Objective To evaluate the predictors of recurrent in-stent restenosis(R-ISR)occurrence in drug-eluting stents(DES).Methods A total of 201 patients with ISR who received percutaneous coronary intervention(PCI)surgery in the First Medical Center of the Chinese PLA General Hospital from January 2010 to August 2023 were selected as the study objects,and the patients were divided into R-ISR group and non-R-ISR group according to their post-discharge angiography review.The clinical baseline data and the features of interventional surgery during the first ISR-PCI were retrospectively analyzed.Results Among the 201 patients,168 were males and 33 were females,with an average age of(61.97±10.02)years.The median interval between initial and follow-up angiography was 1.5 years.Patients were divided into two groups based on their radiographic reviews:R-ISR group(98 patients and 104 ISR lesions)and non-R-ISR group(103 patients and 111 ISR lesions).Multivariate Logistic regression analysis showed that the incidence of R-ISR was correlated with Ostial disease(OR 2.987,95％CI 1.343-6.642,P=0.007),plain old balloon angioplasty(POBA)performed for ISR lesions(OR 3.081,95％CI 1.293-7.343,P=0.011)and the maximum diameter stenosis rate of ISR lesions before surgery(OR 1.016,95％CI 1.002-1.030,P=0.022).Conclusions In patients currently receiving interventional therapy for ISR,Ostial disease,POBA treatment for ISR disease,and maximum diameter stenosis rate of ISR disease were associated predictors of R-ISR development.

The genomic island(GI)characteristics and virulence factor differences of clinical isolates of Burkholderia pseudomallei in Hainan Province,China were analyzed to provide a scientific basis for diagnosis and treatment of melioidosis.In total,52 B.pseudomallei isolates were collected for detection of virulence-related GIs by PCR.The whole genome sequence annotation format file was submitted on Islandviwer 4 platform,and the genomes of the same species and close relatives were added for comparison.Two algorithms,SIGI-HMM and IslandPath-DIMOB,were integrated to predict GIs and sequence a-lignments were conducted to identify specific GIs and differences in virulence factors.The genomes of 52 clinical strains could be divided into three branches based on evolutionary distance,with 82.69％(43/52)of strains concentrated in branch 1.In to-tal,828 GIs were identified among the 52 B.pseudomallei genomes,which formed 157 GI clusters based on sequence similari-ty.GIs accounted for 2.05％-6.38％of the genome content.While GI clusters 1 and 2 were present in all strains,a total of 84(53.50％)GI clusters only clustered within a single genome isolate.Of 10 GI likely specific clusters,five were from the same genus,two from another genus,and three with uncertain origins.Moreover,25 GI clusters were associated with virulence,which included eight shared by B.pseudomallei BP76 and BP169,which had the highest number of virulence-associated GIs among all isolates.O the 52 B.pseudomallei isolates,variations were identified in the virulence genes fhaB1,fhaB2,BPSL1661,cheY1,wzM,tssH-5/clpV,tssA-5,boaA,and boaB.Comparisons of these findings with clinical isolates from Thailand and Australia showed that B.pseudomallei isolates from Hainan had significant differences in the sequences of boaA,boaB,cheY1,and chbp.Additionally,fhaB1,fhaB3,and bimA displayed significant variations specifically within the Australian isolates.B.pseudomallei GI was conserved and specific to Hainan.The identification of specific GI and virulence factors was useful to clarify the source of horizontal gene transfer and differences in virulence at the molecular level.

One patient was admitted to a hospital due to"sepsis,chronic kidney disease,type 2 diabetes,shock,and cerebral infarction".Patient's blood specimen was taken for clinical examination.Aerobic and anaerobic culture results of catheter blood and venous blood were both positive.The pathogen was identified as Staphylococcus pas-teuri by VITEK MS,and the patient was diagnosed as catheter-related bloodstream infection caused by Staphylo-coccus pasteuri.Clinical empirical use of piperacillin for anti-infection treatment was ineffective,and vancomycin was eventually used for treatment based on in vitro antimicrobial susceptibility testing.Patient's condition improved after removing the venous catheter.There are currently no reported cases of Staphylococcus pasteuri in China.Ear-ly identification of pathogen and adjustment of treatment plans based on antimicrobial susceptibility testing results are crucial for effective treatment of this case.

