Objective To investigate the expression of human epidermal growth factor receptor 2(HER2),carbohydrate antigen 199(CA199)and microtubule-associated protein 1 light chain 3β(LC3B)in gastric canc-er tissues and their relationship with recurrence after radical gastrectomy.Methods A total of 95 patients with gastric cancer who underwent radical gastrectomy in the hospital from January 2021 to December 2022 were retrospectively selected.The expressions of HER2,CA199 and LC3B in gastric cancer tissues and adja-cent tissues were compared,and the clinicopathological characteristics were analyzed.According to the postop-erative recurrence of gastric cancer patients,they were divided into recurrence group(n=19)and non-recur-rence group(n=76).Univariate analysis and multivariate Logistic regression analysis were used to analyze the influencing factors of recurrence in patients with gastric cancer after radical resection.Results The ex-pression levels of HER2,CA199 and LC3B in gastric cancer tissues were significantly higher than those in pa-racancerous tissues(P<0.05).The positive expression rates of HER2,CA199 and LC3B in gastric cancer tis-sues(38.95%,38.95%and 35.79%,respectively)were higher than those in adjacent tissues(9.47%,7.37%and 11.58%,respectively),and the differences were statistically significant(P<0.05).The positive expres-sion rate of HER2 in gastric cancer tissues was significantly different in patients with different TNM stage and lymph node metastasis(P<0.05).There were significant differences in the positive expression rates of CA199 and LC3B in gastric cancer patients with different tumor maximum diameter,TNM stage and lymph node metastasis(P<0.05).The maximum diameter of tumor≥5 cm,TNM stage Ⅲ/Ⅳ,lymph node metas-tasis,positive expression of HER2,positive expression of CA199 and positive expression of LC3B were inde-pendent risk factors for recurrence of gastric cancer patients after radical resection(P<0.05).Conclusion The gene expression and positive expression rates of HER2,CA199 and LC3B in gastric cancer tissues are high,which are related to the maximum tumor diameter,TNM stage and lymph node metastasis.The positive expression of HER2,CA199 and LC3B may increase the risk of recurrence of gastric cancer after radical gastrectomy.

Objective To investigate the clinical characteristics and outcomes of Coronavirus Dis-ease 2019 in immunocompromised hosts.Methods A retrospective analysis was conducted on the clinical data of 230 hospitalized patients diagnosed with Coronavirus Disease 2019 at Nanjing Yimin Hospital from December 2022 to November 2023.The patients were divided into three groups based on their immune status:immunocompromised group(n=59),relatively immunocompromised group(n=129),and immunocompetent group(n=42).The clinical characteristics(such as clinical manifesta-tions,imaging features,and laboratory examinations)and outcomes(such as length of hospital stay and in-hospital mortality)were compared among three groups.Results Compared with there latively immunocompromised and immunocompetent groups,the immunocompromised group showed no obvious specific clinical manifestations.However,the proportions of patients with symptoms such as cough and expectoration were lower,and the occurrences of symptoms such as myalgia and fatigue were less fre-quent in the immunocompromised group(P＜0.05).The chest CT findings in the immunocompro-mised group also lacked specific changes,mainly presenting as subpleural ground-glass opacities and consolidations with multilobar distribution,but fibrotic changes were more common(P＜0.05).The proportion of patients with decreased absolute lymphocyte counts in the immunocompromised group was higher than that in the immunocompetent group,and the proportion of patients with elevated procalcitonin levels was higher than that in the other two groups(P＜0.05).The proportion of severe case sand the length of hospital stay in the immunocompromised group were higher and longer than those in the relatively immunocompromised and immunocompetent groups(P＜0.05).The in-hospital mortality rates in the immunocompromised,relatively immunocompromised,and immunocompetent groups were 10.17％,6.98％,and 2.38％,respectively,with no statistically significant difference(P＞0.05).Conclusion After Coronavirus Disease 2019,immunocompromised hosts do not show obvi-ous clinical and imaging features.However,they have a prolonged length of hospital stay,a signifi-cantly higher proportion of severe cases,and a tendency towards increased in-hospital mortality,which should be given high clinical attention.

