Objective:To explore the predictive value of preoperative peripheral hematological parameters combined with clinicopathological features for cervical lymph node metastasis（CLNM） in patients with laryngeal squamous cell carcinoma（LSCC）, and to construct and validate a nomogram model for CLNM. Methods:A retrospective analysis was conducted on the clinical data of 264 LSCC patients who underwent surgical treatment and were pathologically confirmed, collected from the Second Affiliated Hospital of Shandong First Medical University and Taian 88 Hospital. Specifically, 161 patients from one hospital were allocated to the training cohort, while 103 patients from another hospital constituted the validation cohort. Based on postoperative pathological results, patients were categorized into CLNM-positive and CLNM-negative groups. The general clinical data, clinicopathological features, and hematological parameters of the two groups were analyzed and compared. A preoperative predictive model for CLNM was developed using logistic regression analysis, followed by validation and sensitivity analysis to evaluate the robustness of the model's predictive performance. Results:The results showed that there were significant differences in tumor location, tumor size, tumor differentiation, neutrophil percentage, lymphocyte count, lymphocyte percentage, c-reactive protein（CRP）, fibrinogen, neutrophil-to-lymphocyte ratio（NLR）, platelet-to-lymphocyte ratio（PLR）, systemic immune-inflammation index（SII）, systemic inflammation response index（SIRI）, and prognostic inflammatory index（PIV） between the CLNM-positive and CLNM-negative groups（P<0.05）. Lasso regression identified tumor location, clinical T stage, tumor size, tumor differentiation degree, red blood cell distribution width（RDW） -coefficient of variation（RDW-CV）, CRP, FIB, D-dimer, NLR, and lymphocyte-to-monocyte ratio（LMR） were the most predictive parameters. Multivariate logistic regression revealed that tumor location, tumor size, tumor differentiation degree, CRP, and NLR were independent risk factors for CLNM in LSCC patients（P<0.05）. A nomogram was constructed based on these five factors. The model demonstrated excellent discrimination, with a C-index of 0.837（95%CI 0.766-0.908） in the training cohort and 0.809（95%CI 0.698-0.920） in the validation cohort. Calibration curves and DCA curves in both cohorts confirmed the clinical utility of the model. Sensitivity analysis further supported the robustness of the results, showing good discrimination and calibration across different age and BMI subgroups. Conclusion:Tumor location, tumor size, tumor differentiation degree, CRP, and NLR were independent risk factors for CLNM in LSCC patients. The nomogram based on these variables exhibits strong discrimination, calibration, and clinical applicability, and may serve as a valuable tool for preoperative risk assessment and individualized treatment planning.
Humans ; Nomograms ; Laryngeal Neoplasms/blood* ; Retrospective Studies ; Lymphatic Metastasis ; Carcinoma, Squamous Cell/blood* ; Lymph Nodes/pathology* ; Male ; Female ; Middle Aged ; Neck ; C-Reactive Protein ; Aged ; Logistic Models ; Neutrophils ; Prognosis

OBJECTIVES: To study the impact of SURF4 expression level on long-term prognosis of gastric cancer (GC) and biological behaviors of GC cells. METHODS: SURF4 expression level in GC and its association with long-term patient prognosis were analyzed using publicly available databases and in 155 GC patients with low and high SURF4 expressions detected immunohistochemically. The Cox proportional hazard model and Kaplan-Meier survival curves were used to analyze independent prognostic predictors of GC and the 5-year survival rate of the patients with different SURF4 expression levels. Informatics analyses were conducted to explore the correlation of SURF4 expression level with immune cell infiltration in GC, SURF4-related differential genes and their associated pathways. In cultured GC cell line HGC-27, the effects of SURF4 knockdown and overexpression on proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) were investigated. RESULTS: Analysis of GEPIA dataset and immunohistochemical results suggested significant SURF4 overexpression in GC (P<0.05), which was associated with shortened 5-year survival time of the patients (χ²=38.749, P<0.001). The prognosis of GC was closely related to tumor stage T3-4, N2-3, CEA≥5 μg/L and CA19-9≥37 kU/L (P<0.05). SURF4 expression level was negatively correlated with activated B cells, NK cells and CD8⁺ effector memory T cells (P<0.05) and positively correlated with CD4⁺ T cells (P<0.05). GO and KEGG enrichment analysis suggested that SUFR4 may participate in GC carcinogenesis by promoting EMT through the tight junction pathway. In HGC-27 cells, SURF4 overexpression significantly decreased E-cadherin expression, increased N-cadherin expression, inhibited ZO-1 and claudin-1 expressions, and promoted cell proliferation, migration and invasion. CONCLUSIONS SURF4 is highly expressed in GC, and its overexpression is associated with a shortened 5-year survival of the patients possibly by enhancing tumor cell proliferation, migration and invasion via inhibiting tight junction proteins and promoting EMT.
