OBJECTIVE To investigate the potential mechanism of Sanqi danshen tablets in the treatment of non-alcoholic fatty liver disease （NAFLD）. METHODS Core targets of Sanqi danshen tablets in the treatment of NAFLD were explored by network pharmacological methods. Gene ontology （GO） functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were also performed. Based on the results obtained from network pharmacological studies， using SD rats as subjects， the NAFLD model was induced by feeding them high-fat diet. The effects of Sanqi danshen tablets on pathological changes such as lipid droplet vacuoles and lipid accumulation in the liver tissue of NAFLD rats， as well as its impact on relative indicators of lipid metabolism， inflammatory responses and oxidative stress， were investigated. RESULTS A total of 20 core targets for the treatment of NAFLD with Sanqi danshen tablets were screened， primarily involved in GO functions such as biological regulation， cellular membrane and binding， and enriched in signaling pathways related to inflammatory responses， oxidative stress and lipid metabolism. Compared with the model group， lipid droplet vacuoles were reduced significantly in low-dose， medium-dose， high-dose groups of Sanqi danshen tablets and positive control （simvastatin） group， the number of lipid droplets decreased significantly and the color became lighter. The contents of total cholesterol， triglyceride （except for medium- dose group of Sanqi danshen tablets）， aspartate transaminase， alanine transaminase， tumor necrosis factor-α （except for low-dose group of Sanqi danshen tablets）， interleukin-17 （except for Sanqi danshen tablets groups） and malondialdehyde （except for low- dose group of Sanqi danshen tablets） in liver tissue were significantly decreased， while the content of superoxide dismutase was significantly increased （P＜0.01 or P＜0.05）. CONCLUSIONS Sanqi danshen tablets exert anti-inflammatory， antioxidant and lipid metabolism regulating effects by influencing the levels of inflammation， oxidative stress and lipids metabolism-related indicators， thereby improving NAFLD in rats.

Objective To investigate the relationship between the expression of long non-coding RNA HOXA-AS2(lncRNA HOXA-AS2),long non-coding RNA FOXD2-AS1(lncRNA FOXD2-AS1),and long non-coding RNA CRNDE(lncRNA CRNDE)in endometrial carcinoma and the clinical pathological character-istics and prognosis of patients.Methods Collect samples of endometrial carcinoma cancer tissues and adja-cent tissues excised during surgery from 119 endometrial carcinoma patients admitted to a hospital from Octo-ber 2017 to February 2020.The relative expression levels of HOXA-AS2,FOXD2-AS1 and CRNDE in tissues were retrospectively analyzed,as well as their relationship with clinicopathological features and 3-year survival rate of patients.Results The relative expression levels of HOXA-AS2,FOXD2-AS1 and CRNDE in cancer tissues of endometrial carcinoma patients were higher than those in adjacent tissues,with statistical signifi-cance(P＜0.05).The relative expression levels of HOXA-AS2,FOXD2-AS1 and CRNDE in cancer tissues of endometrial carcinoma patients were positively correlated(rHOXA-As2 vs.FOXD2-AS1=0.384,P=0.001;rHoXA-AS2 vs.CRNDE=0.576,P＜0.001;rFoXD2-AS1 vs.CRNDE=0.326,P=0.003).In the HOXA-AS2,FOXD2-AS1 and CRNDE high expression group,the proportion of patients with international federation of gynecology and ob-stetrics(FIGO)stage Ⅲ+Ⅳ,lymph node metastasis,deep infiltration and low differentiation was higher than that in the low expression group,with statistical significance(P＜0.05).The 3-year survival rate of low HOXA-AS2 expression group in endometrial cancer patients(52/60,86.67％)was higher than that of high HOXA-AS2 expression group(40/59,67.79％),the difference was statistically significant(x2=6.039,P＜0.05).The 3-year survival rate of patients with endometrial cancer with low FOXD2-AS1 expression group(53/59,89.83％)was higher than that of patients with endometrial cancer with high FOXD2-AS1 expression group(39/60,65.00％),and the difference was statistically significant(x2=10.456,P＜0.05).The 3-year sur-vival rate of low CRNDE expression group in endometrial cancer patients(51/60,85.00％)was higher than that of high CRNDE expression group(41/59,69.49％),and the difference was statistically significant(x2=4.079,P＜0.05).HOXA-AS2,FOXD2-AS1,and CRNDE were risk factors for death in endometrial carcinoma patients(P＜0.05).Conclusion The expression of HOXA-AS2,FOXD2-AS1,and CRNDE in endometrial carcinoma cancer tissue is closely related to the clinical pathological characteristics and prognosis of patients.

