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.

Objective:To discuss the effect of downregulating of high mobility group box protein 2(HMGB2)expression on the biological behavior of the liver cancer cells and the epithelial-mesenchymal transition(EMT)process,and to clarify its mechanism.Methods:The human liver cancer LM3 cells at logarithmic growth phase were divided into negative control group and HMGB2 RNA interference group(HMGB2 siRNA group);the cells in two groups were transfected with RNA oligonucleotides(RNA oligos)with irrelevant sequences and RNA oligos designed to knock down HMGB2,and the Lipofectamine 2000 was regarded as the vector.The expression levels of HMGB2 mRNA and protein in the cells in two groups were detected by real-time fluorescence quantitative PCR(RT-qPCR)and Western blotting methods;cell scratch assay and Transwell chamber assay were used to detect the migration and invasion abilities of the cells in two groups;the expression levels of E-cadherin,N-cadherin,and Vimentin proteins and protein kinase B(AKT)/mammalian target of rapamycin(mTOR)pathway related proteins in the cells in two groups were detected by Western blotting method.Results:Compared with negative control group,the expression levels of HMGB2 mRNA and protein in the cells in HMGB2 siRNA group were significantly decreased(P<0.05),the cell scratch healing rate was significantly decreased(P<0.01),the number of invasion cells was significantly decreased(P<0.01),and the expression level of E-cadherin protein in the cells was significantly increased(P<0.01),while the expression levels of N-cadherin,Vimentin,mTOR,AKT,and phosphorylated AKT(p-AKT)proteins in the cells were significantly decreased(P<0.05 or P<0.01).Conclusion:Downregulating the expression of HMGB2 can reduce the migration and invasion abilities of the liver cancer LM3 cells and inhibit the EMT,and its mechanism may be related to regulating the expression of the AKT/mTOR pathway related proteins.

Objective:To investigate the effects of repeated high acceleration(+Gz)on implant osseointegration in SD rats.Methods:18 SD rats were divided into+Gz and control groups randomly(n=9),and 1 implant was placed in each femur of the rat's lower limb.24 hours postoperatively,the experimental rats were exposed to+Gz of 4 to 9 G with 1 G/s environment 3 times a week,while the con-trol rats were fed normally.3 rats from each of the 2 groups were sacrificed at 2,4 and 8 weeks after implantation.Micro-CT,sequential fluorescence double labeling,and histological examination were perfomed for the analysis of implant osseointegration.Results:The bone volume fraction(BV/TV),trabecular number(Tb.N),mineral apposition rate(MAR),implant-bone contact rate(BIC)and bone area in implant thread(BA)of the+Gz group were significantly lower than those of the control group at 2 weeks(P＜0.05),and so as to MAR,BA at 4 weeks(P＜0.05),while there was no significant difference of the parameters at 8 weeks after implantation.Conclusion:In SD rats early exposure to+Gz environment postoperatively may have a negative effect on initial osseointegration by slowing bone forma-tion.However,it will not lead to poorer bone mass when sustained over a long period.

