Head and neck squamous cell carcinoma (HNSCC) is the seventh most common malignant tumor in the world, with a 5-year survival rate of only about 50%. Thus, discovering more effective diagnostic and therapeutic approaches is an urgent need. The metabolic reprogramming of tumor cells is a key feature in the development of HNSCC, which widely exhibits alterations in glycolytic metabolism, lipid metabolism, and amino acid metabolism compared with normal cells. Metabolic reprogramming affects the energy supply and biosynthesis of tumor cells. It also participates in the regulation of the tumor microenvironment and promotes key biological processes such as proliferation, invasion, and metastasis of HNSCC. With the progressive understanding of the complexity of tumor biology, targeted-therapy strategies against metabolic reprogramming in HNSCC are emerging as a promising therapeutic approach. These metabolically targeted therapies have performed well in preclinical studies, but their clinical application requires further validation. In the future, we need to deeply explore the more complex features of metabolic reprogramming and its biological significance in HNSCC, with the aim of discovering more effective diagnostic and therapeutic targets, as well as providing new strategies to improve the prognosis of HNSCC patients.

Objective To investigate the effects of metformin(Met)on the proliferation of pancreatic cancer cells under different glucose concentration culture conditions,and to find the potential role of miR-139-5p in the process.Methods PANC-1 cells were treated with different concentrations of metformin(0/5/10/20 mmol/L)in 25 mmol/L(high-glucose group,HG)or 5 mmol/L(normal-glucose group,NG)glucose culture,cell proliferation,apoptosis,migration and cell cycle were detected after 48 h.The expression of miR-139-5p was quantitatively detected by RT-qPCR,and the miR-139-5p mimics were transfected into PANC-1 cells to clarify the role of miR-139-5p.Results Metformin inhibited the proliferation,promoted apoptosis,and induced S phase and G2/M phase arrest of PANC-1 cells under in high glucose and normal glucose culture conditions,and its anti-proliferation and pro-apoptosis effects were more significant in the normal glucose groups.The expression of miR-139-5p was up-regu-lated by metformin treatment in normal but not in high glucose culture.Further studies showed that miR-139-5p mimics inhibited of PANC-1 cells proliferation without metformin pre-incubation and enhanced the anti-prolifera-tion effect of 5 mmol/L metformin.The pro-apoptotic effect of 10 mmol/L metformin in normal glucose culture conditions.Conclusions In normal-glucose culture conditions,metformin can inhibit proliferation,induce apop-tosis and cell cycle arrest of PANC-1 cells more significantly than in higher-glucose culture,which may be partly related to the up-regulation of miR-139-5p.

Objective To evaluate the radiation dose of interventional procedure for children with congenital heart disease, and to analyze the differences in radiation dose and influencing factors. Methods A total of 94 children who underwent interventional procedure for congenital heart disease at a grade A tertiary hospital in Jinan, Shandong Province, China from June 2021 to September 2022 were included in this study. The patients were divided into three groups according to the type of procedure: ventricular septal defect occlusion group (VSD, 48 cases), patent ductus arteriosus occlusion group (PDA, 29 cases), and atrial septal defect occlusion group (ASD, 17 cases). The basic information of patients and postoperative dose reports were recorded. A statistical analysis was performed using SPSS software. Results The median cumulative air kerma (CAK) of VSD, PDA, and ASD was 100.5, 43.7, and 12.1 mGy, respectively. The median air kerma area product (KAP) of VSD, PDA, and ASD was 3.309, 1.313, and 0.540 Gy·cm², respectively. The median KAP·kg⁻¹ of VSD, PDA, and ASD was 0.179, 0.088, and 0.031 Gy·cm²·kg⁻¹, respectively. There were significant differences in fluoroscopy time, number of cine images, CAK, KAP, and KAP·kg⁻¹ among the three types of interventional procedures (P<0.05). Compared with PDA and ASD, VSD showed significantly higher fluoroscopy time, number of cine images, CAK, KAP, and KAP·kg⁻¹ (P<0.05). Multiple linear regression analysis found that age (B=52.445, P<0.05), weight (B=13.077, P<0.05), fluoroscopy time (B=0.425, P<0.05), tube current (B=0.872, P<0.05), and number of cine images (B=0.660, P<0.05) were positively correlated with KAP, while there was no significant association between height and KAP (P>0.05). Conclusion There are differences in radiation dose among the three types of procedures. Reducing fluoroscopy time, tube current, and number of cine images while meeting the procedure requirements is of great significance for reducing the radiation dose received by children.