Objective:To explore expression of each member of miR17-92 cluster in peripheral blood mononuclear cells(PBMCs)of patients with gout,to predict their possible targets and pathways of action,and to evaluate their possible mechanism and clinical significance in gout.Methods:A total 67 gouty arthritis(GA)patients were selected,including 22 patients with acute gout arthritis(AG)and 45 patients with intermittent gout(IG),and 35 normal health control(HC)were selected in Affiliated Hospital of North Sichuan Medical College.RT-qPCR measured expressions of miR17-92 cluster,IFN-γ,IL-10 and some members of JAK-STAT pathway,and relevant laboratory indicators were collected to analyze correlation between each other.Results:Relative expressions of miR17,miR18a,miR19a,miR20a and miR19b were significantly changed in AG,IG and HC(H=8.753,P<0.05;H=6.338,P<0.05;H=6.523,P<0.05;H=9.061,P<0.05;H=9.729,P<0.01).JAK3 and STAT2 expressions were statistically different in AG,IG and HC groups(H=10.349,P<0.01;H=14.801,P<0.01).Expression of IFN-γ was statistically different among AG,IG and HC groups(H=8.734,P<0.05).In AG patients,miR18a expression was inversely correlated with IBIL,Crea,MO and HGB.miR19a ex-pression was negatively associated and TC,UA and HGB.miR20a expression was negatively associated with Crea.miR19b expression was negatively associated with UA and HGB.In IG patients,miR17 expression was negatively associated with IBIL,WBC,LY and MO.miR18a expression was positively associated with ALP,miR19a expression was negatively associated with TC and UA,and miR20a expression was negatively associated with ADA and UA.Conclusion:miR17-92 cluster may regulate development and partici-pate in clinical pathology of gout by targeting JAK-STAT pathway.

Objective:To explore the role of mechanical hemodynamic support (MHS) in mapping and catheter ablation of patients with hemodynamically unstable ventricular tachycardia (VT), report single-center experience in a cohort of consecutive patients receiving VT ablation during MHS therapy, and provide evidence-based medical evidence for clinical practice.Methods:This was a retrospective cohort study. Patients with hemodynamically unstable VT who underwent catheter ablation with MHS at Beijing Anzhen Hospital, Capital Medical University between August 2021 and December 2023 were included. Patients were divided into rescue group and preventive group according to the purpose of treatment. Their demographic data, periprocedural details, and clinical outcomes were collected and analyzed.Results:A total of 15 patients with hemodynamically unstable VT were included (8 patients in the rescue group and 7 patients in the preventive group). The acute procedure was successful in all patients. One patient in the rescue group had surgical left ventricular assist device (LVAD) implantation, remaining 14 patients received extracorporeal membrane oxygenation (ECMO) for circulation support. ECMO decannulation was performed in 12 patients due to clinical and hemodynamic stability, of which 6 patients were decannulation immediately after surgery and the remaining patients were decannulation at 2.0 (2.5) d after surgery. Two patients in the rescue group died during the index admission due to refractory heart failure and cerebral hemorrhage. During a median follow-up of 30 d (1 d to 12 months), one patient with LVAD had one episode of ventricular fibrillation at 6 months after discharge, and no further episodes of ventricular fibrillation and/or VT occurred after treatment with antiarrhythmic drugs. No malignant ventricular arrhythmia occurred in the remaining 12 patients who were followed up.Conclusions:MHS contributes to the successful completion of mapping and catheter ablation in patients with hemodynamically unstable VT, providing desirable hemodynamic status for emergency and elective conditions.

