ObjectiveTo investigate the dynamic trajectories of prognostic scores and key clinical indicators in hepatitis B virus-related acute-on-chronic liver failure （HBV-ACLF） patients without liver cirrhosis， to clarify their association with outcomes， and to provide new evidence for individualized prognostic assessment. MethodsA prospective study was conducted for the data of 154 non-cirrhotic HBV-ACLF patients who attended Beijing YouAn Hospital of Capital Medical University from January 2016 to December 2023， including prognostic scores and key biochemical indicators on Days 3， 7， 14， 21， and 28 of the disease course. According to the outcome of patients at 1 year， they were divided into death/liver transplantation group with 43 patients， liver cirrhosis group with 23 patients， and non-liver cirrhosis group with 88 patients， and the trajectory heterogeneity of different outcome subgroups was analyzed. A one-way analysis of variance was used for comparison of normally distributed continuous data among the three groups； the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data among the three groups； the Wilcoxon test was used between two groups. the chi-square test was used for comparison of categorical data between groups. The mean and its 95% confidence interval （CI） were calculated for each indicator at difference time points； the linear interpolation method was used to connect the means at adjacent time points and construct the group-specific longitudinal trend curve； the 95%CI was visualized using the semi-transparent ribbon area， with the transparency parameter （α=0.2） optimized to enhance the visual discrimination of overlapping intervals across multiple groups. A linear mixed-effects model was used to compare the longitudinal changing trend of each indicator between the patients with different outcomes； likelihood ratio was used to evaluate the significance of the interaction effect between time and group， and in case of the significant interaction effect， the slope based on the estimated marginal mean was used for comparison between two groups. ResultsThere were significant differences between the three groups in the incidence rates of ascites and grade Ⅲ — Ⅳ hepatic encephalopathy， MELD score， MELD-Na score， CLIF-C ACLF score， COSSH-ACLF Ⅱ score， total bilirubin （TBil）， international normalized ratio （INR）， alpha-fetoprotein， blood sodium， alanine aminotransferase， and procalcitonin at the baseline（all P0.05）. The analysis of dynamic trajectories showed that the death/liver transplantation group had high levels of prognostic scores and the biochemical parameters of TBil and INR （TBil400 μmol/L， INR2.5）， as well as a low level of platelet count （PLT） （100×10⁹/L）. The non-liver cirrhosis group had rapid improvements in indicators， with TBil200 μmol/L， INR1.5， and PLT100×10⁹/L by day 28， while the liver cirrhosis group showed a trend of recovery， with TBil200 μmol/L， INR2.0， and PLT 100×10⁹/L on day 28， with significant global heterogeneity in the temporal trends of the above indicators across the three groups （all P0.01）. ConclusionDynamic monitoring of prognostic scores and key clinical indicators can effectively stratify the 1-year outcomes of non-cirrhotic patients with HBV-ACLF. Patients with poor prognosis were typically characterized by INR 2.5 and TBil 400 μmol/L. Among those who survived beyond 1 year， individuals who subsequently progressed to cirrhosis were frequently identified by the presence of INR 1.5， TBil 200 μmol/L， and PLT 100×10⁹/L at day 28.

