Objective To evaluate the efficacy and adverse reactions of BRAF inhibitor vermorafenib on the treat-ment of refractory craniopharyngioma carrying BRAF-V600E mutation.Methods Clinical data of two patients with refractory craniopharyngiomas(CP)were recorded and reviewed.The patients were followed up for 3-5 years.Lit-erature on CPs receiving BRAF or BRAF/MEK therapy was reviewed.Results 1)Papillary CP progressed after multiple operations and radiotherapy in two patients.Further treatments were very difficult.2)The presence of BRAF-V600E mutation in the tumor was confirmed,and vermorafenib was administered for 6.5-7.5 months.Tumor volumes remarkably shrank by 95%-99%.No tumor relapse was observed during the follow-up of 3-5 years after discontinuation of vemurafenib.3)The main adverse reaction was rash,which was dose dependent.4)Litera-ture review showed the volume shrank by 50%-100%in 33/34 tumors during BRAF or BRAF/MEK inhibitor therapy.Conclusions BRAF inhibitor vemurafenib is effective in treating refractory craniopharyngioma carrying BRAF-V600E mutation with endurable side effects,which may bring some changes to the management of CP in future.

Objective:To compare the clinical efficacy of neoadjuvant chemoradiotherapy (nCRT) and neoadjuvant chemo-immunotherapy (nCIT) for locally advanced esophageal squamous cell carcinoma (ESCC).Methods:Clinical data of patients who received nCRT or nCIT followed by esophagectomy for locally advanced ESCC between January 2010 and December 2022 were retrospectively collected from Zhejiang Cancer Hospital, with 155 patients in the nCRT group and 470 patients in the nCIT group. Propensity score matching (PSM) was performed in the two groups. After PSM, 120 patients were allocated to the nCRT group and 192 patients to the nCIT group. The pathological response and disease recurrence were compared between the two groups after PSM. Log rank test were used to compare the survival outcomes before and after PSM. Univariate and multivariate Cox regression analyses were performed to identify the prognostic factors for locally advanced ESCC.Results:After PSM, the R0 resection rate in the nCRT group and the nCIT group was 93.3% (112/120) and 93.8% (180/192), respectively, with no statistical significance ( P=0.884). However, the pathological complete response rate in the nCRT group [36.7% (44/120)] was higher than that in the nCIT group [21.4% (41/192), P=0.003]. For patients with R0 resection, the major recurrence pattern was distant metastasis [18.8% (21/112)] in the nCRT group, while the pattern was locoregional recurrence [12.2% (22/180)] in the nCIT group. The 3-year disease-free survival rates were 52.7% and 66.1% ( P=0.022) and the 3-year overall survival rates were 59.2% and 75.5% ( P=0.002) in the nCRT and nCIT groups, respectively. Multivariate Cox regression analysis also revealed that the neoadjuvant therapy mode was an independent prognostic factor for patients with locally advanced ESCC. Compared with nCRT, nCIT could significantly prolong disease-free survival ( HR=0.58, 95% CI: 0.40-0.86) and overall survival ( HR=0.53, 95% CI: 0.35-0.79). Conclusion:These results suggest that nCIT could significantly improve disease-free survival rate and overall survival rate over nCRT in locally advanced ESCC, even with lower pathological complete response rate.

