Cerebral edema is characterized by fluid accumulation, and the glymphatic system (GS) plays a pivotal role in regulating fluid transport. Using the Tenecteplase system, magnesium salt of salvianolic acid B/ginsenoside Rg1 (SalB/Rg1) was injected intravenously into mice 4.5 h after middle cerebral artery occlusion and once every 24 h for the following 72 h. GS function was assessed by Evans blue imaging, near-infrared fluorescence region II (NIR-II) imaging, and magnetic resonance imaging (MRI). SalB/Rg1 had significant effects on reducing the infarct volume and hemorrhagic transformation score, improving neurobehavioral function, and protecting tissue structure, especially inhibiting cerebral edema. Meanwhile, the influx/efflux drainage of GS was enhanced by SalB/Rg1 according to NIR-II imaging and MRI. SalB/Rg1 inhibited matrix metalloproteinase-9 (MMP-9) activity, reduced cleaved β-dystroglycan (β-DG), and stabilized aquaporin-4 (AQP4) polarity, which was verified by colocalization with CD31. Our findings indicated that SalB/Rg1 treatment enhances GS function and attenuates cerebral edema, accompanying the regulation of the MMP9/β-DG/AQP4 pathway.
Animals ; Ginsenosides/administration & dosage* ; Brain Edema/etiology* ; Male ; Benzofurans/administration & dosage* ; Glymphatic System/diagnostic imaging* ; Mice ; Infarction, Middle Cerebral Artery/drug therapy* ; Aquaporin 4/metabolism* ; Disease Models, Animal ; Mice, Inbred C57BL ; Matrix Metalloproteinase 9/metabolism* ; Neuroprotective Agents/pharmacology* ; Depsides

Objectives:To evaluate the role of pancreas multidisciplinary team(MDT) clinic in the diagnosis of pancreatic diseases,patient compliance with MDT advice,and the impact of MDT on the postoperative survival of patients with pancreatic cancer.Methods:The study included 927 patients(554 males,373 females,aged (58.1±13.3)years (range: 15 to 89 years)) that had visited the pancreas MDT clinic of Zhongshan Hospital from May 2015 to December 2021,and 677 patients(396 males, 281 females, aged (63.6±8.9)years(range: 32 to 95 years)) who underwent radical surgery and with pathologically confirmed pancreatic adenocarcinoma from January 2012 to December 2020,of whom 79 patients had attended the pancreas MDT. The clinical and pathological data were collected and analyzed retrospectively. Diseases were classified in accordance with 2010 WHO classification of tumors of the digestive system and usual clinical practices. The Kaplan-Meier method was used for drawing the survival curve and calculating the survival rate. The univariate analysis was done by Log-rank test and the multivariate analysis was done by COX proportional hazards model. Survival rates were compared using χ 2 test. Results:Among the 927 patients that had visited the MDT clinic,233 patients(25.1%) were referred due to undetermined diagnosis. A direct diagnosis was made in 109 cases (46.8%,109/233) by the MDT clinic, of which 98 were consistent with the final diagnosis,resulting in an accuracy of 89.9%(98/109). The direct diagnosis rate in the recent years(36.6%(41/112),from June 2019 to December 2021) decreased compared to that in the previous years(56.2%(68/121),from May 2015 to May 2019),yet the accuracy in the recent years(90.2%,37/41) was basically the same as before (89.7%,61/68). The rate of compliance of the entire cohort was 71.5%(663/927), with the compliance rate in the recent two and a half years(81.4%,338/415) remarkably higher than that in the previous four years(63.4%,325/512). Patients with pancreatic cancer that attended the MDT exhibited a trend toward longer median postoperative survival than patients that did not attend the MDT,but the difference was not statistically significant(35.2 months vs.30.2 months, P>0.05). The 1-year and 3-year survival rates of patients that attended the MDT were significanly higher than patients that did not attend the MDT(88.6% vs. 78.4%, P<0.05;32.9% vs. 21.9%, P<0.05,respectively),but the 5-year survival rate was not statistically different(7.6% vs. 4.8%, P>0.05). Conclusions:The pancreas MDT clinic is an accurate and convenient way to diagnose intractable pancreatic diseases,and in the recent years the patients′ compliance rate with MDT advice has increased. Pancreatic cancer patients that have attended the MDT have higher 1-year and 3-year postoperative survival rates,but the long-term survival benefits of MDT still needs to be proved by clinical studies on a larger scale.

