ObjectiveTo investigate the impact of hepatocellular carcinoma （HCC） on the prognosis of patients with liver cirrhosis undergoing emergency endoscopic therapy for esophagogastric variceal bleeding， as well as independent influencing factors for the prognosis of liver cirrhosis patients without HCC after emergency endoscopic therapy for esophagogastric variceal bleeding. MethodsA total of 117 liver cirrhosis patients without HCC and 119 liver cirrhosis patients with HCC who underwent emergency endoscopic therapy for esophagogastric variceal bleeding in Renmin Hospital of Wuhan University from January 2017 to July 2023 were enrolled. Basic information including age and sex was collected from all patients， as well as the presence or absence of chronic diseases such as hypertension， diabetes， and coronary heart disease， the time of emergency endoscopy after admission， and liver function parameters including international normalized ratio， albumin， creatinine， sodium， total bilirubin， alanine aminotransferase， and aspartate aminotransferase （AST）. The independent-samples t test was used for comparison of normally distributed continuous variables between two groups， and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous variables between two groups； the chi-square test was used for comparison of categorical variables between groups. The covariance analysis and the multivariate logistic regression analysis were used for comparison of outcome variables after control of baseline variables， and the Kaplan-Meier survival curve was plotted for each group. The univariate and multivariate Cox regression analyses were performed for survival time in the non-HCC group to investigate the independent influencing factors for survival time， and then the Kaplan-Meier curve analysis and the log-rank test were performed to validate such independent influencing factors and analyze the independent influencing factors for secondary outcomes. ResultsCompared with the non-HCC group， the HCC group had significantly higher red blood cell transfusion units （6.00［2.00～9.00］ vs 4.00［1.75～7.00］， Z=-2.050， P=0.040， F=4.869， adjusted P=0.028）， a significantly shorter survival time （29.77±16.01 days vs 38.07±11.43 days， t=4.574， P<0.001， F=17.294， adjusted P<0.001）， and a significantly higher 5-day rebleeding rate （22.69% vs 6.84%， χ²=11.736， P<0.001， adjusted P=0.021）. The Kaplan-Meier curve analysis showed that the risk of 42-day mortality in the HCC group was 3.897 （95% confidence interval ［CI］： 2.338 ‍— 6.495， P<0.001） times that in the non-HCC group. The multivariate Cox regression analysis of the non-HCC group showed that the total length of hospital stay （hazard ratio ［HR］=0.793， 95%CI： 0.644 ‍— ‍0.976， P=0.029） was an independent protective factor for 42-day survival. The Kaplan-Meier curve analysis showed that a length of hospital stay of >9 days was beneficial for the prognosis of patients （HR=4.302， 95%CI： 1.439 — 12.870， P=0.037）. Blood sodium level （odds ratio ［OR］=0.523， 95%CI： 0.289 ‍— ‍0.945， P=0.032） and MELD-Na score （OR=0.495， 95%CI： 0.257 ‍— ‍0.954， P=0.036） were independent protective factors against 5-day rebleeding， while AST level was an independent risk factor for 5-day rebleeding （OR=1.023， 95%CI： 1.002 ‍— ‍1.043， P=0.028） and in-hospital death （OR=1.036， 95%CI： 1.001‍— ‍1.073， P=0.045）. ConclusionLiver cirrhosis patients with variceal bleeding and HCC tend to have a worse prognosis， and for the non-HCC group， in-hospital mortality rate increases with the increase in AST level. The total length of hospital stay is an independent protective factor for survival time in the non-HCC group， and it is recommended to appropriately prolong the length of hospital stay for such patients.

