ObjectiveTo investigate the in vivo anti-inflammatory effects of the triterpenoid saponin-enriched fraction Fr.B4 from the She medicine Clematis florida (C. florida) in a rat model of phenol-induced cervicitis and to preliminarily explore its potential mechanisms of action. MethodsThirty 6–8-week-old female SPF-grade SD rats were randomly assigned to three groups: control, cervicitis model, and C. florida treatment group, with 10 rats in each group. The model and C. florida treatment groups were induced with cervicitis by vaginal injection of 25% phenol gel (once every 2 d, for a total of three injections), and the vulva and cervix were examined to assess the effectiveness of model establishment. After successful modeling, the C. florida treatment group was administered Fr.B4 at 290 mg/kg daily by gavage (dissolved in normal saline), whereas the model group received an equal volume of normal saline; both treatments continued for 2 weeks. The control group received no modeling procedure and was administered normal saline for 2 weeks. After the last intervention, fresh feces and urine samples were collected from all rats. The rats were euthanized after anesthesia with 40 mg/kg Zoletil 50, and the serum and cervical tissue samples were harvested. ELISA was used to measure the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in rat serum and cervical tissue. Hematoxylin and eosin (HE) staining was performed to observe the pathological changes in cervical tissue. Liquid chromatography-mass spectrometry was employed to analyze differential metabolites in feces and urine, followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and core metabolite analysis. 16S rDNA sequencing was used to assess the gut microbiota structure and diversity in each group. Statistical analysis was conducted using GraphPad Prism 9.0. ResultsCompared with the control group, rats in the model group exhibited cervical redness, swelling, and erosion, with significant increases in TNF-α, IL-1β, and IL-6 levels in both serum and cervical tissue (P<0.05 or P<0.01). Pathological examination of cervical tissue showed thickening of the squamous epithelium, infiltration of inflammatory cells, and edema. Compared with the model group, rats with C. florida treatment showed marked alleviation of cervicitis symptoms, with significantly reduced levels of pro-inflammatory cytokines in serum and cervical tissue (P<0.05 or P<0.01). Cervical tissue edema was alleviated, inflammatory cells were reduced, and squamous epithelium thickening was ameliorated. Metabolomics analysis revealed 346 and 564 differential metabolites in the feces and urine between the model and control groups, respectively. After treatment with Fr.B4, 236 and 451 metabolites in the feces and urine showed significant shifts toward control levels, involving pathways including cyclic adenosine monophosphate (cAMP) signaling, AMP-activated protein kinase (AMPK) signaling, and glutathione metabolism. Anti-inflammatory metabolites like boswellic acid and oleanolic acid were increased (P<0.01 or P<0.001). Gut microbiota analysis showed dysbiosis in the model group, with an imbalance in the Firmicutes/Bacteroidetes ratio. The Fr.B4 treatment remodeled the gut microbiota. The α-diversity of microbiota shifted toward that of the control group. Specific bacterial genera were found to correlate significantly with metabolites (P<0.05 or P<0.01). ConclusionThe triterpenoid saponin-enriched fraction Fr.B4 from She medicine C. florida may exert anti-cervicitis effects by reducing pro-inflammatory cytokine levels, modulating the gut microbiota balance, and remodeling metabolism.

Objective To systematically evaluate the clinical effects of remote ischaemic preconditioning (RIPC) in elective vascular surgery. Methods Electronic searches were conducted in The Cochrane Library, PubMed, EMbase, Web of Science, CNKI, Wanfang Data, VIP Database, and CBM. Relevant randomized controlled trials (RCTs) were screened according to inclusion and exclusion criteria. Meta-analysis was performed using RevMan 5.3 software, and the risk of bias was assessed using the Cochrane risk of bias tool. Results A total of 15 studies involving 1 382 patients were included. The meta-analysis results showed no statistically significant difference between RIPC and non-RIPC groups in reducing perioperative mortality in elective vascular surgery (P>0.05). There were also no statistically significant differences between the two groups of vascular surgery patients regarding the incidence of myocardial infarction, renal injury, postoperative stroke, postoperative length of hospital stay, duration of surgery or total anesthesia time, or the incidence of limb injury, arrhythmia, heart failure, and pneumonia (P>0.05). Conclusion For patients undergoing elective vascular surgery, there are no significant differences between RIPC and non-RIPC in terms of perioperative mortality and other clinical endpoint outcomes.

