ObjectiveTo investigate the clinical application value of thromboelastographic parameters in assessing coagulation function by analyzing the thromboelastographic features of patients with primary liver cancer （PLC）， and to provide a basis for coagulation management and prognostic evaluation in liver cancer patients. MethodsA retrospective analysis was performed for 1 253 PLC patients who were admitted to The First Affiliated Hospital of Xi’an Jiaotong University from May 2015 to December 2022. According to the presence or absence of cirrhosis， the patients were divided into non-cirrhosis group with 262 patients and cirrhosis group with 991 patients， and according to the presence or absence of HBV infection， they were divided into HBV infection group with 1 055 patients and non-HBV infection group with 198 patients. The patients were stratified based on the severity of liver cirrhosis （Child-Pugh class and MELD score） and liver reserve function （indocyanine green retention rate at 15 minutes ［ICGR15］）， and thromboelastography was used to measure thromboelastographic parameters （reaction time ［R］， coagulation formation time ［K］， α-angle， maximum thrombosis amplitude ［MA］， and coagulation composite index ［CI］） and conventional coagulation markers. The t-test was used for comparison of normally distributed continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the Kruskal-Wallis H test was used for comparison between multiple groups， and the Bonferroni correction method was used for further comparison between two groups. The chi-square test was used for comparison of categorical data between grouips， and the Spearman test was used for correlation analysis. ResultsAmong the 991 patients in the cirrhosis group， 826 had Child-Pugh class A （5 — 6 points）， and 165 had Child-Pugh class B （7 — 9 points）； 812 had an MELD score of <10， and 179 had an MELD score of ≥10； 679 had an ICGR15 of <10%， and 294 had an ICGR15 of ≥10%. Compared with the patients with Child-Pugh class A， the patients with Child-Pugh class B had a significantly longer K time and significant reductions in α-angle， MA， and CI （all P <0.001）； compared with the MELD score <10 group， the MELD score ≥10 group had a significantly longer K time and significant reductions in α-angle， MA， and CI （all P<0.001）； compared with the ICGR15 <10% group， the ICGR15 ≥10% group had a significantly longer K time and a significant reduction in MA （both P <0.001）. Among the 1 253 patients， MA was strongly positively correlated with fibrinogen and platelet count （r=0.675 and 0.667， both P<0.001）； The MA had a weak correlation with Child-Pugh score， MELD score， and ICGR15 （r=-0.112， -0.250， and -0.117， all P<0.001）， while the K time，α-angle and CI were weakly correlated with the MELD score （r=0.222， -0.184， and -0.183， all P<0.001），R time was negatively correlated with ICGR15 （r=-0.080， P=0.005）. The HBV infection group had significantly higher MA and CI than the non-HBV infection group （P<0.05）. ConclusionThromboelastography can sensitively identify the hypocoagulable state associated with the progression of liver cirrhosis and the hypercoagulable tendency in HBV-related liver cancer， which provides an important reference for individualized anticoagulant therapy in clinical practice.

ObjectiveTo investigate the impact of Buzhong Yiqitang combined with cisplatin on the proliferation of human lung adenocarcinoma （A549） cells through regulation of the pyruvate dehydrogenase kinase 1 （PDK1）/protein kinase B （Akt） signaling pathway and influence on glycolysis. MethodsTranscriptome sequencing （RNA-seq） was employed to compare the expression of glycolysis-related genes between A549 cells and cisplatin-resistant human lung adenocarcinoma cells （A549/DDP）. Small interfering RNA （siRNA） was employed to knock down PDK1， and the knockdown efficiency was verified by Western blot and Read-time PCR. The cell counting kit-8 （CCK-8） assay was used to assess the survival and viability of A549 cells under the following conditions： siRNA negative control+cisplatin （128， 64， 32， 16， 8， 4， 0 μmol·L^-1）， siPDK1+cisplatin （128， 64， 32， 16， 8， 4， 0 μmol·L^-1）， and siPDK1+cisplatin （128， 64， 32， 16， 8， 4， 0 μmol·L^-1）+Buzhong Yiqitang （10%）-containing serum. The 20% inhibitory concentration （IC₂₀） of the siRNA negative control+cisplatin group （7.832 μmol·L^-1） was calculated and used as the subsequent cisplatin concentration. Colony formation assay was performed to evaluate the proliferation of A549 cells. Lactate and adenosine triphosphate （ATP） assay kits were used to measure lactate and ATP production. The mitochondrial membrane potential was detected with the fluorescent probe JC-1. Western blotting was conducted to examine the expression levels of PDK1， phosphorylated （p）-Akt， Akt， pyruvate kinase M2 （PKM2）， glucose transporter 1 （GLUT1）， pyruvate dehydrogenase （PDH）， and lactate dehydrogenase A （LDHA）. Confocal immunofluorescence was employed to detect PDK1 and p-Akt. ResultsRNA-seq results identified PDK1 as a highly expressed differential gene in glycolysis metabolism between A549 cells and A549/DDP cells， and it was highly expressed in tumor cells. Gene Set Enrichment Analysis （GSEA） revealed upregulated and downregulated genes in glycolysis and gluconeogenesis pathways. Western blot and RT-qPCR confirmed that PDK1-si-2 had the highest transfection efficiency， with a PDK1 knockdown rate exceeding 60%. CCK-8 assay determined the half-maximal inhibitory concentration （IC₅₀） values for each group as （30.698±5.348）， （16.372±3.562）， （13.237±1.573） μmol·L^-1， while the IC₂₀ of cisplatin in siRNA negative control-transfected A549 cells was （7.832±0.672） μmol·L^-1. Compared with the siRNA negative control group， the siRNA negative control+cisplatin group showed decreased colony formation rate， reduced lactate production， lowered mitochondrial membrane potential， downregulated protein levels of p-Akt， GLUT1， PDK1， PDH， and LDHA， and reduced PDK1 fluorescence intensity （P<0.05）. The siPDK1 group exhibited decreased colony formation rate， reduced lactate production， increased ATP production， lowered mitochondrial membrane potential， downregulated protein levels of p-Akt， PKM2， GLUT1， PDK1， PDH， and LDHA， and reduced PDK1 and p-Akt fluorescence intensity （P<0.05）. Compared with the siPDK1 group， the siPDK1+Buzhong Yiqitang group showed decreased colony formation rate， reduced lactate production， downregulated protein levels of PKM2， GLUT1， and PDK1， and reduced PDK1 fluorescence intensity （P<0.05）. The siPDK1+cisplatin group exhibited decreased colony formation rate， reduced lactate production， increased ATP production， lowered mitochondrial membrane potential， downregulated protein levels of PKM2， GLUT1， PDK1， and PDH， and reduced PDK1 and p-Akt fluorescence intensity （P<0.05）. The siPDK1+cisplatin+Buzhong Yiqitang group demonstrated decreased colony formation rate， reduced lactate production， increased ATP production， lowered mitochondrial membrane potential， downregulated protein levels of p-Akt， PKM2， GLUT1， PDK1， PDH， and LDHA， and reduced PDK1 and p-Akt fluorescence intensity （P<0.05）. Compared with the siPDK1+Buzhong Yiqitang group， the siPDK1+cisplatin group showed decreased colony formation rate， downregulated protein levels of p-Akt and PDH， and reduced PDK1 and p-Akt fluorescence intensity （P<0.05）. The siPDK1+cisplatin+Buzhong Yiqitang group exhibited decreased colony formation rate， reduced lactate production， increased ATP production， lowered mitochondrial membrane potential， downregulated protein levels of p-Akt， GLUT1， PDH， and LDHA， and reduced PDK1 and p-Akt fluorescence intensity （P<0.05）. Compared with the siPDK1+cisplatin group， the siPDK1+cisplatin+Buzhong Yiqitang group showed decreased colony formation rate， increased ATP production， and downregulated protein levels of p-Akt， PKM2， and LDHA （P<0.05）. ConclusionBuzhong Yiqitang combined with cisplatin can suppress lung adenocarcinoma cell proliferation by modulating glycolysis through the PDK1/Akt signaling pathway.

ObjectiveTo investigate the urate-lowering effect of Shenling Qushi prescription in the mouse model of hyperuricaemia. MethodsSixty-three C57BL/6N mice were randomly assigned to the following groups （n=9）： Control， model， low-dose （6 g·kg^-1） Shenling Qushi prescription， medium-dose （12 g·kg^-1） Shenling Qushi prescription， high-dose （24 g·kg^-1） Shenling Qushi prescription， medium-dose Shenling Qushi prescription plus febuxostat （12+0.003 g·kg^-1）， and febuxostat （3 mg·kg^-1）. A mouse model of persistent hyperuricaemia was established via intraperitoneal injection of potassium oxazolamide （250 mg·kg^-1） combined with oral administration of allopurinol （300 mg·kg^-1） over a 28-day period. Concurrently， the prescription was administered orally at the specified doses once daily for 21 consecutive days. Throughout the experiment， mouse body weight， food intake， water consumption， and urine output were measured and recorded. Kidney and liver indices were calculated. Renal histopathological changes were observed by haematoxylin and eosin staining. Serum uric acid （SUA） and urinary uric acid （UUA） levels， along with xanthine oxidase （XOD） and adenosine deaminase （ADA）， alanine aminotransferase （ALT） and aspartate aminotransferase （AST） activities， were determined. Real-time PCR was employed to assess the mRNA levels of urate anion transporter 1 （URAT1） and glucose transporter 9 （GLUT9） in the renal tissue， alongside those of XOD and ADA in the liver tissue. The protein levels of URAT1 and GLUT9 in the renal tissue were determined by Western blot. ResultsCompared with the normal group， model mice exhibited reduced food intake and body weight （P<0.01）， decreased water consumption yet increased urine output， no significant change in the liver index but increased kidney index （P<0.01）. Pathological findings revealed renal tissue damage including glomerular atrophy， epithelial cell detachment， and inflammatory cell infiltration. Furthermore， the model group exhibited elevated UUA and SUA levels （P<0.01）， enhanced activities of ALT， AST， XOD， and ADA in the liver tissue （P<0.05， P<0.01）， upregulated mRNA and protein levels of URAT1 and GLUT9 in the renal tissue （P<0.05）， alongside markedly elevated mRNA levels of XOD and ADA in the liver （P<0.01）. Compared with the model group， the Shenling Qushi prescription groups showed no significant changes in body weight or food intake， with water consumption and urine output remaining within normal ranges， alleviated glomerular atrophy， with reduced pathological damage such as inflammatory infiltration， declined UUA and SUA levels （P<0.01）， and increased activities of ALT， AST， XOD， and ADA in the serum （P<0.01）. Real-time PCR results demonstrated that Shenling Qushi prescription downregulated the mRNA levels of URAT1 and GLUT9 in the renal tissue （P<0.05， P<0.01） and XOD and ADA in the hepatic tissue （P<0.05， P<0.01）. Western blot results demonstrated Shenling Qushi prescription reduced the protein levels of URAT1 and GLUT9 （P<0.05， P<0.01）. ConclusionShenling Qushi prescription modulates fluid balance and reduces uric acid levels， thereby alleviating renal injury in hyperuricaemic mice. This effect is highly likely mediated through inhibition of uric acid synthesis and reabsorption.

Objective:To develop a rapid assessment scale for healthy aging suitable for the Chinese population.Methods:Based on existing healthy aging assessment scales, national standards, and expert consensus, an initial Healthy Aging Rapid Assessment Scale was drafted through two rounds of expert consultation. A pre-survey was conducted with 3 220 subjects recruited from Guangzhou between July 2023 and July 2024. Items were screened through item analysis and exploratory factor analysis to form the final scale. Reliability and validity of the final scale were validated across five cities: Guangzhou, Dongguan, Shenzhen, Baoding, and Chuxiong.Results:The initial version comprised 36 items, while the finalized scale contained 18 items across three dimensions: metabolic health, mental health, and cognitive health. Test-retest reliability ranged from 0.71 to 0.81 across all study sites. The Spearman-Brown coefficient varied between 0.91-0.96, Cronbach′s α between 0.77-0.83, comparative fit index (CFI) between 0.90-0.98, goodness-of-fit index (GFI) between 0.90-0.99, and root-mean-square error of approximation (RMSEA) between 0.03-0.09. For the three dimensions, reliability and validity metrics demonstrated consistency: Spearman-Brown coefficients 0.87-0.99, Cronbach′s α 0.77-0.83, CFI 0.90-0.98, GFI 0.90-0.99, and RMSEA 0.03-0.09 across four regions.Conclusion:The developed Healthy Aging Rapid Assessment Scale for the Chinese population exhibits robust reliability and validity.

