BACKGROUND: Delayed platelet engraftment is a common complication after umbilical cord blood transplantation (UCBT), and there is no standard therapy. Avatrombopag (AVA) is a second-generation thrombopoietin (TPO) receptor agonist (TPO-RA) that has shown efficacy in immune thrombocytopenia (ITP). However, few reports have focused on its efficacy in patients diagnosed with thrombocytopenia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: We conducted a retrospective study at the First Affiliated Hospital of the University of Science and Technology of China to evaluate the efficacy of AVA as a first-line TPO-RA in 65 patients after UCBT; these patients were compared with 118 historical controls. Response rates, platelet counts, megakaryocyte counts in bone marrow, bleeding events, adverse events and survival rates were evaluated in this study. Platelet reconstitution differences were compared between different medication groups. Multivariable analysis was used to explore the independent beneficial factors for platelet implantation. RESULTS: Fifty-two patients were given AVA within 30 days post-UCBT, and the treatment was continued for more than 7 days to promote platelet engraftment (AVA group); the other 13 patients were given AVA for secondary failure of platelet recovery (SFPR group). The median time to platelet engraftment was shorter in the AVA group than in the historical control group (32.5 days vs . 38.0 days, Z  = 2.095, P  = 0.036). Among the 52 patients in the AVA group, 46 achieved an overall response (OR) (88.5%), and the cumulative incidence of OR was 91.9%. Patients treated with AVA only had a greater 60-day cumulative incidence of platelet engraftment than patients treated with recombinant human thrombopoietin (rhTPO) only or rhTPO combined with AVA (95.2% vs . 84.5% vs . 80.6%, P  <0.001). Patients suffering from SFPR had a slightly better cumulative incidence of OR (100%, P  = 0.104). Patients who initiated AVA treatment within 14 days post-UCBT had a better 60-day cumulative incidence of platelet engraftment than did those who received AVA after 14 days post-UCBT (96.6% vs . 73.9%, P  = 0.003). CONCLUSION Compared with those in the historical control group, our results indicate that AVA could effectively promote platelet engraftment and recovery after UCBT, especially when used in the early period (≤14 days post-UCBT).
Humans ; Female ; Male ; Thrombocytopenia/etiology* ; Adult ; Retrospective Studies ; Cord Blood Stem Cell Transplantation/adverse effects* ; Middle Aged ; Adolescent ; Young Adult ; Thiazoles/adverse effects* ; Platelet Count ; Receptors, Thrombopoietin/agonists* ; Child ; Thiophenes

BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

Objective To evaluate the application effect of ciprofol-alfentanil in short urological surgery.Methods A total of 80 patients who were to undergo urological general anesthesia surgery in this hospital were divided into two groups by random number method:ciprofol-alfentanil group(group C)and propofol-alfentanil group(group P).Group C was injected with ciprofol 0.4 mg/kg,group P was injected with propofol 1.5-2.0 mg/kg,and when the bispectral index(BIS)was<60,the intravenous injection of alfen-tanil(10 μg/kg)and rocuronium bromide(0.6 mg/kg)was continued.When the modified alertness/sedation score(MOAA/S score)was 0,the laryngeal mask was placed and mechanical ventilation was used.During the maintenance period,ciprofol 0.8-1.2 mg·kg-1·h-1 was infused intravenously in group C,and propofol 4-6 mg·kg-1·h-1 was infused intravenously in group P.The heart rate(HR),blood pressure(BP),oxygen saturation(SpO2),end-tidal carbon dioxide(PetCO2),BIS and MOAA/S score were recorded at the begin-ning of anesthesia induction(T0),laryngeal mask insertion(T1),ureteroscopy entry(T2),10 min after sur-gery(T3)and the end of surgery(T4).The consciousness disappearance time,operation time,anesthesia re-covery time,drug dosage,injection pain during induction,hypotension,bradycardia and other adverse reactions during the operation were recorded.Results There was no significant difference in HR,SpO2,PetCO2,BIS value,MOAA/S score,operation time,consciousness disappearance time,and anesthesia recovery time be-tween the two groups at each time point(P>0.05).The dosage of sedative drugs in group C was less than that in group P(P<0.05).Compared with group P,systolic blood pressure and diastolic blood pressure at T1-T3 and diastolic blood pressure at T4 increased in group C(P<0.05).Compared with T0,systolic blood pressure at T1-T4 in group C and group P decreased,diastolic blood pressure at T2-T4 in group C de-creased,and diastolic blood pressure at T1-T4 in group P decreased(P<0.05).Compared with group P,the injection pain and the incidence of intraoperative hypotension were reduced in group C(P<0.05).Conclusion Cipro-fol-alfentanil is superior to propofol-alfentanil in short urological surgery.