Objective:To determine the levels of interleukin-2 (IL-22) and interleukin-26 (IL-26) in pleural effusion and serum in patients with tuberculous pleurisy, and analyze the diagnostic value of their combination for tuberculous pleurisy.Methods:From January 2016 to December 2023, 310 patients with tuberculous pleurisy admitted to Xi′an Hi-tech Hospital were included as the study group, and another 310 patients with non tuberculous pleurisy were regarded as the control group. The pleural effusion and serum samples of hospitalized patients were collected. Serum samples were collected from patients at 2 months after treatment for testing of IL-22 and IL-26 levels. The diagnostic value and correlation of IL-22 and IL-26 levels in pleural effusion and serum were analyzed.Results:Compared with the control group, the levels of pleural effusion and serum IL-26 and IL-22 in the study group were increased: (84.68 ± 12.17) ng/L vs. (69.33 ± 9.82) ng/L, (82.45 ± 11.75) ng/L vs. (39.53 ± 5.66) ng/L and (74.38 ± 10.57) ng/L vs. (53.32 ± 7.54) ng/L, (21.45 ± 3.14) ng/L vs. (14.45 ± 2.05) ng/L, and the differences were statistically significant ( P<0.01). Compared with before treatment, serum IL-26 and IL-22 levels decreased after treatment: (61.66 ± 8.72) ng/L vs. (74.38 ± 10.57) ng/L, (17.38 ± 2.59) ng/L vs. (21.45 ± 3.14) ng/L, and the difference was statistically significant ( P<0.01). The AUC of IL-26 and IL-22 in pleural effusion and serum samples in the diagnosis of tuberculous pleurisy was 0.895, 0.820, 0.929 and 0.893, respectively. The AUC of IL-26 and IL-22 combined detection in pleural effusion and serum samples in the diagnosis of tuberculous pleurisy was 0.964 and 0.970, respectively. Pleural effusion IL-26 was positively correlated with serum IL-26 ( r = 0.733, P<0.01) and positively correlated with pleural effusion IL-22 ( r = 0.544, P<0.01); pleural effusion IL-22 was positively correlated with serum IL-22 ( r = 0.532, P<0.01); serum IL-22 was positively correlated with serum IL-26 ( r = 0.619, P<0.01). Conclusions:The levels of IL-22 and IL-26 in pleural effusion and serum of patients with tuberculous pleurisy are elevated, and the two may jointly participate in the immune regulation of tuberculous pleurisy. It can be used as one of the biochemical diagnostic methods for patients with tuberculous pleurisy.

Objective To systematically evaluate the impact of pulmonary hypertension (PH) on the prognosis of patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). Methods A computerized search was conducted in CNKI, Wanfang Data, VIP, CBM, PubMed, The Cochrane Library, EMbase, and Web of Science databases from inception to June 2023 for cohort studies on the prognostic impact of PH in severe AS patients undergoing TAVR. Two researchers independently screened the literature, extracted data, and assessed the quality of included studies. Stata 17.0 software was used for meta-analysis. Results A total of 16 cohort studies were included, all with Newcastle-Ottawa Scale scores≥7. Meta-analysis results showed that, compared with AS patients without PH, those with PH had significantly higher 1-year all-cause mortality after TAVR [OR=2.10, 95%CI (1.60, 2.75), P<0.01], 30-day all-cause mortality [OR=2.09, 95%CI (1.54, 2.83), P<0.01], and cardiovascular mortality [OR=1.49, 95%CI (1.18, 1.90), P<0.01]. The differences between the two groups in major bleeding events, stroke, myocardial infarction, pacemaker implantation, and postoperative renal failure were not statistically significant. For outcome indicators with significant heterogeneity, subgroup analyses were performed based on PH measurement methods, diagnostic criteria, and different types of PH. The results showed that most subgroup combined results were consistent with the overall findings and that heterogeneity was significantly reduced. Conclusion PH significantly increases the 30-day all-cause mortality, 1-year all-cause mortality, and cardiovascular mortality in patients with severe AS undergoing TAVR.