Objective:To explore the genotype and the clinical phenotype of SCN2A-related developmental delay in children. Methods:A case series study was adopted. Collect clinical data from 10 cases of children with SCN2A gene variants diagnosed with global developmental delay/intellectual disability who were admitted to the Children′s Hospital between July 2019 and March 2023. Summarize the clinical phenotype and genotype based on clinical data such as general information, clinical manifestations, imaging examinations, laboratory tests, genetic testing results, and comprehensive pediatric neuropsychological development assessment. Results:A total of 10 patients were recruited, including 7 males and 3 females, with an age range of 27 days to 5 years and 9 months. 9 patients underwent children′s neuropsychological and behavioral assessments, and the results were consistent with global developmental delay, including 2 mild cases, 4 moderate cases, and 3 severe cases. 3 cases had autism spectrum disorder, and 2 cases had epilepsy. 6 patients underwent complete head MRI examination, and 4 of them showed abnormalities, including delayed myelination, widening of the local extra brain space in the frontal lobe, and abnormal frontal lobe morphology. All 10 cases had point variants. Among them, 9 cases are de novo and 1 case is maternal inheritance. Out of 10 cases, there were 5 cases with copy number variations, but all of them were of unknown significance. Among the 10 variants, 8 have been reported and 2 have not been reported, namely c.4145A>T(p.N1382I) and c.4937T>A(p.I1646N). In this study, 4 out of 10 patients with SCN2A variants had variation sites located in the S4 segment of domain which constitute Nav1.2, the sodium ion channel encoded by SCN2A. The developmental quotient level was lower when the variation sites were located in the S4 segment of domain, and the difference was statistically significant ( t=-3.101, P=0.017), indicating that the severity of developmental delay may be related to the localization of amino acids corresponding to variant sites within the protein domain. Conclusion:SCN2A mutations are strongly associated with diverse neurodevelopmental disorders. In this study, the phenotypic spectrum of SCN2A variants encompassed epilepsy, global developmental delay, and autism spectrum disorder. Affected individuals exhibited early-onset developmental delays, predominantly moderate to severe in severity. Voltage-sensing domain dysfunction in sodium channels may constitute a critical pathomechanism underlying neurodevelopmental impairments. Further electrophysiological characterization and molecular mechanistic studies are warranted todelineate the genotype-phenotype correlations between specific variant loci and clinical severity.

Objective:To develop a rapid assessment scale for healthy aging suitable for the Chinese population.Methods:Based on existing healthy aging assessment scales, national standards, and expert consensus, an initial Healthy Aging Rapid Assessment Scale was drafted through two rounds of expert consultation. A pre-survey was conducted with 3 220 subjects recruited from Guangzhou between July 2023 and July 2024. Items were screened through item analysis and exploratory factor analysis to form the final scale. Reliability and validity of the final scale were validated across five cities: Guangzhou, Dongguan, Shenzhen, Baoding, and Chuxiong.Results:The initial version comprised 36 items, while the finalized scale contained 18 items across three dimensions: metabolic health, mental health, and cognitive health. Test-retest reliability ranged from 0.71 to 0.81 across all study sites. The Spearman-Brown coefficient varied between 0.91-0.96, Cronbach′s α between 0.77-0.83, comparative fit index (CFI) between 0.90-0.98, goodness-of-fit index (GFI) between 0.90-0.99, and root-mean-square error of approximation (RMSEA) between 0.03-0.09. For the three dimensions, reliability and validity metrics demonstrated consistency: Spearman-Brown coefficients 0.87-0.99, Cronbach′s α 0.77-0.83, CFI 0.90-0.98, GFI 0.90-0.99, and RMSEA 0.03-0.09 across four regions.Conclusion:The developed Healthy Aging Rapid Assessment Scale for the Chinese population exhibits robust reliability and validity.

Objective:To investigate the protective effect of fluoxetine on neurons in rats with subarachnoid hemorrhage (SAH) and explore its mechanism based on the chemokine receptor 4 (CXCR4)/nucleotide-binding oligomerization domain-like receptor protein 1 (NLRP1) pathway.Methods:Seventy-five rats were randomly divided into a normal control group and a model group. The SAH model was established by the internal carotid artery puncture method in the model group. After modeling, rats were randomly divided into the model group, fluoxetine low-, medium-, and high-dose groups, and nimodipine group, with 12 rats in each group. The fluoxetine low-, medium-, and high-dose groups were intravenously injected with fluoxetine at doses of 5, 10, and 15 mg/kg, respectively; the nimodipine group was intraperitoneally injected with nimodipine at 0.2 mg/kg; the normal control group and model group were intraperitoneally injected with an equal volume of normal saline, once a day for 7 consecutive days. The shuttle box was used to determine the number of avoidance responses and avoidance response time of rats. The water content of brain tissue and Evans blue exudation volume were calculated. Enzyme-linked immunosorbent assay (ELISA) kits were used to detect the levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH) in the hippocampal tissue. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of hippocampal tissue. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the mRNA levels of CXCR4 and NLRP1 in the hippocampal tissue. Western blot was used to determine the protein levels of CXCR4, NLRP1, LC3-Ⅱ, and Beclin1 in the hippocampal tissue.Results:Compared with the normal control group, the model group had a lower number of avoidance responses, lower levels of SOD, CAT, GSH, CXCR4 mRNA, CXCR4, LC3-Ⅱ, and Beclin1 protein in the hippocampal tissue (all P<0.05); while the avoidance response time, brain water content, Evans blue exudation volume, levels of IL-6, TNF-α, MDA, and mRNA and protein levels of NLRP1 in the hippocampal tissue were higher (all P<0.05). Compared with the model group, the fluoxetine groups (all doses) and nimodipine group had a higher number of avoidance responses, higher levels of SOD, CAT, GSH, CXCR4 mRNA, CXCR4, LC3-Ⅱ, and Beclin1 protein in the hippocampal tissue (all P<0.05); while the avoidance response time, brain water content, Evans blue exudation volume, levels of IL-6, TNF-α, MDA, and mRNA and protein levels of NLRP1 in the hippocampal tissue were lower (all P<0.05); moreover, the changes in various indicators were more significant with the increase of fluoxetine dose. HE staining results showed that there were no pathological changes in the hippocampal tissue of the normal control group; in the model group, the number of hippocampal neurons decreased, nuclei were pycnotic, and cell arrangement was irregular. Compared with the model group, the number of hippocampal neurons increased, cell arrangement was regular, and hippocampal pathology was significantly restored in the fluoxetine groups (all doses) and nimodipine group. Conclusions:Fluoxetine can significantly alleviate the pathological progression of cerebral edema, repair neuronal damage, improve neurological function, and regulate mitochondrial autophagy in SAH rats, whose mechanism may be related to the regulation of the CXCR4/NLRP1 pathway.

