ObjectiveTo investigate the influence of phosphoinositide 3-Kinase-C2-gamma (PI3Kγ)on pancreas acinar cells autophagy in experimental acute pancreatitis in mice and explore its significance.MethodsEighteen C57BL/6 wild type (WT) and eighteen PI3Kγ knockout (KO) mice were randomly divided into control group (n =6) and acute panereatitis (AP) group (n =12),respectively.AP models were induced by intraperitoneal injection of 50 μg cerulein/kg body weight,once the other hour for seven times.The mice were sacrificed 7 hours after model induction.The pathological changes of the pancreas were observed through microscope,LC3 dots were determined by immunofluorescence,the trypsin activity was measured by fluorescence spectrophotometer,and the expression of autophagy related protein beclin1,p62 and LC3- Ⅱ were measured by Western blot.ResultsThe autophagy vacuoles counts in pancreatic tissue of WT mice and KO mice were (5.14 ±0.85),(2.25 ±0.54)/HPF,the LC3 immunofluorescence dots counts were (78.6 ±9.38),( 26.4 ± 4.21 )/HPF,the trypsin activities were ( 0.827 ± 0.126 ),( 0.358 ± 0.098 ) pmol/mg protein,the difference between the two groups was statistically significant ( P ＜ 0.05 ).The p62 protein expression was greatly decreased in WT mice compared with their KO counterpart (0.11 vs 0.92,P ＜ 0.05 ),while the expressions of LC3 Ⅱ,beclin1 were greatly increased in WT mice compared with their KO counterpart ( 1.82 vs 0.93,1.43 vs 1.05,P ＜ 0.05 ).Conclusions PI 3 Kγmay up- regulate autophagy of pancreatic acinar cells during acute pancreatitis in mice,then promote trypsinogen activation and necrosis of acinar cells.

Objective To study the role and mechanism of phosphatidylinositide 3-kinase gamma (P13Kγ) in mediating acinar cell necrosis in rat models with acute pancreatitis.Methods Twelve male C57BL/6 wild-type and twelve male P13Ky knockout mice were randomly divided into saline group and pancreatitis group.The pancreatitis group received an intraperitoneal injection of cerulean (50 μg/kg) to induce acute panreatitis.Pathologic changes in the two groups were observed by measuring the trypsin,cathepsin B,and cathepsin L activity.The protein expressions of cathepsin B and cathepsin L were detected by the Western blot assay.Results Compared with the wild-type mice,the P13Kγγknockout mice had fewer acinar cell necrosis [(2.25± 0.54)/HP vs (5.14±0.85)/HP] and vacuoles [(1.24±0.21)/HP vs (2.36± 0.34)/HP]according to histology.The cathepsin B activity [(1232± 21)pmolAMC/min/mg vs (1891 ±35)pmolAMC/min/mg] and trypsin activity [(0.358± 0.098)pmol/mg vs (0.827± 0.126)pmol/mg] were significantly decreased in the pancreatitis group (P＜0.05) compared to the saline group.However,the cathepsin L activity [ (415 ±11 ) pmolAMC/ min/mg vs (346 ± 6)pmolAMC/min/mg] was significantly higher in P13Kγγ knockout mice than in wild-type mice(P＜0.01).Conclusions P13Kγmay promote cell necrosis in acute pancreatitis by possibly changing the balance between eathepsin B and cathepsin L levels to promote the activation of trypsinogen.

Objective:To construct a reasonable and efficient clinical nursing pathway for elderly patients with acute chest pain in the emergency department, and to provide a standardized and rapid treatment process for such patients.Methods:Through literature review and theoretical analysis, the basic framework of clinical nursing pathway was preliminarily drawn up. Twenty one clinical medical and nursing experts from all over the country were selected to conduct two rounds of expert consultation with Delphi method, and the clinical nursing path was finally determined.Results:The recovery rates of the two rounds of questionnaires were 100.00% and 95.24%, and the rates of submission expert suggestions were 61.90% and 45.00%, the authority coefficients of experts were 0.85 and 0.88, and the coordination coefficients were 0.23 and 0.30. Finally, the clinical nursing pathway was constructed after two rounds of consultation.Conclusion:The positive coefficient and authority coefficient of the two rounds of experts were both high, and the variable coefficient and coordination coefficient were in line with the statistical requirements, so the clinical nursing path of the elderly patients with acute chest pain had high scientificity and reliability.

Background::Pathological scars are a disorder that can lead to various cosmetic, psychological, and functional problems, and no effective assessment methods are currently available. Assessment and treatment of pathological scars are based on cutaneous manifestations. A two-photon microscope (TPM) with the potential for real-time non-invasive assessment may help determine the under-surface pathophysiological conditions in vivo. This study used a portable handheld TPM to image epidermal cells and dermal collagen structures in pathological scars and normal skin in vivo to evaluate the effectiveness of treatment in scar patients. Methods::Fifteen patients with pathological scars and three healthy controls were recruited. Imaging was performed using a portable handheld TPM. Five indexes were extracted from two dimensional (2D) and three dimensional (3D) perspectives, including collagen depth, dermo-epidermal junction (DEJ) contour ratio, thickness, orientation, and occupation (proportion of collagen fibers in the field of view) of collagen. Two depth-dependent indexes were computed through the 3D second harmonic generation image and three morphology-related indexes from the 2D images. We assessed index differences between scar and normal skin and changes before and after treatment.Results::Pathological scars and normal skin differed markedly regarding the epidermal morphological structure and the spectral characteristics of collagen fibers. Five indexes were employed to distinguish between normal skin and scar tissue. Statistically significant differences were found in average depth ( t = 9.917, P <0.001), thickness ( t = 4.037, P <0.001), occupation ( t= 2.169, P <0.050), orientation of collagen ( t = 3.669, P <0.001), and the DEJ contour ratio ( t = 5.105, P <0.001). Conclusions::Use of portable handheld TPM can distinguish collagen from skin tissues; thus, it is more suitable for scar imaging than reflectance confocal microscopy. Thus, a TPM may be an auxiliary tool for scar treatment selection and assessing treatment efficacy.