Objectives:To investigate the impact of the Micra AV leadless pacemaker on cardiac function.Methods:A total of 76 patients who received the implantation of Micra AV leadless pacemaker due to sick sinus syndrome or atrioventricular block at Ruijin Hospital,Shanghai Jiao Tong University School of Medicine from September 2022 to April 2023 were included in this study.Among them,26 patients(34.2%)had sick sinus syndrome,and 50 patients(65.8%)had atrioventricular block.The patients were followed up for 1 year postoperatively.Cardiac function was evaluated by echocardiography,and the parameters of the pacemaker were collected through the outpatient clinic programming system.Results:After a follow-up of 120(87,181)days,compared with the preoperative state,the left ventricular ejection fraction(LVEF)decreased postoperatively([66.6±5.6]%vs.[63.8±5.2]%,P<0.001),and the cardiac output increased[(4.3±1.2)L/min vs.(5.3±1.5)L/min,P<0.001].There were no statistically significant differences in various cardiac function indexes of patients with sick sinus syndrome between the postoperative and preoperative states(all P>0.05).Compared with the preoperative state,in patients with atrioventricular block,the LVEF decreased postoperatively([67.0±5.1]%vs.[63.4±4.4]%,P<0.001),the cardiac output increased([4.2±1.1]L/min vs.[5.2±1.2]L/min,P<0.001),and the left ventricular end-diastolic diameter decreased[(49.9±5.4)mm vs.(48.6±5.0)mm,P=0.044].Firth's logistic regression analysis indicated that the preoperative LVEF(for every 1%increase,OR=1.56,95%CI:1.12-2.17,P=0.001),stroke volume(for every 1 ml increase,OR=1.15,95%CI:1.04-1.28,P=0.001),body mass index(for every 1 kg/m2 increase,OR=1.49,95%CI:1.02-2.17,P=0.020),and hypertension(OR=12.71,95%CI:1.11-145.13,P=0.039)were independent risk factors for the decrease in LVEF after surgery in patients with atrioventricular block.After the implantation of the MciraTM AV leadless pacemaker,the overall atrioventricular synchrony rate was 81.2%(68.8%,89.0%).The atrioventricular synchrony rates of patients with sick sinus syndrome and those with atrioventricular block were 70.6%(59.5%,83.4%)and 82.4%(74.2%,89.3%)respectively(P<0.05).Firth's logistic regression analysis indicated that sick sinus syndrome(OR=0.26,95%CI:0.07-0.89,P=0.029)and preoperative LVEF(for every 1%increase,OR=1.18,95%CI:1.03-1.35,P=0.015)were independent predictive factors for the atrioventricular synchrony rate>80%.Conclusions:There are differences in the impacts of the Micra AV leadless pacemaker on the LVEF and atrioventricular synchrony rate between patients with sick sinus syndrome and those with atrioventricular block.The preoperative LVEF,stroke volume,body mass index,and hypertension have independent predictive effects on the decrease in postoperative LVEF in patients with atrioventricular block.Sick sinus syndrome and preoperative LVEF are independent predictive factors for the atrioventricular synchrony rate>80%after surgery.