ObjectiveTo investigate the effects of Scutellariae Radix combined with epidermal growth factor receptor-tyrosine kinase inhibitors （EGFR-TKIs） on cell proliferation， apoptosis， cancer stem cell （CSC） marker expression， and metabolism in non-small cell lung cancer （NSCLC） cells. MethodsThe anti-tumor effects of Scutellariae Radix and EGFR-TKIs （gefitinib or osimertinib） in NSCLC cells were evaluated using the cell counting kit-8 （CCK-8） and Annexin V-FITC/propidium iodide （PI） double staining apoptosis assay. The activity of Scutellariae Radix and EGFR-TKIs in three-dimensional （3D） cultures of NSCLC cells was assessed using the CellTiter-Glo® 3D cell viability assay. The mRNA and protein expression levels of CSC markers， sex determining region y box protein 2 （SOX2） and aldehyde dehydrogenase 1 family member A1 （ALDH1A1）， were detected by quantitative real-time polymerase chain reaction （Real-time PCR） and Western blot， respectively. Changes in intracellular reactive oxygen species （ROS） levels were detected by ROS staining， and the redox ratio was detected by femtosecond laser labeling free imaging （FLI）. ResultsUnder both two-dimensional （2D） and 3D culture conditions， compared with the blank group and EGFR-TKI group， the combination group showed significantly reduced cell viability and increased apoptosis rate （P<0.05）. Compared with the EGFR-TKI group， the mRNA and protein levels of CSC markers were significantly downregulated in the combination group （P<0.05）. Additionally， the redox ratio was significantly elevated （P<0.05）， and ROS levels were also increased in the combination group compared with the EGFR-TKI group. ConclusionIn NSCLC cells， Scutellariae Radix enhances the redox ratio and increases ROS levels， thereby inhibiting the expression of CSC markers and strengthening the anti-tumor effects of EGFR-TKIs. This provides a novel molecular mechanism by which Scutellariae Radix may enhance the sensitivity of targeted therapies.

ObjectiveTraditional Chinese medicine (TCM) constitutes a valuable cultural heritage and an important source of antitumor compounds. Poria (Poria cocos (Schw.) Wolf), the dried sclerotium of a polyporaceae fungus, was first documented in Shennong’s Classic of Materia Medica and has been used therapeutically and dietarily in China for millennia. Traditionally recognized for its diuretic, spleen-tonifying, and sedative properties, modern pharmacological studies confirm that Poria exhibits antioxidant, anti-inflammatory, antibacterial, and antitumor activities. Pachymic acid (PA; a triterpenoid with the chemical structure 3β-acetyloxy-16α-hydroxy-lanosta-8,24(31)-dien-21-oic acid), isolated from Poria, is a principal bioactive constituent. Emerging evidence indicates PA exerts antitumor effects through multiple mechanisms, though these remain incompletely characterized. Neuroblastoma (NB), a highly malignant pediatric extracranial solid tumor accounting for 15% of childhood cancer deaths, urgently requires safer therapeutics due to the limitations of current treatments. Although PA shows multi-mechanistic antitumor potential, its efficacy against NB remains uncharacterized. This study systematically investigated the potential molecular targets and mechanisms underlying the anti-NB effects of PA by integrating network pharmacology-based target prediction with experimental validation of multi-target interactions through molecular docking, dynamic simulations, and in vitro assays, aimed to establish a novel perspective on PA’s antitumor activity and explore its potential clinical implications for NB treatment by integrating computational predictions with biological assays. MethodsThis study employed network pharmacology to identify potential targets of PA in NB, followed by validation using molecular docking, molecular dynamics (MD) simulations, MM/PBSA free energy analysis, RT-qPCR and Western blot experiments. Network pharmacology analysis included target screening via TCMSP, GeneCards, DisGeNET, SwissTargetPrediction, SuperPred, and PharmMapper. Subsequently, potential targets were predicted by intersecting the results from these databases via Venn analysis. Following target prediction, topological analysis was performed to identify key targets using Cytoscape software. Molecular docking was conducted using AutoDock Vina, with the binding pocket defined based on crystal structures. MD simulations were performed for 100 ns using GROMACS, and RMSD, RMSF, SASA, and hydrogen bonding dynamics were analyzed. MM/PBSA calculations were carried out to estimate the binding free energy of each protein-ligand complex. In vitro validation included RT-qPCR and Western blot, with GAPDH used as an internal control. ResultsThe CCK-8 assay demonstrated a concentration-dependent inhibitory effect of PA on NB cell viability. GO analysis suggested that the anti-NB activity of PA might involve cellular response to chemical stress, vesicle lumen, and protein tyrosine kinase activity. KEGG pathway enrichment analysis suggested that the anti-NB activity of PA might involve the PI3K/AKT, MAPK, and Ras signaling pathways. Molecular docking and MD simulations revealed stable binding interactions between PA and the core target proteins AKT1, EGFR, SRC, and HSP90AA1. RT-qPCR and Western blot analyses further confirmed that PA treatment significantly decreased the mRNA and protein expression of AKT1, EGFR, and SRC while increasing the HSP90AA1 mRNA and protein levels. ConclusionIt was suggested that PA may exert its anti-NB effects by inhibiting AKT1, EGFR, and SRC expression, potentially modulating the PI3K/AKT signaling pathway. These findings provide crucial evidence supporting PA’s development as a therapeutic candidate for NB.

