Autophagy is a cellular self-degradation process that maintains homeostasis and has been shown to promote tumor progression in advanced stages.Pancreatic cancer cells and the surrounding stromal cells exhibit high levels of autophagy.Therefore,targeting au-tophagy has emerged as a promising therapeutic strategy for pancreatic cancer.This review focuses on research targeting autophagy in pancreatic cancer treatment,elaborating on the roles and underlying mechanisms of autophagy in pancreatic cancer cell proliferation,metas-tasis,modulation of the tumor immune microenvironment,and drug resistance.Additional-ly,we summarize preclinical and clinical studies investigating autophagy-targeted therapies both as monotherapy and in combination with other treatments,aiming to provide new theo-retical rationale and therapeutic strategies for pancreatic cancer management.

Objective To explore the effect of transcutaneous auricular vagus nerve stimulation(taVNS)combined with dual-task training(DTT)on upper limb function recovery in patients with ischemic stroke.Methods From January to October,2024,60 ischemic stroke patients with upper limb dysfunction admitted to Zhejiang Rehabilitation Medical Center were selected and randomly divided into control group(n=30)and observation group(n=30).Both groups received conventional rehabilitation training.The control group underwent sham-taVNS combined with DTT,while the observation group received active taVNS combined with DTT,for four weeks.Before and after treatment,they were assessed with Fugl-Meyer Assessment-Upper Extremities(FMA-UE),Action Research Arm Test(ARAT),modified Barthel Index(MBI)and motor-evoked potential(MEP)tests.Results The FMA-UE scores,ARAT scores,MBI scores,MEP amplitude and MEP latency improved in both groups af-ter treatment(|t|>3.670,P<0.01),and were superior in the observation group than in the control group(|t|>3.081,P<0.01).Conclusion The combination of taVNS and DTT can significantly improve upper limb function,enhance activities of daily living,and promote neurological recovery in patients with ischemic stroke.

Objective To explore the effect of transcutaneous auricular vagus nerve stimulation(taVNS)combined with dual-task training(DTT)on upper limb function recovery in patients with ischemic stroke.Methods From January to October,2024,60 ischemic stroke patients with upper limb dysfunction admitted to Zhejiang Rehabilitation Medical Center were selected and randomly divided into control group(n=30)and observation group(n=30).Both groups received conventional rehabilitation training.The control group underwent sham-taVNS combined with DTT,while the observation group received active taVNS combined with DTT,for four weeks.Before and after treatment,they were assessed with Fugl-Meyer Assessment-Upper Extremities(FMA-UE),Action Research Arm Test(ARAT),modified Barthel Index(MBI)and motor-evoked potential(MEP)tests.Results The FMA-UE scores,ARAT scores,MBI scores,MEP amplitude and MEP latency improved in both groups af-ter treatment(|t|>3.670,P<0.01),and were superior in the observation group than in the control group(|t|>3.081,P<0.01).Conclusion The combination of taVNS and DTT can significantly improve upper limb function,enhance activities of daily living,and promote neurological recovery in patients with ischemic stroke.

Autophagy is a cellular self-degradation process that maintains homeostasis and has been shown to promote tumor progression in advanced stages.Pancreatic cancer cells and the surrounding stromal cells exhibit high levels of autophagy.Therefore,targeting au-tophagy has emerged as a promising therapeutic strategy for pancreatic cancer.This review focuses on research targeting autophagy in pancreatic cancer treatment,elaborating on the roles and underlying mechanisms of autophagy in pancreatic cancer cell proliferation,metas-tasis,modulation of the tumor immune microenvironment,and drug resistance.Additional-ly,we summarize preclinical and clinical studies investigating autophagy-targeted therapies both as monotherapy and in combination with other treatments,aiming to provide new theo-retical rationale and therapeutic strategies for pancreatic cancer management.