Objective:To investigate the effects of gene silencing inducible cyclooxygenase-2 (COX-2) combined with hyperbaric oxygen (HBO) on neuronal cell edema, apoptosis, autophagy and neural functional recovery in rats with intracerebral hemorrhage.Methods:SPF-grade adult male SD rats ( n=96) were used to establish a cerebral hemorrhage model through stereotactic injection of thrombin VII into the caudate nucleus. They were randomized (random number) into 4 groups ( n=24/group): control group, hyperbaric oxygen (HBO) group, COX-2 RNAi group and combined group (COX-2 RNAi+HBO). The siRNA plasmid targeting silencing COX-2 gene expression was constructed. After group treatment, the four rats were randomly selected from each group for testing in each category. Postoperative day 1, 7, and 14 were assessed using the modified neurological severity score (mNSS) for evaluating neurofunctional deficits. On the 7th day, the water content of the brain tissue was measured using the dry/wet weight method. The blood-brain barrier permeability was assessed using the Evans method. Annexin V and TUNEL assays were employed to assess the apoptotic rate of neural cells. The mRNA expression level of COX-2 in brain tissue was determined using the RT-PCR method. The protein expression levels of Beclin-1, COX-2, aquaporin 4 (AQP-4), B cell lymphoma/lewkmia-2 (Bcl-2), caspase-3, hypoxia-inducible factor-1α (HIF-1α) and matrix metalloprotein-2/9 (MMP-2/9) were detected by Western blot (WB). SPSS software was used for data analysis. One-way ANOVA was used for inter group comparisons and LSD- t test was used for further pairwise comparison. Results:The SD rat intracerebral hemorrhage model and plasmid construction were successfully achieved. The mNSS scores were significantly decreased in COX-2 RNAi, HBO and combined groups compared with control group on the 7th day and 14th day (all P<0.01), especially in combined group ( P<0.01). The contents of Evans blue and the water content of brain tissue of all treatment groups were significantly lower than those in control group (all P<0.05), especially in combined group ( P<0.01). The apoptotic rate of neural cells decreased in all treatment groups compared with the control group (all P<0.05), and the combined group decreased the most ( P<0.01). The mRNA expression levels of COX-2 were significantly decreased in all treatment groups compared with the control group (all P<0.01), and combined group silenced COX-2 expression most obviously ( P<0.05). The results of WB showed that the protein expression levels of Beclin-1, COX-2, AQP-4, Caspase-3, HIF-1α, MMP-2/9 were significantly lower than control group (all P<0.05), while the expression of Bcl-2 was increased in all treatment groups (all P<0.01). Among them, the combined group exhibited the most pronounced trend ( P<0.01). Conclusions:Gene silencing of COX-2 in combination with hyperbaric oxygen therapy can effectively restore neurological function in rats with cerebral hemorrhage. The mechanism may be associated with reduced blood-brain barrier permeability, alleviated brain edema, and inhibition of neuronal apoptosis and autophagy.

Objective:To analyze the clinical characteristics of patients undergoing extracorporeal cardiopulmonary resuscitation (ECPR), and to explore the risk factors leading to poor prognosis.Methods:The clinical data of 95 patients with ECPR admitted to the First Affiliated Hospital of Zhengzhou University from January 2020 to May 2023 were retrospectively analyzed. According to the survival status at the time of discharge, the patients were divided into the survival group and death group. The difference of clinical data between the two groups was compared to explore the risk factors related to death and poor prognosis. Risk factors associated with death were identified by Binary Logistic regression analysis. Results:A total of 95 patients with ECPR were included in this study, 62 (65.3%) died and 33 (34.7%) survived at discharge. Patients in the death group had longer low blood flow time [40 (30, 52.5) min vs. 30 (24.5, 40) min ] and total cardiac arrest time[40 (30, 52.5) min vs. 30(24.5, 40) min], shorter total hospital stay [3 (2, 7.25) d vs. 19 (13.5, 31) d] and extracorporeal membrane oxygenation (ECMO) assisted time [26.5 (17, 50) h vs. 62 (44, 80.5) h], and more IHCA patients (56.5% vs. 33.3%) and less had spontaneous rhythm recovery before ECMO (37.1% vs. 84.8%). Initial lactate value [(14.008 ± 5.188) mmol/L vs.(11.23 ± 4.718) mmol/L], APACHEⅡ score [(30.10 ± 7.45) vs. (25.88 ± 7.68)] and SOFA score [12 (10.75, 16) vs. 10 (9.5, 13)] were higher ( P< 0.05). Conclusions:No spontaneous rhythm recovery before ECMO, high initial lactic acid and high SOFA score are independent risk factors for poor prognosis in ECPR patients.