Objective:To compare the clinical efficacy of transendoscopic retrograde cholangiopancreatography (ERCP) lithotripsy with that of traditional surgical procedures in the treatment of pancreatic ductal stones.Methods:The clinical data of 47 patients with chronic pancreatitis combined with pancreatic duct stones hospitalized in Yueyang Hospital affiliated to Hunan Normal University and Third Xiangya Hospital of Central South University between November 2017 and November 2022 were retrospectively analyzed. All the patients were divided into ERCP group ( n=19), laparoscopic group ( n=10) and open abdominal group ( n=18) according to the mode of surgical treatment for pancreatic stone, and the general clinical characteristics, the surgical and postoperative recovery indicators, pain level grading, one-stage stone removal rate, complication rate and evaluation of pancreatic function were compared among the three groups. Results:The age, gender, body mass index, etiology, duration of disease, symptoms (abdominal pain, diarrhea), stone location, stone size, preoperative tumor markers (CEA, AFP, CA19-9) and serum inflammatory factor (CRP) level were not statistically significant among three groups. In ERCP group, the operation time (1.47±0.51) h, the time of the first postoperative intestinal ventilation (1.16±0.20) days, the time of drainage removal (8.68±3.30) days, the length of hospitalization (11.37±4.59) days and intraoperative blood loss (109.5±16.5) ml, the CRP on the first postoperative day (11.24±2.62) mg/L, and the treatment cost (35 238±10 663) were obviously shorter or lower than those of laparoscopic and open abdominal group; in the laparoscopic group, the time to first postoperative bowel ventilation (2.40±0.70) days, drainage removal time (12.10±5.36) days and intraoperative blood loss (195.0±83.2) ml, postoperative CRP on day one (14.52±3.62) mg/L, and the treatment cost (69 908±11 310) were greatly shorter or lower than those in open abdominal group; and all the differences were statistically significant (all P value <0.05). Those with moderate and severe pain in ERCP group (10.53%) were lower than those in laparoscopic group (70.00%) and open abdominal group (83.38%), and the difference was statistically significant (all P value <0.05). There was no statistically significant difference between ERCP group and laparoscopic and open abdominal group in terms of phase I stone removal rate, complication rate, and postoperative glycated haemoglobin level, but patients' weight loss (26.32%) and incidence of diarrhea (21.05%) were lower than those of laparoscopic and open abdominal group, and all the difference was statistically significant (all P value <0.05). Conclusions:ERCP lithotripsy is an effective, safe, minimally invasive and economical treatment for pancreatic duct stone and is suitable for most patients with pancreatic duct stone, but patients with embedded or complex pancreatic duct stones should be treated with laparoscopic or open abdominal surgery according to the actual situation.

