Background::The potential impact of pre-existing coronary artery stenosis (CAS) on acute pulmonary embolism (PE) episodes remains underexplored. This study aimed to investigate the association between pre-existing CAS and the elevation of high-sensitivity cardiac troponin I (hs-cTnI) levels in patients with PE.Methods::In this multicenter, prospective case-control study, 88 cases and 163 controls matched for age, sex, and study center were enrolled. Cases were patients with PE with elevated hs-cTnI. Controls were patients with PE with normal hs-cTnI. Coronary artery assessment utilized coronary computed tomographic angiography or invasive coronary angiography. CAS was defined as ≥50% stenosis of the lumen diameter in any coronary vessel >2.0 mm in diameter. Conditional logistic regression was used to evaluate the association between CAS and hs-cTnI elevation.Results::The percentage of CAS was higher in the case group compared to the control group (44.3% [39/88] vs. 30.1% [49/163]; P = 0.024). In multivariable conditional logistic regression model 1, CAS (adjusted odds ratio [OR], 2.680; 95% confidence interval [CI], 1.243–5.779), heart rate >75 beats/min (OR, 2.306; 95% CI, 1.056–5.036) and N-terminal pro-B type natriuretic peptide (NT-proBNP) >420 pg/mL (OR, 12.169; 95% CI, 4.792–30.900) were independently associated with elevated hs-cTnI. In model 2, right CAS (OR, 3.615; 95% CI, 1.467–8.909) and NT-proBNP >420 pg/mL (OR, 13.890; 95% CI, 5.288–36.484) were independently associated with elevated hs-cTnI. Conclusions::CAS was independently associated with myocardial injury in patients with PE. Vigilance towards CAS is warranted in patients with PE with elevated cardiac troponin levels.

Aim To investigate the effect of homocys-teine(Hcy)on the permeability of pulmonary micro-vascular endothelial cells(PMVECs)and the role and mechanism of RASAL1.Methods CBS+/-mice were fed a high methionine diet(HMD)for 16 weeks to replicate an animal model of hyperhomocysteinemia(HHcy).HE staining was used to observe the changes in lung tissue structure.qRT-PCR was used to detect the levels of RASAL1 and DNMT1 mRNA in lung tis-sue.Western blot was used to detect the expression of RASAL1,DNMT1,ZO-1,and VE cadherin proteins.Methylation specific PCR was used to detect methyla-tion in the RASAL1 promoter region.PMVECs were transfected with Ad-RASAL1 to detect the expression of ZO-1 and VE cadherin.The si-DNMT1 interference fragment was transfected into PMVECs,and the ex-pression of the RASAL1 was detected by qRT-PCR and Western blot.Results Serum Hcy level of HMD mice was significantly raised,and HE staining showed severe structural disorder in lung tissue.The expres-sion of RASAL1,ZO-1,and VE cadherin was de-creased,while the expression of DNMT1 was in-creased.The degree of methylation in the RASAL1 promoter region was raised.The expression of ZO-1 and VE cadherin increased after PMVECs were trans-fected with Ad-RASAL1.After knocking down DN-MT1,RASAL1 expression was increased.Conclusion Hcy can increase the permeability of PMVECs,and its mechanism is related to the upregulation of RASAL1 methylation level.

Objective To investigate the preliminary clinical effect of closed reduction and cannulated nail internal fixa-tion for femoral neck fracture assisted by robot navigation and positioning system.Methods From July 2019 to January 2020,16 cases of femoral neck fracture(navigation group)were treated with closed reduction and internal fixation guided by robot system,including 7 males and 9 females,aged 25 to 72 years old with an average of(53.61±5.45)years old;Garden classification of fracture:3 cases of type Ⅰ,3 cases of type Ⅱ,8 cases of type Ⅲ,2 cases of type Ⅳ.Non navigation group(control group):20 cases of femoral neck fracture were treated with closed reduction and hollow nail internal fixation,8 males and 12 females,aged 46 to 70 years old with an average of(55.23±4.64)years old;Garden type Ⅰ in 2 cases,type Ⅱ in 4 cases,type Ⅲ in 11 cases,type Ⅳ in 3 cases.The operation time,fluoroscopy times,guide needle drilling times,screw adjustment times,intraoperative bleeding volume and other indicators of two groups were evaluated.Results Both groups were followed up for 12 to 18 months with an average of(15.6±2.8)months.The fractures of both groups were healed without delayed union and nonunion.There was no significant difference in healing time between two groups(P=0.782).There was no significant differ-ence in Harris scores between two groups at the last follow-up(P=0.813).There was no significant difference in operation time between two groups(P＞0.05).There were significant differences between two groups in fluoroscopy times,guide needle drilling times,hollow screw replacement times,and intraoperative bleeding volume(P＜0.05).Conclusion Closed reduction and hollow screw internal fixation assisted by robot navigation system for femoral neck fracture has the advantages of minimally invasive operation,precise screw placement,and reduction of X-ray radiation damage during operation.