Humans ; Stomach Neoplasms/metabolism* ; Cell Proliferation ; Cell Movement ; Epithelial-Mesenchymal Transition ; Cell Line, Tumor ; Neoplasm Invasiveness ; Prognosis ; Tight Junction Proteins/metabolism* ; Membrane Proteins/metabolism* ; Female ; Male

Objective To observe the clinical efficacy of Dan Qi Yishen Prescription in treating diabetic nephropathy(DN)and explore its renal protective mechanism.Methods A total of 150 patients with DN of qi-yin deficiency complicated with blood stasis syndrome who admitted to Sanya Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Chinese Medicine from October 2021 to April 2023 were divided into a control group and an observation group according to the random number table method,with 75 patients in each group.Both groups were given conventional therapies such as dietary treatment,blood glucose control,blood pressure control,lipid-lowering treatment and treatment of complications.Additionally,the control group was given intravenous injection of reduced glutathione,while the observation group was given oral use of the decoction of Dan Qi Yishen Prescription and ionic introduction of Dan Qi Yishen Prescription in renal region.Thirty days constituted one course of treatment,and both groups were treated for three courses.Before and after treatment,the scores of traditional Chinese medicine(TCM)syndrome,and the levels of renal function indicators,renal hemodynamic indicators,coagulation and fibrinolysis indicators,and vascular endothelial function indicators in the two groups were observed.Results(1)After treatment,the scores of TCM symptoms such as fatigue and weakness,palpitations and shortness of breath,dizziness and tinnitus,spontaneous sweating and night sweating,restlessness and insomnia,and thirst with preference for drinks in the two groups were decreased compared with those before treatment(P<0.01),and the decrease in the observation group was significantly superior to that in the control group(P<0.01).(2)After treatment,the levels of renal function indicators such as blood urea nitrogen(BUN),serum creatinine(SCr),collagen Ⅳ(CⅣ),and plasma laminin(LN)of patients in the two groups were improved compared with those before treatment(P<0.01),and the improvement in the observation group was significantly superior to that in the control group(P<0.01).(3)After treatment,the levels of renal hemodynamic indicators such as systolic maximum blood flow velocity(Vsmax)and diastolic minimum blood flow velocity(Vdmin)of the main renal artery(MRA)and interlobar artery(IRA)in the two groups were increased compared with those before treatment(P<0.05 or P<0.01),while the resistance index(RI)and pulsatility index(PI)of MRA and RI of IRA in the two group as well as PI of IRA in the observation group were decreased compared with those before treatment(P<0.05 or P<0.01).The increase of Vsmax and Vdmin of MRA and IRA as well as the decrease of RI and PI of MRA and IRA in the observation group was significantly superior to that in the control group(P<0.05 or P<0.01).(4)After treatment,the levels of coagulation and fibrinolysis indicators such as prothrombin time(PT),activated partial thromboplastin time(APTT),D-dimer(D-D),and fibrinogen(FIB)in the two groups were improved compared with those before treatment(P<0.01),and the improvement in the observation group was significantly superior to that in the control group(P<0.01).(5)The analysis of vascular endothelial function indicators showed that after treatment,the serum vasohibin 1(VASH-1)level in the two groups was increased compared with that before treatment(P<0.01),and the serum vascular endothelial growth factor(VEGF)and endothelin 1(ET-1)levels were decreased compared with those before treatment(P<0.01),and the increase of serum VASH-1 level as well as the decrease of serum VEGF and ET-1 levels in the observation group was significantly superior to that in the control group(P<0.01).Conclusion Dan Qi Yishen Prescription exerts good clinical efficacy in treating patients with DN of qi-yin deficiency complicated with blood stasis syndrome,and it has protective effect on renal function probably by improving the coagulation and fibrinolysis system and vascular endothelial function of the patients.