Objectives:To investigate the impact of the Micra AV leadless pacemaker on cardiac function.Methods:A total of 76 patients who received the implantation of Micra AV leadless pacemaker due to sick sinus syndrome or atrioventricular block at Ruijin Hospital,Shanghai Jiao Tong University School of Medicine from September 2022 to April 2023 were included in this study.Among them,26 patients(34.2%)had sick sinus syndrome,and 50 patients(65.8%)had atrioventricular block.The patients were followed up for 1 year postoperatively.Cardiac function was evaluated by echocardiography,and the parameters of the pacemaker were collected through the outpatient clinic programming system.Results:After a follow-up of 120(87,181)days,compared with the preoperative state,the left ventricular ejection fraction(LVEF)decreased postoperatively([66.6±5.6]%vs.[63.8±5.2]%,P<0.001),and the cardiac output increased[(4.3±1.2)L/min vs.(5.3±1.5)L/min,P<0.001].There were no statistically significant differences in various cardiac function indexes of patients with sick sinus syndrome between the postoperative and preoperative states(all P>0.05).Compared with the preoperative state,in patients with atrioventricular block,the LVEF decreased postoperatively([67.0±5.1]%vs.[63.4±4.4]%,P<0.001),the cardiac output increased([4.2±1.1]L/min vs.[5.2±1.2]L/min,P<0.001),and the left ventricular end-diastolic diameter decreased[(49.9±5.4)mm vs.(48.6±5.0)mm,P=0.044].Firth's logistic regression analysis indicated that the preoperative LVEF(for every 1%increase,OR=1.56,95%CI:1.12-2.17,P=0.001),stroke volume(for every 1 ml increase,OR=1.15,95%CI:1.04-1.28,P=0.001),body mass index(for every 1 kg/m2 increase,OR=1.49,95%CI:1.02-2.17,P=0.020),and hypertension(OR=12.71,95%CI:1.11-145.13,P=0.039)were independent risk factors for the decrease in LVEF after surgery in patients with atrioventricular block.After the implantation of the MciraTM AV leadless pacemaker,the overall atrioventricular synchrony rate was 81.2%(68.8%,89.0%).The atrioventricular synchrony rates of patients with sick sinus syndrome and those with atrioventricular block were 70.6%(59.5%,83.4%)and 82.4%(74.2%,89.3%)respectively(P<0.05).Firth's logistic regression analysis indicated that sick sinus syndrome(OR=0.26,95%CI:0.07-0.89,P=0.029)and preoperative LVEF(for every 1%increase,OR=1.18,95%CI:1.03-1.35,P=0.015)were independent predictive factors for the atrioventricular synchrony rate>80%.Conclusions:There are differences in the impacts of the Micra AV leadless pacemaker on the LVEF and atrioventricular synchrony rate between patients with sick sinus syndrome and those with atrioventricular block.The preoperative LVEF,stroke volume,body mass index,and hypertension have independent predictive effects on the decrease in postoperative LVEF in patients with atrioventricular block.Sick sinus syndrome and preoperative LVEF are independent predictive factors for the atrioventricular synchrony rate>80%after surgery.

Objective:To determine the levels of interleukin-2 (IL-22) and interleukin-26 (IL-26) in pleural effusion and serum in patients with tuberculous pleurisy, and analyze the diagnostic value of their combination for tuberculous pleurisy.Methods:From January 2016 to December 2023, 310 patients with tuberculous pleurisy admitted to Xi′an Hi-tech Hospital were included as the study group, and another 310 patients with non tuberculous pleurisy were regarded as the control group. The pleural effusion and serum samples of hospitalized patients were collected. Serum samples were collected from patients at 2 months after treatment for testing of IL-22 and IL-26 levels. The diagnostic value and correlation of IL-22 and IL-26 levels in pleural effusion and serum were analyzed.Results:Compared with the control group, the levels of pleural effusion and serum IL-26 and IL-22 in the study group were increased: (84.68 ± 12.17) ng/L vs. (69.33 ± 9.82) ng/L, (82.45 ± 11.75) ng/L vs. (39.53 ± 5.66) ng/L and (74.38 ± 10.57) ng/L vs. (53.32 ± 7.54) ng/L, (21.45 ± 3.14) ng/L vs. (14.45 ± 2.05) ng/L, and the differences were statistically significant ( P<0.01). Compared with before treatment, serum IL-26 and IL-22 levels decreased after treatment: (61.66 ± 8.72) ng/L vs. (74.38 ± 10.57) ng/L, (17.38 ± 2.59) ng/L vs. (21.45 ± 3.14) ng/L, and the difference was statistically significant ( P<0.01). The AUC of IL-26 and IL-22 in pleural effusion and serum samples in the diagnosis of tuberculous pleurisy was 0.895, 0.820, 0.929 and 0.893, respectively. The AUC of IL-26 and IL-22 combined detection in pleural effusion and serum samples in the diagnosis of tuberculous pleurisy was 0.964 and 0.970, respectively. Pleural effusion IL-26 was positively correlated with serum IL-26 ( r = 0.733, P<0.01) and positively correlated with pleural effusion IL-22 ( r = 0.544, P<0.01); pleural effusion IL-22 was positively correlated with serum IL-22 ( r = 0.532, P<0.01); serum IL-22 was positively correlated with serum IL-26 ( r = 0.619, P<0.01). Conclusions:The levels of IL-22 and IL-26 in pleural effusion and serum of patients with tuberculous pleurisy are elevated, and the two may jointly participate in the immune regulation of tuberculous pleurisy. It can be used as one of the biochemical diagnostic methods for patients with tuberculous pleurisy.