Objective:The primary goal of this study is to explore the safety and effectiveness of a new modified eversion carotid endarterectomy (MECEA).Methods:This is a retrospective case series study. One hundred patients were consecutively treated with MECEA by the same operator at Department of Vascular Surgery,Peking Union Medical College Hospital from January 2019 to December 2023. There were 77 males and 23 females. The age was (66.0±8.6)years (range: 39 to 85 years). Twenty-four (24.0%) patients were symptomatic with the degree of carotid stenosis over 50%,76 patients (76.0%) were asymptomatic with the degree of stenosis over 70%. All these patients meet the indication of carotid endarterectomy. The main difference between MECEA and traditional eversion carotid endarterectomy was the anterior,lateral,and posterior walls of the internal carotid artery were incised obliquely from the origin of the internal carotid artery toward the common carotid artery,leaving the wall of internal carotid artery intact at the bifurcation. The surgical process,cardiovascular and cerebrovascular complications and other surgical complications were recorded. The incidences of complications,restenosis of intraoperative target lesions and re-intervention were collected during follow-up.Results:All procedures were performed successfully under general anesthesia. The total operation time was (36.5±10.1)minutes (range: 22 to 65 minutes),and carotid clamping time was (15.0±6.3)minutes (range: 7 to 31 minutes). One patient (1.0%) occurred postoperative cerebrovascular accident,1 patient (1.0%) developed cerebral hyperperfusion syndrome (CHS),and another 1 patient (1.0%) suffered myocardial infarction. All these patients were recovered after medical treatment within a week. The follow-up time( M(IQR)) was 24 (28) months (range: 6 to 62 months). Two patients (2.0%) were reported to have hemodynamically significant restenosis within 2 years,with one patient requiring intervention. No patient suffered from ipsilateral ischemic stroke. Conclusions:MECEA is a safe and effective surgical method of treating carotid artery stenosis. This method can reduce carotid clamping time and lowers the risk of ischemic stroke. Meantime,it preserves the integrity of the adventitia at the bifurcation of carotid artery,reduces the chance of restenosis. Moreover,it might be helpful to prevent postoperative CHS due to reducing damage to the carotid body and carotid sinus nerve.

Objective:The primary goal of this study is to explore the safety and effectiveness of a new modified eversion carotid endarterectomy (MECEA).Methods:This is a retrospective case series study. One hundred patients were consecutively treated with MECEA by the same operator at Department of Vascular Surgery,Peking Union Medical College Hospital from January 2019 to December 2023. There were 77 males and 23 females. The age was (66.0±8.6)years (range: 39 to 85 years). Twenty-four (24.0%) patients were symptomatic with the degree of carotid stenosis over 50%,76 patients (76.0%) were asymptomatic with the degree of stenosis over 70%. All these patients meet the indication of carotid endarterectomy. The main difference between MECEA and traditional eversion carotid endarterectomy was the anterior,lateral,and posterior walls of the internal carotid artery were incised obliquely from the origin of the internal carotid artery toward the common carotid artery,leaving the wall of internal carotid artery intact at the bifurcation. The surgical process,cardiovascular and cerebrovascular complications and other surgical complications were recorded. The incidences of complications,restenosis of intraoperative target lesions and re-intervention were collected during follow-up.Results:All procedures were performed successfully under general anesthesia. The total operation time was (36.5±10.1)minutes (range: 22 to 65 minutes),and carotid clamping time was (15.0±6.3)minutes (range: 7 to 31 minutes). One patient (1.0%) occurred postoperative cerebrovascular accident,1 patient (1.0%) developed cerebral hyperperfusion syndrome (CHS),and another 1 patient (1.0%) suffered myocardial infarction. All these patients were recovered after medical treatment within a week. The follow-up time( M(IQR)) was 24 (28) months (range: 6 to 62 months). Two patients (2.0%) were reported to have hemodynamically significant restenosis within 2 years,with one patient requiring intervention. No patient suffered from ipsilateral ischemic stroke. Conclusions:MECEA is a safe and effective surgical method of treating carotid artery stenosis. This method can reduce carotid clamping time and lowers the risk of ischemic stroke. Meantime,it preserves the integrity of the adventitia at the bifurcation of carotid artery,reduces the chance of restenosis. Moreover,it might be helpful to prevent postoperative CHS due to reducing damage to the carotid body and carotid sinus nerve.

The integrity of lysosomes is of vital importance to survival of tumor cells. We demonstrated that LW-218, a synthetic flavonoid, induced rapid lysosomal enlargement accompanied with lysosomal membrane permeabilization in hematological malignancy. LW-218-induced lysosomal damage and lysosome-dependent cell death were mediated by cathepsin D, as the lysosomal damage and cell apoptosis could be suppressed by depletion of cathepsin D or lysosome alkalization agents, which can alter the activity of cathepsins. Lysophagy, was initiated for cell self-rescue after LW-218 treatment and correlated with calcium release and nuclei translocation of transcription factor EB. LW-218 treatment enhanced the expression of autophagy-related genes which could be inhibited by intracellular calcium chelator. Sustained exposure to LW-218 exhausted the lysosomal capacity so as to repress the normal autophagy. LW-218-induced enlargement and damage of lysosomes were triggered by abnormal cholesterol deposition on lysosome membrane which caused by interaction between LW-218 and NPC intracellular cholesterol transporter 1. Moreover, LW-218 inhibited the leukemia cell growth