Nucleic acid-based molecular diagnostic methods are considered the gold standard for detecting infectious pathogens.However,when applied to portable or on-site rapid diagnostics,they still face various limitations and challenges,such as poor specificity,cumbersome operation,and portability difficulties.The CRISPR(Clustered regularly interspaced short palindromic repeats)/CRISPR-associated protein(Cas)-fluorescence detection method holds the potential to significantly enhance the specificity and signal-to-noise ratio of nucleic acid detection.In this study,we developed a portable grayscale reader detection system based on loop-mediated isothermal amplification(LAMP)-CRISPR/Cas.On one hand,in the presence of CRISPR RNA(crRNA),the CRISPR/Cas12a system was employed to achieve precise fluorescent detection of self-designed LAMP amplification reactions for influenza A and influenza B viruses.This further validated the high selectivity and versatility of the CRISPR/Cas system.On the other hand,the accompanying independently developed portable grayscale reader allowed for low-cost collection of fluorescence signals and high-reliability visual interpretation.At the end of the detection process,it directly provided positive or negative results.Practical sample analyses using this detection system have verified its reliability and utility,demonstrating that this system can achieve highly sensitive and highly specific portable analysis of influenza viruses.

Objective To explore the molecular mechanism of chronic osteomyelitis and to clarify the role of MAPK signal pathway in the pathogenesis of chronic osteomyelitis,by collecting and analyzing the transcriptional information of bone tissue in patients with chronic osteomyelitis.Methods Four cases of traumatic osteomyelitis in limbs from June 2019 to June 2020 were selected,and the samples of necrotic osteonecrosis from chronic osteomyelitis(necrotic group),and normal bone tissue(control group)were collected.Transcriptome information was collected by Illumina Hiseq Xten high throughput sequencing platform,and the gene expression in bone tissue was calculated by FPKM.The differentially expressed genes were screened by comparing the transcripts of the Necrotic group and control group.Genes were enriched by GO and KEGG.MAP3K7 and NFATC1 were selected as differential targets in the verification experiments,by using rat osteomyelitis animal model and im-munohistochemical analysis.Results A total of 5548 differentially expressed genes were obtained by high throughput sequenc-ing by comparing the necrotic group and control group,including 2701 up-regulated and 2847 down-regulated genes.The genes enriched in MAPK pathway and osteoclast differentiation pathway were screened,the common genes expressed in both MAPK and osteoclast differentiation pathway were(inhibitor of nuclear factor κ subunit Beta,IκBKβ),(mitogen-activated protein ki-nase 7,MAP3K7),(nuclear factor of activated t cells 1,NFATC1)and(nuclear factor Kappa B subunit 2,NFκB2).In rat os-teomyelitis model,MAP3K7 and NFATC1 were highly expressed in bone marrow and injured bone tissue.Conclusion Based on the transcriptome analysis,the MAPK signaling and osteoclast differentiation pathways were closely related to chronic os-teomyelitis,and the key genes IκBKβ,MAP3K7,NFATC1,NFκB2 might be new targets for clinical diagnosis and therapy of chronic osteomyelitis.

