Objective To investigate the clinical value of coronary computed tomography angiography(CCTA)based CT derived fractional flow reserve(CT-FFR)and ΔCT-FFR in improving the diagnostic efficiency for coronary abnormal hemodynamics in patients with severe calcification.Methods We retrospectively analyzed the clinical data of coronary artery disease(CAD)patients who underwent CCTA,CT-FFR,invasive coronary angiography(ICA)and FFR during hospitalization from January 2018 to June 2019 in Chinese PLA General Hospital.Severe calcification was defined as coronary artery calcium score(CACS)≥100 on single vessel level.A total of 107 CAD patients with 149 coronary arteries were included in the present study.The enrolled coronary arteries were assigned to CACS≥100 group(n=56)and CACS<100 group(n=93).CT-FFR was performed on the deep FFR platform based on machine learning(ML)algorithms and ΔCT-FFR was defined as CT-FFR difference between proximal and distal to the coronary lesion.The correlation and consistency between CT-FFR and FFR values were analyzed by Pearson and Bland-Altman methods.We attempted to analyze the incremental value of ΔCT-FFR for coronary functional evaluation,especial for coronary arteries with severe calcification,regarding FFR≤0.8 as the diagnostic gold standard.Comparison of receiver operating characteristic curves(ROC)between different diagnostic methods was presented by Delong test.Results Pearson and Bland-Altman analyses showed appreciable correlation(CACS≥100 group,r=0.71,P<0.01;CACS<100 group,r=0.73,P<0.01)and consistency(CACS≥100 group,Mean=-0.01,P=0.25;CACS<100 group,Mean=0,P=0.96)between CT-FFR and FFR values in both groups.FFR(0.80±0.08 vs.0.84±0.09,P=0.004)and CT-FFR(0.81±0.06 vs.0.85±0.06,P<0.001)levels were significant lower in CACS≥100 group than those in CACS<100 group,while ΔCT-FFR(0.14±0.06 vs.0.09±0.06,P<0.001)levels were significant higher in CACS≥100 group.Moreover,the diagnostic efficiency of CT-FFR in CACS≥100 group was inferior to that in CACS<100 group[AUC=0.792(95%CI 0.663-0.889)vs.AUC=0.929(95%CI 0.856-0.972),P=0.04],while it achieved significant improvement after ΔCT-FFR adjustment[AUC=0.876(95%CI 0.760-0.949)vs.AUC=0.792(95%CI 0.663-0.889),P=0.02]and was similar to that in CACS<100 group(P=0.37).Conclusion For coronary arteries with severe calcification,CT-FFR demonstrated significant incremental value in improving the diagnostic efficiency of coronary abnormal hemodynamics after ΔCT-FFR adjustment.

Objective To explore the effects of long non-coding RNA(lncRNA)MIR4435-2HG(MIR4435-2HG)on the proliferation,migration,invasion and apoptosis of cholangiocarcinoma cells and its regulatory effect on microRNA-376a-3p(miR-376a-3p).Methods qRT-PCR method was used to detect the expression of MIR4435-2HG and miR-376a-3p in human intrahepatic bile duct epithelial cells HIBEpic and human cholangiocarcinoma cells RBE.si-NC,si-MIR4435-2HG,miR-NC,miR-376a-3p mimics,si-MIR4435-2HG and anti-miR-NC,and si-MIR4435-2HG and anti-miR-376a-3p were transfected into RBE cells,respectively,as the si-NC group,the si-MIR4435-2HG group,the miR-NC group,the miR-376a-3p group,the si-MIR4435-2HG+anti-miR-NC group,the si-MIR4435-2HG+ anti-miR-376a-3p group.MTT method,Transwell chamber method and flow cytometry were used to detect cell proliferation,migration,invasion and apoptosis;dual luciferase reporter gene assay was used to verify the targeting relationship between MIR4435-2HG and miR-376a-3p.Western blot was used to detect the expression of related proteins.Results The expression of MIR4435-2HG was increased in RBE cells,while the expression of miR-376a-3p was decreased(P<0.05).Compared with the si-NC group,the MIR4435-2HG expression,cell viability,and protein levels of CyclinD1,MMP-2,MMP-9 in the si-MIR4435-2HG group were reduced(P<0.05),the numbers of migrating and invading cells were reduced(P<0.05),while the MIR4435-2HG expression and apoptosis rate were increased(P<0.05).Compared with the miR-NC group,the cell viability and protein levels of CyclinD1,MMP-2,MMP-9 in the miR-376a-3p group were decreased(P<0.05),the numbers of migrating and invading cells were decreased(P<0.05),while the MIR4435-2HG expression and apoptosis rate were increased(P<0.05).MIR4435-2HG was of targeted regulation on miR-376a-3p.Compared with the si-MIR4435-2HG+ anti-miR-NC group,the cell viability and protein levels of CyclinD1,MMP-2,MMP-9 in the si-MIR4435-2HG+anti-miR-376a-3p group were increased(P<0.05),the numbers of migrating and invading cells were increased(P<0.05),while the MIR4435-2HG expression and apoptosis rate were decreased(P<0.05).Conclusion Knockdown of MIR4435-2HG can inhibit the proliferation,migration,invasion and induce apoptosis of RBE cells by targeting miR-376a-3p.