Transcatheter aortic valve replacement(TAVR)is the use of interventional catheter to transport the artificial heart valve to the aortic valve area through the patient's arterial,venous system or left ventricular apex,then release it to replace the original aortic valve to achieve normal physiological function.The"suicide left ventricle"phenomenon refers to the paradoxical hemodynamic collapse of dynamic left ventricular obstruction caused by left ventricular hypertrophy and hypersystole after the removal of the fixed valve obstruction of aortic stenosis after TAVR.The clinical manifestation is abnormal continuous hypotension that is ineffective to positive inotropic drugs during the operation or within a few hours after the operation.With the indications for transcatheter aortic valve surgery covering patients with low,medium and high risk of severe aortic stenosis,surgery-related complications have been reported to increase gradually."Suicide left ventricle"is worth studying and exploring as a fatal potential complication.This article mainly reviews four aspects of the overview of"suicide left ventricle",pathological mechanism,risk-related indicators,prevention strategies and treatment methods to be highly vigilant and make corresponding emergency plans for patients with aortic stenosis who may have suicide left ventricle risk,so as to minimize perioperative mortality.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

AIM:To investigate the molecular mechanisms of KG-1 cell proliferation by profiling its responses to various protein kinase inhibitors.METHODS:CCK-8 assay,real time quantitative PCR(qRT-PCR)and Western-blot were used to detect the effect of various protein kinase inhibitors on KG-1 cell proliferation,the expression levels of mRNA and phosphorylation level of signaling pro-teins in the FGFR1 downstream pathways.RE-SULTS:NVP-BGJ398 and PD173074 effectively in-hibited the proliferation of KG-1 cells,indicative of a crucial role of FGFR downstream signaling.After treatment with FGFR inhibitors,the levels of p-FG-FR1OP2-FGFR1 and p-STAT5 decreased significantly(P<0.001),p-AKT decreased slightly(P<0.05),with-out affecting the p-ERK level(P>0.05).CONCLU-SION:FGFR1OP2-FGFR1 mainly acts on the down-stream STAT5 signaling pathway to promote cell proliferation.Comprehensive protein kinase inhibi-tion analysis is a reliable and direct approach to identify functional drivers of cancer cell prolifera-tion.

Ketamine,an antagonist of the glutamate N-methyl-D-aspartate(NMDA)receptor,is cur-rently one of the most widely abused psychoactive substances.Prolonged abuse can result in damages to various systems in the body,making it crucial to investigate the regulatory mechanism of ketamine addic-tion and screening related biomarkers.In this study,zebrafish embryos/larvae were initially exposed a-cutely to ketamine.Then,a ketamine addiction model was established in 6-month-old zebrafish through conditioned place preference(CPP)experiments.The zebrafish brain transcriptome was analyzed using RNA-seq,while qPCR and Western blotting were employed to detect the expression of key genes.Results revealed significant reductions in the spontaneous tail coiling,embryo hatching rate,and survival rate of zebrafish embryos in the ketamine-treated group compared to the control group.The distance moved also decreased significantly,from 1904.2 mm in the control group to 319.0 mm in the high dose of ketamine group(300 μmol/L).Conditional positional preference experiments demonstrated that the control ze-brafish did not exhibit significant changes in activity in the CPP tank.In contrast,the ketamine-treated group increased their activity time in the light zone of the tank from 385.2 s before training to 706.4 s af-ter training,representing a 26.8％increase(***P＜0.001).This suggests a preference for ketamine stimulation in zebrafish.KEGG analysis indicated enrichment of differentially expressed genes in the neu-roactive ligand-receptor interaction pathway in the ketamine-treated samples.GSEA analysis further re-veals a significant upregulation of the glutamatergic synapse pathway(NES=1.5).In addition,compared with the control group,the mRNA levels of Grin2b and Gria2 in the ketamine group increased by 4.6 and 1.4 times,respectively,while the protein levels increased by 2.0 and 1.4 times,respectively.These findings suggest that ketamine can induce addiction in zebrafish,potentially through upregulation of the glutamatergic synaptic pathway.