Objective: To find a viable alternative to reduce the number of doses required for the patients with post-traumatic stress disorder (PTSD), and to improve efficacy and patient compliance. Methods: In this study, we used ginger oil, a phytochemical with potential therapeutic properties, to prepare ginger oil patches. High-performance liquid chromatography (HPLC) was used to quantify the main active component of ginger oil, 6-gingerol. Transdermal absorption experiments were conducted to optimize the various pressure-sensitive adhesives and permeation enhancers, including their type and concentration. Subsequently, the ginger oil patches were optimized and subjected to content determination and property evaluations. A PTSD mouse model was established using the foot-shock method. The therapeutic effect of ginger oil patches on PTSD was assessed through pathological sections, behavioral tests, and the evaluation of biomarkers such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), brain-derived neurotrophic factor (BDNF), and melatonin (MT). Results: The results demonstrated that ginger oil patches exerted therapeutic effects against PTSD by inhibiting inflammatory responses and modulating MT and BDNF levels. Pharmacokinetic experiments revealed that ginger oil patches maintained a stable blood drug concentration for at least one day, addressing the rapid metabolism drawback of 6-gingerol and enhancing its therapeutic efficacy. Conclusions Ginger oil can be prepared as a transdermal drug patch that meets these requirements, and the bioavailability of the prepared patch is better than that of oral administration. It can improve PTSD with good patient compliance and ease of administration. Therefore, it is a promising therapeutic formulation for the treatment of PTSD.

Objective:To compare the therapeutic efficacy of laparoscopic versus open hepatectomy based on three-dimensional image reconstruction in the treatment of hepatocellular carcinoma (HCC) in the central region of liver.Methods:Clinical data of 118 patients with HCC located in the central region of liver undergoing hepatectomy in the People's Hospital of Zhengzhou University from January 2020 to December 2023 were retrospectively analyzed, including 85 males and 33 females, aged (57.5±8.9) years old. According to surgical approach, patients were divided into two groups: the open surgery group ( n=66) and laparoscopic surgery group ( n=52). All patients underwent three-dimensional image reconstruction preoperatively to determine the tumor location and its relationship with the hepatic vessels. The operative duration, intraoperative blood loss, incidence of postoperative complications, postoperative hospital stay, and prognosis were compared between the groups. Results:Compared to open surgery, patients in laparoscopic group were younger [(55±9) years old vs. (59±8) years old], and experienced a longer operative time [212.5 (152.5, 262.3) min vs. 161.5 (135.8, 210.0) min] and a shorter postoperative hospital stay [11.0(9.0, 13.0) d vs. 13.0(11.0, 15.3) d] (all P<0.05). Postoperative pathology indicated that R0 resection was achieved in both groups. The incidence of postoperative complications were comparable between the two groups [34.6% (18/52) vs. 39.4% (26/66), χ2=0.28, P=0.594]. The 1-year and 3-year recurrence-free survivals were 69.7% and 53.0% in laparoscopic group, similar to those in open group (71.2% and 53.8%, respetctively, P=0.953). Conclusion:Laparoscopic hepatectomy based on three-dimensional image reconstruction is safe and feasible for HCC in central region in terms of clinical prognosis. Laparoscopic surgery is also associated with a shorter postoperative hospital stay.

Detailed characterizations of genomic alterations have not identified subtype-specific vulnerabilities in adult gliomas. Mapping gliomas into developmental programs may uncover new vulnerabilities that are not strictly related to genomic alterations. After identifying conserved gene modules co-expressed with EGFR or PDGFRA (EM or PM), we recently proposed an EM/PM classification scheme for adult gliomas in a histological subtype- and grade-independent manner. By using cohorts of bulk samples, paired primary and recurrent samples, multi-region samples from the same glioma, single-cell RNA-seq samples, and clinical samples, we here demonstrate the temporal and spatial stability of the EM and PM subtypes. The EM and PM subtypes, which progress in a subtype-specific mode, are robustly maintained in paired longitudinal samples. Elevated activities of cell proliferation, genomic instability and microenvironment, rather than subtype switching, mark recurrent gliomas. Within individual gliomas, the EM/PM subtype was preserved across regions and single cells. Malignant cells in the EM and PM gliomas were correlated to neural stem cell and oligodendrocyte progenitor cell compartment, respectively. Thus, while genetic makeup may change during progression and/or within different tumor areas, adult gliomas evolve within a neurodevelopmental framework of the EM and PM molecular subtypes. The dysregulated developmental pathways embedded in these molecular subtypes may contain subtype-specific vulnerabilities.
Humans ; Brain Neoplasms/pathology* ; Neoplasm Recurrence, Local/metabolism* ; Glioma/pathology* ; Neural Stem Cells/pathology* ; Oligodendrocyte Precursor Cells/pathology* ; Tumor Microenvironment