Objective To study the mechanism of the amelioration of renal injury in immunoglobulin A nephropathy(IgAN)rats by multi-glycosides of Tripterygium wilfordii(GTW)based on the sphingosine kinase 1(Sphk1)/sphingosine 1-phosphate receptor 2(S1PR2)signalling pathway.Methods An IgAN rat model was established by means of bovine serum albumin gavage+castor oil and carbon tetrachloride subcutaneous injection+lipopolysaccharide tail vein injection.The rats were randomly divided into the model,control and experimental groups,with 9 rats in each group,and 10 normal rats were taken as the blank group.In the control group,6.25 mg·kg-1·d-1 prednisone was given by gavage;in the experimental group,9.375 mg·kg-1·d-1GTW was given by gavage;and in the blank and model groups,0.5 mL·100 g-1·d-1 0.9％NaCl was given by gavage,and the drugs were administered to the rats once a day in each group.At the end of the 15th week,urine samples were collected and blood albumin(ALB),blood urea nitrogen(BUN),24 hour-urine protein quantification(24 h-UTP),and urine erythrocyte counts were determined in each group,and the expression levels of Sphk1/S1PR2 proteins in each group were detected by Western blotting.Results The renal pathological changes in the control and experimental groups were significantly reduced compared with those in the model group by hematoxylin-eosin staining and immunofluorescence.The levels of ALB in the blank,model,control and experimental groups were(32.49±2.23),(22.98±0.51),(26.01±1.33)and(26.53±1.92)g·L-1;the levels of BUN were(6.11±1.71),(13.75±2.96),(6.71±1.35)and(4.77±0.99)mmol·L-1;the levels of 24 h-UTP were(5.72±1.96),(9.12±2.15),(5.78±2.05)and(4.75±1.50)mg·24 h-1;the urine erythrocyte counts were(9.73±2.40),(14.62±2.60),(9.90±1.59)and(9.46±2.94)cell·μL-1;the relative expression levels of Sphk1 protein were 0.85±0.02,1.47±0.02,1.06±0.02 and 1.09±0.02;the relative expression levels of S1PR2 protein were 0.27±0.02,0.88±0.01,0.43±0.02,and 0.42±0.02,respectively.The above indexes in the model group were statistically significant when compared with those of the control group and the experimental group(all P＜0.01).Conclusion GTW may reduce the proliferation of mesangial cells by inhibiting the Sphk1/S1PR2 signalling pathway,thus attenuating kidney injury in IgAN rats.

