ObjectiveTo investigate the effect and mechanism of long intergenic non-coding RNA02086 （LINC02086） overexpression mediated macrophage polarization on the proliferation， migration and invasion of gastric cancer cells. MethodsThe expression levels of LINC02086 in the human gastric epithelial cell line GES-1 and human gastric cancer cell lines HCG-27， NCI-N87， and AGS were determined by qRT-PCR. Human acute monocytic leukemia cells （THP-1） were induced to differentiate into M0 macrophages using phorbol 12-myristate 13-acetate （PMA）. HGC-27 cells were infected with either LINC02086 overexpression lentivirus （OE-LINC02086） or its negative control lentivirus （Vector）， and the culture supernatants were collected as conditioned medium （CM1）. M0 macrophages were co-cultured with the infected HGC-27 cells， and the resulting supernatants were designated as conditioned medium 2 （CM2）. M0 macrophages were treated with CM1 alone or in combination with Wnt/β-catenin pathway inhibitor IWR-1， forming the Vector+CM1， OE-LINC02086+CM1， and OE-LINC02086+CM1+IWR-1 groups， respectively. Flow cytometry was used to detect mannose receptor C-type 1 （CD206） expression， and qRT-PCR was employed to measure mRNA levels of interleukin-10 （IL⁃10）， transforming growth factor-β （TGF⁃β）， vascular endothelial growth factor （VEGF）， and chemokine ligand 22 （CCL22）. Western blot was performed to evaluate protein expression of CD206， VEGF， and key components of the Wnt/β-catenin pathway—Wnt family member 3a （Wnt3a）， glycogen synthase kinase-3β （GSK-3β）， and β-catenin. HGC-27 cells were treated with CM2 alone or combined with IWR-1， establishing the Vector+CM2， OE-LINC02086+CM2， and OE-LINC02086+CM2+IWR-1 groups. CCK-8 assay was used to evaluate cell proliferation， and Transwell assays were conducted to assess migration and invasion capabilities. ResultsCompared with GES-1 cells， the expression levels of LINC02086 were upregulated in HCG-27， NCI-N87， and AGS cells （P < 0.05）， with the smallest increase observed in HCG-27 cells. Compared with Vector+CM1 group， the level of CD206 and the expression levels of IL⁃10， TGF⁃β， VEGF and CCL22 mRNA in macrophages stimulated by OE-LINC02086+CM1 increased （P<0.05）. Meanwhile， the expression levels of Wnt3a and β-catenin proteins in cells increased （P<0.05）， and the expression level of GSK-3β protein decreased （P<0.05）. However， co-treatment with IWR-1 markedly reversed the promoting effects of LINC02086 overexpression on the expression of M2 polarization markers， including CD206， IL⁃10， and TGF⁃β mRNA， in macrophages （P<0.05）， as well as its activation of the Wnt/β-catenin signaling pathway （P<0.05）. Compared with Vector+CM2 group， HGC-27 cells infected with OE-LINC02086+CM2 had increased proliferation activity and increased number of migration and invasion cells （P<0.05）. However， the combined intervention of IWR-1 significantly reversed the promotion of LINC02086 overexpression on the proliferation， migration and invasion of HGC-27 cells （P<0.05）. ConclusionLINC02086 overexpression promotes the proliferation， migration and invasion of gastric cancer cells by activating Wnt/β-catenin pathway to mediate M2 polarization of macrophages.

