Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

OBJECTIVE To investigate the improvement effects of azithromycin on bronchopulmonary dysplasia （BPD） in neonatal rats based on hypoxia-inducible factor-1α（HIF-1α）/HIF-2α/vascular endothelial growth factor （VEGF） pathway. METHODS Sixty newborn SD rats were randomly divided into negative control group （NC）， BPD group， azithromycin group and budesonide group （positive control）， with 15 rats in each group. Rats in NC group were given normal breathing air， while rats in other three groups were exposed to high-concentration oxygen for 14 days to establish BPD rat models. After successful modeling， rats in azithromycin group were intraperitoneally injected with azithromycin 200 mg/kg， and rats in budesonide group were atomized with budesonide 1.5 mg/kg once a day for 14 consecutive days， while rats in BPD group and NC group were not treated. Pathological changes of lung tissue， radial alveolar count and mean alveolar intercept of rats were observed in each group. The white blood cell count in bronchoalveolar lavage fluid （BALF） and the levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， IL-1β， superoxide dismutase （SOD）， catalase （CAT） and malondialdehyde （MDA） were detected； mRNA and protein expressions of VEGF， HIF-1α， HIF-2α were also detected. RESULTS Compared with NC group， the lung tissue in BPD group was obviously damaged； the white blood cell count， average alveolar intercept and the levels of TNF-α， IL-6， IL-1β and MDA were significantly increased； the radial alveolar count， SOD and CAT levels， the relative expressions of VEGF， HIF-1α， HIF-2α mRNA and protein were significantly decreased （P＜0.05）. Compared with BPD group， the changes of the above indexes in azithromycin group and budesonide group were significantly reversed （P＜0.05）. CONCLUSIONS Azithromycin can obviously improve the symptoms of BPD in rats， reduce inflammation and oxidative stress， and exert lung protection， the mechanism of which may be realized by activating HIF-1α/HIF-2α/VEGF pathway.

Objective:To evaluate the effect of individualized positive end-expiratory pressure (PEEP) titration based on open-lung strategy on the intraoperative thoracic fluid content (TFC) in elderly patients undergoing transurethral ultrasound-guided laser-induced prostatectomy (TULIP).Methods:Eighty-six American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, patients, aged 65-80 yr, with body mass index of 18-28 kg/m 2, scheduled for elective TULIP, were divided into 2 groups ( n=43 each) by the random number table method: fixed PEEP group (group C) and individualized PEEP titration group (group P). PEEP was set at 4 cmH 2O after routine mechanical ventilation in group C. Patients underwent pulmonary recruitment maneuvers combined with individualized PEEP titration during surgery in group P. TFC was measured using a non-invasive cardiac output monitor at 5 min after tracheal intubation (T 0), 30 min after PEEP titration and ventilation (T 1), 5 min before surgery (T 2), and 5 min before leaving the recovery room (T 3). Cardiac output, oxygenation index and stroke volume index were recorded from T 0-T 2, arterial blood gas analysis was simultaneously performed to record peak airway pressure and dynamic lung compliance, and oxygenation index was calculated. The duration of postanesthesia care unit stay, pulmonary complications within 7 days after surgery, and length of hospital stay were also recorded. Results:Eighty-three patients were finally included, with 42 in group C and 41 in group P. Compared with group C, TFC was significantly decreased at T 1-T 3, cardiac index, cardiac output and stroke volume index were decreased at T 1, dynamic lung compliance, PaO 2 and oxygenation index were increased at T 1 and T 2, PaCO 2 was decreased, the incidence of postoperative pulmonary complications was reduced, and the duration of postanesthesia care unit stay and postoperative length of hospital stay were shortened in group P ( P<0.05). Conclusions:Individualized PEEP titration based on open-lung strategy can effectively decrease TFC and improve intraoperative oxygenation and prognosis in elderly patients undergoing TULIP.