Objective:To analyze KCNJ5 mutation of adenomas in patients with aldosterone-producing adenoma (APA) companying with hypokalemia, and to compare the clinical characteristics of patients with and without KCNJ 5 mutations.Methods:Clinical data of 144 APA patients were retrospectively analyzed. DNA were extracted from adenoma tissues, and amplified and sequenced for KCNJ5 gene. The serum potassium level and cardiac complications in patients with and without KCNJ5 gene mutation were compared.Results:Among 144 tumors, 131 tumors (91%) had KCNJ5 mutation, including 68 tumors with G151R, 56 tumors with L168R, 5 tumors with E145Q, and two tumors with novel mutations, V156_K160delITE and G151delinsVR. Compared with patients without KCNJ5 mutation, patients with KCNJ5 mutation had lower preoperative serum potassium levels, more cardiac complications, lower postoperative systolic blood pressure, and better postoperative hypertension relief. There were no statistical differences in age, gender, blood pressure, serum potassium level, plasma renin activity or plasma aldosterone concertration.Conclusion:91% adenomas in patients with APA and hypokalemia had KCNJ5 mutation, suggesting that KCNJ5 mutation is the main cause in these patients.

Objective:To study the real-world outcome of China FDA-approved Sofosbuvir (SOF)/Velpatasvir (VEL) in Northwest China.Methods:In this multicenter, prospective, real-world cohort study, we recruited patients from 10 sites from Northwest China, who were chronically infected with HCV GTs 1-6 from 06/2018 to 09/2019. Patients received SOF (400mg)/VEL (100mg) for 12 weeks, and with ribavirin 900-1200 mg for GT3 cirrhosis and for any genotype decompensated cirrhosis. The primary endpoint was sustained virological response at 12-weeks post-treatment (SVR12) and safety. The secondary endpoint was the change of liver function after the achievement of SVR12.Results:Totally, 143 patients were enrolled in the study, four patients were lost to follow-up and one died during the follow-up, 138 patients were included in per-protocol analysis. Of the 138 patients, the mean age 53 years, 53.6% male, 94.2% Han nationality, 53.6% liver cirrhosis, 10.1% HBsAg +, 6.5% renal dysfunction, 5.1% treatment-experienced, and 16.7% patients received ribavirin treatment. The genotype distribution was as follows: 35.5% GT1, 42.8% GT2, 15.9% GT3, and 5.8% un-typed. The SVR12 rate was 96.5% (138/143, 95% CI: 93.5%-99.6%) for intention-to-treat analysis, and in per-protocol analysis, all 138 patients obtained SVR12 (100%). Compared with baseline, the serum total bilirubin, ALT and AFP levels decreased (all P < 0.05), as well as increased ALB and platelet count (all P < 0.001) at post-treatment 12-weeks. Overall adverse events (AEs) rate is 29.0%, and the most common AEs were anemia (14.5%) and fatigue (8.0%). Severe side effects (edema and fatigue) occurred in 2 patients, one of whom needed a short-term interruption of treatment due to fatigue. Conclusion:In this real-world cohort study, 12-week SOF/VEL regimen with or without ribavirin achieved high SVR12 rates (96.5%-100% overall) with excellent safety profile among patients with HCV GT1/2/3 infection including patients with GT3 and cirrhosis, and led to improvement of liver function.

Objective:To analyze the association between the Charlson Comorbidity Index(CCI)and the risk of early in-hospital death in cerebral hemorrhage inpatients.Methods:Basic personal and medical information about sex, age, surgery, frequency of hospitalization, days of hospitalization, and ICD-10 diagnosis code was collected for intracerebral hemorrhage patients aged 60 or above admitted to a tertiary general hospital from January 1, 2017 to December 31, 2019.The CCI score was calculated based on diagnoses at the time of discharge.Using the CCI score as the dependent variable and in-hospital death as the independent variable, univariate and multiple logistic regression analysis was conducted to examine the association between CCI and in-hospital death.The receiver operator characteristic curve(ROC)was used to assess the value of CCI in predicting death.Results:A total of 504 cerebral hemorrhage inpatients were included in the study, with an average age of 69.48±7.55 years, and 52 died during the period.Univariate Logistic regression showed that, compared with inpatients with CCI=3, the OR values(95% CI)for inpatients with CCI=4 and CCI≥5 were 2.145(1.056-4.355)and 4.769(2.168-10.494), respectively.Multiple Logistic regression showed that, compared with inpatients with CCI=3, the OR(95% CI)for inpatients with CCI≥5 was 4.453(1.474-13.456), The area under the ROC curve was 0.718, with 95% CI at 0.642-0.793( P<0.001). Conclusions:The CCI score was associated with the risk of early in-hospital death in elderly patients with cerebral hemorrhage and can be used to assess and predict the risk of early in-hospital death for these patients.