Interventions for endometriosis(EMs)include surgical excision of lesions and hormonal therapy,which usually have limited efficacy and adverse drug reactions.Traditional Chinese medicine(TCM)has the multi-component and multi-target characteristics,which can help patients achieve good clinical benefits by intervening in different parts of the disease.In this paper,we briefly discuss the modern pharmacology of Sanlang and Curcuma longa,and deeply summarize the possible mechanisms of action of TCM monomer and classical compound extracts and their active ingredients through signal pathways in inflammation,immune system,angiogenesis,hormone regulation,etc.,so as to provide theoretical bases for the clinical use of TCM monomers,drug-to-drug groups and compounds in the treatment of EMs.

Objective To evaluate the bioequivalence of the vardenafil hydrochloride tablets in fasting and fed conditions in healthy Chinese adult subjects with the test and reference formulations.Methods A randomized,open,single-dose,two-preparation,two-sequence,two-period,crossover design was used,and 40 healthy male subjects enrolled in the fasting state and 66 healthy male subjects enrolled in the fed state.The trial was conducted in two cycles,with 20 mg of either the subject formulation or the reference formulation,vardenafil hydrochloride tablets,being administered in each cycle.The drug concentration of vardenafil in plasma was determined by the liquid chromatography-tandem mass spectrometry(LC/MS-MS)method.Pharmacokinetic parameters were calculated using the non-compartment model,and the safety evaluation indexes were statistically analyzed using SAS 9.4 or above version program data statistical software.Results Arithmetic mean values of the main pharmacokinetic parameters of the subject formulation of vardenafil hydrochloride tablets and the reference formulation in the fasting state:Cmaxwere(34.94±18.33)and(36.69±19.45)ng·mL-1;AUC0-t were(74.38±34.11)and(74.25±33.37)ng·mL-1·h;AUC0-∞ were(76.70±34.36)and(76.46±33.84)ng·mL-1·h,respectively.Arithmetic mean values of the main pharmacokinetic parameters of the subject formulation of vardenafil hydrochloride tablets and the reference formulation in the fed state:Cmax were(22.84±12.48)and(21.68±11.12)ng·mL-1;AUC0_twere(70.82±35.88)and(72.71±34.63)ng·mL-1·h;AUC0-∞ were(73.48±36.44)and(75.29±35.12)ng·mL-1·h,respectively.The 90％confidence intervals for the geometric mean ratios of the main pharmacokinetic parameters such as Cmax,AUC0-t and AUC0-∞ of the prototype drug vardenafil in plasma after oral administration of 20 mg of the test and reference formulations of vardenafil tablets to the subjects in fasting and postprandial states fell within the equivalence interval of 80.00％to 125.00％.Conclusion The subject formulation of vardenafil hydrochloride tablets was bioequivalent to the reference formulation in fasting and fed conditions in healthy Chinese subjects.

Objective: To compare the efficacy of intravascular ultrasound (IVUS) and coronary angiography guided drug eluting stent (DES) implantation for the treatment of left main coronary artery (LMCA) lesions. Methods: Randomized controlled trials (RCT) and observational studies, which compared IVUS with coronary angiography guided DES implantation for the treatment of LMCA lesions published before August 2021 were searched in PubMed, Embase and Cochrane Library databases. Baseline data, interventional procedures and endpoint events of each study were collected. The primary endpoint was major cardiovascular adverse events (MACE), and the secondary endpoints were all-cause death, cardiac death, myocardial infarction (MI), target lesion revascularization (TLR) and target vessel revascularization (TVR). The Newcastle-Ottawa Scale (NOS) and the Cochrane Collaboration Risk of Bias tool were used to evaluate the quality of the included studies. Results: Nine studies were included, including 3 RCT and 6 observational studies, with a total of 5 527 cases of LMCA. All the 6 observational studies had NOS scores≥6, and the 3 RCT had a low risk of overall bias. The results of meta-analysis showed that compared with coronary angiography guided group, MACE rate (OR=0.55, 95%CI 0.47-0.66, P<0.001), all-cause death (OR=0.56, 95%CI 0.43-0.74, P<0.001), cardiac death (OR=0.43, 95%CI 0.30-0.61, P<0.001), MI (OR=0.64, 95%CI 0.52-0.79, P<0.001), TLR (OR=0.49, 95%CI 0.28-0.86, P=0.013) and TVR (OR=0.77, 95%CI 0.60-0.98, P=0.037) were all significantly lower in the IVUS guided group. Conclusions: Compared with angiography guided, IVUS guided PCI with DES implantation in LMCA lesions could significantly reduce the risk of MACE, death, MI, TLR and TVR. IVUS is thus superior to coronary angiography for guiding PCI treatment among patients with LMCA.
Humans ; Coronary Artery Disease/complications* ; Coronary Angiography ; Drug-Eluting Stents/adverse effects* ; Treatment Outcome ; Percutaneous Coronary Intervention/methods* ; Ultrasonography, Interventional/methods* ; Risk Factors ; Myocardial Infarction/etiology*