Objective:To investigate the clinical characteristics and prognosis of patients with left ventricular assist device (LVAD) implantation during the perioperative period.Methods:This retrospective study included 14 patients with end-stage heart failure who underwent LVAD implantation in the department of intensive care medicine of Nanjing Hospital Affiliated to Nanjing Medical University from February 2022 to March 2023, including 12 males and 2 females patients, the mean age was (57.6±9.8)years old. All patients were implanted with Corheart 6 implantable left ventricular assist system, did not use other mechanical assisted circulatory devices. The clinical data of enrolled patients were collected, and the clinical characteristics and prognosis during ICU treatment were analyzed.Results:Dilated cardiomyopathy (DCM) was the most common primary cause of heart failure. The results of transthoracic echocardiography showed that the left ventricular ejection fraction (0.297±0.074 vs. 0.238±0.064, P=0.031) of patients was significantly increased, while the left ventricular end diastolic diameter[69.0(65.8, 74.3)mm vs. 76.5(72.8, 83.0)mm, P=0.003]and systolic end systolic diameter[61.5(53.7, 65.3)mm vs. 68.3(63.8, 71.9)mm, P=0.005]were significantly decreased post LVAD implantation as compared to before LVAD implantation. Within one week after implantation, there was no significant difference in LVAD rotational speed, flow rate, and pulsation index ( P>0.05). During ICU treatment, dobutamine (13 cases) was the most commonly used vasoactive agent. 9 patients used phosphodiesterase Ⅲ inhibitors for perioperative pulmonary hypertension. Targeted management of volume and pressure indicators was conducted for enrolled patients to prevent postoperative right heart failure and to reduce right heart burden. Within 72 hours after LVAD implantation, the average pulmonary artery pressure of patients was 24 (22, 26) mmHg to 26 (21, 28)mmHg (1 mmHg=0.133 kPa), while the fluid balance was(-581±778)ml to(-1 209±1 134)ml. All enrolled patients survived to 28 days after LVAD implantation. The length of stay in the ICU was (8.0±1.8) days and the total length of hospital stay was 33 (29, 41)days, while the time of mechanical ventilation was 8 (5, 28)h. Conclusion:LVAD implantation can help improve left ventricular systolic function, prolong survival time so as to serve as an important means of terminal treatment or bridging therapy for heart transplantation of patients with end-stage heart failure. To strengthen the perioperative hemodynamic regulation and maintain the cardiac function of patients with LVAD implantation is the important purposes of ICU postoperative management.

Objective To analyze the interaction between voriconazole(VRC)and immunosuppressants such as tacrolimus and cyclosporine and the effect of CYP2C19 gene polymorphism on the interaction and adverse reactions(ADR)based on the results of CYP2C19 gene polymorphism and therapeutic drug monitoring,so as to provide a basis for the development of individualized VRC combined with immunosuppressants.Methods Two-dimensional liquid chromatography and pyrosequencing was used to detect the concentration of VRC and the CYP2C19 gene pol-ymorphism,respectively.And the concentration of immunosuppressants was detected at the same time.The rela-tionship among CYP2C19 gene polymorphism,the concentration of VRC and immunosuppressant and ADR was an-alyzed.Results A total of 61 patients were enrolled in this study,and the mutation rates of CYP2C19*2 and CYP2C19*3 were 54.1％(33/61)and 9.84％(6/61),respectively.The concentrations of VRC in patients with extensive metabolism(EMs),intermediate metabolism(IMs)and poor metabolism(PMs)were(4.44±3.46),(3.62±3.02)and(10.05±1.46)μg/ml(P＜0.05),respectively.The concentration of tacrolimus af-ter combined with VRC significantly increased compared to tacrolimus alone[(13.4±9.2)ng/ml vs(6.5±3.6)ng/ml;P=0.002],and the concentration of tacrolimus increased along with an increasing of VRC concentration.The concentration of VRC in patients combined with tacrolimus was lower than that in patients without immunosup-pressants[(3.81±3.48)μg/ml vs(5.84±3.71)μg/ml;P=0.032].The concentration of VRC inpatients with cyclosporine significantly decreased(P＜0.01),while tacrolimus and mycophenolate mofetil had no signifi-cant effect on the concentration of VRC.45.90％(28/61)of the patients had adverse reactions,the concentration of VRC in patients with ADR was significantly higher than that in patients without ADR[(7.07±3.43)μg/ml vs(3.06±2.90)μg/ml;P＜0.001].And the concentration of VRC in patients with ADR was higher than patients without ADR with based on CYP2C19 genotype.Conclusion CYP2C19 gene polymorphism can significantly affect the concentration and adverse reactions of VRC,and VRC has significant interaction with immunosuppressants such as tacrolimus.CYP2C19 gene polymorphism combined with therapeutic drug monitoring can improve the individual-ized treatment of tacrolimus and voriconazole,and is expected to minimize toxicity and improve treatment effects.