Objective:To investigate the expression and mechanism of microRNA-98-5p(miR-98-5p)and DNA methyltransferase 3A(DNMT3A)in patients with ulcerative colitis(UC)and animal model of ulcerative colitis.Methods:One-hundred UC patients in our hospital from January 2021 to December 2022 were collected as the observation group,another 100 healthy subjects were collected as the control group,serum miR-98-5p,DNMT3A mRNA and protein ex-pression were detected,the relationship between miR-98-5p,DNMT3A mRNA and clinical pathological characteristics of UC was analyzed;the UC rat model was established and randomly grouped into a blank group(CT group),a model group(UC group),a miR-98-5p control group(antagomiR-NC group),and a miR-98-5p inhibitor group(antagomiR-98-5p group),ELISA was applied to measure the levels of serum interleukin-1(IL-1),IL-6,and tumor necrosis factor(TNF),HE staining was applied to observe the histopathology changes of the colon,RT-qPCR and Western blot were applied to detect miR-98-5p,DNMT3A mRNA and protein expression levels in colon tissue.Results:Compared with the control group,the serum miR-98-5p expression of UC patients was increased,DNMT3A mRNA and DNMT3A were decreased,the expression of miR-98-5p and DNMT3A mRNA were associated with disease grading,mucopurulent bloody stools,mucosal acute and chronic inflammation,and atypical hyperplasia(P＜0.05);compared with the CT group,the colon mucosal layer of rats in the UC group showed defects,and obvious infil-tration of inflammatory cells,serum IL-1,IL-6,TNF and colon miR-98-5p expression were in-creased,the DNMT3A mRNA and protein expression were decreased(P＜0.05);compared with the antagomiR-NC group,the mucosal layer defect and inflammatory cell infiltration in the an-tagomiR-98-5p group were reduced,and the structure was clearer,serum IL-1,IL-6,TNF,and colon miR-98-5p expression were decreased,DNMT3A mRNA and protein expression were in-creased(P＜0.05);miR-98-5p had a targeted binding site with DNMT3A.Conclusion:Serum miR-98-5p expression of UC patients and the colon tissue of model rats was increased,while DNMT3A expression was decreased.Down-regulating miR-98-5p expression can promote the expression of DNMT3A and improve UC symptoms.

Objective:To explore potential predictors of refractory Mycoplasma pneumoniae pneumonia (RMPP) in early stage. Methods:The prospective multicenter study was conducted in Zhejiang, China from May 1 st, 2019 to January 31 st, 2020. A total of 1 428 patients with fever >48 hours to <120 hours were studied. Their clinical data and oral pharyngeal swab samples were collected; Mycoplasma pneumoniae DNA in pharyngeal swab specimens was detected. Patients with positive Mycoplasma pneumoniae DNA results underwent a series of tests, including chest X-ray, complete blood count, C-reactive protein, lactate dehydrogenase (LDH), and procalcitonin. According to the occurrence of RMPP, the patients were divided into two groups, RMPP group and general Mycoplasma pneumoniae pneumonia (GMPP) group. Measurement data between the 2 groups were compared using Mann-Whitney U test. Logistic regression analyses were used to examine the associations between clinical data and RMPP. Receiver operating characteristic (ROC) curves were used to analyse the power of the markers for predicting RMPP. Results:A total of 1 428 patients finished the study, with 801 boys and 627 girls, aged 4.3 (2.7, 6.3) years. Mycoplasma pneumoniae DNA was positive in 534 cases (37.4%), of whom 446 cases (83.5%) were diagnosed with Mycoplasma pneumoniae pneumonia, including 251 boys and 195 girls, aged 5.2 (3.3, 6.9) years. Macrolides-resistant variation was positive in 410 cases (91.9%). Fifty-five cases were with RMPP, 391 cases with GMPP. The peak body temperature before the first visit and LDH levels in RMPP patients were higher than that in GMPP patients (39.6 (39.1, 40.0) vs. 39.2 (38.9, 39.7) ℃, 333 (279, 392) vs. 311 (259, 359) U/L, both P<0.05). Logistic regression showed the prediction probability π=exp (-29.7+0.667×Peak body temperature (℃)+0.004×LDH (U/L))/(1+exp (-29.7+0.667×Peak body temperature (℃)+0.004 × LDH (U/L))), the cut-off value to predict RMPP was 0.12, with a consensus of probability forecast of 0.89, sensitivity of 0.89, and specificity of 0.67; and the area under ROC curve was 0.682 (95% CI 0.593-0.771, P<0.01). Conclusion:In MPP patients with fever over 48 to <120 hours, a prediction probability π of RMPP can be calculated based on the peak body temperature and LDH level before the first visit, which can facilitate early identification of RMPP.

