Objective:To study the clinical characteristics of congenital esophageal atresia (CEA) and risk factors of mortality associated with esophageal repair (ER) surgery.Methods:From January 2010 to December 2022, patients diagnosed of CEA using chest and abdomen X-ray and esophagography in our hospital were retrospectively reviewed. The patients were assigned into ER group and non-ER group according to the treatments. The ER group was subgrouped into survival group and death group according to the prognosis. Clinical data and outcomes were collected and compared between the groups.Results:A total of 553 cases were enrolled. According to Gross classification, 29 patients (5.2%) were type A, 2 patients (0.4%) were type B, 504 patients (91.1%) were type C, 6 patients (1.1%) were type D and 11 patients (2.0%) were type E. One patient had simple transluminal septal atresia of the esophagus. 406 patients were in ER group and 147 in non-ER group. Compared with ER group, non-ER group had significantly higher incidences of preterm birth, low birth weight and overall malformations (all P<0.05). In ER group, 152 patients (37.4%) received open thoracic surgery (OTS), 243 (59.9%) had video-assisted thoracoscopic surgery (VATS) and 11 (2.7%) were VATS converted to OTS. Postoperative anastomotic leakage (PAL) occurred in 92 patients (22.7%) and 15 patients (3.7%) died after surgery. The median length of hospital stay was 23 (17, 36) d. Compared with the survival group, the death group had higher incidences of preterm birth, low birth weight, VATS converted to OTS, mechanical ventilation after ER, and shorter length of hospital stay (all P<0.05). After adjusted for birth weight, VATS converted to OTS ( OR=9.585, 95% CI 1.899-48.374) and mechanical ventilation after ER ( OR=7.821, 95% CI 1.002-61.057) were risk factors of mortality in ER patients. Conclusions:Non-ER patients have higher incidences of preterm birth, low birth weight and overall malformations than ER patients. VATS is the method of choice for CEA. Preterm birth, low birth weight, VATS converted to OTS and mechanical ventilation after ER are risk factors of mortality in ER patients.

Objective To study the compliance and correctness of hand hygiene(HH)of staff in intensive care units(ICUs)of a tertiary first-class hospital,and provide theoretical basis for HH intervention.Methods In April 2023,staff in 17 ICUs of this hospital were performed on-site survey by infection control staff,and monitoring forms about HH compliance and correctness were filled out.Results A total of 874 HH opportunities were ob-served with the concealed observation method,501 HH opportunities were implemented,the compliance rate was 57.32％,273 HH opportunities were correctly implemented,with an correct rate of 54.49％.The compliance and correct rate of HH among staff in different ICUs varied significantly.Compliance and correct rates of HH among staff with different jobs were statistically different:HH compliance rate of cleaners(31.97％)was lower than that of nurses(63.83％),doctors(58.77％)and other personnel(58.14％);HH correct rate of cleaners(30.77％)was lower than that of nurses(58.17％).The causes for not implementing HH among staff with different jobs and at different HH opportunities were statistically different:the rate of not implementing any HH measures after con-tact with patients(84.75％)was higher than before contact with patients(41.27％),before clean and sterile ma-nipulation(30.00％),as well as after contact with blood and body fluid(45.45％).The rate of not implementing any HH measures after contact with the patient's surrounding environment(66.67％)was higher than before con-tact with patient as well as before clean and sterile manipulation.The rates of incomplete HH steps and insufficient HH time among staff with different jobs were statistically different:The rates of incomplete HH steps of other per-sonnel(82.35％)was higher than that of doctors(52.63％).The rates of insufficient HH time of doctors(82.46％)and nurses(78.18％)were higher than that of cleaners(51.85％).Conclusion The implementation of HH among different occupational groups and at different HH implementation opportunities in ICU is significantly different,which should be intervened based on their characteristics.

PI3Kγ and PI3Kδ have important regulatory roles in the immune system, and targeting these two subtypes helps to reshape the tumor microenvironment. PI3Kγ and PI3Kδ are potential targets for tumor immunotherapy. In this study, a series of new pyrazolopyrimidine derivatives were designed and synthesized on the basis of our previously reported PI3K inhibitors, resulting in the discovery of compound 16l as a potent and selective PI3Kγ/δ dual inhibitor. Compound 16l demonstrated strong biochemical potencies against PI3Kγ and PI3Kδ with IC₅₀ values of 0.11 and 0.79 nmol·L^-1. In cell-based assays, it potently inhibited the PI3Kγ and PI3Kδ mediated Akt S473 phosphorylation with EC₅₀ values of 3 and 7 nmol·L^-1. In vivo, compound 16l exhibited acceptable pharmacokinetic properties in Sprague-Dawley (SD) rats and suppressed the tumor growth in a MC38 syngeneic mouse model. The animal experiments were approved by the Animal Ethics Committee of Hefei Institutes of Physical Science, Chinese Academy of Sciences (approval number: DWLL-2000-06). In addition, no appreciable human ether-a-go-go-related gene (hERG) inhibition was observed for compound 16l even at 30 μmol·L^-1. These results suggested that compound 16l might be a potential research tool for studying the PI3Kγ/δ mediated signaling pathways.

Objective:To explore whether transjugular intrahepatic portosystemic shunt (TIPS) can improve the prognosis of esophagogastric variceal bleeding (EGVB) combined with sarcopenia in cirrhotic patients.Methods:A retrospective cohort study was performed. A total of 464 cases with cirrhotic EGVB who received standard or TIPS treatment between January 2017 and December 2019 were selected. Regular follow-up was performed for the long-term after treatment. The primary outcome was transplantation-free survival. The secondary endpoints were rebleeding and overt hepatic encephalopathy (OHE). The obtained data were statistically analyzed. The t-test and Wilcoxon rank-sum test were used to compare continuous variables between groups. The χ2 test, or Fisher's exact probability test, was used to compare categorical variables between groups. Results:The age of the included patients was 55.27±13.86 years, and 286 cases were male. There were 203 cases of combined sarcopenia and 261 cases of non-combined sarcopenia. The median follow-up period was 43 months. The two groups had no statistically significant difference in follow-up time. There was no statistically significant difference in transplant-free survival between the TIPS group and the standard treatment group in the overall cohort ( HR=1.31, 95% CI: 0.97-1.78, P=0.08). The TIPS patient group with cirrhosis combined with sarcopenia had longer transplant-free survival (median survival: 47.76 vs. 52.45, χ2=4.09; HR=1.55, 95 CI: 1.01~2.38, P=0.04). There was no statistically significant difference in transplant-free survival between the two kinds of treatments for patients without sarcopenia ( HR=1.22, 95% CI: 0.78~1.88, P=0.39). Rebleeding time was prolonged in TIPS patients with or without sarcopenia combination (patients without combined sarcopenia: median rebleeding time: 39.48 vs. 53.61, χ2=18.68; R=2.47, 95 CI: 1.67~3.65, P<0.01; patients with sarcopenia: median rebleeding time: 39.91 vs. 50.68, χ2=12.36; HR=2.20, 95 CI: 1.42~3.40, P<0.01). TIPS patients had an increased 1-year OHE incidence rate compared to the standard treatment group (sarcopenia patients: 6.93% vs. 16.67%, χ2=3.87, P=0.049; patients without sarcopenia combination: 2.19% vs. 9.68%, χ2=8.85, P=0.01). There was no statistically significant difference in the long-term OHE incidence rate between the two kinds of treatment groups ( P>0.05). Conclusion:TIPS can significantly prolong transplant-free survival compared to standard treatment as a secondary prevention of EGVB concomitant with sarcopenia in patients with cirrhosis. However, its advantage is not prominent for patients with cirrhosis in EGVB without sarcopenia.

Objective:To explore the efficacy and safety of bortezomib or thalidomide combined with recombinant human erythropoietin(rhEPO)in the treatment of multiple myeloma(MM).Methods:A total of 80 patients with MM who were treated in the Second People's Hospital ofWuhu from January 2013 to December 2018 were selected as the research subjects,and they were divided into bortezomib group(n=40)and thalidomide group(n=40)by the simple randomization method.The bortezomib group received bortezomib regimen combined with rhEPO therapy,and the thalidomide group was given thalidomide regimen combined with rhEPO therapy,and all patients were treated for 3 courses with every 3 weeks as a course of treatment.The clinical efficacy after 3 courses of treatment,and tumor-related biochemical indicators[lactate dehydrogenase(LDH),β 2-microglobulin([3 2-MG),vascular endothelial growth factor(VEGF),apoptosis inhibitory protein Survivin],bone marrow-related indicators[serum M-protein,bone marrow plasma cells,hemoglobin(Hb)]and coagulation function indicators[activated partial thromboplastin time(APTT),prothrombin time(PT),plasminogen activator inhibitor(PAI),total circulating microparticles(TMPs)]before treatment and after 3 courses of treatment were compared between the two groups of patients.The occurrence of adverse reactions during the treatment in the two groups of patients was recorded.Results:After 3 courses of treatment,the ORR rate of 92.5％in bortezomib group was higher than 90.0％in thalidomide group,but the difference was not statistically significant(P＞0.05).The levels of LDH,[3 2-MG,VEGF,Survivin,serum M-protein,bone marrow plasma cells,APTT,PT,PAI and TMPs in the two groups after 3 courses of treatment were significantly lower or shorter than those before treatment,and the above indicators in bortezomib group were significantly lower or shorter than those in thalidomide group(P＜0.05).After 3 courses of treatment,the expression level of Hb in the two groups was significantly higher than that before treatment,and the Hb level in bortezomib group was significantly higher than that in thalidomide group(P＜0.05).During the treatment process,the incidence rates of adverse reactions in bortezomib group were significantly lower than those in thalidomide group(P＜0.05).Conclusion:Thalidomide regimen or bortezomib regimen combined with rhEPO has similar clinical efficacy on MM,but bortezomib regimen combined with rhEPO is more prominent and safer on improving tumor-related biochemical indicators,bone marrow-related indicators and coagulation status in patients with MM.

Objective:To explore the effects of RNF113A on the proliferation,migration,in-vasion,apoptosis,and autophagy of hepatocellular carcinoma cells.Methods:Hep3B cells were divided into control group and RNF113A overexpression group(RNF113A-OE),HepG2 was divided into control group and RNF113A knockdown group(si-RNF113A),CCK-8 assay was used to detect changes in cell viability,clone formation assay was used to detect changes in cell proliferation abili-ty,Transwell assay was used to detect changes in cell invasion ability,wound healing assay was used to detect changes in cell migration ability,and flow cytometry was used to detect changes in cell apoptosis ability,Western blot experiments were used to detect changes in protein expression of autophagy related genes and AMPK signaling pathway related genes.Results:Compared with the control group,the proliferation,cloning,invasion,and migration abilities of Hep3B cells in the RNF113A-OE group were improved,while apoptosis and autophagy abilities were decreased,and the AMPK signaling pathway was inhibited;In the si-RNF113A group,the proliferation,cloning,in-vasion,and migration abilities of HepG2 cells were significantly reduced,while apoptosis and au-tophagy abilities were increased,and the activation of the AMPK signaling pathway was promoted.Conclusion:RNF113A promotes the proliferation,cloning,invasion,and migration of hepatocel-lular carcinoma cells,and inhibited apoptosis and autophagy by inhibiting the AMPK signaling path-way.