OBJECTIVE: To compare the efficacy and safety of intravenous colistin sulfate combined with nebulized inhalation versus intravenous monotherapy for pulmonary infections caused by carbapenem-resistant organism (CRO). METHODS: A multicenter retrospective cohort study was conducted. Clinical data were collected from patients admitted to the intensive care unit (ICU) of 10 tertiary class-A hospitals in Henan Province between July 2021 and May 2023, who received colistin sulfate for CRO pulmonary infections. Data included baseline characteristics, inflammatory markers [white blood cell count (WBC), neutrophil count (NEU), procalcitonin (PCT), C-reactive protein (CRP)], renal function indicators [serum creatinine (SCr), blood urea nitrogen (BUN)], life support measures, anti-infection regimens, clinical efficacy, microbiological clearance rate, and prognostic outcomes. Patients were divided into two groups: intravenous group (colistin sulfate monotherapy via intravenous infusion) and combination group ((intravenous infusion combined with nebulized inhalation of colistin sulfate). Changes in parameters before and after treatment were analyzed. RESULTS: A total of 137 patients with CRO pulmonary infections were enrolled, including 89 in the intravenous group and 48 in the combination group. Baseline characteristics, life support measures, daily colistin dose, and combination regimens (most commonly colistin sulfate plus carbapenems in both groups) showed no significant differences between two groups. The combination group exhibited higher clinical efficacy [77.1% (37/48) vs. 59.6% (52/89)] and microbiological clearance rate [60.4% (29/48) vs. 39.3% (35/89)], both P < 0.05. Pre-treatment inflammatory and renal parameters showed no significant differences between two groups. Post-treatment, the combination group showed significantly lower WBC and CRP [WBC (×10⁹/L): 8.2±0.5 vs. 10.9±0.6, CRP (mg/L): 14.0 (5.7, 26.6) vs. 52.1 (24.4, 109.6), both P < 0.05], whereas NEU, PCT, SCr, and BUN levels showed no significant between two groups. ICU length of stay was shorter in the combination group [days: 16 (10, 25) vs. 21 (14, 29), P < 0.05], although mechanical ventilation duration and total hospitalization showed no significant differences between two groups. CONCLUSIONS Intravenous colistin sulfate combined with nebulized inhalation improved clinical efficacy and microbiological clearance in CRO pulmonary infections with an acceptable safety profile.
Humans ; Colistin/therapeutic use* ; Retrospective Studies ; Administration, Inhalation ; Anti-Bacterial Agents/therapeutic use* ; Carbapenems/pharmacology* ; Male ; Female ; Middle Aged ; Gram-Negative Bacteria/drug effects* ; Aged ; Treatment Outcome ; Respiratory Tract Infections/drug therapy*

Objective To investigate the effects of menaquinone-4(MK4)on the activation and function of CD8+T cells.Methods An in vitro culture system for primary mouse CD8+T cells was established by isolating these cells from the spleen using CD8a T cell isolation kit.The isolated CD8+T cells were then incubated and activated in a 96-well plate coated with anti-CD3/CD28 antibodies.The impact of MK4 on the activation and cytokine secretion of CD8+T cells was explored by quantifying the expression levels of CD8+T cell activation receptors and cytokines using flow cytometry.Additionally,the concentrations of these cytokines in the culture supernatant were measured by enzyme-linked immunosorbent assay(ELISA).The influence of MK4 on the anti-tumor function of CD8+T cells was evaluated by co-culturing colorectal cancer MC38 cells of mice with CD8+T cells at different ratios,and the effect of MK4 was assessed by detecting tumor cell apoptosis.Results High-purity primary CD8+T cells of mice(97.5％)were isolated using the magnetic bead,which could be activated by pre-coated CD3/CD28 antibodies and showed proliferation.Compared with the control group,the MK4-treated group exhibited increased expressions of CD25,CD69 and CD44 on CD8+T cells,as well as higher production and secretion levels of interleukin-2(IL-2),interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α)and granzyme B.In addition,CD8+T cells in the MK4-treated group induced a higher percentage of tumor cell apoptosis(36.7％)compared with the control group(29.1％).Conclusion MK4 can enhance the activation of CD8+T cells and promote anti-tumor functions.

Mitochondrial disease is one of the major types of inherited metabolic disease that can affect all age groups,particularly in children where it has a high mortality and disability rate.With the development of biochemical,molecular,and cellular biology techniques,the laboratory diagnosis of mitochondrial disease has undergone rapid development.The diagnostic pathways and strategies have gradually transitioned from highly invasive laboratory tests to mainly non-invasive screenings.However,the challenge remains that the positive diagnostic rate of single testing strategies is insufficient,and the proportion of missed and pending investiga-tions remains high.Consequently,new mitochondrial disease laboratory diagnostic techniques continue to e-merge and are used to aid in disease diagnosis.This review attempts to summarize the current progress in mi-tochondrial disease laboratory diagnostics at three levels:genetics,enzyme biochemistry,and metabolic biolo-gy,providing references for the selection of laboratory diagnostic strategies in specific scenarios,as well as suggestions for the development of future detection technologies.

OBJECTIVE To provide reference for the safe use of bevacizumab in cancer patients. METHODS The diagnosis and treatment of a 65-year-old female lung adenocarcinoma patient with diabetic ketoacidosis （DKA） induced by bevacizumab was retrospectively analyzed， and the possible mechanisms and causes were analyzed based on literature review. RESULTS & CONCLUSIONS The diagnosis and treatment process of patients were analyzed， and DKA caused by other drugs and disease factors were excluded. DKA was considered to be caused by the use of bevacizumab according to Naranjo’s ADR evaluation scale； the acidosis of the patient improved rapidly after one hemodialysis treatment. DKA caused by bevacizumab is rare in clinic， clinicians should be aware that bevacizumab may affect pancreatic function and induce DKA， and early detection and treatment should be achieved to improve the prognosis.

Objective: To explore the effectiveness of machine learning in predicting adolescent Internet gaming disorder, so as to provide guidance for formulating effective intervention measures. Methods: From June to September，2023，a total of 2 100 students from 3 middle schools and 3 high schools in Bijie City, Qianxi City and Jinsha County, Guizhou Province were selected by stratified random cluster sampling as research subjects. Data was collected by using several instruments, including the Nine item Internet Gaming Disorder Scale-Short From (IGDS9-SF), Parental Psychological Control and Autonomy Support Questionnaire(PPCASQ), Motivation Structure Questionnaire, Relative Deprivation Questionnaire, Deviant Peer Association Questionnaire, and Dual Systems of Self control Scale. Descriptive statistical analysis was conducted to characterize the sample features, and the distribution differences of categorical variables were analyzed by using Chi square test and Mann-Whitney U test. Demographic variables and various influencing factors were served as independent variables, and whether adolescents were addicted to Internet gaming was the dependent variable. Various machine learning algorithms, including random forest, Logistic regression, support vector machine, gradient boosting trees, decision trees, and adaptive boosting were employed to construct predictive models. Results: The detection rate of Internet gaming disorder among adolescents was 4.57% (96 cases). Males and middle school students had higher Internet gaming disorder detection rates (5.52%,6.29%) than females and high school students (3.32%,3.62%), and the differences were statistically significant ( χ 2=5.71,7.86, P ＜0.01).The scores of relative deprivation,deviant peer affiliation, paternal psychological control, maternal psychological control, control motivation, impulsive system and its dimensions (impulsivity, distractibility, low delay of gratification) in Internet gaming disorder group were higher than in non Internet gaming disorder, while the score of parental autonomy support was lower than that in the non Internet gaming disorder group ( Z =-2.88,-9.32,-4.13,-4.48, -6.58 ,-7.50,-7.18,-7.56,-7.43,-2.27, P <0.05). The adaptive boosting algorithm performed the best (accuracy=99%, recall=95%, F1 score=97%, AUC=0.96). Random forest and gradient boosting trees also performed excellently (accuracy=98%, recall=95%, F1 score=97%, 96%, AUC=0.96). Conclusions Compared to other models, the adaptive boosting algorithm shows a good predictive effectiveness for adolescent Internet gaming disorder. Appropriate models should be selected to identify individuals with Internet gaming disorder as early as possible, to develop effective intervention strategies and reduce the risk of Internet gaming disorder.

Objective To investigate the value of histone deacetylase 3(HDAC3)in evaluating the risk of slow/no reflow in AMI patients after PCI.Methods A total of 280 AMI patients undergo-ing PCI in our hospital from June 2020 to June 2022 were recruited,and according to TIMI blood flow grading,they were divided into slow/no reflow group(TIMI≤grade 11,n=54)and normal flow group(TIMI＞grade Ⅱ,n=226).The demographic characteristics,underlying diseases,baseline data at admission,and preoperative results of coronary angiography and laboratory tests were compared between the two groups.Multivariate logistic regression analysis was used to determine the influencing factors for slow/no reflow in AMI patients after PCI,and ROC curve was drawn to analyze the predictive value of related indicators for slow/no reflow.Results Obvi-ously larger proportions of smoking history and Killip grade Ⅱ,higher heart rate,longer reperfu-sion time,and higher serum levels of LDL-C,NLR,D-D and HDAC3 were observed in the slow/no reflow group than the normal flow group(P＜0.05,P＜0.01).Multivariate logistic regression analysis showed that reperfusion time,NLR and HDAC3 were influencing factors for slow/no reflow in AMI patients after PCI(P＜0.05,P＜0.01).The AUC value of reperfusion time+NLR in predicting the slow/no reflow after PCI in AMI patients was 0.798(95％CI:0.664-0.922,P=0.002),with a sensitivity and specificity of 0.87 and 0.73,respectively.And when serum HDAC3 level was combined in the prediction,the AUC value was 0.903(95％CI:0.790-0.922,P＜0.01),with a sensitivity and specificity of 0.93 and 0.84,respectively.Conclusion Preoperative HDAC3 level is an influencing factor for slow/no reflow in AMI patients after PCI.Based on reperfusion time and NLR,combination of the 3 indicators can provide additional predictive value for slow/no reflow in these patients.