Objectives:To assess the prognostic impact of the neoadjuvant rectal (NAR) score following neoadjuvant short-course radiotherapy and consolidation chemotherapy in locally advanced rectal cancer (LARC), as well as its value in guiding decisions for adjuvant chemotherapy.Methods:Between August 2015 and August 2018, patients were eligible from the STELLAR phase III trial (NCT02533271) who received short-course radiotherapy plus consolidation chemotherapy and for whom the NAR score could be calculated. Based on the NAR score, patients were categorized into low (＜8), intermediate (8-16), and high (＞16) groups. The Kaplan-Meier method, log rank tests, and multivariate Cox proportional hazard regression models were used to evaluate the impact of the NAR score on disease-free survival (DFS).Results:Out of the 232 patients, 24.1%, 48.7%, and 27.2% had low (56 cases), intermediate (113 cases), and high NAR scores (63 cases), respectively. The median follow-up period was 37 months, with 3-year DFS rates of 87.3%, 68.3%, and 53.4% ( P＜0.001) for the low, intermediate, and high NAR score groups. Multivariate analysis demonstrated that the NAR score (intermediate NAR score: HR, 3.10, 95% CI, 1.30-7.37, P=0.011; high NAR scores: HR=5.44, 95% CI, 2.26-13.09, P＜0.001), resection status ( HR, 3.00, 95% CI, 1.64-5.52, P＜0.001), and adjuvant chemotherapy ( HR, 3.25, 95% CI, 2.01-5.27, P＜0.001) were independent prognostic factors for DFS. In patients with R0 resection, the 3-year DFS rates were 97.8% and 78.0% for those with low and intermediate NAR scores who received adjuvant chemotherapy, significantly higher than the 43.2% and 50.6% for those who did not ( P＜0.001, P=0.002). There was no significant difference in the 3-year DFS rate (54.2% vs 53.3%, P=0.214) among high NAR score patients, regardless of adjuvant chemotherapy. Conclusions:The NAR score is a robust prognostic indicator in LARC following neoadjuvant short-course radiotherapy and consolidation chemotherapy, with potential implications for subsequent decisions regarding adjuvant chemotherapy. These findings warrant further validation in studies with larger sample sizes.

Trichinosis is a global food-borne zoonotic parasitic disease caused by Trichinella spiralis(T.spiralis),which causes serious harm to animal production,and the public health safety of humans and animals.T.spiralis has a complex devel-opment history,and its entire life cycle is completed in the same host.To coexist with the host,it has evolved various immune escape mechanisms for avoiding immune clearance by the host,thus establishing long-term chronic infection.In this study,to aid in understanding the pathogenic mechanism of T.spiralis,the immune escape mechanism of Trichinella is discussed from three aspects:the molecular role of antigens in various stages,the immune regulatory effect on the host,and the formation of cysts to generate immune isolation.

Objective:To conduct a comparative analysis of the radiation damage to zebrafish embryos and the associated biological mechanism after ultra-high dose rate (FLASH) and conventional dose rate irradiation.Methods:Zebrafish embryos at 4 h post-fertilization were exposed to conventional and FLASH irradiation (9 MeV electron beam). The mortality and hatchability of zebrafish after radiation exposure were recorded. Larvae at 96 h post-irradiation underwent morphological scoring, testing of reactive oxygen species (ROS) levels, and analysis of changes in oxidative stress indicators.Results:Electron beam irradiation at doses of 2-12 Gy exerted subtle effects on the mortality and hatchability of zebrafish embryos. However, single high-dose irradiation (≥ 6 Gy) could lead to developmental malformation of larvae, with conventional irradiation showing the most significant effects ( t = 0.87-9.75, P < 0.05). In contrast, after FLASH irradiation (≥ 6 Gy), the ROS levels in zebrafish and its oxidative stress indicators including superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) were significantly reduced ( t = 0.42-15.19, P < 0.05). There was no statistically significant difference in ROS levels in incubating solutions after conventional and FLASH irradiation ( P > 0.05). Conclusions:Compared to conventional irradiation, FLASH irradiation can reduce radiation damage to zebrafish embryos, and this is in a dose-dependent manner. The two irradiation modes lead to different oxidative stress levels in zebrafish, which might be a significant factor in the reduction of radiation damage with FLASH irradiation.