Objective To investigate the effects of parecoxib sodium injection combined with dexmedetomidine hydrochloride injection on postoperative cognitive function and stress response in patients with osteoporotic compression fractures.Methods The patients with osteoporotic compression fractures were divided into treatment group and control group according to the treatment plan.The control group was given intravenous injection of dexmedetomidine hydrochloride injection 0.2 μg·kg-1load dose,then micro pump injection 0.2 μg·kg-1·min-1 maintenance dose,until 30 min before the end of the operation;patients in the treatment group were intravenously injected with parecoxib sodium injection 20 mg before local anesthesia and 30 min before the end of operation on the basis of the control group.The pain,sedation,hemodynamics[mean arterial pressure(MAP),heart rate(HR)],cognitive function and safety evaluation were compared between the two groups before operation(T0),2 h after operation(T1),6 h after operation(T2),12 h after operation(T3)and 24 h after operation(T4).Results There were 39 cases in the treatment group and 41 cases in the control group.Visual analogue scale(VAS)scores in treatment group and control group were(3.09±0.55)and(3.41±0.62)scores at T1;VAS scores were(3.02±0.57)and(3.35±0.48)scores at T2;VAS scores were(2.64±0.44)and(2.90±0.46)scores at T3;VAS scores were(2.02±0.41)and(2.35±0.47)scores at T4;MMSE scores were(25.28±1.57)and(24.33±1.42)scores at T2;MMSE scores were(28.16±1.01)and(27.25±0.89)scores at T4;MoCA scores were(24.63±1.60)and(23.59±1.25)scores at T2;MoCA scores were(27.20±0.97)and(26.48±0.83)scores at T4.There were statistically significant differences in the above indexes between the treatment group and the control group(all P＜0.05).Adverse drug reactions in the treatment group included bradycardia,hypotension,nausea vomiting and hypokalemia;adverse drug reactions in the control group included bradycardia,hypotension and nausea vomiting.The total incidence rates of adverse drug reactions were 12.82％and 9.76％,without statistically significant difference(P＞0.05).Conclusion Compared with using dexmedetomidine alone,parecoxib sodium combined with dexmedetomidine is beneficial for relieving postoperative pain in patients with osteoporotic compression fractures,improving postoperative cognitive function.

Objective:To investigate the molecular mechanisms of chronic rhinosinusitis (CRS), to identify key cell subgroups and genes, to construct effective diagnostic models, and to screen for potential therapeutic drugs.Methods:Key cell subgroups in CRS were identified through single-cell transcriptomic sequencing data. Essential genes associated with CRS were selected and diagnostic models were constructed by hdWGCNA (high dimensional weighted gene co-expression network analysis) and various machine learning algorithms. Causal inference analysis was performed using Mendelian randomization and colocalization analysis. Potential therapeutic drugs were identified using molecular docking technology, and the results of bioinformatics analysis were validated by immunofluorescence staining. Graphpad Prism, R, Python, and Adobe Illustrator software were used for data and image processing.Results:An increased proportion of basal and suprabasal cells was observed in CRS, especially in eosinophilic CRS with nasal polyps (ECRSwNP), with P=0.001. hdWGCNA revealed that the "yellow module" was closely related to basal and suprabasal cells in CRS. Univariate logistic regression and LASSO algorithm selected 13 key genes ( CTSC, LAMB3, CYP2S1, TRPV4, ARHGAP21, PTHLH, CDH26, MRPS6, TENM4, FAM110C, NCKAP5, SAMD3, and PTCHD4). Based on these 13 genes, an effective CRS diagnostic model was developed using various machine learning algorithms (AUC=0.958). Mendelian randomization analysis indicated a causal relationship between CTSC and CRS (inverse variance weighted: OR=1.06, P=0.006), and colocalization analysis confirmed shared genetic variants between CTSC and CRS (PPH4/PPH3>2). Molecular docking results showed that acetaminophen binded well with CTSC (binding energy:-5.638 kcal/mol). Immunofluorescence staining experiments indicated an increase in CTSC +cells in CRS. Conclusion:This study integrates various bioinformatics methods to identify key cell types and genes in CRS, constructs an effective diagnostic model, underscores the critical role of the CTSC gene in CRS pathogenesis, and provides new targets for the treatment of CRS.

Objective To explore the microbiological characteristics of Staphylococcus aureus(S.aureus)with no-vel incomplete hemolytic phenotype(SIHP).Methods Hemolytic phenotypes were detected and categorized by u-sing the three-point inoculation method.A total of 11 novel SIHP and 33 randomly matched S.aureus with com-plete hemolytic phenotype(SCHP)were included.Antibiotic susceptibility test was performed using broth microdi-lution method.Coagulase test was performed with freeze-dried rabbit plasma.Catalase activity was detected by slide catalase test.Expression of hemolysin genes was detected by qRT-PCR.Toxicity to human red blood cells was as-sessed by microplate method.Microplate biofilm formation was measured using crystal violet staining method.Growth kinetic determination was performed through microcultivation assay.Results Compared with SCHP,the expression profiles of the four hemolysin genes(hla,hlb,hlc,and hld)in the new SIHP were different.The new SIHP had higher resistance rates to penicillin,oxacillin,gentamicin,quinolones,clindamycin,and trimethoprim-sulfamethoxazole.Furthermore,the new SIHP had stronger hemolytic toxicity,plasma coagulase activity,and bio-film formation ability.Additionally,the new SIHP grown faster in the logarithmic phase.Conclusion Taken to-gether,the microbiological characteristics of the new SIHP are different from those of SCHP,including stronger an-tibiotic resistance and pathogenicity,which should be paid more attention by clinicians.