Objective:To compare the clinical efficacy of neoadjuvant chemoradiotherapy (nCRT) and neoadjuvant chemo-immunotherapy (nCIT) for locally advanced esophageal squamous cell carcinoma (ESCC).Methods:Clinical data of patients who received nCRT or nCIT followed by esophagectomy for locally advanced ESCC between January 2010 and December 2022 were retrospectively collected from Zhejiang Cancer Hospital, with 155 patients in the nCRT group and 470 patients in the nCIT group. Propensity score matching (PSM) was performed in the two groups. After PSM, 120 patients were allocated to the nCRT group and 192 patients to the nCIT group. The pathological response and disease recurrence were compared between the two groups after PSM. Log rank test were used to compare the survival outcomes before and after PSM. Univariate and multivariate Cox regression analyses were performed to identify the prognostic factors for locally advanced ESCC.Results:After PSM, the R0 resection rate in the nCRT group and the nCIT group was 93.3% (112/120) and 93.8% (180/192), respectively, with no statistical significance ( P=0.884). However, the pathological complete response rate in the nCRT group [36.7% (44/120)] was higher than that in the nCIT group [21.4% (41/192), P=0.003]. For patients with R0 resection, the major recurrence pattern was distant metastasis [18.8% (21/112)] in the nCRT group, while the pattern was locoregional recurrence [12.2% (22/180)] in the nCIT group. The 3-year disease-free survival rates were 52.7% and 66.1% ( P=0.022) and the 3-year overall survival rates were 59.2% and 75.5% ( P=0.002) in the nCRT and nCIT groups, respectively. Multivariate Cox regression analysis also revealed that the neoadjuvant therapy mode was an independent prognostic factor for patients with locally advanced ESCC. Compared with nCRT, nCIT could significantly prolong disease-free survival ( HR=0.58, 95% CI: 0.40-0.86) and overall survival ( HR=0.53, 95% CI: 0.35-0.79). Conclusion:These results suggest that nCIT could significantly improve disease-free survival rate and overall survival rate over nCRT in locally advanced ESCC, even with lower pathological complete response rate.

Malignant insulinoma is a kind of rare and challenging neuroendocrine tumor. It is often accompanied by distant metastasis, among which liver metastasis is most common, and the prognosis is often non-promising. In this paper, we report a case of multiple liver metastases from malignant insulinoma. The patient, a 70-year-old male, was admitted to the hospital due to "episodic consciousness disorder for more than four months." Blood glucose monitoring revealed recurrent hypoglycemia in the early morning, after meals, and at night. Pancreatic perfusion CT and dynamic enhanced MRI of the liver revealed a mass in the uncinate process of the pancreatic head and multiple liver metastases. Percutaneous liver biopsy confirmed the diagnosis of insulinoma. After multidisciplinary discussions, hepatic artery embolization and radiofrequency ablation were performed in stages, in combination with everolimus treatment. Thereafter, the enhanced CT demonstrated that some liver metastases shrank. The patient had regular meals, and the blood sugar gradually increased and remained normal thereafter. This article discusses this case's clinical characteristics and multidisciplinary collaborative diagnosis and treatment, aiming to provide experience for the comprehensive clinical diagnosis and treatment of malignant insulinoma patients.

Strengthening the construction of hospital work style is a concrete manifestation of implementing strict govern-ance of the Party,an inevitable requirement for serving the health of the people,and an important guarantee for deepening the re-form of the medical and health system.By reviewing the current situation of the construction of hospital work style in public hospi-tals,analyzing the difficulties encountered in the practice,such as insufficient understanding of work style construction,poor ef-fectiveness of work style publicity and education,imperfect management system and working mechanism,and incomplete assess-ment indicators,this study proposes optimization strategies,including improving the hospital work style publicity and education system,optimizing the management system and working mechanism of work style construction,and establishing an assessment and evaluation system for hospital work style construction.These strategies provide reference for establishing a long-term mechanism for the construction of hospital work style in the context of the new era,and further promote the high-quality development of hospi-tals.

Objective:To investigate the application value of antegrade splenic superior region dissection first in laparoscopic total gastrectomy of obesity gastric cancer.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 21 obesity patients with gastric cancer who underwent laparoscopic total gastrectomy in Renji Hospital of Shanghai Jiaotong University School of Medicine from July 2018 to October 2023 were collected. There were 16 males and 5 females, aged (58±13)years. All 21 patients underwent laparoscopic total gastrec-tomy with antegrade splenic superior region dissection first. Observation indicators: operation time, volume of intraoperative blood loss, laparotomy conversion, intraoperative splenic hemorrhage or gastric hemorrhage, lymph node dissection, time to postoperative first flatus, time to postoperative initial liquid food intake, duration of postoperative hospital stay, postoperative complication. Measure-ment data with normal distribution were represented as Mean± SD, and count data were expressed as absolute numbers. Results:All 21 patients underwent laparoscopic total gastrectomy success-fully, with the operation time of (283±47)minutes, time for splenogastric ligament and vascular manage-ment of (34±12)minutes, volume of intraoperative blood loss of (143±86)mL, and no laparotomy conversion. There was no intraoperative splenic hemorrhage or gastric haemorrhage. The total number of lymph node dissected in 21 patients was 375, with the number of lymph node dissected as (21±9)per case. Time to postoperative first flatus, time to postoperative initial liquid food intake and duration of postoperative hospital stay in 21 patients were (3.1±0.7)days, (4.0±0.8)days and (10.1±3.0)days, respectively. There were 2 patients with postoperative complications, including 1 case of incision infection and 1 case of lung infection. The 2 patients with postoperative com-plications were recovered and discharged after conservative treatment. There was no death during the postoperative 30 days.Conclusion:The application of antegrade splenic superior region dissec-tion first in laparoscopic total gastrectomy is safe and feasible, which can reduce surgical difficulty.