Objective To investigate the effect and mechanism of Xuanfu Daizhe Decoction on the proliferation,migration,and invasion activities of esophageal cancer cells.Methods Human e-sophageal cancer cell line EC 109 was treated with Xuanfu Daizhe Decoction at different concentrations,and the cells were divided into high-concentration group(200 μg/mL),medium-concentration group(100 μg/mL),low-concentration group(50 μg/mL),and blank group(0 μg/mL)based on the concentration.CCK-8 assay,wound healing assay,and Transwell invasion assay were used to detect the proliferation,migration,and invasion activities of the cells in each group,respectively.Western blot and cellular immunofluorescence staining were employed to detect the protein expression levels of glycolysis-related enzymes[hexokinase 2(HK2),lactate dehydrogenase A(LDHA),and phospho-fructokinase 1(PFK1)]in the cells of each group,and real-time quantitative fluorescent polymerase chain reaction(qRT-PCR)was used to detect the relative expression levels of mRNA encoding these enzymes.A nude mouse tumor-bearing model was established and divided into control group and Xuanfu Daizhe Decoction-fed group(20 mg/kg)to observe the effect of Xuanfu Daizhe Decoction on the growth of esophageal cancer in vivo.Results The results of CCK-8 assay,wound healing as-say,and Transwell invasion assay showed that Xuanfu Daizhe Decoction could inhibit the prolifera-tion,migration,and invasion activities of EC 109 cells in a concentration-dependent manner.West-ern blot and cellular immunofluorescence analysis revealed that compared with the blank group,the protein expression levels of HK2,LDHA,and PFK1 in the low-concentration,medium-concentra-tion,and high-concentration groups were decreased(P＜0.05).The qRT-PCR results showed that compared with the blank group,the relative expression levels of HK2 mRNA,LDHA mRNA,and PFK1 mRNA in the low-concentration,medium-concentration,and high-concentration groups were all reduced(P＜0.01 or P＜0.000 1).The tumor volume in the subcutaneous tissue on the back of nude mice in the Xuanfu Daizhe Decoction-fed group was smaller than that in the control group,and the protein expression level of LDHA in the tumor tissue of the Xuanfu Daizhe Decoction-fed group was lower than that in the control group,while the expression level of the pro-apoptotic protein Bax was higher than that in the control group(P＜0.05).Conclusion Xuanfu Daizhe Decoction can inhibit the glycolysis process of esophageal cancer cells in a concentration-dependent manner,there-by inhibiting cell proliferation,migration,invasion,and tumor growth in vivo.