Objective:To analyze the clinical characteristics of hemodialysis patients with corona virus disease 2019(COVID-19)in a single-center from Beijing.Methods:Patients with COVID-19 who re-ceived regular hemodialysis at Peking University Third Hospital from November 30,2022 to January 4,2023 were selected as the study objects.Clinical symptoms,severity and duration of symptoms during the period of virus positive were investigated in the form of questionnaires,and the basic information of the patients,as well as the results of blood tests(routine blood and blood biochemistry,etc.)before and af-ter infection,dialysis treatment and the outcome of the disease were collected by consulting medical re-cords.Results:A total of 203 subjects were included in this study,including 148 mild cases(72.91％),23 medium cases(11.33％),32 severe and critical cases(15.76％),and 16(7.88％)deaths occured during the follow-up.Clinical symptoms mainly included respiratory symptoms(among which 81.77％had cough,68.97％had expectoration),fever(81.28％)and fatigue(65.52％),and fatigue and weakness had the longest duration[9(5,15)days]among all symptoms.Twenty-six patients(12.8％)reduced the dialysis sessions[1(1,2)times],25 patients(12.32％)had the behavior of early finishing dialysis(27 times),reducing the dialysis time by 30.0(20.0,30.5)minutes.Univa-riate analysis showed that the hemoglobin,creatinine,urea nitrogen and ultrafiltration decreased signi-ficantly after infection(P＜0.05).There were significant differences in age,albumin,hemoglobin,creatinine levels and vascular access types among the patients with different clinical subtypes,and the changes of dialysis sessions,fever,expectoration and fatigue degree were also different among the patients with different clinical subtypes(P＜0.05).Multivariate Logistic regression analysis showed that age(OR=1.051,95％CI:1.017-1.086,P=0.003)and albumin levels(OR=0.905,95％CI:0.803-1.019,P=0.098)corrected by fever,expectoration and fatigue levels were still associated with the oc-currence of pneumonia.Conclusion:The morbidity of pneumonia and the proportion of deaths in hemo-dialysis patients with COVID-19 were higher,and some clinical symptoms lasted for a longer time than the general population.During the infection period,the incidence of dialysis-related complications in-creased,hemoglobin and nutritional status decreased.Elderly patients and patients with low albumin level had a higher risk of developing pneumonia after infection.

Objective Analyze the clinical manifestations,endoscopic and histopathological features of eosinophilic gastrointestinal disease (EGID) to improve the understanding of the EGID and reduce the rate of missed diagnosis and misdiagnosis.Methods A retrospective analysis was conducted on the patients of general information,clinical manifestations,laboratory tests,endoscopic and pathological examinations,treatment prognosis and follow-up of 84 patients.Results With the history of food and drug allergies or allergic diseases in 38.1％ cases (32/84),had a clear predisposition before the onset of illness in 25.0％ (21/84).The main clinical symptom was abdominal pain in 79.8％ (67/84).Peripheral blood eosinophil (EOS) count increased significantly in 63 cases (63/84,75.0％) and EOS percentage (EOS％) increased significantly in 71 cases (71/84,84.5％).14 cases (16.7％) tested positive for serum allergen total immunoglobulin E (IgE) antibodies.Among the 68 cases of abdominal ultrasoud examination,there were 5 cases (5/68,7.4％) of ascites and 2 cases (2/68,2.9％) of pelvis effusion.64 cases were examined by CT,suggesting thickening of digestive tract wall in 13 cases (13/64,20.3％),10 cases were examined by small intestine CT,suggesting thickening and narrowing of digestive tract wall in 6 cases (6/10,60.0％).Endoscopic manifestations were nonspecific manifestations such as hyperemic redness,erosion and ulceration.The pathological examination showed mucosal inflammation with a large number of EOS infiltration,with the highest positive rate of biopsy at the duodenum and terminal ileum (P<0.05).Glucocorticoid therapy in 48 cases and symptomatic supportive care in 36 cases,they all achieved clinical remission (P<0.05).Glucocorticoid therapy remained effective in 5 cases with relapse.Conclusion Abdominal pain is a common clinical manifestation in patients with EGID,often with an elevated EOS count.The imaging and endoscopic findings of EGID lack specificity.Tissue biopsy with a large number of EOS infiltration is critical in the diagnosis.Simple antiallergy with acid-suppressing or application of glucocorticoid therapy has a good prognosis.

Objective Analyze the clinical manifestations,endoscopic and histopathological features of eosinophilic gastrointestinal disease (EGID) to improve the understanding of the EGID and reduce the rate of missed diagnosis and misdiagnosis.Methods A retrospective analysis was conducted on the patients of general information,clinical manifestations,laboratory tests,endoscopic and pathological examinations,treatment prognosis and follow-up of 84 patients.Results With the history of food and drug allergies or allergic diseases in 38.1％ cases (32/84),had a clear predisposition before the onset of illness in 25.0％ (21/84).The main clinical symptom was abdominal pain in 79.8％ (67/84).Peripheral blood eosinophil (EOS) count increased significantly in 63 cases (63/84,75.0％) and EOS percentage (EOS％) increased significantly in 71 cases (71/84,84.5％).14 cases (16.7％) tested positive for serum allergen total immunoglobulin E (IgE) antibodies.Among the 68 cases of abdominal ultrasoud examination,there were 5 cases (5/68,7.4％) of ascites and 2 cases (2/68,2.9％) of pelvis effusion.64 cases were examined by CT,suggesting thickening of digestive tract wall in 13 cases (13/64,20.3％),10 cases were examined by small intestine CT,suggesting thickening and narrowing of digestive tract wall in 6 cases (6/10,60.0％).Endoscopic manifestations were nonspecific manifestations such as hyperemic redness,erosion and ulceration.The pathological examination showed mucosal inflammation with a large number of EOS infiltration,with the highest positive rate of biopsy at the duodenum and terminal ileum (P<0.05).Glucocorticoid therapy in 48 cases and symptomatic supportive care in 36 cases,they all achieved clinical remission (P<0.05).Glucocorticoid therapy remained effective in 5 cases with relapse.Conclusion Abdominal pain is a common clinical manifestation in patients with EGID,often with an elevated EOS count.The imaging and endoscopic findings of EGID lack specificity.Tissue biopsy with a large number of EOS infiltration is critical in the diagnosis.Simple antiallergy with acid-suppressing or application of glucocorticoid therapy has a good prognosis.

Protein arginine methyltransferases (PRMTs) are attractive targets for developing therapeutic agents, but selective PRMT inhibitors targeting the cofactor SAM binding site are limited. Herein, we report the discovery of a noncanonical but less polar SAH surrogate YD1113 by replacing the benzyl guanidine of a pan-PRMT inhibitor with a benzyl urea, potently and selectively inhibiting PRMT3/4/5. Importantly, crystal structures reveal that the benzyl urea moiety of YD1113 induces a unique and novel hydrophobic binding pocket in PRMT3/4, providing a structural basis for the selectivity. In addition, YD1113 can be modified by introducing a substrate mimic to form a "T-shaped" bisubstrate analogue YD1290 to engage both the SAM and substrate binding pockets, exhibiting potent and selective inhibition to type I PRMTs (IC₅₀ < 5 nmol/L). In summary, we demonstrated the promise of YD1113 as a general SAH mimic to build potent and selective PRMT inhibitors.

Objective:To investigate the application value of intravoxel incoherent motion (IVIM) imaging in preoperative evaluating perineural invasion (PNI) of esophageal squamous cell carcinoma (ESCC).Methods:The prospective study was conducted. The clinicopathological data of 63 ESCC patients who underwent IVIM imaging before surgery in the Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital from January 2016 to April 2019 were selected. Patients underwent routine magnetic resonance imaging scan and IVIM sequence examination. The apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudodiffusion coefficient (D*) and pseudodiffusion fraction (f) values were measured. Observation indicators: (1) situations of enrolled patients; (2) IVIM examination of PNI of ESCC and its diagnostic efficiency. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range), and comparison between groups was analyzed using the Wilcoxon rank sum test. Count data were described as absolute numbers, and comparison between groups was analyzed using the chi-square test. The interclass correlation coefficient (ICC) was used to evaluate cosistency of results. The receiver operating characrteristic curve was used to evaluate diagnostic efficiency. Results:(1) Situations of enrolled patients. A total of 63 patients were selected for eligibility. There were 41 males and 22 females, aged 60(range, 43?74)years. Of the 63 ESCC patients, 17 cases had PNI and 46 cases had no PNI. Cases with well differentiated tumor, moderate differentiated tumor or low differentiated tumor, cases in stage T1, T2, T3, T4 of infiltra-tion depth, cases with or without lymph node metastasis were 0, 6, 11, 0, 3, 13, 1, 15, 2 in patients with PNI, versus 6, 24, 16, 1, 22, 23, 0, 12, 34 in patients without PNI, showing significant differences between them ( Z=?2.32, ?2.49, χ2=19.58, P<0.05). (2) IVIM examination of PNI of ESCC and its diagnostic efficiency. The ADC, D, D*, f values were (2.21±0.33)×10 ?3 mm 2/s, (1.46±0.31)×10 ?3 mm 2/s, 32.50 (15.55,46.75)×10 ?3 mm 2/s, (0.34±0.09)×10 ?3 mm 2/s in patients with PNI, versus (2.45±0.45)×10 ?3 mm 2/s, (1.72±0.38)×10 ?3 mm 2/s, 34.85(23.43,51.20)×10 ?3 mm 2/s, (0.42±0.13)×10 ?3 mm 2/s in patients without PNI, showing significant differences in the ADC, D and f values between them ( t=?2.03, ?2.52, ?2.34, P<0.05) and no significant difference in the D* value between them ( Z=?0.84, P>0.05). The cosistency of ADC, D, D* and f values in the 63 ESCC patients measured by 2 radiologists was good, with the ICC as 0.96, 0.92, 0.89 and 0.95. The receiver operating characrteristic curve demons-trated the best cut-off value of ADC, D and f values were 2.50×10 ?3 mm 2/s, 1.68×10 ?3 mm 2/s and 0.41, with the areas under the curve as 0.67 (95% confidence interval as 0.54?0.79), 0.70 (95% confidence interval as 0.58?0.81) and 0.69 (95% confidence interval as 0.57?0.80), respectively. The combina-tion of D and f value for diagnosing PNI of ESCC had the area under the curve as 0.74 (95% confidence interval as 0.62?0.84), with the cut-off value as 0.20, sensitivity and specificity as 94.1% and 56.5%. Conclusions:IVIM parameters D and f values can evaluate and predict the PNI of ESCC preopera-tively. The combination of D and f values can further improve the diagnostic efficiency.

Objective:To explore the value of intravoxel incoherent motion (IVIM) DWI in preoperative prediction of angiolymphatic invasion in esophageal squamous cell carcinoma (ESCC).Methods:From April 2016 to April 2019, 63 ESCC patients who planned to undergo resection of esophageal cancer were prospectively collected at Henan Cancer Hospital.According to the postoperative pathological results, 63 patients were divided into angiolymphatic invasion group (30 cases) and no angiolymphatic invasion group (33 cases). All patients underwent IVIM sequence and routine MRI examination before operation. The ADC, true diffusion coefficient (D), pseudodiffusion coefficient (D *) and pseudodiffusion fraction (f) were measured. The differences of parameter values between ESCC with and without angiolymphatic invasion were analyzed using Student′s t test or Wilcoxon rank sum test.The logistic regression was used to analyze the significance of various parameters. For the parameters with statistical significance, the ROC curves were performed to evaluatethe diagnostic performance of parameters for identifying angiolymphatic invasion.The Z test was used to compare the area under the ROC curves(AUC) of parameters. Results:The difference of ADC, D and f values between angiolymphatic invasion group and no angiolymphatic invasion group were statistically signi?cant ( t=4.476, 5.033 and 5.712 respectively, all P<0.001). The D * values showed no statistically signi?cant di?erence ( Z=0.184, P=0.854). The logistic regression analysis showed that D (OR=9.042) and f (OR=26.221) were in correlation with angiolymphatic invasion. The ROC analyses demonstrated that the AUCs of ADC, D and f values in predicting angiolymphatic invasion of ESCC were 0.787, 0.822 and 0.853, respectively. D combined with f had highest AUC (0.917) in predicting the angiolymphatic invasion of ESCC, sensitivity and specificity were 93.3% and 75.8%. D combined with f showed better diagnostic performance than the D and the f value, and the difference were statistically significant ( Z=2.403, 2.289, P=0.016, 0.022). Conclusions:IVIM can be used as an effective functional imaging modality for preoperative evaluation and prediction of the angiolymphatic invasion of ESCC. D value combined with f value can further improve prediction performance of angiolymphatic invasion.