In many neurodegenerative diseases,eye movement is disrupted,which is a common and early characteris-tic of neurodegenerative diseases.Characterizing eye movement is important for the diagnosis of neurodegenerative disea-ses,helping to track disease progression and response to treatment.In recent years,eye tracking technology has been ap-plied to the assessment of cognitive function in patients with neurodegenerative diseases.Compared to traditional cognitive assessment methods,the technology has higher temporal and spatial resolution for sensitive quantification.Eye tracking da-ta confirms that executive dysfunction is common in Parkinson's disease and amyotrophic lateral sclerosis,while attention deficit is a characteristic of Alzheimer's disease and multiple sclerosis.Research using eye tracking to evaluate the cogni-tive function of epilepsy patients is still in its early stages,but this method has shown advantages.In this article,the appli-cation of eye tracking technology in neurodegenerative diseases is reviewed.

Objective:To explore the relationship between serum retinol binding protein(RBP)and metabolic-associated fatty liver disease(MAFLD)in elderly patients with type 2 diabetes mellitus(T2DM)and possible underlying metabolic mechanisms.Methods:A total of 3384 elderly T2DM patients hospitalized and with complete clinical records at the Department of Endocrinology and Metabolism, Sixth People's Hospital Affiliated to Shanghai Jiao Tong University between January 2003 and December 2012 were recruited in this retrospective study.Patients were divided into four groups according to the quartiles of serum RBP levels: the first quartile of serum RBP levels(<35 mg/L, 844 cases), the second quartile of serum RBP levels(35 mg/L≤ RBP ≤41 mg/L, 773 cases), the third quartile of serum RBP levels(42 mg/L≤ RBP ≤51 mg/L, 902 cases), and the fourth quartile of serum RBP levels(RBP>51 mg/L, 865 cases). Clinical data and laboratory test results were collected.Differences in the prevalence of MAFLD were compared between the four groups.The association between RBP and MAFLD was analyzed via binary logistic regression.Results:After adjusting for age and sex, the proportion of obesity( χ2=15.222, P<0.01), the percentage using lipid-lowering drugs( χ2=88.552, P<0.01), systolic blood pressure( F=12.002, P<0.01), diastolic blood pressure( F=6.872, P<0.01), waist circumference( F=9.563, P<0.01), waist-hip ratio( F=7.972, P<0.01), body mass index( F=9.057, P<0.01), serum creatinine( χ2=185.445, P<0.01), serum uric acid( χ2=314.691, P<0.01), 24-hour urinary albumin( χ2=91.012, P<0.01), alanine aminotransferase( χ2=17.049, P=0.003), γ-glutamyl transpeptidase( χ2=50.514, P<0.01), total cholesterol( F=45.669, P<0.01), triglycerides( χ2=361.269, P<0.01), low-density lipoprotein( F=8.772, P<0.01), fasting C-peptide( χ2=165.756, P<0.01), 2h postprandial C-peptide( χ2=120.690, P<0.01), and the homeostasis model assessment of insulin resistance(HOMA2-IR)( χ2=148.884, P<0.01)in elderly patients with T2DM all showed a clear upward trend.The prevalence of MAFLD also gradually increased across the quartiles of serum RBP levels[26.5%(224/844), 30.1%(233/773), 36.6%(330/902), and 41.8%(362/865)], respectively( χ2=52.526, P<0.01). Elderly T2DM patients with MAFLD had a significantly higher value of HOMA2-IR than those without MAFLD[2.0(1.31-2.8) vs.1.39(0.86-2.06), F=220.826, P<0.01]. After correcting for other confounding factors, binary logistic regression showed that serum RBP was strongly associated with the presence of MAFLD in elderly patients with T2DM( β=0.209, 95% CI: 1.079-1.408, OR=1.232, χ2=9.441, P<0.01). Conclusions:Elevated serum RBP levels are an independent risk factor for the development of MAFLD in elderly T2DM patients, possibly through increased insulin resistance induced by RBP.