OBJECTIVE: To observe the anatomical features and relative position of the brachiocephalic trunk and the trachea to provide an anatomical basis for diagnosis and treatment of mechanical airway obstruction and for facilitating the performance of tracheotomy. METHODS: A total of 91 formalin- fixed adult cadavers (70 male and 21 female) were used in this study. The whole length of the larynx and the trachea were separated and exposed from the neck to the chest, followed by separation of the aortic arch and its 3 branches to observe the anatomical position of the brachiocephalic trunk and the trachea. RESULTS: The brachiocephalic trunk and the trachea did not intersect in 3.30%, partially intersected in 71.43%, and completely intersected in 25.27% of the 91 cadaveric specimens. The male specimens all showed greater outer diameter of the aortic arch, the brachiocephalic trunk and the trachea with a greater length of the trachea than the female specimens (P < 0.05), while the distances from the aortic arch to the brachiocephalic trunk or the cricoid cartilage did not differ significantly between them (P > 0.05). The number of the tracheal cartilage rings above the brachiocephalic trunk ranged from 3 to 10, and the mean number did not differ significantly between the male and female specimens (P > 0.05). CONCLUSION The brachiocephalic trunk has complex anatomical relationship with the trachea, and caution should be taken to avoid injuries of the brachiocephalic trunk and the aortic arch in the diagnosis and treatment of mechanical respiratory obstruction and during tracheotomy.
Adult ; Female ; Male ; Humans ; Trachea ; Brachiocephalic Trunk ; Larynx ; Cadaver ; Formaldehyde

Objective: To observe the effect of the acupuncture plus medication on the expression of silent information regulator of transcription 1 (SIRT1) and transcription factor forkhead box protein O3a (FOXO3a) in the hippocampus, the malondialdehyde (MDA) content, and the superoxide dismutase (SOD) activity of rats with Alzheimer disease (AD), and to explore the possible mechanism of combining acupuncture and medication in improving AD-related neurological symptoms. Methods: Sixty male Sprague-Dawley rats were divided into a normal group, a model group, an electroacupuncture (EA) group, a drug group, and an acupuncture-medication combined group by the random number table method, with 12 rats in each group. The model was established by micro-injection of streptozotocin into the bilateral lateral ventricles. After successful modeling, rats in the EA group received EA at Zusanli (ST36) and Dazhui (GV14), those in the drug group received intragastric administration of resveratrol at a dose of 44 mg/(kg·bw), and those in the acupuncture- medication combined group received the combined intervention of EA and resveratrol. Rats in each group received intervention once a day for 4 consecutive weeks. Morris water maze was used to detect the rat behavioral changes. Nissl staining method was used to observe the cell morphology and changes in the number of rat hippocampal neurons. Western blotting and immunohistochemical staining methods were used to observe the expression changes of SIRT1 and FOXO3a. The thiobarbituric acid method was used to detect the MDA content. SOD activity was determined by the hydroxylamine method. Results: Compared with the normal group, the escape latency was significantly prolonged (P<0.05); the percentage of stay in the target quadrant was reduced (P<0.05), the hippocampal neuronal cells were shrunken, nucleoli were unclear, and cell number was reduced (P<0.05); the SIRT1 expression and SIRT1 positive cell number were decreased, while the FOXO3a expression and FOXO3a positive cell number were increased significantly (P<0.05); the MDA content was increased significantly, and the SOD activity was decreased significantly (P<0.05) in the model group. Compared with the model group, the escape latency was shortened (P<0.05); the percentage of stay in the target quadrant was increased (P<0.05); the shape and number of hippocampal neurons tended to be normal (P<0.05); the SIRT1 protein expression and the SIRT1 positive cell numbers were increased, the FOXO3a protein expression and the FOXO3a positive cell number were decreased (P<0.05); the MDA content was significantly decreased, and the SOD activity was significantly increased (P<0.05) in the EA group, the drug group, and the acupuncture-medication combined group. The changes in the acupuncture-medication combined group were more obvious (P<0.05). Conclusion: Both EA and resveratrol improve the learning and memory ability of AD rats by regulating the expression of SIRT1 and FOXO3a and improving the levels of MDA and SOD in the hippocampus and protect the hippocampal neurons, while the combined use of EA and medication is more effective than EA or resveratrol alone, suggesting that this combined treatment is more effective in AD treatment.