OBJECTIVE: To investigate the anti-coronavirus potential and the corresponding mechanisms of the two ingredients of Reduning Injection: quercetin and luteolin. METHODS: A pseudovirus system was designed to test the efficacy of quercetin and luteolin to inhibit SARS-CoV-2 infection and the corresponding cellular toxicity. Luteolin was tested for its activities against the pseudoviruses of SARS-CoV-2 and its variants. Virtual screening was performed to predict the binding sites by Autodock Vina 1.1.230 and PyMol. To validate docking results, surface plasmon resonance (SPR) was used to measure the binding affinity of the compounds with various proteins of the coronaviruses. Quercetin and luteolin were further tested for their inhibitory effects on other coronaviruses by indirect immunofluorescence assay on rhabdomyosarcoma cells infected with HCoV-OC43. RESULTS: The inhibition of SARS-CoV-2 pseudovirus by luteolin and quercetin were strongly dose-dependent, with concentration for 50% of maximal effect (EC₅₀) of 8.817 and 52.98 µmol/L, respectively. Their cytotoxicity to BHK21-hACE2 were 177.6 and 405.1 µmol/L, respectively. In addition, luetolin significantly blocked the entry of 4 pseudoviruses of SARS-CoV-2 variants, with EC₅₀ lower than 7 µmol/L. Virtual screening and SPR confirmed that luteolin binds to the S-proteins and quercetin binds to the active center of the 3CLpro, PLpro, and helicase proteins. Quercetin and luteolin showed over 99% inhibition against HCoV-OC43. CONCLUSIONS The mechanisms were revealed of quercetin and luteolin inhibiting the infection of SARS-CoV-2 and its variants. Reduning Injection is a promising drug for COVID-19.
Humans ; SARS-CoV-2 ; COVID-19 ; Luteolin ; Quercetin

Objective: To investigate the regulatory effect and mechanism of specific antagonist of acid-sensitive ion channel 3 (APETx2) on visceral sensitivity in mice with post-infectious irritable bowel syndrome (PI-IBS) ． Methods: The PI-IBS model was established by National Institutes of Health (NIH) mice infected with Trichinella spiralis．Gastrointestinal transport function was assessed by measuring the time to first black stool and the number of fecal pellets collected for 6 hours ; abdominal wall withdrawal reflex (AWR) was used to assess visceral sensitivity ; the expression of calcitonin gene-related peptide ( CGRP) in the colon tissue was detected by immunohistochemistry ; the expression of brain-derived neurotrophic factor (BDNF) and CGRP mRNA in the colon tissues was detected by quantitative real time polymerase chain reaction ( qRT-PCR) ． The expression levels of acid sensing ion channel 3 (ASIC3) ，CGRP，and transient receptor potential vanilloid 1 (TRPV1) protein in brain tissue were detected by Western blot analysis. Results: Compared with the control group，the PI-IBS group significantly reduced the time of first black stool，the number of fecal particles and AWR score within 6 hours significantly increased，the protein expression of CGRP in colon tissue，BDNF and CGRP mRNA significantly increased，and the protein expression of CGRP，ASIC3 and TRPV1 in brain tissue significantly increased．Compared with the control group，the PI-IBS group significantly reduced the time to first black stool，the number of fecal particles and AWR score within 6 hours significantly increased，the expression of CGRP protein in colon tissue，the expression of BDNF and CGRP mRNA significantly increased，and the protein expression of CGRP，ASIC3 and TRPV1 in brain tissue significantly increased ; compared with the PI-IBS group，the first time of black stool clearance in the APETx2 group was significantly prolonged，the number of fecal particles and AWR score within 6 hours were significantly reduced，the expression of CGRP protein in colon tissue，the expression of BDNF and CGRP mRNA was significantly reduced，the protein expression of CGRP，ASIC3 and TRPV1 in brain tissue was significantly reduced，and the difference was statistically significant (P＜0. 05) ． Conclusion APETx2 can alleviate visceral sensitivity and regulate gastrointestinal motility in PI-IBS mice by downregulating the expression of BDNF，CGRP，ASIC3 and TRPV1．APETx2 may provide a new therapeutic option for the treatment of IBS.