This study aims to investigate the mechanism of Qingrun Decoction in alleviating hepatic insulin resistance in type 2 diabetes mellitus(T2DM) rats through the reprogramming of amino acid metabolism. A T2DM rat model was established by inducing insulin resistance through a high-fat diet combined with intraperitoneal injection of streptozotocin. The model rats were randomly divided into five groups: model group, high-, medium-, and low-dose Qingrun Decoction groups, and metformin group. A normal control group was also established. The rats in the normal and model groups received 10 mL·kg~(-1) distilled water daily by gavage. The metformin group received 150 mg·kg~(-1) metformin suspension by gavage, and the Qingrun Decoction groups received 11.2, 5.6, and 2.8 g·kg~(-1) Qingrun Decoction by gavage for 8 weeks. Blood lipid levels were measured in different groups of rats. Pathological damage in rat liver tissue was assessed by hematoxylin-eosin(HE) staining and oil red O staining. Transcriptome sequencing and untargeted metabolomics were performed on rat liver and serum samples, integrated with bioinformatics analyses. Key metabolites(branched-chain amino acids, BCAAs), amino acid transporters, amino acid metabolites, critical enzymes for amino acid metabolism, resistin, adiponectin(ADPN), and mammalian target of rapamycin(mTOR) pathway-related molecules were quantified using quantitative real-time polymerase chain reaction(qRT-PCR), Western blot, and enzyme-linked immunosorbent assay(ELISA). The results showed that compared with the normal group, the model group had significantly increased serum levels of total cholesterol(TC), triglycerides(TG), low-density lipoprotein cholesterol(LDL-C), and resistin and significantly decreased ADPN levels. Hepatocytes in the model group exhibited loose arrangement, significant lipid accumulation, fatty degeneration, and pronounced inflammatory cell infiltration. In liver tissue, the mRNA transcriptional levels of solute carrier family 7 member 2(Slc7a2), solute carrier family 38 member 2(Slc38a2), solute carrier family 38 member 4(Slc38a4), and arginase(ARG) were significantly downregulated, while the mRNA transcriptional levels of solute carrier family 1 member 4(Slc1a4), solute carrier family 16 member 1(Slc16a1), and methionine adenosyltransferase(MAT) were upregulated. Furthermore, the mRNA transcription and protein expression levels of branched-chain α-keto acid dehydrogenase E1α(BCKDHA) and DEP domain-containing mTOR-interacting protein(DEPTOR) were downregulated, while mRNA transcription and protein expression levels of mTOR, as well as ribosomal protein S6 kinase 1(S6K1), were upregulated. The levels of BCAAs and S-adenosyl-L-methionine(SAM) were elevated. The serum level of 6-hydroxymelatonin was significantly reduced, while imidazole-4-one-5-propionic acid and N-(5-phospho-D-ribosyl)anthranilic acid levels were significantly increased. Compared with the model group, Qingrun Decoction significantly reduced blood lipid and resistin levels while increasing ADPN levels. Hepatocytes had improved morphology with reduced inflammatory cells, and fatty degeneration and lipid deposition were alleviated. Differentially expressed genes and differential metabolites were mainly enriched in amino acid metabolic pathways. The expression levels of Slc7a2, Slc38a2, Slc38a4, and ARG in the liver tissue were significantly upregulated, while Slc1a4, Slc16a1, and MAT expression levels were significantly downregulated. BCKDHA and DEPTOR expression levels were upregulated, while mTOR and S6K1 expression levels were downregulated. Additionally, the levels of BCAAs and SAM were significantly decreased. The serum level of 6-hydroxymelatonin was increased, while those of imidazole-4-one-5-propionic acid and N-(5-phospho-D-ribosyl)anthranilic acid were decreased. In summary, Qingrun Decoction may improve amino acid metabolism reprogramming, inhibit mTOR pathway activation, alleviate insulin resistance in the liver, and mitigate pathological damage of liver tissue in T2DM rats by downregulating hepatic BCAAs and SAM and regulating key enzymes involved in amino acid metabolism, such as BCKDHA, ARG, and MAT, as well as amino acid metabolites and transporters.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Insulin Resistance ; Diabetes Mellitus, Type 2/genetics* ; Male ; Liver/drug effects* ; Amino Acids/metabolism* ; Rats, Sprague-Dawley ; Humans ; Metabolic Reprogramming

In recent decades,the incidence of human papillomavirus(HPV)-associated oropharyngeal squamous cell carcinoma(OPSCC)has shown a marked increase.Significant changes have also occurred in the OPSCC diagnosis and treatment paradigm.Deter-mining HPV status prior to treatment is now essential,and radiotherapy/chemotherapy,immunotherapy,and minimally invasive surgical techniques have progressively emerged as key modalities for managing OPSCC.However,alongside these paradigm shifts,a comprehen-sive technical consensus guiding the entire diagnostic and therapeutic process for OPSCC patients is currently lacking.Given China's large population base and the rising incidence of OPSCC,an expert panel convened to develop a clinical technical consensus on OPSCC diagno-sis and management tailored to China's specific context.This consensus aims to further enhance and standardize understanding of OPSCC management techniques among relevant healthcare professionals.