Objective To investigate disease characteristics and hospitalization costs of children with Mycoplasma Pneumoniae pneumonia(MPP)admitted to Shanghai municipal medical hospitals from 2019 to 2023.Methods Depending on the Shanghai Municipal Hospital Pediatric Alliance,we retrospectively investigated community acquired MPP pediatric patients hospitalized in 22 municipal hospitals with pediatric qualifications(including 4 children's hospitals)in Shanghai from Jan 2019 to Dec 2023.We collected the patients'diagnosis codes,gender,age,length of hospital stay,hospitalization costs,and whether they progressed to severe Mycoplasma pneumoniae pneumonia(SMPP).Results From 2019 to 2023,a total of 29 045 hospitalized children with MPP were treated,with 6 035 cases(20.8%)identified as SMPP in the 22 hospitals.Trend analysis revealed a rising trend with years in the proportion of SMPP patients(χ2trend=365.498,P<0.001).Among the 4 children's hospitals,there were 18 710 cases with MPP,including 4 078 cases(21.8%)of SMPP.The proportion of SMPP patients also showed an increasing trend with years(χ2trend=14.548,P<0.001),and the proportion in 2023(23.0%)was higher than that in previous years with statistical significance.There were statistical differences in the seasonal distribution of MPP cases between different years,with higher proportions in summer and autumn overall.The age distribution of hospitalized MPP children varied among different years,with school-age children accounting for the majority(56.8%)in 2023.There was no difference in the distribution of severe cases between different genders,but there were differences in the proportion of severe cases among different age groups in different years,with a gradual increase in severe cases among children aged 1 to 3 years(χ2trend=191.567,P<0.001).The average length of hospital stay for MPP during the epidemic was higher than that during non-epidemic periods,and there were statistically significant differences in the average length of hospital stay between different years(P<0.001).The individual hospitalization costs during the epidemic were higher than in other years,and there were statistically significant differences in individual hospitalization costs between different years(P<0.001).The total hospitalization costs were still higher in 2019 and 2023.The individual hospitalization costs for SMPP were higher than for non-SMPP cases.Conclusion MPP outbreaks occurred in Shanghai in 2019 and 2023,with the higher proportions in summer and autumn overall.Compared to previous years,the number of hospitalized MPP children in Shanghai was higher in 2023,with a higher proportion of SMPP cases,especially among children under 3 years old.The individual per capita hospitalization expenses for SMPP cases were higher than for non-SMPP cases.

This study was aimed at understanding the genomic characteristics of the Vibrio cholerae O1 group isolated from humans in Fujian Province,to provide essential data for the molecular epidemiological study of cholera.From 2008 to 2022,16 strains of the V.cholerae O1 group from patients and carriers were collected,and antibiotic sensitivity was determined accord-ing to the minimum inhibitory concentration(MIC).The whole genome sequences obtained through second generation sequen-cing were analyzed in open source software,including snippy,Roary,and Prokka,as well as online analysis websites,inclu-ding NCBI and BacWGSTdb,for core-genome multilocus sequence typing(cgMLST),core-genome single nucleotide polymor-phism analysis(cgSNP),virulence gene analysis,drug resistance gene prediction,and pan-genomic diversity analysis.The whole genome sequences of V.cholerae were divided into five sequence types(STs),among which the newly discovered ST182 and ST1480 were the evolutionary branches of the current dominant clonal group ST75 in China,and were highly related to two strains isolated from Taiwan in 2010 and 2013,respectively.Both toxigenic strains and non-toxigenic strains carried a variety of virulence factors and showed gene variation to varying degrees.Thirteen drug resistance genes in seven categories were predicted,among which the distribution of colistin and tetracycline resistance genes was consistent with the drug resistance phenotype.Pan-ge-nomic analysis indicated that V.cholerae had an open pan-genome,and Roary cluster analysis showed higher resolution than cgMLST.In summary,V.cholerae O1 group isolates from humans in Fujian Province have polymorphisms in genome structure and function,and the newly discovered ST1480 clone group has epidemic potential.Therefore,the monitoring of such strains must be strengthened.