Objectives: To investigate the role of donor change in the second hematopoietic stem cell transplantation (HSCT2) for hematological relapse of malignant hematology after the first transplantation (HSCT1) . Methods: We retrospectively analyzed patients with relapsed hematological malignancies who received HSCT2 at our single center between Mar 1998 and Dec 2020. A total of 70 patients were enrolled[49 males and 21 females; median age, 31.5 (3-61) yr]. Results: Forty-nine male and 21 female patients were enrolled in the trial. At the time of HSCT2, the median age was 31.5 (3-61) years old. Thirty-one patients were diagnosed with acute myeloid leukemia, 23 patients with ALL, and 16 patients with MDS or other malignant hematology disease. Thirty patients had HSCT2 with donor change, and 40 patients underwent HSCT2 without donor change. The median relapse time after HSCT1 was 245.5 (26-2 905) days. After HSCT2, 70 patients had neutrophil engraftment, and 62 (88.6%) had platelet engraftment. The cumulative incidence of platelet engraftment was (93.1±4.7) % in patients with donor change and (86.0±5.7) % in patients without donor change (P=0.636). The cumulative incidence of CMV infection in patients with and without donor change was (64.0±10.3) % and (37.0±7.8) % (P=0.053), respectively. The cumulative incidence of grade Ⅱ-Ⅳ acute graft versus host disease was (19.4±7.9) % vs (31.3±7.5) %, respectively (P=0.227). The cumulative incidence of TRM 100-day post HSCT2 was (9.2±5.1) % vs (6.7±4.6) % (P=0.648), and the cumulative incidence of chronic graft versus host disease at 1-yr post-HSCT2 was (36.7±11.4) % versus (65.6±9.1) % (P=0.031). With a median follow-up of 767 (271-4 936) days, 38 patients had complete remission (CR), and three patients had persistent disease. The CR rate was 92.7%. The cumulative incidences of overall survival (OS) and disease-free survival (DFS) 2 yr after HSCT2 were 25.8% and 23.7%, respectively. The cumulative incidence of relapse, OS, and DFS was (52.6±11.6) % vs (62.4±11.3) % (P=0.423), (28.3±8.6) % vs (23.8±7.5) % (P=0.643), and (28.3±8.6) % vs (22.3±7.7) % (P=0.787), respectively, in patients with changed donor compared with patients with the original donor. Relapses within 6 months post-HSCT1 and with persistent disease before HSCT2 were risk factors for OS, DFS, and CIR. Disease status before HSCT2 and early relapse (within 6 months post-HSCT1) was an independent risk factor for OS, DFS, and CIR post-HSCT2. Conclusion: Our findings indicate that changing donors did not affect the clinical outcome of HSCT2.
Humans ; Male ; Female ; Adult ; Child, Preschool ; Child ; Adolescent ; Young Adult ; Middle Aged ; Retrospective Studies ; Hematologic Neoplasms/therapy* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Leukemia, Myeloid, Acute/therapy* ; Recurrence ; Graft vs Host Disease/etiology* ; Chronic Disease

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis