BACKGROUND:The phosphatidylinositol 3-kinase/protein kinase(PI3K/AKT)signaling pathway plays a pivotal role in regulating osteoclast activation,which is essential for maintaining bone homeostasis.Bone destruction in osteoarticular tuberculosis is caused by aberrant osteoclastogenesis induced by Mycobacterium tuberculosis infection.However,the role of the PI3K signaling pathway in Mycobacterium tuberculosis-induced aberrant osteoclastogenesis remains unclear. OBJECTIVE:To investigate the effects and mechanisms of the PI3K/AKT signaling pathway inhibitor BYL-719 on aberrant osteoclastogenesis induced by Mycobacterium tuberculosis. METHODS:RAW264.7 cells were infected with bovine Mycobacterium tuberculosis bacillus calmette-cuerin vaccine,and Ag85B was used for cellular immunofluorescence staining.The cell counting kit-8 assay was employed to determine the safe concentration of BYL-719.There were four groups in the experiment:blank control group,BYL-719 group,BCG group,and BCG+BYL-719 group.Under the induction of receptor activator of nuclear factor kappa-B ligand,the effects of BYL-719 on post-infection osteoclast differentiation and fusion were explored through tartrate-resistant acid phosphatase staining and phalloidin staining.RT-PCR and western blot were used to detect the expression of osteoclast-related genes and proteins,and further investigate the mechanism of action. RESULTS AND CONCLUSION:Immunofluorescence staining showed that RAW264.7 cells phagocytosed Mycobacterium tuberculosis.Cell counting kit-8 data indicated that 40 nmol/L BYL-719 was non-toxic to cells.Tartrate-resistant acid phosphatase staining and phalloidin staining showed that BYL-719 inhibited the generation and fusion ability of osteoclasts following infection.RT-PCR and western blot results also indicated that BYL-719 suppressed the upregulation of osteoclast-specific genes(including c-Fos,NFATc1,matrix metalloproteinase 9,and CtsK)induced by Mycobacterium tuberculosis infection(P<0.05).Western blot and immunofluorescence staining revealed that BYL-719 inhibited excessive osteoclast differentiation induced by Mycobacterium tuberculosis by downregulating the expression of IκBα-p65.To conclude,BYL-719 inhibits aberrant osteoclastogenesis induced by Mycobacterium tuberculosis through the downregulation of IκBα/p65.Therefore,the IκBα/p65 signaling pathway is a potential therapeutic target for osteoarticular tuberculosis,and BYL-719 holds potential value for the preventing and amelioration of bone destruction in osteoarticular tuberculosis.BYL-719 has the potential to prevent and ameliorate bone destruction in osteoarticular tuberculosis.

Objective To explore the clinical and immunological significance of CCDC97 in hepatocellular carcinoma (HCC). Methods Clinical data and RNA sequencing results from HCC patients were retrieved from TCGA and ICGC databases. Bioinformatics analysis and in vitro experiments were performed to investigate the role of CCDC97 in HCC. Results The expression level of CCDC97 was elevated in HCC patients and HCC cells, closely associated with pathological features and prognosis. CCDC97 was identified as a novel prognostic biomarker. It is linked to the spliceosome pathway, which is significantly active in tumors and potentially promotes carcinogenesis. CCDC97 is also highly expressed in various immune cells and is associated with microenvironment. Furthermore, knocking down CCDC97 in vitro suppressed cell migration, invasion, and proliferation. Conclusion CCDC97 plays a critical role in HCC progression and the immune microenvironment, making it a potential target for prognosis and therapeutic intervention.
Humans ; Carcinoma, Hepatocellular/metabolism* ; Liver Neoplasms/metabolism* ; Tumor Microenvironment/genetics* ; Cell Movement/genetics* ; Cell Proliferation ; Prognosis ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Biomarkers, Tumor/genetics* ; Male

OBJECTIVE: To compare and analyze the changes of aggregation rate and routine parameters of platelets stored in temperature cycle, cold storage at 4 ℃ and oscillating storage at 22 ℃, so as to provide more experimental data for platelet preservation methods. METHODS: Blood samples were collected at 5 time points on the 1^st, 2^nd, 3^rd, 4^th and 6^th day after platelet cycling preservation at temperature, cold storage at 4 ℃, and oscillating storage at 22 ℃. Platelet maximum aggregation rate (MAR) and routine parameters including platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW) and platelet-larger cell ratio (P-LCR) were detected. RESULTS: The platelet MAR of three groups showed a significant decrease trend with the preservation time, the fastest decrease was in the 22 ℃ group, the slowest was in the 4 ℃ group, and the temperature cycle group was between the two groups. On the 3^rd day of preservation, the platelet MAR in 4 ℃ group was still in the normal range (MAR>60%), while in temperature cycle group was about 50%, and in 22 ℃ group was the lowest. On the 4^th day of preservation, platelet MAR in all the three groups was lower than 50%, and that in temperature cycle group was significantly lower than in 4 ℃ group but higher than in 22 ℃ group (both P < 0.05). On the 6^th day of preservation, platelet MAR in the temperature cycle group was significantly lower than that in the 4 ℃ group ( P <0.05), but there was no statistically significant difference compared to 22 ℃ group (P >0.05). PLT values in the three groups were all significantly decreased with the preservation time extension, and were significantly lower than those in the early stage of preservation within 6 days (all P < 0.05). PDW in temperature cycle group had no significant change within 6 days of preservation, but MPV and P-LCR were significantly increased. MPV, PDW and P-LCR all decreased significantly in 4 ℃ group within 6 days of preservation but increased in 22 ℃ group. Under the same storage days, PLT value of temperature cycle group had no significant difference with that of 4 ℃ group and 22 ℃ group, while MPV, PDW and P-LCR values were significantly higher than 4 ℃ group but lower than 22 ℃ group (all P < 0.05). CONCLUSION The aggregation function and routine parameters changes of temperature circulating preserved platelets are between 4 and 22 ℃.
Humans ; Platelet Aggregation ; Blood Preservation/methods* ; Temperature ; Blood Platelets ; Platelet Count ; Mean Platelet Volume ; Cryopreservation/methods* ; Cold Temperature

Objective To investigate the risk factors and preventive strategies of pancreaticoduodenectomy postoperative hemorrhage.Methods A total of 208 patients who underwent pancreaticoduodenectomy in the Department of Hepatobiliary Surgery of the 904th Hospital of Joint Logistics Support Force,PLA from January 2017 to December 2021 were enrolled.Twenty-one patients with postoperative hemorrhage were retrospectively analyzed.Results Univariate analysis indicated that postoperative hemorrhage was mainly associated with pancreatic leakage,biliary leakage,abdominal infection,hypoproteinemia,diabetes,improper use of ultrasound knife,skeletonization,intraoperative blood loss,preoperative jaundice,etc.(P<0.05),but not gender and age(P>0.05).Among the 21 patients with postoperative hemorrhage,4 cases recovered after conservative treatment such as hemostasis and blood transfusion,6 cases underwent interventional treatment,11 cases underwent abdominal exploration,and 2 cases died of postoperative multiple organ failure.Pancreatic leakage(OR=3.963,95%CI:1.120-14.025),biliary leakage(OR=4.013,95%CI:1.173-13.734)and abdominal infection(OR=7.545,95%CI:1.833-31.051)were independent risk factors for postoperative hemorrhage.Conclusions The improvement of anastomotic manipulation,reduction of anastomotic leakage,and control and prevention of abdominal infection are important to prevent postoperative hemorrhage of pancreaticoduodenectomy.Surgical treatment should be performed as soon as possible for the patients with poor conservative treatment effect.

Objective To explore the causal association between gut microbes and non-alcoholic fatty liver disease(NAFLD)by Mendelian randomisation analysis.Methods Genetic instrumental variables for gut microbiota were identified from a gene-wide association study of 18 340 participants,and summary statistics for NAFLD were ob-tained from the FinnGen database,which provided data on 894 NAFLD cases and 217 898 controls using the IVW method as the primary analysis.In order to test the robustness of the results,MR-Egger method,WM method,Simple Mode method,Weighted Mode method were used for Mendelian randomisation analysis,and heterogeneity test,sensitivity analysis,and multiplicity analysis were performed.Results class Gammaproteobacteria IVW re-sults showed(OR=0.621,95％CI=0.412～0.934,P=0.022);family Enterobacteriaceae IVW results showed(OR=1.481,95％CI=1.069～2.053,P=0.018);genus Lachnospiraceae IVW results showed(OR=1.405,95％CI=1.036～1.904,P=0.029);genus Prevotella7 IVW results showed(OR=0.834,95％CI=0.714～0.974,P=0.021);genus Prevotella9 IVW results showed(OR=1.251,95％CI=1.025～1.527,P=0.027);order Desulfovibrionales IVW results showed(OR=0.714,95％CI=0.519～0.982,P=0.038);or-der Enterobacteriales IVW results showed(OR=1.481,95％CI=1.069～2.053,P=0.018).And there was no heterogeneity in the heterogeneity test,and the sensitivity analyses all showed robustness and no pleiotropy was found.Conclusion This study implicates class Gammaproteobacteria,family Enterobacteriaceae,genus Lachno-spiraceae,genus Prevotella7,genus Prevotella9,order Desulfovibrionales,order Enterobacteriales seven species of gut microorganisms have a causal relationship with NAFLD.

Objective     To explore the efficacy of prone positioning ventilation in patients with acute respiratory distress syndrome (ARDS) after acute Stanford type A aortic dissection (STAAD) surgery. Methods     From November 2019 to September 2021, patients with ARDS who was placed prone position after STAAD surgery in the Xiamen Cardiovascular Hospital of Xiamen University were collected. Data such as the changes of blood gas, respiratory mechanics and hemodynamic indexes before and after prone positioning, complications and prognosis were collected for statistical analysis. Results    A total of 264 STAAD patients had surgical treatment, of whom 40 patients with postoperative ARDS were placed prone position. There were 37 males and 3 females with an average age of 49.88±11.46 years. The oxygen partial pressure, oxygenation index and peripheral blood oxygen saturation 4 hours and 12 hours after the prone positioning, and 2 hours and 6 hours after the end of the prone positioning were significantly improved compared with those before prone positioning ventilation (P<0.05). The oxygenation index 2 hours after the end of prone positioning which was less than 131.42 mm Hg, indicated that the patient might need ventilation two or more times of prone position. Conclusion     Prone position ventilation for patients with moderate to severe ARDS after STAAD surgery is a safe and effective way to improve the oxygenation.

Objective To establish a method for HPLC fingerprint analysis and determine three main components of Modified Zengye Decoction.Methods The chromatographic column was Shimadzu WondaSil C18 column(250 mm×4.6 mm,5 μm),the mobile phase was acetonitrile-0.3％aqueous phosphoric acid with a gradient elution procedure,the volume flow rate was 1.0 mL/min,the detection wavelengths were 265,203,310 and 290 nm,the column temperature was 25 ℃,and the injection volume was 20 μL.The HPLC fingerprints of the 10 batches of Modified Zengye Decoction were established,and the similarity analysis was performed by using the similarity evaluation system of chromatographic fingerprint of traditional Chinese medicine(version 2012A).The common peaks were identified and assigned,and the contents of the three main components were quantitatively determined.Results There were 17 common peaks in the fingerprints of 10 batches of Modified Zengye Decoction with similarities ranging from 0.872-0.989.The fingerprints recognized peak 9,14 and 17 as ferulic acid,aurantiamarin and harpagoside,respectively.The contents of ferulic acid,aurantiamarin and harpagoside were 0.067 3-0.174 8,0.498 8-1.522 7,0.270 9-0.802 4 mg/g,and the transfer rate were 30.74％-55.63％,11.77％-35.94％,23.15％-68.56％,respectively.Conclusion The established HPLC fingerprint analysis method combined with main components quantitative analysis method can be used for the quality analysis and control of Modified Zengye Decoction with simple analysis method and reliable results.

Purpose: Numerous studies have produced conflicting findings regarding the efficacy of statins in prostate cancer treatment. Our objective was to examine the correlation between statin usage and clinical outcomes in Taiwanese men with de novo metastatic prostate cancer. Materials and Methods: We identified patients diagnosed with de novo metastatic prostate cancer from the Chang Gung Research Database spanning the years 2007 to 2020. To minimize confounding bias, we employed the inverse probability of treatment weighting (IPTW) method. Clinical outcomes were assessed using IPTW-adjusted Kaplan-Meier curves. Multivariate Cox proportional hazard regression analysis was utilized to evaluate the association between mortality and clinical factors. Results: The study cohort comprised 1,716 statin users and 276 non-users. Patients who used statins exhibited a longer median overall survival (85.4 months compared to 58.2 months; p=0.001) and cancer-specific survival (112.6 months compared to 75.7 months; p<0.001) compared to non-users. The median time to the development of castration-resistant status was similar between statin users and non-users (p=0.069). Multivariable Cox proportional hazards regression analysis, after IPTW adjustment, demonstrated that statin use was associated with improved overall survival. Conclusions Our study indicates that the use of statins following a de novo metastatic prostate cancer diagnosis enhances survival outcomes. However, statins did not appear to delay the onset of castration-resistant status. Further large-scale and long-term studies are warranted to investigate the biological effects of statins in men with prostate cancer.

Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

Background: The initiation of sodium-glucose cotransporter-2 inhibitors (SGLT2i) typically leads to a reversible initial dip in estimated glomerular filtration rate (eGFR). The implications of this phenomenon on clinical outcomes are not well-defined. Methods: We searched MEDLINE, Embase, and Cochrane Library from inception to March 23, 2023 to identify randomized controlled trials and cohort studies comparing kidney and cardiovascular outcomes in patients with and without initial eGFR dip after initiating SGLT2i. Pooled estimates were calculated using random-effect meta-analysis. Results: We included seven studies in our analysis, which revealed that an initial eGFR dip following the initiation of SGLT2i was associated with less annual eGFR decline (mean difference, 0.64; 95% confidence interval [CI], 0.437 to 0.843) regardless of baseline eGFR. The risk of major adverse kidney events was similar between the non-dipping and dipping groups but reduced in patients with a ≤10% eGFR dip (hazard ratio [HR], 0.915; 95% CI, 0.865 to 0.967). No significant differences were observed in the composite of hospitalized heart failure and cardiovascular death (HR, 0.824; 95% CI, 0.633 to 1.074), hospitalized heart failure (HR, 1.059; 95% CI, 0.574 to 1.952), or all-cause mortality (HR, 0.83; 95% CI, 0.589 to 1.170). The risk of serious adverse events (AEs), discontinuation of SGLT2i due to AEs, kidney-related AEs, and volume depletion were similar between the two groups. Patients with >10% eGFR dip had increased risk of hyperkalemia compared to the non-dipping group. Conclusion Initial eGFR dip after initiating SGLT2i might be associated with less annual eGFR decline. There were no significant disparities in the risks of adverse cardiovascular outcomes between the dipping and non-dipping groups.