Background::Gastric cancer (GC), a malignant tumor with poor prognosis, is one of the leading causes of cancer-related deaths worldwide; consequently, identifying novel therapeutic targets is crucial for its corresponding treatment. NUF2, a component of the NDC80 kinetochore complex, promotes cancer progression in multiple malignancies. Therefore, this study aimed to explore the potential of NUF2 as a therapeutic target to inhibit GC progression. Methods::Clinical samples were obtained from patients who underwent radical resection of GC at Lanzhou University Second Hospital from 2016 to 2021. Cell count assays, colony formation assays, and cell-derived xenotransplantation (CDX) models were used to determine the effects of NUF2 on GC progression. Flow cytometry was used to detect the effect of NUF2 or quercetin on cell cycle progression and apoptosis. A live-cell time-lapse imaging assay was performed to determine the effect of NUF2 on the regulation of mitotic progression. Transcriptomics was used to investigate the NUF2-associated molecular mechanisms. Virtual docking and microscale thermophoresis were used to identify NUF2 inhibitors. Finally, CDX, organoid, and patient-derived xenograft (PDX) models were used to examine the efficacy of the NUF2 inhibitor in GC. Results::NUF2 expression was significantly increased in GC and was negatively correlated with prognosis. The deletion of NUF2 suppressed GC progression both in vivo and in vitro. NUF2 significantly regulated the mitogen-activated protein kinase (MAPK) pathway, promoted G2/M phase transition, and inhibited apoptosis in GC cells. Additionally, quercetin was identified as a selective NUF2 inhibitor with low toxicity that significantly suppressed tumor growth in GC cells, organoids, CDX, and PDX models. Conclusions::Collectively, NUF2-mediated G2/M phase transition and apoptosis inhibition promoted GC progression; additionally, NUF2 inhibitors exhibited potent anti-GC activity. This study provides a new strategy for targeting NUF2 to suppress GC progression in clinical settings.

The pathogenesis of Alzheimer's disease(AD)is complex and unclear.Existing drugs can only alleviate its symp-toms,and there is an urgent need to develop effective therapeutic drugs.As the representative drugs of tonic and enlightening medicine,ginseng and acorus calamus have pharmacological effects to improve memory,improve learning ability and reduce cognitive impairment,which are commonly used in Chinese med-icine for the treatment of dementia.The combination of ginseng and acorus calamus can further promote the active ingredients in-to brain to exert their medicinal effects,and delay the process of AD through anti-inflammatory,anti-oxidative stress,modulation of neuronal-synaptic plasticity and other multiple pathways,with multi-level,multi-system and multi-target action characteristics.This paper attempts to summarize the existing research results and lay the foundation for further exploring the synergistic mech-anism of action of ginseng-acorus calamus combination and the dose-effect relationship of the combination,so as to provide a sci-entific basis for the development of innovative Chinese medicines for the prevention and treatment of AD.

Aim To investigate the possible mechanism of action of Qingjie Huagong decoction(QJHGD)on acute lung injury(ALI)associated with severe acute pancreatitis(SAP)using network pharmacology,and to verify it by animal experiments.Methods The TC-MSP,BATMAN-TCM,ETCM,and SwissTargetPredic-tion databases were searched to obtain the action tar-gets of the blood-entering active ingredients of each drug in the QJHGD.The GeneCard database was searched to obtain SAP-ALI disease targets.The drug targets and disease targets were intersected to obtain common targets.Subsequently,the common targets were analyzed by STRING database and Cytoscape 3.7.1 software for protein interaction network analysis.GO and KEGG enrichment analysis was performed with the help of DAVID database.Finally,the key signa-ling pathways were verified by animal experiments.Results A total of 28 active ingredients were screened out for the treatment of SAP-ALI with 42 common tar-gets.PPI network analysis showed that STAT3,IL-6,and TGFB1 might be core targets;GO and KEGG en-richment analysis mainly involved cell proliferation,PI3K/AKT signaling pathways,etc.Animal experi-ments confirmed that QJHGD could improve the pathol-ogy of pancreas and lung tissues in SAP-ALI rat mod-el,down-regulate the expression levels of α-amylase,lipase,IL-1 β,IL-6,and TNF-α in serum,and down-regulate the expression levels of proteins and mRNAs related to PI3K/AKT1 signaling pathway in lung tis-sues.Conclusion QJHGD synergistically treats SAP-ALI through multi-component,multi-target,and multi-pathway,with a mechanism that may be related to the inhibition of PI3K/AKT signaling pathway activation.