OBJECTIVES: Long-term treatment of olanzapine, the most widely-prescribed second-generation antipsychotic, remarkably increases the risk of non-alcoholic fatty liver disease (NAFLD), whereas the mechanism for olanzapine-induced NAFLD remains unknown. Excessive hepatic fat accumulation is the basis for the pathogenesis of NAFLD, which results from the disturbance of TG metabolism in the liver. Apolipoprotein A5 (ApoA5) is a key regulator for TG metabolism in vivo that promotes TG accumulation in hepatocytes, thereby resulting in the development of NAFLD. However, there are no data indicating the role of apoA5 in olanzapine-induced NAFLD. Therefore, this study aims to investigate the role of apoA5 in olanzapine-induced NAFLD. METHODS: This study was carried out via animal studies, cell experiment, and ApoA5 gene knockdown experiment. Six-week-old male C57BL/6J mice were randomized into a control group, a low-dose group, and a high-dose group, which were treated by 10% DMSO, 3 mg/(kg·d) olanzapine, and 6 mg/(kg·d) olanzapine, respectively for 8 weeks. The lipid levels in plasma, liver function indexes, and expression levels of ApoA5 were detected. HepG2 cells were treated with 0.1% DMSO (control group), 25 μmol/L olanzapine (low-dose group), 50 μmol/L olanzapine (medium-dose group), and 100 μmol/L olanzapine (high-dose group) for 24 h. HepG2 cells pretreated with 100 μmol/L olanzapine were transfected with siRNA and scrambled siRNA (negative control), respectively. We observed the changes in lipid droplets within liver tissues and cells using oil red O staining and fat deposition in liver tissues using HE staining. The mRNA and protein levels of ApoA5 were determined by real-time PCR and Western blotting, respectively. RESULTS: After intervention with 3 and 6 mg/(kg·d) olanzapine for 8 weeks, there was no significant difference in body weight among the 3 groups (P>0.05). Olanzapine dose-dependently increased the plasma TG, ALT and AST levels, and reduced plasma ApoA5 levels (all P<0.05), whereas there was no significant difference in plasma cholesterol (HDL-C, LDL-C, and TC) levels among the 3 groups (all P>0.05). Olanzapine dose-dependently up-regulated ApoA5 protein levels in liver tissues (all P<0.05), but there was no significant change in ApoA5 mRNA expression among groups (P>0.05). In the control group, the structure of liver tissues was intact, the morphology of liver cells was regular, and only a few scattered lipid droplets were found in the cells. In the olanzapine-treated group, there was a large amount of lipid deposition in hepatocytes, and cells were balloon-like and filled with lipid droplet vacuoles. The nucleus located at the edge of cell, and the number of lipid droplets was increased significantly, especially in the high-dose group. Likewise, when HepG2 cells were treated with olanzapine for 24 h, the number and size of lipid droplets were significantly elevated in a dose-dependent manner. Moreover, olanzapine dose-dependently up-regulated ApoA5 protein levels in HepG2 cells (all P<0.05), but there was no significant difference in ApoA5 mRNA expression among groups (P>0.05). Compared with the HepG2 cells transfected with scrambled siRNA, the number and size of lipid droplets in HepG2 cells transfected with ApoA5 siRNA were significantly reduced. CONCLUSIONS The short-term intervention of olanzapine does not significantly increase body weight of mice, but it can directly induce hypertriglyceridemia and NAFLD in mice. Olanzapine inhibits hepatic apoA5 secretion but does not affect hepatic apoA5 synthesis, resulting in the pathogenesis of NAFLD. Inhibition of apoA5 secretion plays a key role in the development of olanzapine-related NAFLD, which may serve as an intervention target for this disease.
Animals ; Apolipoprotein A-V/genetics* ; Body Weight ; Dimethyl Sulfoxide/metabolism* ; Liver/metabolism* ; Male ; Mice ; Mice, Inbred C57BL ; Non-alcoholic Fatty Liver Disease/chemically induced* ; Olanzapine/metabolism* ; RNA, Messenger/metabolism* ; RNA, Small Interfering ; Triglycerides