Objective To analyze the current application status,research hotspots and develop-ment trends of sedation strategies from both domestic and international perspectives in mechanically ventilated patients in the intensive care unit(ICU).Methods Relevant literature on the application of sedation strategies in mechanically ventilated patients from 2014 to 2024 was retrieved from data-bases including China National Knowledge Infrastructure(CNKI),Wanfang and Web of Science.Visual analysis of publication volume and keywords was conducted using CiteSpace 6.2.R3 software.Results A total of 475 Chinese-language articles and 405 English-language articles were included.Significant differences were observed in publication volume between domestic and international re-search,with early domestic activity followed by a decline,while international research had demonstra-ted robust and sustained growth over the past five years.International studies primarily emphasized protocol-driven sedation processes and standardized strategies,whereas domestic research focused on optimizing the concept of comfort-oriented sedation management and exploring postoperative sedation strategies.Analysis of research hotspots revealed that precise pharmacological regulation,the development of disease-specific sedation strategies,and the establishment of multidisciplinary collaborative protocols were key areas of focus in sedation strategies for ICU mechanically ventilated patients.Conclusion Future research should prioritize shortening the update cycle of clinical guidelines,enhancing the transla-tion of evidence-based practices into clinical settings,establishing clear application standards for disease-specific sedation strategies,improving multicenter collaborative research capabilities,and developing artificial intelligence-based sedation monitoring technologies.

Objective:To summarize and investigate the ultrasound manifestations, clinical characteristics, causes, and prognosis of hepatic portal vein gas (HPVG) after liver transplantation in children.Methods:A case series study. Clinical data of 9 pediatric recipients diagnosed with HPVG by ultrasound after liver transplantation between January 2012 and August 2023 were collected, and the ultrasound manifestations, causes, clinical features, and prognosis of HPVG were analyzed.Results:A total of 1,850 pediatric liver transplantations were performed during the same period in Tianjin First Central Hospital, among which 9 cases (0.48%) developed HPVG; 6 cases occurred within 1 month after surgery, and 3 cases occurred more than 1 month after surgery; the duration ranged from 2 to 15 days, with a median of 7 (4.5, 9.0) days. HPVG was first detected by ultrasound in all cases, with common ultrasound manifestations including bubble-like or punctate strong echoes flowing with blood in the portal vein, and patchy strong echoes with unclear borders in the liver parenchyma. Among the 9 patients, 3 had diarrhea with intestinal flora imbalance, 2 had abdominal distension with incomplete intestinal obstruction, 1 had colonic fistula with repeated replacement of Li's tube and concurrent abdominal distension, 1 was experiencing acute T-cell-mediated rejection of the transplanted liver, and the remaining 2 were asymptomatic. Patients with diarrhea and intestinal dysbiosis were treated with Bifidobacterium Lactobacillus triple viable tablets to regulate flora and montmorillonite powder to relieve diarrhea, which gradually subsided. Patients with abdominal distension and incomplete intestinal obstruction were treated with fasting, intravenous nutrition, and enema, and the obstruction gradually resolved, along with disappearance of HPVG.Conclusion:HPVG after liver transplantation has characteristic ultrasound manifestations, and its occurrence may be related to intestinal gas, obstruction, dysbiosis, or mucosal damage. Treatment may be conservative or surgical depending on the underlying cause and severity.

AIM:To investigate the role and mechanism of cell death-inducing DNA fragmentation factor al-pha(DFFA)-like effector B(Cideb)in promoting palmitic acid(PA)-induced lipid deposition in human hepatoblastoma HepG2 cells.METHODS:The HepG2 cells were divided into control group,model group,negative control silencing(siR-NC)group and Cideb silencing(siR-Cideb)group.The cells were treated with PA to establish a cellular model of lipid deposition.Specific siRNAs were used to silence the expression of Cideb,and the intracellular lipid content was mea-sured.Lipid deposition was observed by oil red O staining.RT-qPCR and Western blot were used to detect the expression levels of Cideb,sterol regulatory element-binding protein 1c(SREBP1c),acetyl-CoA carboxylase 1(ACC1),fatty acid synthase(FAS),stearoyl-CoA desaturase 1(SCD1)and AMP-activated protein kinase α(AMPKα)in the cells.The ef-fects of Cideb overexpression on HepG2 cells were observed by transfection with a Cideb eukaryotic expression plasmid.RESULTS:Compared with control group,the cells in PA model group presented lipid deposition,significantly increased triglyceride(TG)and total cholesterol(TC)content,elevated expression levels of Cideb,SREBP1c,ACC,FAS and SCD1,and decreased expression of AMPKα(P＜0.05).Compared with siR-NC group,the cells in siR-Cideb group pre-sented decreased lipid deposition,reduced intracellular TG and TC content,decreased SREBP1c,ACC,FAS and SCD1 expression levels,and increased AMPKα expression(P＜0.05).The overexpression of Cideb increased the lipid deposi-tion,TG and TC content,and the expression levels of SREBP1c,ACC,FAS and SCD1 in HepG2 cells,but decreased the expression of AMPKα(P＜0.05).CONCLUSION:Reduction of Cideb alleviates PA-induced lipid deposition in HepG2 cells by down-regulating the SREBP1c/ACC/FAS/SCD1 pathway and up-regulating the AMPKα pathway.