Objective To investigate the association of uric acid excretion(UUAE)with obesity and abdominal obesity in newly diagnosed patients with type 2 diabetes mellitus(T2DM).Methods A total of 1175 newly diagnosed T2DM patients hospitalized in the Department of Endocrinology and Metabolism of Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were enrolled in this study from January 2006 to December 2012.According to the quartile of UUAE,they were divided into Q1 group(UUAE＜2383 μmol/24 h,n=295),Q2 group(2383≤UUAE＜2953 μmol/24 h,n=292),Q3 group(2954≤UUAE＜3680 μmol/24 h,n=292)and Q4 group(UUAE＞3680 μmol/24 h,n=293).Clinical data and laboratory examination results were collected,and the prevalence of obesity and abdominal obesity was compared among the four groups.The associations of UUAE with obesity and abdominal obesity were analyzed.Results The prevalence of obesity was 47.9%,while the prevalence of abdominal obesity was 61.9%in the whole study population.After adjusting for age,the prevalence of abdominal obesity was higher in women than in men(P＜0.05).After adjusting for age and gender,the prevalence of obesity and MS was higher in Q4 group than in Q1,Q2,and Q3 groups(P＜0.05),and the prevalence of abdominal obesity was higher in Q4 group than in Q1 and Q2 groups(P＜0.05).Compared with Q1 group,the proportion of men,BMI,WC,DBP,FIns,2 hIns,HOMA-IR,TG,ALT,γ-GT,SUA,UAlb in Q4 group increased(P＜0.05),age,HbA1c,HDL-C decreased(P＜0.05).Logistic regression analysis showed that after adjusting for confounding factors,UUAE was a factor affecting obesity and abdominal obesity.Conclusion UUAE increases the risk of obesity,abdominal obesity and MS in newly diagnosed T2DM patients.UUAE may be used as a simple indicator to assess the risk of metabolic disorders such as obesity and MS in T2DM patients.

Objective: To investigate the inhibition of tanshinoneⅡA (TanⅡA) on the proliferation of lung cancer cells. Methods: Human lung cancer cell lines A549, SK-MES-1, H446 and H460 were cultured in vitro and treated with TanⅡA at concentrations of 0.3, 0.6, 1.3, 2.5, 5.0, 10.0 mg/mL, while untreated cells served as controls. Cell proliferation was measured by using CCK-8 assay, and apoptosis was measured using flow cytometry, while the expression of apoptosis-related proteins was determined using Western blotting. The apoptotic rate of lung cancer cells was compared between Tan ⅡA-treated cells and untreated cells. Results: Tan ⅡA inhibited lung cancer cell proliferation in a time-dependent and concentration-dependent manner, and the survival rates of A549, SK-MS-1, H446 and H460 cells reduced with the concentration of TanⅡA (t=4.503, 2.114, 2.103 and 3.567; all P<0.05) and the duration of TanⅡA treatment (t=5.189, 3.079, 3.023 and 3.845; all P<0.05). The 48 h half maximal inhibitory concentrations (IC50 values) of TanⅡA were (1.18±0.12), (0.78±0.08), (1.55±0.16) and (1.27±0.14) mg/mL against A549, SK-MES-1, H446 and H460 cells, respectively. Following 48 h treatment with Tan ⅡA at a concentration of 2.5 mg/mL, the apoptotic rates of A549, SK-MS-1, H446 and H460 cells were (34.97±3.78)%, (37.62±2.48)%, (18.27±2.98)% and (19.17±2.30)%, which were significantly significantly higher than those of untreated cells [(4.86±0.36) %, (3.21±0.48) %, (3.25±0.26)% and (2.66±0.19)%, all P<0.05]. Reduced Akt1 protein expression, elevated Bax/Bcl-2 expression ratio, and elevated caspase-9 and caspase-3 protein expression were detected in lung cancer cells treated with 2.5 mg/mL TanⅡA for 48 h relative to untreated cells Conclusion TanⅡA may inhibit lung cancer cell proliferation in a time- and concentration-dependent manner via the Bax/Bcl-2/caspase-9/caspase-3 pathway.