Objective:To explore the clinical characteristics and follow-up outcomes of a pedigree of maturity onset diabetes of the young (MODY) induced by a novel mutation of glucokinase (GCK).Methods:The clinical features and laboratory data of a pedigree diagnosed with GCK-MODY in Peking Union Medical College Hospital was analyzed. Genomic DNA was extracted, and Sanger sequencing was performed to detect the gene mutation of the family members. The proband and her father were followed up for 3 years. Wanfang and PubMed were used to search literatures on follow-up studies for treatment of GCK-MOYD.Results:Both the proband and her father were found to have a novel mutation on the GCK gene located in exo10 c.1348G.T (p. Ala450Thr). The proband was treated with diet and exercise control only. At the end of the follow-up, her fasting plasma glucose (FPG, 6.8 mmol/L), 2 h postprandial plasma glucose (2hPG, 7.4 mmol/L), and glycated hemoglobin (HbA1c, 6.3%) were all within the control targets. Additionally, the levels homeostasis model assessment of insulin resistance (HOMA-IR) tended to improved comparing to that at baseline (4.09 to 2.32), and glucose disposition index (DI) was improved compared with baseline (16.22 to 20.05). As to the proband′s father, the treatment with insulin plus acarbose was converted to sulfonylureas monotherapy. His FPG and 2hPG mostly were within the target range, and the levels of HbA1c were significantly reduced by 0.5%-0.7% when compared to that at baseline. The HOMA-IR or islet beta cell function was comparable to those at baseline.Conclusions:Screening patients whose clinical performance meets GCK-MODY and their family members with proper genetic testing is of great importance to reduce misdiagnosis of GCK-MODY, so as to obtain a better glucose control without unnecessary over-treatment and protect islet beta cell function.

Chronic joint pain due to loss of cartilage function, degradation of subchondral bone, and related conditions are common plights of an arthritis patient.Antioxidant compounds could solve the problems in arthritic condition. The objective of this study was to evaluate the anti-arthritic activity of D-carvone against complete Freund’s adjuvant (CFA)-induced arthritis in rats. D-carvone was orally administered for 25 days at the doses of 30 and 60 mg/kg against CFA-induced arthritic rats. Changes in body weight, paw swelling, organ index, hematological parameters, oxidative stress markers, inflammatory cytokines, and histopathology were recorded.Oral treatment of D-carvone significantly improved the body weight, reduced the paw swelling, edema formation, and organ index in arthritic rats. The levels of white blood cells were reduced, red blood cells and hemoglobin levels were improved in D-carvone treated arthritic rats. Lipid peroxidation levels were lowered whereas enzymatic and non-enzymatic antioxidants were significantly elevated by D-carvone administration against arthritic rats. D-carvone significantly modulated inflammatory cytokine levels and improved the ankle joint pathology against CFA-induced arthritic inflammation. In conclusion, D-carvone proved significant anti-arthritic activity against CFA-induced arthritis in rats.

Chronic joint pain due to loss of cartilage function, degradation of subchondral bone, and related conditions are common plights of an arthritis patient.Antioxidant compounds could solve the problems in arthritic condition. The objective of this study was to evaluate the anti-arthritic activity of D-carvone against complete Freund’s adjuvant (CFA)-induced arthritis in rats. D-carvone was orally administered for 25 days at the doses of 30 and 60 mg/kg against CFA-induced arthritic rats. Changes in body weight, paw swelling, organ index, hematological parameters, oxidative stress markers, inflammatory cytokines, and histopathology were recorded.Oral treatment of D-carvone significantly improved the body weight, reduced the paw swelling, edema formation, and organ index in arthritic rats. The levels of white blood cells were reduced, red blood cells and hemoglobin levels were improved in D-carvone treated arthritic rats. Lipid peroxidation levels were lowered whereas enzymatic and non-enzymatic antioxidants were significantly elevated by D-carvone administration against arthritic rats. D-carvone significantly modulated inflammatory cytokine levels and improved the ankle joint pathology against CFA-induced arthritic inflammation. In conclusion, D-carvone proved significant anti-arthritic activity against CFA-induced arthritis in rats.

Objective To compare glycemic profile between diabetic patients receiving peritoneal dialysis and diabetic patients with normal kidney function, and to investigate the impact of peritoneal dialysis on glycemic control through continuous glucose monitor system ( CGMS). Methods 19 diabetic patients with end-stage renal disease receiving regular peritoneal dialysis (DMPD group) and 8 patients with non-diabetic ne-phropathy receiving regular peritoneal dialysis ( PD group) were randomly selected and matched with 20 diabetic patients with normal kidney function (DM group) based on age, gender and 72 hours mean glucose. CGMS were applied on all patients for 72 hours. Glycemic variability parameters were compared among the three groups. Results Peritoneal transport function was positively correlated with mean glucose, glucose standard deviation and mean amplitude of glycemic excursion. Compared with PD group, multiple variation parameters, such as intraday glycemic standard deviation (P<0. 001), covariant efficiency (P=0. 009) and mean of daily difference (P=0. 043), were significantly lower in DMPD group. Though both DMPD and DM group exhibited profile as trough in wee hours and post-prandial hyperglycemia, DMPD had higher glycemic level in wee hours (P<0. 001). Conclusion Diabetic patients with end-stage renal disease receiving regular peritoneal dialysis have smaller glucose variability than diabetic patients with normal renal function.