This study aims to prepare altrenogest extended-release tablets,evaluate their quality and establish a content determination method.The hydrophilic gel skeleton type,dosage and core thick-ness of altrenogest extended-release tablets were used as the investigating factors,and the release degree of the tablets was used as the investigating index,the prescription process of altrenogest ex-tended-release tablets was optimized by one-factor screening and central combinatorial design re-sponse surface method,and quality evaluation was carried out,the in vitro release model was es-tablished,and a high-performance liquid chromatography(HPLC)assay method was set up for the determination of altrenogest extended-release tablets.The results showed that the optimal pre-scription of altrenogest extended-release tablets was 2％as the main drug,70％as the solubilizer,0.5％as the lubricant,19.1％as the filler,8.4％as the hydrophilic gel skeleton material,and the thickness of the tablets was 3.8 mm.The in vitro drug release conformed to the Higuchi model,and the altrenogest showed a good linear relationship with the R2=0.999 98 in the range of 10-80 mg/L.The optimized process for the extended-release tablets was stable and had a good quality.The extended-release tablets were stable and had significant slow-release effect.The HPLC method is accurate and reliable and can be used for the determination of altrenogest in extended-release tablets.

Albendazole sulfoxide and ivermectin compound pouring agent were prepared with dime-thyl sulfoxide and 1,2-propanediol as solvents.The central composite design response surface method was used to optimize the formula of pouring agent.Franz diffusion cell method was used to investigate the transdermal performance of pouring agent in vitro.The permeation amounts of the two drugs were determined by HPLC.The best formula of pouring agent was ivermectin 0.5％,al-bendazole sulfoxide 5％,dimethyl sulfoxide 52％,propylene glycol 39％,and the rest was 100％anhydrous ethanol.The cumulative permeation amounts of ivermectin and albendazole sulfoxide were up to 20.78 μg/cm2 and 249.02 μg/cm2,respectively.The in vitro release model of the two drugs accords with the first-order kinetic equation.There is a good linear relationship between al-bendazole sulfoxide and ivermectin in the range of 1-100 mg/L and the peak area.The precision and stability RSD of the two methods are less than 2％.The preparation process of albendazole sul-foxide compound pouring agent is simple,stable and easy to pour.The established HPLC method is simple and accurate,and can be used for the determination of albendazole sulfoxide and ivermectin in pouring agent.

Objective:To analyze the immune reconstitution after BTKi treatment in patients with chronic lymphocytic leukemia(CLL).Methods:The clinical and laboratorial data of 59 CLL patients admitted from January 2017 to March 2022 in Fujian Medical University Union Hospital were collected and analyzed retrospectively.Results:The median age of 59 CLL patients was 60.5(36-78).After one year of BTKi treatment,the CLL clones(CD5+/CD19+)of 51 cases(86.4％)were significantly reduced,in which the number of cloned-B cells decreased significantly from(46±6.1)× 109/L to(2.3±0.4)× 109/L(P=0.0013).But there was no significant change in the number of non-cloned B cells(CD19+minus CD5+/CD19+).After BTKi treatment,IgA increased significantly from(0.75±0.09)g/L to(1.31±0.1)g/L(P＜0.001),while IgG and IgM decreased from(8.1±0.2)g/L and(0.52±0.6)g/L to(7.1±0.1)g/L and(0.47±0.1)g/L,respectively(P＜0.001,P=0.002).BTKi treatment resulted in a significant change in T cell subpopulation of CLL patients,which manifested as both a decrease in total number of T cells from(2.1±0.1)× 109/L to(1.6±0.4)× 109/L and NK/T cells from(0.11±0.1)× 109/L to(0.07±0.01)× 109/L(P=0.042,P=0.038),both an increase in number of CD4+cells from(0.15±6.1)× 109/L to(0.19±0.4)× 109/L and CD8+cells from(0.27±0.01)× 109/L to(0.41±0.08)× 109/L(both P＜0.001).BTKi treatment also up-regulated the expression of interleukin(IL)-2 while down-regulated IL-4 and interferon(IFN)-γ.However,the expression of IL-6,IL-10,and tumor necrosis factor(TNF)-α did not change significantly.BTKi treatment could also restored the diversity of TCR and BCR in CLL patients,especially obviously in those patients with complete remission(CR)than those with partial remission(PR).Before and after BTKi treatment,Shannon index of TCR in patients with CR was 0.02±0.008 and 0.14±0.001(P＜0.001),while in patients with PR was 0.01±0.03 and 0.05±0.02(P＞0.05),respectively.Shannon index of BCR in patients with CR was 0.19±0.003 and 0.33±0.15(P＜0.001),while in patients with PR was 0.15±0.009 and 0.23±0.18(P＜0.05),respectively.Conclusions:BTKi treatment can shrink the clone size in CLL patients,promote the expression of IgA,increase the number of functional T cells,and regulate the secretion of cytokines such as IL-2,IL-4,and IFN-γ.BTKi also promote the recovery of diversity of TCR and BCR.BTKi treatment contributes to the reconstitution of immune function in CLL patients.