Objective : To study the epidemiological characteristics of coronavirus disease 2019 （COVID-19） in Zhoushan, so as to provide reference for improving the prevention and control capability of COVID-19. Methods : All the confirmed cases of COVID-19 in Zhoushan, diagnosed according to China’s “COVID-19 diagnosis and treatment plan （fifth version） ” and reported from January 19 to February 17, 2020, were extracted from the infectious disease surveillance system. Data of general information, clinical characteristics, laboratory Results, transmission and detection routes were collected and analyzed. Results : By February 17, Ten confirmed cases of COVID-19 in Zhoushan had been reported, including 7 males and 3 females. They were all adults, with an average age of （50.90±15.00） years. Five cases were discharged. The incubation period ranged from 2 to 12 days, with a median of 5 days. The first symptoms were fever （8 cases）, cough （7 cases） and muscle pain （2 cases）. Chest computed tomographic （CT） scans showed ground glass opacities in the lungs of all the cases. Six cases had Wuhan related exposure. SARS-CoV-2 was tested positive in the sputum specimens or throat swabs of all the cases and the faeces of 4 cases. The last suspicious exposure of 5 cases occurred before, and that of another 5 cases occurred after the onset of clinical symptoms in the confirmed maternal cases. Three cases were found in active consultation after clinical symptoms, and another 7 cases were found in the monitoring of close contacts. Conclusions The 10 confirmed cases of COVID-19 reported in Zhoushan are all adults, and most have Wuhan related exposure. SARS-CoV-2 can be detected in the fecal samples, but the existence of fecal-oral transmission needs more research. SARS-CoV-2 has strong infectivity, and may also have infectivity before the onset of symptoms （at the end of incubation period）. Isolation and early detection of close contacts are conducive for early case-finding.

Objective:To study the regulatory effect of miR-9 on the proliferation of breast cancer cells by targeting hexokinase 2 (HK2) .Methods:Breast cancer tissues and paracancer tissues were collected and the expression levels of miR-9 and HK2 were detected. MCF-7 cells were cultured and divided into blank control group, NC group, miR-9 group, NC-siRNA group and HK2-siRNA group. The cell viability, expression levels of HK2 and cleaved caspase-3 were detected, the targeted binding of miR-9 to HK2 was verifed.Results:the expression level of miR-9 in breast cancer was lower than that in paracancer tissue (0.52±0.08 vs 1.05±0.25, t=16.685, P<0.000) , and the expression level of HK2 was higher than that in paracancer tissue (0.73±0.14 vs 0.34±0.08, t=17.587, P<0.000) , and the expression level of miR-9 was negatively correlated with HK2; the OD490 level, the expression level of HK2 and the fluorescence activity of double luciferase reporter gene containing HK2 mRNA 3 'UTR in miR-9 group were lower than those in NC group (0.58±0.09 vs 1.04±0.21, 0.51±0.08 vs 1.18±0.24, 41.11±9.28 vs 148.28±29.59, t/P=4.027/0.007, 5.297/0.002, 6.912/0.001) , and the expression level of cleaved caspase-3 was higher than that in NC group (1.08±0.26 vs 0.42±0.09, t/P=4.797/0.003) . The OD490 level and the expression level of HK in HK-siRNA group were higher than that in NC-siRNA group, and the expression level of cleaved caspase-3 was higher than that of NC-siRNA group. Conclusion:miR-9 can inhibit the proliferation of breast cancer cells, and its mechanism may be related to the targeted inhibition of HK2 expression and the increase of downstream cleaved caspase-3 expression.

Doxorubicin (DOX) is a highly effective chemotherapeutic agent; however, the dose-dependent cardiotoxicity associated with DOX significantly limits its clinical application. In the present study, we investigated whether Rb1 could prevent DOX-induced apoptosis in H9C2 cells via aryl hydrocarbon receptor (AhR). H9C2 cells were treated with various concentrations (−μM) of Rb1. AhR, CYP1A protein and mRNA expression were quantified with Western blot and real-time PCR analyses. We also evaluated the expression levels of caspase-3 to assess the anti-apoptotic effects of Rb1. Our results showed that Rb1 attenuated DOX-induced cardiomyocytes injury and apoptosis and reduced caspase-3 and caspase-8, but not caspase-9 activity in DOX-treated H9C2 cells. Meanwhile, pre-treatment with Rb1 decreased the expression of caspase-3 and PARP in the protein levels, with no effects on cytochrome c, Bax, and Bcl-2 in DOX-stimulated cells. Rb1 markedly decreased the CYP1A1 and CYP1A2 expression induced by DOX. Furthermore, transfection with AhR siRNA or pre-treatment with AhR antagonist CH-223191 significantly inhibited the ability of Rb1 to decrease the induction of CYP1A, as well as caspase-3 protein levels following stimulation with DOX. In conclusion, these findings indicate that AhR plays an important role in the protection of Ginsenoside Rb1 against DOX-triggered apoptosis of H9C2 cells.
Apoptosis* ; Blotting, Western ; Cardiotoxicity ; Caspase 3 ; Caspase 8 ; Caspase 9 ; Cytochrome P-450 CYP1A1 ; Cytochrome P-450 CYP1A2 ; Cytochromes c ; Doxorubicin ; Myocytes, Cardiac ; Real-Time Polymerase Chain Reaction ; Receptors, Aryl Hydrocarbon* ; RNA, Messenger ; RNA, Small Interfering ; Transfection