Objective To observe the therapeutic effect and mechanism of Baoyuan Decoction for chronic heart failure model rat.Methods SD rats were randomly divided into blank group,model group,Baoyuan Decoction group,Captopril group,Baoyuan Decoction+CCT020312[protein kinase R-like endoplasmic reticulum kinase(PERK)activator]group,15 rats in each group.Except for the blank group,the rats in the other groups were induced by Adriamycin to construct a chronic heart failure model.After corresponding drug intervention,cardiac function indexes[left ventricular end-diastolic diameter(LVEDD),left ventricular ejection fraction(LVEF),left ventricular fractional shortening(LVFS),brain natriuretic peptide(BNP),cardiac troponin I(cTnI)],inflammation-related factors[tumor necrosis factor α(TNF-α),interleukin 1β(IL-1β)],oxidative stress factors[malondialdehyde(MDA),superoxide dismutase(SOD)]were detected in each group.Changes in apoptosis-related indicators[B-cell lymphoma 2(Bcl-2),B-cell lymphoma 2-associated X protein(Bax),Caspase-3]and PERK/transcription activator 4(ATF4)signaling pathway-related proteins glucose-regulated protein 78(GRP78),PERK,ATF4,C/EBP homologous protein(CHOP)levels.Results Compared with the blank group,LVEDD,BNP,cTnI,TNF-α,IL-1β,MDA levels,protein expression levels of Bax,Caspase-3,GRP78,PERK,ATF4,CHOP in the model group were significantly increased,LVEF,LVFS,SOD levels and Bcl-2 protein expression level were significantly decreased(all P＜0.05).Compared with the model group and Baoyuan Decoction+CCT020312 group,LVEDD,BNP,cTnI,TNF-α,IL-1β,MDA levels,protein expression levels of Bax,Caspase-3,GRP78,PERK,ATF4,CHOP in Baoyuan Decoction group and Captopril group were significantly decreased,LVEF,LVFS,SOD levels and Bcl-2 protein expression level were significantly increased(all P＜0.05).Compared with the Captopril group,there was no significant change in the above indexes(except CHOP protein expression level)in the Baoyuan Decoction group(P＞0.05).Conclusion Baoyuan Decoction can delay the progression of chronic heart failure rats,and its mechanism may be related to inhibiting the PERK/ATF4 signaling pathway to alleviate cardiomyocyte apoptosis,further reducing the degree of inflammatory response and oxidative stress,thereby promoting the repair of cardiac function and myocardial injury.

Objective To observe the effect of neuromuscular electrical stimulation(NMES)on interleukin-6(IL-6)/STAT3 signaling pathway in mice after spinal cord injury,and to explore the mechanism of its effect on motor function recovery.Methods Seventy-two SPF grade mice were randomly divided into sham operation group,spinal cord injury(SCI)group and NMES group.BMS score,inclined plane test and neuromuscular electrophysiology(EMG)were used to evaluate the recovery of spinal cord injury in mice.Western blotting and Real-time PCR were used to detect the expression of inflammatory factors,IL-6/STAT3,glial fibrillary acidic protein(GFAP)and brain-derived neurotrophic factor(BDNF)in spinal cord tissues of three groups of mice.HE staining was used to observe the pathological changes of spinal cord injury.Results BMS scores and the inclined plane test of mice in the NMES group were higher than those in SCI group(P＜0.05).The maximum amplitude of motor evoked potential in NMES group was higher than that in SCI group(P＜0.05).The expressions of TNF-α,IL-12A and GFAP in the spinal cord of NMES group were lower than that of SCI group(P＜0.05),while the expressions of TGF-β,IL-10 and BDNF were higher than that of SCI group(P＜0.05).The protein expressions of IL-6/STAT3 signaling pathway of NMES group were lower than that of SCI group(P＜0.05).Conclusion Neuromuscular electrical stimulation plays an anti-inflammatory role by inhibiting the IL-6/STAT3 signaling pathway,thereby promoting the recovery of hind limb motor function in mice after spinal cord injury.