells with YYHT-medicated sera and miR-21a-5p inhibitor both significantly enhanced the protein expressions of nephrin and podocin, inhibited the expression of miR-21a-5p, increased the mRNA and protein expressions of FoxO1, PINK1 and Parkin, and upregulated autophagic activity of the cells. Transfection with miR-21a-5p mimic effectively inhibited the transcription of FoxO1 and promoted the binding of miR-21a-5p to FoxO1 in MPC5 cells, and these effects were obviously attenuated by treatment with YYHT-medicated sera. CONCLUSIONS YYHT-medicated sera alleviate high glucose-induced injury in MPC5 cells by regulating miR-21a-5p/FoxO1/PINK1-mediated mitochondrial autophagy.
Animals ; MicroRNAs/genetics* ; Podocytes/pathology* ; Drugs, Chinese Herbal/pharmacology* ; Autophagy/drug effects* ; Rats, Wistar ; Protein Kinases/metabolism* ; Rats ; Forkhead Box Protein O1 ; Mice ; Mitochondria/drug effects* ; Ubiquitin-Protein Ligases/metabolism* ; Glucose ; Diabetic Nephropathies ; Male ; Membrane Proteins/metabolism* ; Intracellular Signaling Peptides and Proteins

Objective To investigate the protective effect of Yiqi Yangyin Huazhuo Tongluo Formula(YYHT)against high glucose-induced injury in mouse renal podocytes(MPC5 cells)and the possible mechanism.Methods Adult Wistar rats were treated with 19,38,and 76 g/kg YYHT or saline via gavage for 7 days to prepare YYHT-medicated or blank sera for treatment of MPC5 cells cultured in high glucose(30 mmol/L)prior to transfection with a miR-21a-5p inhibitor or a miR-21a-5p mimic.The changes in miR-21a-5p expressions and the mRNA levels of FoxO1,PINK1,and Parkin in the treated cells were detected with qRT-PCR,and the protein levels of nephrin,podocin,FoxO1,PINK1,and Parkin were detected with Western blotting.Autophagic activity in the cells were evaluated with MDC staining.The effect of miR-21a-5p mimic on FoxO1 transcription and the binding of miR-21a-5p to FoxO1 were examined with luciferase reporter gene assay and radioimmunoprecipitation assay.Results MPC5 cells exposed to high glucose showed significantly increased miR-21a-5p expression,lowered expressions of FoxO1,PINK1,and Parkin1 mRNAs,and reduced levels of FoxO1,PINK1,parkin,nephrin,and podocin proteins and autophagic activity.Treatment of the exposed cells with YYHT-medicated sera and miR-21a-5p inhibitor both significantly enhanced the protein expressions of nephrin and podocin,inhibited the expression of miR-21a-5p,increased the mRNA and protein expressions of FoxO1,PINK1 and Parkin,and upregulated autophagic activity of the cells.Transfection with miR-21a-5p mimic effectively inhibited the transcription of FoxO1 and promoted the binding of miR-21a-5p to FoxO1 in MPC5 cells,and these effects were obviously attenuated by treatment with YYHT-medicated sera.Conclusion YYHT-medicated sera alleviate high glucose-induced injury in MPC5 cells by regulating miR-21a-5p/FoxO1/PINK1-mediated mitochondrial autophagy.

Expert evidence, expert opinion, and expert consensus are frequently mentioned and used in the process of guideline development. However, due to the lack of clear definitions and standards, there is confusion and misuse among the three in practice. This paper clarifies the meanings, current status, differences, and connections of expert evidence, expert opinion, and expert consensus in the development of guidelines, aiming to provide a reference for guideline developers in China.

【Objective】 To investigate the effects of total flavone of oldenlandia diffusa (FOD) on the proliferation and apoptosis of hepatocellular carcinoma (HCC) stem cells sorted from Huh7. 【Methods】 Human HCC cell lines Huh7 was cultured in vitro; CD133 positive (CD133⁺) stem cells in Huh7 cell line were sorted by flow cytometry, and stem cell markers such as Nanog, Oct4 and Sox2 were tested by Western blotting. CD133⁺-Huh7 was stimulated by different concentrations (0 μg/mL, 50 μg/mL, 100 μg/mL and 400 μg/mL) of FOD for different time (24 h, 48 h, 72 h and 96 h). CCK8 and plate cell cloning assay were used to detect the effect of FOD on CD133⁺-Huh7 proliferation while Annexin V-PE/7-AAD was used to detect the effect of FOD on CD133⁺-Huh7 apoptosis. Western blotting was used to detect the protein expressions of protein 53 (P53), factor associated suicide-Fas-associating protein with a novel death domain (Fas-FADD), B-cell lymphoma-2 (Bcl-2), Cleaved-Caspase3, and Bcl-2 associated X protein (Bax). 【Results】 More than 95% of stem cells were purified for further experiments. Cell proliferation of CD133⁺-Huh7 was significantly inhibited by FOD, with the significant suppression at the concentration of 100 μg/mL for 72 h compared with negative control group (P<0.05). The apoptosis rate was significantly upregulated than that in the negative control group (P<0.05). The protein expression of Bcl2 decreased while Bax and Cleaved-Caspae3 increased via FAS/FADDD and P53 axis. 【Conclusion】 FOD can significantly inhibit the proliferation and promote the apoptosis of CD133⁺-Huh7.