Diabetic encephalopathy(DE)is a complication of the central nervous system induced by diabetes,characterized by insidious onset and complex pathological mechanisms.Recent research has revealed that the pathological mechanisms of DE are closely associated with the imbalance of intercellular communica-tion across multiple organs.Exosomes,serving as vital media-tors of intercellular communication,are involved in the patholog-ical progression of DE and hold promise as diagnostic biomarkers and therapeutic targets for DE.Traditional Chinese medicine(TCM)can improve communication between brain cells and be-tween peripheral and brain tissues by regulating exosomes and their contents,thereby preventing and treating DE.Meanwhile,exosomes,as targeted delivery carriers of active molecules,can carry TCM monomers more easily across the blood-brain barrier to prevent and treat DE.In light of this,this review summarizes the regulatory role of exosomes in the pathological progression of DE and explores the enormous potential of TCM in the preven-tion and treatment of DE by regulating exosomes and using exo-somes as traditional Chinese medicine carriers,aiming to pro-vide new evidence for the prevention and treatment of DE with TCM.

OBJECTIVE To observe the clinical efficacy of Shaoqi Yijia Prescription in the treatment of Hashimoto's thyroiditis(HT)with liver depression and spleen deficiency in the non-hypothyroidism stage and its effect on serum inflammatory factors.METHODS A total of 74 patients with Hashimoto's thyroiditis of liver depression and spleen deficiency type in the non-hypothyroid-ism stage who were treated in Putuo District Central Hospital in Shanghai from June to August 2024 were selected and randomly divided into the observation group and the control group with 37 cases in each group(2 cases dropped out in each group).The control group was treated with oral selenium yeast tablets,and the observation group was treated with Shaoqi Yijia Prescription,both for 12 weeks.The traditional Chinese medicine(TCM)syndrome scores,Hamilton anxiety scale(HAMA),Hamilton depression scale(HAMD)and fatigue self-assessment scale(FSAS)scores were evaluated before and after treatment;the thyroglobulin antibody(TgAb),thyroid peroxidase antibody(TPOAb)and serum inflammatory factors interleukin 4(IL-4),IL-6,IL-10,TNF-α and IFN-γ levels were detected before and after treatment in the two groups of patients.RESULTS After treatment,the total score of TCM syndrome and the scores of epigastric or hypochondrium pain,abdominal distension,poor appetite,depression or irritability,and frequent sighs in the observation group were significantly reduced(P<0.05,P<0.01),and the total score of the observation group was better than that of the control group(P<0.01);after treatment,the serum TPOAb level of the observation group was significantly re-duced(P<0.05),the serum TPOAb level of the control group did not change significantly(P>0.05),and the serum TgAb and TPO-Ab levels of the observation group were better than those of the control group(P<0.05);after treatment,the HAMA and HAMD scores of the observation group were significantly reduced(P<0.01),and the HAMA,HAMD and FSAS scores of the observation group were better than those of the control group(P<0.05);after treatment,the serum IL-4 and IL-10 levels of the observation group were in-creased(P<0.05),and the IL-6,IFN-γ and TNF-α levels were decreased compared with those before treatment(P<0.05).The se-rum IL-4,IL-6 and IL-10 levels of the observation group were significantly different from those of the control group(P<0.05).CONCLUSION Shaoqi Yijia Prescription can alleviate the clinical symptoms of patients with Hashimoto's thyroiditis of liver depres-sion and spleen deficiency type in the non-hypothyroid period,and improve anxiety and depression,which may be related to improving the body's inflammatory response.

Pituitary metastasis(PM), a rare metastatic complication of malignant tumors most commonly seen in lung and breast cancers, exhibits subtle and nonspecific clinical manifestations that complicate its differentiation from other sellar lesions. Symptom development correlates with anatomical involvement: tumors often initially destroy the posterior pituitary, causing diabetes insipidus; subsequently, pituitary stalk compression may trigger hyperprolactinemia, while progressive anterior pituitary destruction ultimately leads to hormonal deficiencies. Additionally, mass effects from the tumor can result in optic chiasm compression, with specific neurological manifestations dependent on the invasion site. Nonspecific symptoms such as fatigue and headache are frequently observed. Pituitary MRI serves as a critical diagnostic tool for distinguishing sellar pathologies. As a distant metastatic event, PM portends a poor overall prognosis. This study presents two cases of lung adenocarcinoma with PM, supplemented by a comprehensive literature review, to summarize clinical characteristics and diagnostic/therapeutic strategies.