OBJECTIVE: To summarize the research progress on the role of macrophage-mediated osteoimmune in osteonecrosis of the femoral head (ONFH) and its mechanisms. METHODS: Recent studies on the role and mechanism of macrophage-mediated osteoimmune in ONFH at home and abroad were extensively reviewed. The classification and function of macrophages were summarized, the osteoimmune regulation of macrophages on chronic inflammation in ONFH was summarized, and the pathophysiological mechanism of osteonecrosis was expounded from the perspective of osteoimmune, which provided new ideas for the treatment of ONFH. RESULTS: Macrophages are important immune cells involved in inflammatory response, which can differentiate into classically activated type (M1) and alternatively activated type (M2), and play specific functions to participate in and regulate the physiological and pathological processes of the body. Studies have shown that bone immune imbalance mediated by macrophages can cause local chronic inflammation and lead to the occurrence and development of ONFH. Therefore, regulating macrophage polarization is a potential ONFH treatment strategy. In chronic inflammatory microenvironment, inhibiting macrophage polarization to M1 can promote local inflammatory dissipation and effectively delay the progression of ONFH; regulating macrophage polarization to M2 can build a local osteoimmune microenvironment conducive to bone repair, which is helpful to necrotic tissue regeneration and repair to a certain extent. CONCLUSION At present, it has been confirmed that macrophage-mediated chronic inflammatory immune microenvironment is an important mechanism for the occurrence and development of ONFH. It is necessary to study the subtypes of immune cells in ONFH, the interaction between immune cells and macrophages, and the interaction between various immune cells and macrophages, which is beneficial to the development of potential therapeutic methods for ONFH.
Humans ; Femur Head/pathology* ; Osteonecrosis/therapy* ; Macrophages/pathology* ; Inflammation ; Femur Head Necrosis/pathology*

Objective To establish a fast,stable,and sensitive zebrafish model of osteoporosis(OP)using different method.Methods OP models were induced by iron overload or prednisolone(Pred),and bone formation and mortality were observed.The groups were divided into:Control group,model group(include FAC group and Pred group),and positive control group(AC group).Ammonium ferric citrate was used as the model drug in the iron-overload induction method.For the Pred induction models,the modeling time for the Pred-3 days post-fertilization(dpf)method was 3～9 dpf,the modeling time for the Pred-5 dpf method was 5～10 dpf,and Pred was administered from 3 dpf and removed from 7～9 dpf for the Pred withdrawal method.To compare the anti-osteoporosis(OP)effects of commonly used drugs such as Alfacalcidol(AC),Calcitriol(CA),and Alendronate(AL),it's important to select a stable and sensitive positive control drug and to further optimize different staining methods and conditions.Results There was no significant effect of ammonium ferric citrate 500 μg/mL on bone formation.Bone formation and the length of the first vertebra were significantly decreased in the Pred group induced by Pred-3 dpf compared with those in the control group(P＜0.01,P＜0.05),but zebrafish mortality was higher.There was no significant difference between the Pred-5 dpf method,but bone formation was significantly reduced in the Pred withdrawal group(P＜0.01),with no mortality.Alfacalcidol,calcitriol,and alendronate all had anti-OP effects,with CA having the most sensitive and stable anti-OP effect.Alizarin red staining showed that the optimal dye parameters were 0.02%concentration for dyeing 2 h,with washing in 0.5%KOH and glycerol under the conditions of a 3∶1 ratio for 3 h followed by a 1∶1 ratio for 14 h.The result of staining showed that calcein was more sensitive for staining bone nodes and ARS staining was more sensitive for staining the first vertebra.Conclusions The Pred withdrawal method can be used to establish a rapid,stable,and sensitive OP model in zebrafish as a reliable model for studying OP.