Ten novel xanthones, garpedunxanthones A-G (1-5, 6a/6b, 7a/7b) and nujiangxanthone Q (8), along with sixteen known analogs (9-24), were isolated from Garcinia pedunculata and G. nujiangensis. Their structures were elucidated through high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) data, comprehensive nuclear magnetic resonance (NMR) spectroscopic analyses, and electronic circular dichroism (ECD) calculations. All compounds without cytotoxicity were assessed for anti-inflammatory properties by measuring the inhibition of nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW264.7 cells. Structure-activity relationships are also discussed. Compounds 7b, 19, and 21 exhibited significant anti-inflammatory activity with IC₅₀ values of 16.44 ± 0.69, 14.28 ± 0.78, and 10.67 ± 3.28 μmol·L^-1, respectively. Enzyme-linked immunosorbent assay (ELISA) demonstrated that compounds 7b, 19, and 21 inhibited the expression of pro-inflammatory cytokines TNF-α and IL-6 in a dose-dependent manner. The inhibitory effect of compound 21 on IL-6 at 20 μmol·L^-1 was comparable to that of the positive control. In network pharmacology studies, potential targets of compounds and inflammation were identified from PharmMapper and GeneCards databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed that the overlapped targets were intricately associated with major pathogenic processes linked to inflammation, including positive regulation of mitogen-activated protein kinase (MAPK) cascade, protein kinase activity, NO synthase regulator activity, MAPK signaling pathway, and EGFR tyrosine kinase inhibitor resistance.
Xanthones/therapeutic use* ; Garcinia ; Anti-Inflammatory Agents/therapeutic use* ; Plant Preparations/therapeutic use* ; Structure-Activity Relationship ; Nitric Oxide/metabolism* ; RAW 264.7 Cells ; Animals ; Mice ; Enzyme-Linked Immunosorbent Assay ; Mitogen-Activated Protein Kinase Kinases/metabolism* ; Circular Dichroism

Gastric cancer (GC) is characterized by high morbidity and mortality rates. Chinese agarwood comprises the resin-containing wood of Aquilaria sinensis (Lour.) Gilg., traditionally utilized for treating asthma, cardiac ischemia, and tumors. However, comprehensive research regarding its anti-GC effects and underlying mechanisms remains limited. In this study, Chinese agarwood petroleum ether extract (CAPEE) demonstrated potent cytotoxicity against human GC cells, with half maximal inhibitory concentration (IC₅₀) values for AGS, HGC27, and MGC803 cells of 2.89, 2.46, and 2.37 μg·mL^-1, respectively, at 48 h. CAPEE significantly induced apoptosis in these GC cells, with B-cell lymphoma-2 (BCL-2) associated X protein (BAX)/BCL-2 antagonist killer 1 (BAK) likely mediating CAPEE-induced apoptosis. Furthermore, CAPEE induced G₀/G₁ phase cell cycle arrest in human GC cells via activation of the deoxyribonucleic acid (DNA) damage-p21-cyclin D1/cyclin-dependent kinase 4 (CDK4) signaling axis, and increased Fe²⁺, lipid peroxides and reactive oxygen species (ROS) levels, thereby inducing ferroptosis. Ribonucleic acid (RNA) sequencing, real-time quantitative polymerase chain reaction (RT-qPCR), and Western blotting analyses revealed CAPEE-mediated upregulation of heme oxygenase-1 (HO-1) in human GC cells. RNA interference studies demonstrated that HO-1 knockdown reduced CAPEE sensitivity and inhibited CAPEE-induced ferroptosis in human GC cells. Additionally, CAPEE administration exhibited robust in vivo anti-GC activity without significant toxicity in nude mice while inhibiting tumor cell growth and promoting apoptosis in tumor tissues. These findings indicate that CAPEE suppresses human GC cell growth through upregulation of the DNA damage-p21-cyclin D1/CDK4 signaling axis and HO-1-mediated ferroptosis, suggesting its potential as a candidate drug for GC treatment.
Animals ; Humans ; Mice ; Antineoplastic Agents, Phytogenic ; Apoptosis/drug effects* ; Cell Line, Tumor ; Cyclin D1/genetics* ; Cyclin-Dependent Kinase 4/genetics* ; DNA Damage/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Ferroptosis/drug effects* ; G1 Phase Cell Cycle Checkpoints/drug effects* ; Heme Oxygenase-1/genetics* ; Mice, Inbred BALB C ; Mice, Nude ; Plant Extracts/pharmacology* ; Stomach Neoplasms/physiopathology* ; Thymelaeaceae/chemistry* ; Up-Regulation/drug effects*