Objective:To investigate the clinical, pathological, and molecular biological characteristics of gastric hepatoid adenocarcinoma (HAS) in order to provide reference for clinical treatment.Methods:Thirty-two patients diagnosed with hepatoid adenocarcinoma after radical gastrectomy for gastric cancer at Shanxi Cancer Hospital were included from January 2019 to December 2021. Immunohistochemistry, in situ hybridization, and next-generation sequencing (NGS) methods were used to analyze immune markers and molecular characteristics in the pathological tissues from 32 patients with HAS. Cox regression analysis and Kaplan-Meier method were used to analyze the prognostic factors of overall survival and disease-free survival.Results:Among the 32 patients with HAS, 26 were male, 6 were female; aged 28-77 years, with an median age 62.0 (53.8, 67.2) years. Fifteen cases of HAS were located in the cardia, 10 cases in the antrum, and 7 cases in the body of the stomach. The maximum diameter of the mass was 3-10 cm, and mainly ulcerative in gross. The immunohistochemistry and in situ hybridization results showed that the positive rates of AFP, SALLA4, and Glypican-3 were 68.8% (22/32), 68.8% (22/32), 78.1% (25/32), respectively; Seven patients had microsatellite status of dMMR. Two cases of HER2 gene amplification and 2 cases of EB virus positivity. The NGS results showed that HAS was often accompanied by multiple gene mutations, with 23 cases having ≥ 2 gene mutations and 6 cases having ≥10 gene mutations. The TP53 gene had the highest mutation frequency; 4 cases had genetic structural variations; 28 cases had copy number variation. In addition, there were 7 cases of MSI-H and 9 cases of TMB-H. Follow-up results showed that 12 cases died, 9 cases developed metastasis, and the shortest survival time was 5 months.Conclusions:Gastric HAS is a type of tumor with high invasiveness and poor prognosis. The combined detection of AFP, SALLA4 and Glypican-3 can improve the diagnostic rate of tumors. dMMR/MSI-H and TMB-H patients in HAS are significantly higher than those in ordinary gastric cancer, and the high frequency mutation genes in HAS are often accompanied by multiple potential therapeutic targets. Immunotherapy combined with chemotherapy and targeted therapy are expected to become the treatment direction of HAS.

Lean six sigma (LSS) emphasizes patient demand-oriented, and continuously optimizing prolesses to achieve efficiency and standardization in medical services. Starting in 2021, a specialized children′s hospital (comprising one main campus and three branch campuses) introduced the LSS management method. Through define, measure, analyze, improve, and control, the hospital utilized tools such as questionnaire surveys, SIPOC models, and fishbone diagrams to identify pain points in the building of multi-campus child-friendly hospital and develop improvement measures.To address the main issues of insufficient cross-campus collaboration, significant disparities in service quality among different campuses, unclear functional positioning of each campus, and inadequate integration with social security mechanisms, the hospital implemented a " homogeneity-differentiation-coordination" management mode. The hospital implemented unified diagnosis and treatment standards and clinical pathways, carried out remote consultations and expert rotations, completed mutual recognition of examination and testing results, optimized child friendly labeling and child friendly environment, and built a " hospital-to-hospitals, hospital to medical schools, and hospital to community health centers" linkage platform, etc., to promote the standardization of diagnosis and treatment processes, clear functional positioning of the hospital area, and efficient resource allocation. Through practice, the outpatient appointment rate and patient satisfaction rate in the main hospital had increased from 86.72% and 98.64% in January December 2021 to 91.87% and 99.72% in January December 2024, respectively; The patient waiting time had been shortened from 26.54 minutes to 21.94 minutes, and the efficiency of medical treatment and service experience had been significantly improved. As of 2024, mutual recognition of 214 inspection and testing items had been achieved cross hospital campuses, forming a collaborative pattern of " main hospital leading, campuses support, and resource complementarity", and significantly improving the level of collaboration and child friendly connotation among multi-campus. This practice explored the integration path of multi-campus collaborative governance and child-friendly services, which could provide reference and inspiration for the similar hospitals.