Objective:To analyze the clinical characteristics of patients of chronic active Epstein-Barr virus infection (CAEBV) with intestinal involvement misdiagnosed as inflammatory bowel disease (IBD).Methods:A retrospective analysis was conducted on the clinical characteristics, laboratory results, digestive endoscopic findings, histological results, treatment and prognosis of 10 patients with CAEBV intestinal involvement who were misdiagnosed as IBD and treated at the Department of Hematology, Beijing Friendship Hospital, Capital Medical University from February 2019 to November 2022. Epstein-Barr virus-encoded small RNA (EBER) was detected by in situ hybridization. Results:Among the 10 patients with CAEBV, eight were males and two were females. Seven patients had been misdiagnosed as ulcerative colitis and three misdiagnosed as Crohn′s disease. The median age of onset was 36 years (ranged from 26 to 52 years), and the median time from onset to CAEBV diagnosis was 18.5 months (ranged from 2.0 to 96.0 months). The main clinical characteristics of these patients included fever >38.5 ℃ in 10 cases, diarrhea in seven cases, abdominal pain in seven cases, abdominal lymph node enlargement in six cases and hematochezia in seven cases. Six patients primarily presented with gastrointestinal symptoms, and seven patients had involvement of extraintestinal organs, three patients developed hemorrhagic shock due to gastrointestinal bleeding. The laboratory findings included anemia in seven cases, elevated erythrocyte sedimentation rate in six cases, decreased natural killer cell activity in five cases, and elevated ferritin in three cases. Epstein-Barr virus (EBV) DNA were detected in the peripheral blood mononuclear cells (PBMCs) of nine patients, with a median viral load of 23 000 copies/mL. Seven patients were tested positive for anti-EBV viral capsid antigen IgG and nuclear antigen 1 IgG. The main endoscopy findings were hyperemia, edema of the affected intestinal wall mucosa, which could be accompanied by erosion, multiple scattered shallow ulcers with varying sizes. There were six patients with total colon involvement. The rectum was involved in three patients, and the esophagus, gastric antrum, duodenum and small intestine were each involved in one patient. Seven patients underwent follow-up colonoscopy after diagnosis, and four cases progressed. All 10 patients showed active chronic inflammation in the histopathological examinations of their intestinal tissue, with crypt changes in four cases and granulomatous changes in one cases. The intestinal tissues of eight patients were positive for EBER staining, and EBER positive cells≥50 cells/high-power field in seven patients. Seven patients were treated with 5-aminosalicylic acid before the correct diagnosis. Five patients had not improved or progressed upon the follow-up colonoscopy. Two patients died of uncontrolled massive hemorrhage of digestive tract.Conclusions:The clinical, endoscopic and pathological findings of patients with CAEBV intestinal involvement lack specificity. For IBD patients initially diagnosed accompanied by fever and evidence of extraintestinal organ involvement, it is recommended to simultaneously detect EBV DNA in PBMCs and blood plasma, EBER in intestinal tissue, and identify the main EBV-infected cells in peripheral blood and/or tissue, to distinguish CAEBV.

Objective:This study aimed to evaluate the global research landscape, identify trends, and determine hotspots concerning hepatoma recurrence post-liver transplantation.Methods:We conducted a bibliometric analysis usinga systematic search was conducted in the Web of Science Core Collection database from Jan. 1992 to Oct. 2023 to identify relevant articles on hepatoma recurrence after liver transplantation. Articles were selected based on inclusion and exclusion criteria and analyzed for publication trends by country/region, journal, author, institution, citation, and keyword. Visualization tools such as Citespace, VOSviewer, and Bibliometric.com were utilized for statistical analysis, identification of emerging trends, and clustering of keyword co-occurrence.Results:Out of 4,936 articles retrieved, 1,189 were included in the final analysis. There was a notable increase in publications on hepatoma recurrence following liver transplantation from 1992 to 2021, peaking in 2021 both globally (n=103) and nationally (n=32). China has the largest number of publications in this field (n=308), maintaining significant collaboration with the United States, South Korea, Japan, Canada. 'Liver Transplantation’ journal had the highest number of publications (n=113). Zhejiang University was the leading institution (n=74), with Academician Zheng Shusen being the most prolific scholar (n=76 publications). Citation emergence detection found that Italian scholar Mazzaferro's Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis published on The Lancet Oncology in 2009 had the highest burst strength (36.98). Five bursting keywords were identified: alpha fetoprotein, model, validation, sorafenib, and risk. Cluster analysis of keyword co-occurrence revealed five primary research themes: the medication for hepatocellular carcinoma recurrence after liver transplantation, recipient selection criteria, prognostic factors, development and validation of recurrence prediction model, and local treatments for hepatocellular carcinoma.Conclusions:The study underscores rapid advancements in the research on hepatocellular carcinoma recurrence post-liver transplantation over the past three decades, with significant contributions from Chinese scholars, particularly from Zhejiang University and Academician Zheng Shusen. The evolving research hotspots have shifted from transplantation experiences and recipient selection criteria to early post-transplant recurrence risk prediction and therapeutic strategy development.