OBJECTIVES: To observe the effects of electroacupuncture (EA) at "Jiaji" (EX-B 2) combined with neurodynamic mobilization (NM) on the cross-sectional area of the gastrocnemius muscle fibers after sciatic nerve injury in rabbits, and the expression of nuclear factor κB (NF-κB) and muscle-specific ring-finger protein 1 (MuRF1). METHODS: A total of 180 common-grade New Zealand rabbits (half male and half female) were randomly divided into five groups, i.e. a normal control group, a model control group, a NM group, an EA group and a combined intervention group, 36 rabbits in each group. Except in the normal control group, clipping method was used to prepare the model of sciatic nerve injury in the rest groups. On the 3rd day of successful modeling, NM was delivered in the NM group. In the EA group, EA was exerted at bilateral "Jiaji" (EX-B 2) of L₄ to L₆, stimulated with disperse-dense wave and the frequency of 2 Hz/100 Hz. In the combined intervention group, after EA delivered at bilateral "Jiaji" (EX-B 2) of L₄ to L₆ , NM was operated. The intervention in each group was delivered once daily, for 6 days a week, and lasted 1, 2 or 4 weeks according to the collection time of sample tissue. After 1, 2 and 4 weeks of intervention, in each group, the toe tension reflex score and the modified Tarlov test score were observed; the morphology of the gastrocnemius muscle was observed by HE staining and the cross-sectional area of muscular fiber was measured; using Western blot method, the expression of NF-κB and MuRF1 of the gastrocnemius muscle was detected. RESULTS: After 1, 2 and 4 weeks of intervention, the toe tension reflex scores and the modified Tarlov scores in the model control group were lower than those of the normal control group (P<0.05), and these two scores in the NM group, the EA group and the combined intervention group were all higher than those of the model control group (P<0.05); the scores in the combined intervention group were higher than those in the EA group and the NM group (P<0.05). The gastrocnemius fibers were well arranged and the myocyte morphology was normal in the normal control group. In the model control group, the gastrocnemius fibers were disarranged, the myocytes were irregular in morphology and the inflammatory cells were infiltrated in the local. In the NM group, the EA group and the combined intervention group, the muscle fibers were regularly arranged when compared with the model control group. After 1, 2 and 4 weeks of intervention, the cross-sectional areas of the gastrocnemius muscle fibers in the model control group were smaller than those of the normal control group (P<0.05). The cross-sectional areas in the NM group, the EA group and the combined intervention group were larger than those of the model control group (P<0.05), and the cross-sectional areas in the combined intervention group were larger than those in the NM group and the EA group (P<0.05). After intervention for 1, 2 and 4 weeks, the protein expressions of NF-κB and MuRF1 in the gastrocnemius muscle were higher in the model control group in comparison of those in the normal control group (P<0.05). In the NM group, the EA group and the combined intervention group, the expressions of NF-κB after intervention for 1, 2 and 4 weeks and the expressions of MuRF1 after 2 and 4 weeks of intervention were lower when compared with those in the model control group (P<0.05). In the combined intervention group, the protein expressions of NF-κB after intervention for 1, 2 and 4 weeks and the expressions of MuRF1 after 2 and 4 weeks of intervention were decreased when compared with those in the NM group and the EA group (P<0.05). CONCLUSIONS Electroacupuncture at "Jiaji" (EX-B 2) combined with NM may increase the muscle strength and sciatic function and alleviate gastrocnemius muscle atrophy in the rabbits with sciatic nerve injury. The underlying mechanism is related to the inhibition of NF-κB and MuRF1 expression.
Animals ; Female ; Male ; Rabbits ; Electroacupuncture ; Muscle, Skeletal ; Muscular Atrophy/therapy* ; NF-kappa B/genetics* ; Peripheral Nerve Injuries ; Rats, Sprague-Dawley ; Sciatic Nerve

Shenfu Injection(SFI) is praised for the high efficacy in the treatment of septic shock. However, the precise role of SFI in the treatment of sepsis-associated lung injury is not fully understood. This study investigated the protective effect of SFI on sepsis-associated lung injury by a clinical trial and an animal experiment focusing on the hypoxia-inducing factor-1α(HIF-1α)-mediated mitochondrial autophagy. For the clinical trial, 70 patients with sepsis-associated lung injury treated in the emergency intensive care unit of the First Affiliated Hospital of Zhengzhou University were included. The levels of interleukin(IL)-6 and tumor necrosis factor(TNF)-α were measured on days 1 and 5 for every patient. Real-time quantitative polymerase chain reaction(RT-qPCR) was performed to determine the mRNA level of hypoxia inducible factor-1α(HIF-1α) in the peripheral blood mononuclear cells(PBMCs). For the animal experiment, 32 SPF-grade male C57BL/6J mice(5-6 weeks old) were randomized into 4 groups: sham group(n=6), SFI+sham group(n=10), SFI+cecal ligation and puncture(CLP) group(n=10), and CLP group(n=6). The body weight, body temperature, wet/dry weight(W/D) ratio of the lung tissue, and the pathological injury score of the lung tissue were recorded for each mouse. RT-qPCR and Western blot were conducted to determine the expression of HIF-1α, mitochondrial DNA(mt-DNA), and autophagy-related proteins in the lung tissue. The results of the clinical trial revealed that the SFI group had lowered levels of inflammatory markers in the blood and alveolar lavage fluid and elevated level of HIF-1α in the PBMCs. The mice in the SFI group showed recovered body temperature and body weight. lowered TNF-α level in the serum, and decreased W/D ratio of the lung tissue. SFI reduced the inflammatory exudation and improved the alveolar integrity in the lung tissue. Moreover, SFI down-regulated the mtDNA expression and up-regulated the protein levels of mitochondrial transcription factor A(mt-TFA), cytochrome c oxidase Ⅳ(COXⅣ), HIF-1α, and autophagy-related proteins in the lung tissue of the model mice. The findings confirmed that SFI could promote mitophagy to improve mitochondrial function by regulating the expression of HIF-1α.
Humans ; Male ; Mice ; Animals ; Leukocytes, Mononuclear ; Mice, Inbred C57BL ; Lung/metabolism* ; Acute Lung Injury/drug therapy* ; Tumor Necrosis Factor-alpha/genetics* ; Sepsis/genetics* ; Hypoxia/pathology* ; Autophagy-Related Proteins ; Body Weight ; Drugs, Chinese Herbal