Objective:To explore the clinical and pathological features and survival outcomes of patients with early-onset intrahepatic cholangiocarcinoma (EOICC).Methods:This is a multicenter, retrospective cohort study. Data of 1 160 intrahepatic cholangiocarcinoma patients undergoing radical resection in 14 tertiary Grade A hospitals in China from January 2010 to November 2021 were retrospectively collected. The cohort included 632 males and 528 females, aged( M (IQR)) 61 (14) years (range: 22 to 93 years). ICC aged ≤50 years at the time of diagnosis was defined as EOICC and >50 years as late-onset intrahepatic cholangiocarcinoma (LOICC). Of these, there were 247 cases in the EOICC group and 913 cases in the LOICC. The clinical and pathological characteristics of both groups were analyzed and compared using the independent sample t-test, Mann-Whitney U test or Kaplan-Meier method. Univariate and multivariate Cox regression models for patient outcomes were constructed and forest graphed. Results:Compared with the patients in the LOICC group, patients in the EOICC group had lower carcinoembryonic antigen levels (2.5(4.0) μg/L vs. 3.1(5.2)μg/L, U=124 899, P=0.009) and CA19-9 level (63.4(524.7)U/ml vs. 77.9(611.3)U/ml, U=120 320, P=0.013), higher levels of ALT (29(35)U/L vs. 24(26)U/L, U=101 214, P=0.013), a lower score of the Eastern US Cooperative Oncology Group (0 score patients: 54.7% vs. 44.1%, χ2=12.472, P=0.014), higher TNM stage ( χ2=11.807, P=0.038), and proportion of lymph node dissection (62.3% vs. 54.1%, χ2=5.355, P=0.021). Patients in the two groups in sex, first diagnosis symptoms, intrahepatic bile duct stone history, nail protein, albumin, total bilirubin, transaminase, liver function Child-Pugh grade, T stage, stage, N stage, preoperative laparoscopic exploration proportion, tumor diameter, vascular invasion proportion, differentiation, margin, intraoperative bleeding, postoperative complications, postoperative hospital days were no statistical significance (all P>0.05). Patients in the EOICC group had better outcomes than the LOICC group (median survival time: 29.7 months vs. 25.0 months, 3-year overall survival: 45.1% vs. 37.8%, P=0.027). Conclusion:EOICC patients are better than LOICC patients in carcinoembryonic antigen, CA19-9, ALT, physical strength status and TNM stage, and the long-term prognosis is also better than LOICC patients.

Postoperative recurrence is one of the primary factors contributing to the poor prognosis of patients with intrahepatic cholangiocarcinoma (ICC). The recurrence patterns of ICC can be classified into intrahepatic,extrahepatic,and intrahepatic-extrahepatic recurrence,while the timing of recurrence can be categorized as very early,early,and late recurrence. Common risk factors for recurrence include positive surgical margins,lymph node metastasis,multifocality,vascular invasion,large tumor size,and concomitant liver cirrhosis. The key to improving the quality of life for ICC patients with postoperative recurrence lies in the accurate preoperative identification of high-risk populations and the implementation of targeted interventions,as well as the formulation of appropriate treatment strategies based on individual patient conditions after recurrence. Interventions for high-risk populations include standardized neoadjuvant therapy,postoperative adjuvant therapy,and high-frequency follow-up. Re-resection remains the most ideal treatment option for recurrence,although the surgical indications are stringent. Non-surgical treatments,including systemic therapy,local therapy,and supportive care,should be tailored to the specific circumstances of each patient.

[Objective]To investigate pulmonary function levels and associated influencing factors among rural elderly in Guangzhou,to identify high-risk populations for poor pulmonary function,and to reveal the relationship between the influencing factors of pulmonary function.[Methods]We recruited 1 500 residents aged 60 to 94 years from rural area of Conghua District,Guangzhou City using convenience sampling in 2023.Data on demographics,body measurements,medical history and lifestyle were collected via face-to-face questionnaires and physical examination.Meanwhile,expiratory function parameters including forced expiratory volume in one second(FEV1),forced vital capacity(FVC),FEV1/FVC,and the prevalence of airflow obstruction(AFO)were assessed using a portable spirometer.Age and sex distribution of pulmonary function in older adults at 5-year intervals was reported,and risk factors of AFO using multifactorial logistic regression models were analyzed.Furthermore,path analysis was further employed to explore the role of lifestyle in the association between other influencing factors and lung function.[Results]Among the 1 500 participants,the median age was 71 years(67-75),and 44.2%were male.Subjects identified as AFOs were generally older,more likely male,less educated,and had lower rates of moderate to vigorous physical activity(＜1 time/week)and lower lean body mass.Mean FEV1/FVC ratio was(82.0±16.4)%.FEV1/FVC was(79.80±17.58)%in men and(83.66±15.22)%in women.Older age,lower education,male sex and leanness were negatively associated with all pulmonary function outcomes(all P values＜0.05).Path analysis identified that age,gender,marital status,occupation and income may influence pulmonary function indirectly through lifestyle.[Conclusion]Rural elderly in Guangzhou exhibited lower pulmonary function levels,and male sex,non-married status,advanced age,lower education,smoking habits,insufficient engagement in moderate to vigorous physical activity,and lean body type were all associated with worse pulmonary function.