Aim To investigate the dynamic changes of neuronal cells at different time points following acute cerebral ischemia-reperfusion injury by establishing a model of brain ischemia-reperfusion injury.Methods Thirty male Sprague-Dawley(SD)rats were ran-domly divided into six groups:sham group and cere-bral ischemia-reperfusion injury(IR)groups at differ-ent time points.Focal cerebral ischemia-reperfusion injury model was established using the middle cerebral artery occlusion(MCAO)technique.The Longa sco-ring method was used to assess neurobehavioral scores in rats.After successful model preparation,routine paraffin sections were made,and TUNEL staining and immunohistochemistry staining with NeuN antibody were performed to observe cell apoptosis and neuronal cell survival,respectively.Immunohistochemistry stai-ning was also performed to investigate the changes in glial fibrillary acidic protein(GFAP)as a marker for astrocytes,ionized calcium-binding adapter molecule 1(IBA-1)as a marker for microglia,and CD31 as a marker for endothelial cells at different time points.Results No significant changes were observed in neu-ronal cells of the sham group at different time points.In the cerebral ischemia-reperfusion injury groups,cell apoptosis was activated at IR3h and increased in quan-tity with morphological damage as time progressed.Ne-uN+neurons showed signs of ischemic injury after IR3h,with abnormal cell morphology.From 12 h,Ne-uN+neurons decreased in a time-dependent manner and reached their peak severity at 24 h.GFAP+astro-cytes decreased significantly after IR3h,while poorly labeled GFAP+astrocytes increased at IR 6 h and al-most disappeared in the infarcted area at 24 h and 48 h.The number of IBA-1+microglia-positive cells de-creased at IR3h,and their volume increased at IR6h.Microglial cell death was observed in the infarcted area at IR12h.CD31+endothelial cells around the infarc-ted cortex and striatum increased significantly after IR3h and persisted until 48 h.Conclusions After cerebral ischemia-reperfusion injury,the number of ap-optotic cells increases with the prolongation of time,and NeuN+neurons exhibit the most severe damage at 24 h.GFAP+astrocytes and microglial cells gradually die over time.The number of CD31+endothelial cells increases significantly around the infarcted cortex and striatum after 3 h of reperfusion and persists until 48 h.

Aim To investigate the mechanisms of Ke-chuanting granules(KCT)inhibiting the IL-33/ILC2s pathway and pathogenic T cells to intervene in allergic airway inflammation.Methods Network pharmacolo-gy was utilized to analyze the potential targets and mechanisms of KCT-treated asthma.Allergic asthma models were induced in mice using OVA.Lung histo-pathology was conducted to observe injury changes.ELISA and quantitative PCR were utilized to measure key inflammatory factors and their mRNA expression levels in Th2-type asthma.Western blot was used to detect the phosphorylation levels of relevant proteins in the MAPK pathway.Flow cytometry was performed to evaluate the proportions of ILC2s,Th1,Th 17,Th2 and Treg cells.Results Network pharmacology iden-tified 227 main active components and 143 key targets of KCT in treating asthma,primarily enriched in signa-ling pathways such as MAPK and IL-17.Further vali-dation experiments demonstrated that KCT significantly alleviated lung inflammatory injury in asthmatic mice,reduced the number of B cells,production of I L-4,TNF-α and TGF-β,downregulated JNK phosphoryla-tion levels in lung tissue,as well as mRNA levels of Il-33,Bcl11b,Rorα,Tcf-7,Jun,Mapk3 and Mapk14.KCT intervention reduced the numbers of ILC2s and Th 17 cells in lungs and spleens of mice,and inhibited Th2 cell infiltration in lungs.Conclusions KCT ex-hibits therapeutic effects on allergic airway inflamma-tion in asthma,closely associated with the inhibition of the IL-33/ILC2s pathway,pathogenic T cell subsets,and JNK-MAPK signaling pathway.