Objective: To investigate the impact of intensified maintenance therapy on the prognosis of children and adolescents with advanced lymphoblastic lymphoma (LBL) . Methods: Retrospective analysis on the treatment results of children and adolescents with stage Ⅲ and stage Ⅳ LBL who underwent BFM-NHL-90/-95 regimen without prophylactic radiotherapy. The intensified therapy group included the patients admitted from 1998 to 2005, while others were classified as the non-intensified therapy group. Patients in the intensified therapy group were intravenously treated with "etoposide phosphate plus cytrarabine" and high-dose methotrexate alternately per 2.5-3 months in addition to the oral chemotherapy with 6-mercaptopurine and methotrexate during the maintenance phase. Results: A total of 187 LBL patients were enrolled. The rates of 5-year event free survival were (76.9 ± 5.8) % and (77.9 ± 4.3) % (χ²=0.249, P=0.617) respectively, in the intensified therapy (n=52) and the non-intensified therapy groups (n=135) , while the rates of 5-year overall survival of them were (78.8 ± 5.7) % and (79.8±4.1) % (χ²=0.353, P=0.552) , respectively. Stratified by stage, immunological type as well as risk stratification, the rates of long-term survival were similar between the two groups. During the maintenance phase, the rates of grade Ⅲ and Ⅳ myelosuppression in the intensified therapy and the non-intensified maintenance groups were 55.8% and 18.5%, respectively (χ²=25.363, P<0.05) . Conclusion Intensified maintenance therapy failed to improve the prognosis of patients with advanced LBL.

In order to find the most suitable algorithm of T-wave end point detection for clinical detection, we tested three methods, which are not just dependent on the threshold value of T-wave end point detection, i. e. wavelet method, cumulative point area method and trapezium area method, in PhysioNet QT database (20 records with 3 569 beats each). We analyzed and compared their detection performance. First, we used the wavelet method to locate the QRS complex and T-wave. Then we divided the T-wave into four morphologies, and we used the three algorithms mentioned above to detect T-wave end point. Finally, we proposed an adaptive selection T-wave end point detection algorithm based on T-wave morphology and tested it with experiments. The results showed that this adaptive selection method had better detection performance than that of the single T-wave end point detection algorithm. The sensitivity, positive predictive value and the average time errors were 98.93%, 99.11% and (--2.33 ± 19.70) ms, respectively. Consequently, it can be concluded that the adaptive selection algorithm based on T-wave morphology improves the efficiency of T-wave end point detection.
Algorithms ; Electrocardiography ; Humans ; Wavelet Analysis

OBJECTIVETo evaluate the diagnostic value of salivary and plasma miR-21 in patients with esophageal cancer (EC).

METHODSTotal RNA was extracted from saliva and plasma samples from 50 stage I and 50 stage II patients with EC and 50 healthy controls for measurement of miR-21 levels using qPCR. The diagnostic values of salivary and plasma miR-21 levels were assessed for stage I, stage II, and stage I+II EC.

RESULTSSalivary and plasma miR-21 were significantly higher in the EC patients than in the control group. The diagnostic sensitivities of plasma miR-21 for stage I, stage II, and stage I+II EC were 96%, 64% and 97%, with specificities of 44%, 84%, and 56%, respectively; the sensitivities of salivary miR-21 were 90%, 88%, and 89%, respectively, with the same specificities of 64%. Regardless of EC staging, the expression of plasma miR-21 showed a significant positive correlation with that of salivary miR-21, and their diagnostic values were comparable.

CONCLUSIONBoth salivary and plasmatic miR-21 can be sensitive biomarkers for EC, and salivary miR-21 detection has the potential to replace plasma detection for EC diagnosis.

Biomarkers, Tumor ; blood ; chemistry ; Esophageal Neoplasms ; blood ; diagnosis ; Humans ; MicroRNAs ; blood ; Plasma ; chemistry ; Real-Time Polymerase Chain Reaction ; Saliva ; chemistry ; Sensitivity and Specificity

Objective To evaluate the diagnostic value of salivary and plasma miR-21 in patients with esophageal cancer (EC). Methods Total RNA was extracted from saliva and plasma samples from 50 stage I and 50 stage II patients with EC and 50 healthy controls for measurement of miR-21 levels using qPCR. The diagnostic values of salivary and plasma miR-21 levels were assessed for stage I, stage II, and stage I+II EC. Results Salivary and plasma miR-21 were significantly higher in the EC patients than in the control group. The diagnostic sensitivities of plasma miR-21 for stage I, stage II, and stage I+II EC were 96%, 64%and 97%, with specificities of 44%, 84%, and 56%, respectively;the sensitivities of salivary miR-21 were 90%, 88%, and 89%, respectively, with the same specificities of 64%. Regardless of EC staging, the expression of plasma miR-21 showed a significant positive correlation with that of salivary miR-21, and their diagnostic values were comparable. Conclusion Both salivary and plasmatic miR-21 can be sensitive biomarkers for EC, and salivary miR-21 detection has the potential to replace plasma detection for EC diagnosis.