Objective To investigate the expression of TSR2 in gastric cancer and explore its correlation with progression of gastric cancer and the possible mechanism.Methods We retrospectively analyzed TSR2 expression in clinical specimens from 105 gastric cancer patients and the impact of TSR2 expression level on disease progression and 5-year postoperative survival of the patients.GO and KEGG enrichment analyses were used to predict the biological functions and mechanisms of TSR2.In gastric cancer MGC-803 cells with lentivirus-mediated TSR2 overexpression or knockdown,the changes in cell proliferation,invasion,and migration were assessed with CCK-8 and Transwell assays,and the expressions of p-PI3K and p-AKT were detected using Western blotting.Results TSR2 expression was significantly lower in gastric cancer tissues than in the adjacent tissues with significant correlations with CEA level,CA19-9 level,and T and N staging(P<0.05).A low TSR2 expression,CEA≥5 μg/L,CA19-9≥37 kU/L,T3-T4 stages,and N2-N3 staged were identified as independent risk factors affecting 5-year survival rate of the patients following radical surgery(P<0.05),and a high TSR2 expression was associated with a higher 5-year survival rate of the patients(P<0.001).Bioinformatics analysis suggested the functional involvement of TSR2 with the PI3K/AKT signaling pathway.MGC-803 cells overexpressing TSR2 showed significantly lowered proliferation,migration,and invasion capacities(P<0.05),while TSR2 knockdown produced the opposite effects(P<0.05).Western blotting showed that TSR2 overexpression reduced the phosphorylation of PI3K and AKT,and TSR2 knockdown caused the opposite changes in MGC-803 cells(P<0.05).Conclusion TSR2 is lowly expressed in gastric cancer tissues to adversely affect the patients'prognosis,and its overexpression inhibits gastric cancer cell proliferation,invasion,and migration possibly by downregulating the PI3K/AKT pathway.

Objective To investigate the effect of compound betamethasone adjuvant on break-through pain after unicompartmental knee arthroplasty under sciatic nerve combined with femoral nerve block.Methods A total of 100 patients underwent unicondylar knee arthroplasty,32 males and 68 females,aged 55-75 years,BMI 18.5-35.0 kg/m2,ASA physical status Ⅰ-Ⅲ,were divided into three groups according to random number table method:no adjuvant group(group C,n=34),dexamethasone adjuvant group(group D,n=33)and compound betamethasone adjuvant group(group B,n=33).The patients in the three groups received sciatic nerve block and 0.4％ropivacaine 15 ml before anesthesia in-duction,then femoral nerve block,0.4％ropivacaine 15 ml in group C,0.4％ropivacaine 15 ml in group D(containing dexamethasone 5 mg),and 0.4％ropivacaine 15 ml in group B(containing compound beca-methasone 4 mg).The occurrence of breakthrough pain,the number of effective analgesic pump compres-sions,opioid dosage,and the number of remedial analgesia cases were recorded.The ground movement dis-tance was recorded 0-24 hours,24-48 hours,and 48-72 hours after operation.The sleep quality scores and adverse events were also recorded.Results Compared with group C,the incidence rate of breakthrough pain was lower(P＜0.05),the number of effective analgesia pump compressions,the dosage of opioid,and the sleep quality score on the first night after operation were significantly decreased in group B(P＜0.05).Compared with group D,the incidence rate of breakthrough pain and breakthrough pain score were lower(P＜0.05),the number of effective analgesia pump compressions,the dosage of opioid,and the sleep quality score on the 1 st night after operation were significantly decreased in group B(P＜0.05).There was no significant difference in the ground movement distance of in different time periods and inci-dence of adverse events among the three groups.Conclusion Compound betamethasone adjuvant can reduce the incidence of breakthrough pain after unicompartmental knee arthroplasty under sciatic nerve com-bined with femoral nerve block,provide perfect analgesic effect,reduce postoperative opioid consumption,and improve the sleep quality of patients on the first night after surgery.