Objective To explore the difference in the effectiveness between proximal femoral nail anti-rotation(PFNA)and proximal femoral locking compression plate(PFLCP)of intertrochanteric fracture in the elderly patients combined with knee osteoarthritis.Methods The clinical data of 65 intertrochanteric femoral fractures combined with knee osteoarthritis be-tween June 2015 and February 2021 were retrospectively analyze.They were divided into two groups according to the different surgical methods.PFNA group was composed of 36 patients,12 males and 24 females,aged from 61to 88 years old with an av-erage of(77.0±6.4)years old.There were 17 cases of left injury and 19 cases of right injury.According to modified Evans clas-sification,there were 3 cases of type Ⅱ,19 cases of type Ⅲ,10 cases of type Ⅳ,and 4 cases of type Ⅴ.PFLCP group was com-posed of 29 patients,11 males and 18 females,aged from 60 to 92 years old with an average of(78.8±6.5)years old.There were 14 cases of left injury and 15 cases of right injury.According to modified Evans classification,there were 2 cases of typeⅡ,18 cases of type Ⅲ,7 cases of type Ⅳ,and 2 cases of type Ⅴ.Comparison of operation time,intraoperation blood loss,postoperative bed time,incidence of postoperative complications,Harris score at 6 months and 1 year postoperation.Results All 65 patients were followed up ranging from 12 to 24 months with an average of(16.9±3.6)months.In the PFNA and PFLCP groups,the operation time was respectively(57.6±6.8)min and(77.4±6.5)min,the intraoperative blood loss was(128.3±50.3)ml and(156.3±23.9)ml,postoperative bed time was(4.0±2.5)days and(8.1±2.0)days,Harris score at 6 months post-operative was(45.3±8.6)points and(36.3±7.0)points.There were significant differences between two groups(P＜0.05).Inci-dence of postoperative complications was 19.4％(7/36)and 34.5％(10/29),Harris score at 1 year postoperative was(60.8±6.7)points and(59.0±8.1)points.There was no significant difference between the two groups(P＞0.05).Conclusion Compared with PFLCP,PFNA treatment of elderly patients with knee osteoarthritis between the femoral intertrochanteric fractures shorter surgical time,less intraoperative blood loss,bed rest after surgery,short-term hip function recovery better,when the affected knee joint can tolerate traction,can be used as a priority.

Objective Personalized calculation of contrast agent dose based on body surface area(BSA)was conducted to explore the feasibility of obtaining virtual single energy or reconstruction fusion through dual-energy CT without affecting the enhancement effect of portal vein trunk under the condition of reducing the contrast agent dose.Methods A total of 60 patients who received enhanced upper abdominal CT examination in the First Affiliated Hospital of Army Medical University were selected and divided into the normal dose group and the reduced dose group.The normal dose group used the BSA estimated value as the contrast agent dose,and the reduced dose group used the BSA estimated value reduced by 20%as the contrast agent dose.Both groups of patients were treated with dual-energy CT scanning in portal vein stage,and the scanning parameters were the same.After scanning,Syngo dual-energy post-processing software of Siemens multi-mode image workstation was used to reconstruct and fuse the 5 mm layer thickness image of the portal vein stage in the reduced dose group by two methods:"optimum contrast(OC)"and"monoenergetic(Mono)".The CT value and SD value of the portal vein trunk and the normal liver parenchyma of images in each group were measured.The contrast to noise ratio(CNR)of theportal vein and the liver parenchyma and portal vein signal to ratio(SNR)were calculated.Results Compared with the normal dose group,there was no statistically significant difference in the subjective score in the reduced dose OC group(P>0.05),but the CNR and SNR of the portal vein trunk in the images were significantly improved(P<0.05).The portal vein CT value and the difference between portal vein and liver parenchyma in the reduced dose Mono group were significantly lower than those in the normal dose group,and the subjective score was the lowest,with statistical differences(P<0.05).Conclusion In the case of reducing the contrast agent dose by 20%,the dual-energy CT reconstruction fusion method can not only reduce the damage of contrast agent to patients,but also significantly improve the lesion display,and improve the consistency of liver enhancement image quality.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.