Objective To observe the effects of implementing lung protective ventilation strategies on lung dynamic compliance and oxygenation function in elderly emergency surgery patients.Methods A total of 126 elderly patients undergoing emergency surgery admitted to Northern Jiangsu People's Hospital from December 2021 to December 2022 were selected.They were randomly divided into an observation group and a control group,with 63 patients in each group,using a random number table method.All selected cases underwent general anesthesia mechanical ventilation during surgery.The control group chose conventional ventilation mode,while the observation group adopted lung protective ventilation.The lung dynamic compliance,oxygenation function,inflammatory indicators,and complications of the two groups of patients were compared.Results Within 30 minutes of surgery,the mean airway pressure(Pmean)and peak airway pressure(Ppeak)levels of both groups of patients increased compared to preoperative levels.The observation group had a smaller increase than the control group(P<0.05),and the pulmonary dynamic compliance(Cdyn)levels were lower than preoperative levels.The observation group had a lower increase than the control group(P<0.05).After 2 hours of surgery,the levels of Pmean and Ppeak in both groups of patients decreased compared to 30 minutes during surgery,and the decrease in the observation group was smaller than that in the control group(P<0.05).The levels of Cdyn in both groups decreased compared to before surgery,and the observation group was lower than that in the control group(P<0.05).24 hours after surgery,the blood oxygen saturation(SpO2)and arterialpartial pressure of oxygen(PaO2)levels in both groups of patients decreased compared to before surgery,and the observation group was lower than the control group(P<0.05).The alveolar-arterial oxygen partial pressure difference[P(A-a)DO2]levels between the two groups increased compared to preoperative levels,and the observation group was higher than the control group(P<0.05).48 hours after surgery,the SpO2 and PaO2 levels in the observation group were higher than those in the control group,and the P(A-a)DO2 levels were lower than those in the control group(P<0.05).24 hours after surgery,the serum C-reactive protein(CRP)and white blood cell(WBC)levels in both groups were significantly increased compared to preoperative levels,and the observation group was higher than those in the control group(P<0.05).48 hours after surgery,the serum CRP and WBC levels of both groups of patients decreased compared to 24 hours after surgery,and the observation group was lower than the control group(P<0.05).The incidence of complications in the observation group was lower than that in the control group(7.94％vs.25.40％)(P<0.05).Conclusion Implementing lung protective ventilation strategies for elderly emergency surgical patients is beneficial for improving lung dynamic compliance and oxygenation function,inhibiting the release of inflammatory cytokines,reducing the incidence of postoperative pulmonary complications,and effectively exerting lung protective effects.

Objective To investigate the effects of clopidogrel on behavioral,content of inflamma-tory cytokines,and microglial in mice with comorbidity of pain and depression.Methods Twenty-four male pathogen-free C57BL/6J mice,aged 8 weeks,weighing 23-27 g,were selected.The mice were randomly divided into three groups:sham group(group C),spared nerve injury(SNI)group(group S),and SNI+clopidogrel group(group L),8 mice in each group.The surgical procedure in group C was consistent with the SNI model,but the nerve and maintained nerve integrity were not damaged.Group S was prepared with the SNI model,and group L was given clopidogrel 10 mg/kg since 21 days after the SNI model was prepared for 14 days continuously.Mechanical withdrawal threshold(MWT)was detected 1 day before surgery,7,14,21,28,and 35 days after surgery.The tail suspension test(TST)and forced swim test(FST)were performed 35 and 37 days after surgery,and the motionless time was calculated.Then the mice were killed,and the right hippocampal tissue was harvested to detect the concentration of IL-1β,IL-6,and TNF-α by enzyme-linked immunosorbent assay(ELISA),the expression of IL-1β,IL-6,and TNF-α mRNA by reverse transcription-polymerase chain reaction(RT-PCR),and the number of microglia by immunofluores-cence staining.Results Compared with group C,MWT were significantly decreased 7,14,21,28,and 35 days after operation,the immobility time of TST and FST were significantly prolonged,the concentrations and mRNA expressions of IL-1β,IL-6,and TNF-α were significantly increased,and the number of micro-glia were significantly increased in groups S and L(P＜0.05).Compared with group S,MWT were signifi-cantly increased 28 and 35 days after operation,the immobility time of TST and FST were significantly short-ened,the concentrations and mRNA expressions of IL-1β,IL-6,and TNF-α were significantly decreased,and the number of microglia was significantly reduced in group L(P＜0.05).Conclusion Clopidogrel can reduce the concentrations and mRNA expressions of IL-1β,IL-6,and TNF-α,inhibit the inflammatory reaction,reduce the number of activated microglia,and improve the and chronic neuropathic pain and de-pression in mice with comorbidity of pain and depression.