BACKGROUND: Patients with atrial fibrillation (AF) and prior stroke history have a high risk of cardiovascular events despite anticoagulation therapy. It is unclear whether catheter ablation (CA) has further benefits in these patients. METHODS: AF patients with a previous history of stroke or systemic embolism (SE) from the prospective Chinese Atrial Fibrillation Registry study between August 2011 and December 2020 were included in the analysis. Patients were matched in a 1:1 ratio to CA or medical treatment (MT) based on propensity score. The primary outcome was a composite of all-cause death or ischemic stroke (IS)/SE. RESULTS: During a total of 4.1 ± 2.3 years of follow-up, the primary outcome occurred in 111 patients in the CA group (3.3 per 100 person-years) and in 229 patients in the MT group (5.7 per 100 person-years). The CA group had a lower risk of the primary outcome compared to the MT group [hazard ratio (HR) = 0.59, 95% CI: 0.47-0.74, P < 0.001]. There was a significant decreasing risk of all-cause mortality (HR = 0.43, 95% CI: 0.31-0.61, P < 0.001), IS/SE (HR = 0.73, 95% CI: 0.54-0.97, P = 0.033), cardiovascular mortality (HR = 0.32, 95% CI: 0.19-0.54, P < 0.001) and AF recurrence (HR = 0.33, 95% CI: 0.30-0.37, P < 0.001) in the CA group compared to that in the MT group. Sensitivity analysis generated consistent results when adjusting for time-dependent usage of anticoagulants. CONCLUSIONS In AF patients with a prior stroke history, CA was associated with a lower combined risk of all-cause death or IS/SE. Further clinical trials are warranted to confirm the benefits of CA in these patients.

Objective: To summarize the pathological diagnosis, clinical features, treatment methods and outcomes of pediatric-type follicular lymphoma (PTFL). Methods: Clinical data including the pathology, clinical features, treatment methods, and follow-up results of 9 PTFL patients admitted to Henan Cancer Hospital from February 2017 to February 2023 were analyzed retrospectively. Results: The age of onset in 9 children was 6 to 18 years, all the patients were males. The clinical manifestation was local painless lymph node enlargement in the head and neck, with a stage of Ⅰ-Ⅱ. The histomorphological characteristics of PTFL were similar to those of classic follicular lymphoma (FL). The germinal center of most follicles were enlarged, the mantle zone disappeared, centroblasts were easily visible, and the histological grade were mostly grade Ⅲ, which may be accompanied by the "starry sky" phenomenon. Monoclonal peaks can be seen in B cell clonal rearrangements (BCR). Immunohistochemistry (IHC) showed CD20 positive, CD10 positive, Bcl-6 positive, Bcl-2 negative, C-myc negative, and Ki-67 was 70%-95%. Fluorescence in situ hybridization (FISH) test was negative for t (14, 18), Bcl-2 translocation, and C-myc translocation. Six cases underwent surgical resection, and 3 cases underwent surgical resection combined with chemotherapy. Up to February 2023, with a follow-up time of 45 to 72 months, all children survived without any recurrence and were in a complete remission state. Conclusions: PTFL is mainly characterized by adolescent male onset, with early clinical manifestations and pathological manifestations of high-level histological status, high proliferation index, and lack of t (14; 18)/Bcl-2 translocation and Bcl-2 expression. It is mainly treated by localized surgical excision and has a good prognosis.
Child ; Adolescent ; Humans ; Male ; Female ; Lymphoma, Follicular/pathology* ; Lymphoma, B-Cell/pathology* ; In Situ Hybridization, Fluorescence ; Retrospective Studies ; Proto-Oncogene Proteins c-bcl-2/genetics*

Objective To study the effect and mechanism of estradiol (E