Objective To investigate the cardiac structural and functional characteristics in the patients with heart failure with preserved ejection fraction (HFpEF) and type 2 diabetes mellitus (T2DM),and predict the factors influencing the characteristics. Methods A total of 783 HFpEF patients diagnosed in the Department of Geriatric Cardiology,the First Hospital of Lanzhou University from April 2009 to December 2020 were enrolled in this study.Echocardiography and tissue Doppler technique were employed to evaluate cardiac structure and function.According to the occurrence of T2DM,the patients were assigned into a HFpEF+T2DM group (n=332) and a HFpEF group (n=451).Propensity score matching (PSM)(in a 1∶1 ratio) was adopted to minimize confounding effect.According to urinary albumin excretion rate (UAER),the HFpEF+T2DM group was further divided into three subgroups with UAER<20 μg/min,of 20-200 μg/min,and>200 μg/min,respectively.The comorbidities,symptoms and signs,and cardiac structure and function were compared among the groups to clarify the features of diabetes related HFpEF.Multivariate linear regression was conducted to probe the relationship of systolic blood pressure,blood glucose,glycosylated hemoglobin,and UARE with cardiac structural and functional impairment. Results The HFpEF+T2DM group had higher prevalence of hypertension (P=0.001) and coronary heart disease (P=0.036),younger age (P=0.020),and larger body mass index (P=0.005) than the HFpEF group,with the median diabetic course of 10 (3,17) years.After PSM,the prevalence of hypertension and coronary heart disease,body mass index,and age had no significant differences between the two groups(all P>0.05).In addition,the HFpEF+T2DM group had higher interventricular septal thickness (P=0.015),left ventricular posterior wall thickness (P=0.040),and left ventricular mass (P=0.012) and lower early diastole velocity of mitral annular septum (P=0.030) and lateral wall (P=0.011) than the HFpEF group.Compared with the HFpEF group,the HFpEF+T2DM group showed increased ratio of early diastolic mitral filling velocity to early diastolic mitral annular velocity (E/e') (P=0.036).Glycosylated hemoglobin was correlated with left ventricular mass (P=0.011),and the natural logarithm of UAER with interventricular septal thickness (P=0.004),left ventricular posterior wall thickness (P=0.006),left ventricular mass (P<0.001),and E/e' ratio (P=0.049). Conclusion The patients with both T2DM and HFpEF have thicker left ventricular wall,larger left ventricular mass,more advanced left ventricular remodeling,severer impaired left ventricular diastolic function,and higher left ventricular filling pressure than the HFpEF patients without T2DM.Elevated blood glucose and diabetic microvascular diseases might play a role in the development of the detrimental structural and functional changes of the heart.
Humans ; Aged ; Heart Failure/diagnosis* ; Diabetes Mellitus, Type 2 ; Stroke Volume ; Glycated Hemoglobin ; Blood Glucose ; Propensity Score ; Ventricular Function, Left ; Hypertension

This study compared the chemical profiles, component content, dry paste yield, and pharmacological effects of samples obtained from the mixed single decoctions and the combined decoction of Gegen Qinlian Decoction(GQD), aiming to provide an experimental foundation for evaluating the equivalence of the two decocting methods and the suitability of TCM formula granules in clinical application. The same decoction process was used to prepare the combined decoction and mixed single decoctions of GQD. Ultra-performance liquid chromatography coupled with Q-Exactive Orbitrap mass spectrometry(UPLC-Q-Exactive Orbitrap MS) was employed to compare the chemical profiles between the two groups. High-performance liquid chromatography(HPLC) was used to compare the content of nine characteristic components between the two groups. Then, a delayed diarrhea mouse model induced by irinotecan was established to compare the pharmacological effects of the two groups on chemotherapy-induced diarrhea. The UPLC-Q-Exactive Orbitrap MS in ESI~+ and ESI~- modes identified 59 chemical components in the compound decoction and mixed single decoctions, which showed no obvious differences in component species. The content of baicalin and wogonoside was higher in the compound decoction, while that of puerarin, daidzein-8-C-apiosylglucoside, berberine, epiberberine, wogonin, glycyrrhizic acid, and daidzein was higher in the mixed single decoctions. Further statistical analysis revealed no significant difference in the content of the nine characteristic components between the compound decoction and the mixed single decoctions. The dry paste yield had no significant difference between the two groups. Compared with the model group, both compound decoction and mixed single decoctions alleviated the weight loss and reduced diarrhea index in mice. Both of them lowered the levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), cyclooxygenase-2(COX-2), intercellular adhesion molecule-1(ICAM-1), interleukin-10(IL-10), malondialdehyde(MDA), and nitric oxide(NO) in the colon tissue. Furthermore, they significantly increased the levels of glutathione peroxidase(GSH-Px) and superoxide dismutase(SOD). Hematoxylin-eosin(HE) staining showed that colon tissue cells were tightly arranged with clear nuclei in both groups without obvious difference. The compound decoction and mixed single decoctions showed no significant differences in chemical component species, content of nine characteristic components, dry paste yield, or the pharmacological effects on alleviating chemotherapy-induced diarrhea. The findings provide a reference for evaluating the flexibility and superiority of combined or single decocting method in the preparation of TCM decoctions or formula granules.
Animals ; Mice ; Biological Products ; Chromatography, High Pressure Liquid ; Coleoptera ; Cyclooxygenase 2 ; Diarrhea/drug therapy* ; Antineoplastic Agents