Objective:To investigate the clinical, pathological, and molecular biological characteristics of gastric hepatoid adenocarcinoma (HAS) in order to provide reference for clinical treatment.Methods:Thirty-two patients diagnosed with hepatoid adenocarcinoma after radical gastrectomy for gastric cancer at Shanxi Cancer Hospital were included from January 2019 to December 2021. Immunohistochemistry, in situ hybridization, and next-generation sequencing (NGS) methods were used to analyze immune markers and molecular characteristics in the pathological tissues from 32 patients with HAS. Cox regression analysis and Kaplan-Meier method were used to analyze the prognostic factors of overall survival and disease-free survival.Results:Among the 32 patients with HAS, 26 were male, 6 were female; aged 28-77 years, with an median age 62.0 (53.8, 67.2) years. Fifteen cases of HAS were located in the cardia, 10 cases in the antrum, and 7 cases in the body of the stomach. The maximum diameter of the mass was 3-10 cm, and mainly ulcerative in gross. The immunohistochemistry and in situ hybridization results showed that the positive rates of AFP, SALLA4, and Glypican-3 were 68.8% (22/32), 68.8% (22/32), 78.1% (25/32), respectively; Seven patients had microsatellite status of dMMR. Two cases of HER2 gene amplification and 2 cases of EB virus positivity. The NGS results showed that HAS was often accompanied by multiple gene mutations, with 23 cases having ≥ 2 gene mutations and 6 cases having ≥10 gene mutations. The TP53 gene had the highest mutation frequency; 4 cases had genetic structural variations; 28 cases had copy number variation. In addition, there were 7 cases of MSI-H and 9 cases of TMB-H. Follow-up results showed that 12 cases died, 9 cases developed metastasis, and the shortest survival time was 5 months.Conclusions:Gastric HAS is a type of tumor with high invasiveness and poor prognosis. The combined detection of AFP, SALLA4 and Glypican-3 can improve the diagnostic rate of tumors. dMMR/MSI-H and TMB-H patients in HAS are significantly higher than those in ordinary gastric cancer, and the high frequency mutation genes in HAS are often accompanied by multiple potential therapeutic targets. Immunotherapy combined with chemotherapy and targeted therapy are expected to become the treatment direction of HAS.

Objective To analyze the risk factors for catheter-related thrombosis(CRT)in the upper arm infusion port(UAP)and to construct a machine-learning prediction model.Methods A total of 6028 patients,who received UAP implantation at Shanghai Renji Hospital of China from February 2014 to February 2023,were enrolled in this study.The patients were divided into training set(n=4 219)and validation set(n=1 809).Six machine-learning prediction models,including Least Absolute Shrinkage and Selection Operator(LASSO)regression,random forest,decision tree,neural network,XGBoost and logistic,were constructed,and the model having best performance was selected as the optimal model.SHapely Additive exPlanations(SHAP)analysis was used to explain the neural network model,and DALEXtra package was used to explain the continuous variables.Results The neural network model was chosen as the final model.The variables,in order of the degree of importance from high to low,included sex,the diameter of catheter,catheter tip confirmation method,the length of catheter,inpatient or outpatient status,history of central venous catheter implantation,the length of subcutaneous tunnel,age,body mass index(BMI),primary tip displacement,and left or right venous approach.The learning curve,i.e.the area under curve(AUC)of the receiver operating characteristic(ROC)curve,for the training set was＞0.6,and the Delong testing and Bootstrap Methods Test showed that the neural network model performed well(P＜0.05).The Kolmogorov-Smirnov plot(KS plot)value was 0.313 5,indicating that the model had the good ability of discrimination.The clinical impact curve(CIC)assessment revealed that the model had good clinical value.Conclusion The machine-learning prediction model of upper arm infusion port with CRT has been successfully constructed.For minimizing the risk of CRT,it is recommended to prioritize the use of 5 F diameter catheters,adopt left-sided venous approach and positioning the tip of the catheter based on anatomical measurements,besides,the catheter length should be not shorter than 36.56 cm,and the subcutaneous tunnel length should not be less than 5 cm.The basic features associated with higher CRT risk include age of 50-65 years,BMI being between 18.69 kg/m2 and 20.81 kg/m2 or between 23.68 kg/m2 and 23.94 kg/m2 and male.