Objective:To investigate the role of RNA helicase DDX5 in renal interstitial fibrosis and its potential mechanism, and provide possible molecular target for the diagnosis and treatment of renal interstitial fibrosis.Methods:The animal and cell models of unilateral ureteral obstruction (UUO) and DDX5-pharmacological and genetic blocking were established. Twenty-four male mice aged 6-8 weeks and weighting about 18-22 g were divided into sham operation group, UUO group, sham operation+RX5902 group and UUO+RX5902 group by random number table method, with 6 mice in each group. Supinoxin (RX5902, a phosphorylated DDX5 inhibitor, 75 mg/kg) was administered by gavage in mice in the sham operation+RX5902 group and UUO+RX5902 group on day 0 and day 3 after the operation, respectively. The mice were sacrificed to collect kidney specimens one week after the surgery. The human renal tubular epithelial cell line (HK-2 cells) was routinely cultured and divided into control group, scramble siRNA group, DDX5 siRNA group, TGF-β1 group, scramble siRNA+TGF-β1 group and DDX5 siRNA +TGF-β1 group. The dosage of RX5902 was 20 nmol/L, and the dosage of transforming growth factor-β1 (TGF-β1) was 10 ng/ml. HE staining and Masson staining were used to evaluate renal tubule injury and collagen fiber deposition. Western blotting, immunofluorescence and immunohistochemistry were used to detect the protein expression levels of DDX5 and fibrosis-related indexes such as fibronectin and α-smooth muscle actin (α-SMA). The flow cytometry was used to detect the cell cycle. Results:In comparison to sham operation group, UUO group exhibited significantly elevated protein expression levels of fibronectin, α-SMA and DDX5 in kidney tissues (all P<0.05), accompanied by notable nuclear translocation of DDX5. TGF-β1 stimulation facilitated the upregulation of fibronectin, α-SMA, and DDX5 expression, as well as DDX5 nuclear translocation in HK-2 cells (all P<0.05). Pharmacological and genetic inhibition of DDX5 attenuated UUO or TGF-β1-induced elevated protein levels of fibronectin and α-SMA. Compared with scramble siRNA+TGF-β1 group, DDX5 siRNA+TGF-β1 group exhibited reduced protein expression levels of fibronectin, α-SMA and DDX5 in HK-2 cells (all P<0.05). Compared with UUO group, UUO+RX5902 group showed alleviation of renal epithelial cell exfoliation, renal tubule atrophy or lumen dilation and decreased scores of both tubular injury and interstitial collagen deposition, along with reduced protein expression levels of fibronectin, α-SMA and DDX5 (all P<0.05). Similarly, RX5902 inhibited TGF-β1-induced fibrotic responses in HK-2 cells (all P<0.05). Flow cytometry analysis results revealed that TGF-β1 stimulation resulted in a significant increase in the proportion of HK-2 cells in the G2/M phase. Conversely, silencing of DDX5 led to a significant reduction in the proportion of HK-2 cells in the G2/M phase (all P<0.05). Conclusions:DDX5 is significantly elevated in the renal tissues of UUO mice and TGF-β1-induced HK-2 cells. The pharmacological and genetic blockade of DDX5 can delay renal fibrosis by reducing cell cycle arrest and alleviating cell damage.

Objective:To investigate the prognostic value and safety of thoracic radiotherapy in patients with synchronous oligometastatic, driver gene-negative non-small cell lung cancer (NSCLC) receiving immune checkpoint inhibitors (ICIs) as first-line treatment.Methods:Data were retrospectively collected from 55 patients diagnosed with synchronous oligometastatic, driver gene-negative NSCLC who received first-line ICIs from January 2017 to March 2022. These patients were categorized into two groups based on the administration of thoracic radiotherapy: the thoracic radiotherapy group ( n = 27) and the non-thoracic radiotherapy group ( n = 28). Comparative analyses were conducted to evaluate survival outcomes and safety profiles between the two groups. Results:Among the 55 patients, 27 (49.1%) received thoracic radiotherapy. The median follow-up time was 37.0 months (2.2-76.7 months). Patients in the thoracic radiotherapy group exhibited significantly improved median overall survival (OS: 53.4 vs. 21.3 months, P = 0.049) and median progression-free survival (PFS: 13.6 vs. 8.3 months, χ2=4.11, P = 0.043) compared to those in the non-thoracic radiotherapy group. Multivariate Cox regression analysis identified thoracic radiotherapy as an independent prognostic factor for OS ( HR = 0.39, 95% CI: 0.17-0.90, P = 0.027) and PFS ( HR = 0.53, 95% CI: 0.28-0.99, P = 0.046). The most common grade 3 or higher toxicity was bone marrow suppression, occurring in seven patients (12.7%). There was no significant difference between both groups in the incidence of grade 3 or higher treatment-related adverse events, including pneumonitis. Conclusion:In patients with driver gene-negative, synchronous oligometastatic NSCLC, first-line immunotherapy combined with thoracic radiotherapy may improve survival outcomes without increasing the incidence of severe treatment-related adverse events. Further large-scale, randomized prospective trials are needed to verify the findings of this study.