Alcoholic liver disease (ALD) results from continuous and heavy alcohol consumption. The current treatment strategy for ALD is based on alcohol withdrawal coupled with antioxidant drug intervention, which is a long process with poor efficacy and low patient compliance. Alcohol-induced CYP2E1 upregulation has been demonstrated as a key regulator of ALD, but CYP2E1 knockdown in humans was impractical, and pharmacological inhibition of CYP2E1 by a clinically relevant approach for treating ALD was not shown. In this study, we developed a RNAi therapeutics delivered by lipid nanoparticle, and treated mice fed on Lieber-DeCarli ethanol liquid diet weekly for up to 12 weeks. This RNAi-based inhibition of Cyp2e1 expression reduced reactive oxygen species and oxidative stress in mouse livers, and contributed to improved ALD symptoms in mice. The liver fat accumulation, hepatocyte inflammation, and fibrosis were reduced in ALD models. Therefore, this study suggested the feasibility of RNAi targeting to CYP2E1 as a potential therapeutic tool to the development of ALD.

Objective To investigate the functions of the KIFC1 gene in tumor cells and its effect on the proliferation of cervical cancer cells. Methods We designed sgRNAs targeting the KIFC1 gene and constructed a recombinant plasmid based on the pSpCas9 (BB)-2A-GFP vector, which was co-transfected into HeLa cells. We screened monoclonal knockout cell lines through flow cytometry sorting, limited dilution inoculation of cells, and sequencing. RT-qPCR, Western blot, and immunofluorescence were used to detect the transcription and protein expression levels of KIFC1 in knockout cells. Cell phenotypes such as nucleus and microtubule cytoskeleton were observed using phase-contrast microscopy and fluorescence confocal microscopy. Cell proliferation, cell cycle, and apoptosis were analyzed by growth curve plotting, EdU labeling, and acridine orange staining. Results The deletion of the KIFC1 gene resulted in the abnormal phenotypes of HeLa cells, with increased numbers of multinuclei, micronucleus, and disordered microtubules. The cell cycle was disrupted, accompanied with a significant increase in the ratio of late apoptotic cells and a decrease in cell proliferation (all P < 0.05). Conclusion KIFC1 gene deletion affects the assembly of microtubules and cell division in HeLa cells, leading to abnormal nuclear morphology, chromatin elimination, cell cycle arrest, and increased cell apoptosis.

Objective:To analyze the changes of peripheral perfusion index (PPI) with late-onset sepsis (LOS) in very low birth weight infants during hospitalization.Methods:Very low birth weight infants admitted to the neonatal intensive care unit of Children′s Hospital of Fudan University from August 1, 2021 to August 31, 2022 were consecutively included.Infants with admission age ≥three days and unstable circulation, or positive blood culture within three days after birth were excluded.From the day of admission, the PPI values of the right hand and either foot of the infants were measured with Masimo SET Radical-7 everyday while whether LOS occurred during hospitalization was observed.The mean PPI curve of very and extremely low birth weight infants without LOS was plotted.For those with LOS confirmed by blood culture, the PPI change trajectory three days before and after the occurrence of LOS was drawn, and the change trend of PPI before the occurrence of LOS was analyzed by trend chi-square test.Non-parametric test was used to analyze the effect of LOS on pre- and post-ductal PPI values.Results:A total of 107 very low birth weight infants were included in the final analysis.Among them, there were 11 infants confirmed as LOS by blood culture, 37 infants diagnosed as clinical LOS, and 59 infants without LOS.Pre-and post-ductal PPI values of very low birth weight infants without LOS were 2.06±1.30 and 1.72±0.92, respectively; those with clinical LOS were 1.90±0.94 and 1.58±0.83, respectively; those with LOS confirmed by blood culture were 1.92±1.11 and 1.62±0.82, respectively.For infants with LOS confirmed by blood culture, the pre-and post-ductal PPI values showed a continuous downward trend during three days before the onset of disease, with the lowest PPI values on the first day before the diagnosis of blood culture.The downtrend of pre-ductal PPI was statistically significant ( χtrend2=5.57, P<0.05). Conclusion:The PPI value of very low birth weight infants show a downward trend when LOS occurs.It should be observed dynamically in clinical practice, which is helpful to suspect or identify LOS as early as possible.