The unique characteristics of the tumor microenvironment (TME) could be exploited to develop antitumor nanomedicine strategies. However, in many cases, the actual therapeutic effect is far from reaching our expectations due to the notable tumor heterogeneity. Given the amplified characteristics of TME regulated by vascular disrupting agents (VDAs), nanomedicines may achieve unexpected improved efficacy. Herein, we fabricate platelet membrane-fusogenic liposomes (PML/DP&PPa), namely "platesomes", which actively load the hypoxia-activated pro-prodrug DMG-PR104A (DP) and physically encapsulate the photosensitizer pyropheophorbide a (PPa). Considering the different stages of tumor vascular collapse and shutdown induced by a VDA combretastatin-A4 phosphate (CA4P), PML/DP&PPa is injected 3 h after intraperitoneal administration of CA4P. First, CA4P-mediated tumor hemorrhage amplifies the enhanced permeation and retention (EPR) effect, and the platesome-biological targeting further promotes the tumor accumulation of PML/DP&PPa. Besides, CA4P-induced vascular occlusion inhibits oxygen supply, followed by photodynamic therapy-caused acute tumor hypoxia. This prolonged extreme hypoxia contributes to the complete activation of DP and then high inhibitory effect on tumor growth and metastasis. Thus, such a combining strategy of artificially-regulated TME and bio-inspired platesomes pronouncedly improves tumor drug delivery and boosts tumor hypoxia-selective activation, and provides a preferable solution to high-efficiency cancer therapy.

Objective:To investigate the mechanism of neurofibromin 1 (NF1) in gallbla-dder cancer.Methods:The experimental study was conducted. Human gallbladder cancer cell lines, including GBC-SD, NOZ, SGC996, EH-GB1, ZJU0428, human embryonic kidneys cell line 293T and human cervical cancer cell line HELA, were cultured. The recombinant plasmids (mRFP-YAP1 FL-FLAG and eGFP-MYC-NF1 2650?2750-HA) were constructed for co-immunoprecipitation experiment. The truncated Yes associated protein 1(YAP1) and NF1 recombinant proteins were purified in vitro. The interaction between NF1 and YAP1 in vitro or in vivo were verified by isothermal titration calori-metry (ITC) assay, GST pull-down experiment, co-immunoprecipitation, immunofluorescence, laser confocal microscopy, and the expression of NF1 protein in different gallbladder cancer cell lines was verified by Western blot experiments. Observation indicators: (1) interaction between NF1 and YAP1 in vitro; (2) interaction between NF1 and YAP1 in cells; (3) expression of NF1 protein in different human gallbladder cancer cell lines. The dissociation constants were exported from ITC 200 software and represented as Mean± SD. Count data were represented as absolute numbers. Results:(1) Interaction between NF1 and YAP1 in vitro. ① Results of ITC assay showed that there was interac-tion between PPQY and YAP1-WW1, between PPQY and YAP1 (Amino acid residues 162?275), and the dissociation constants between PPQY and YAP1-WW1, between PPQY and YAP1(Amino acid residues 162?275) were (0.42±0.06)mmol/L, (0.69±0.14)mmol/L, respectively. ② GST pull-down results indicated that the target protein His-Sumo-YAP1 WW1 was obviouly observed in protein lane of reaction system between GST-PPQY recombinant protein and His-Sumo-YAP1 WW1, relative to the reaction system between GST protein and His-Sumo-YAP1 WW1. The target protein His-Sumo-YAP1 WW2 was obviouly observed in protein lane of reaction system between GST-PPQY recombinant protein and His-Sumo-YAP1 WW2, relative to the reaction system between GST protein and His-Sumo-YAP1 WW2. (2) Interaction between NF1 and YAP1 in cells. ① Co-immunoprecipitation results indica-ted that NF1 protein was observed in cell lysis solution which was incubated by FLAG gel beads and cotransfected with mRFP-YAP1 FL-FLAG and eGFP-MYC-NF1 2650?2750-HA. ② Immuno-fluorescence and laser confocal microscopy results indicated that YAP1 and NF1 with obvious fluorescence were co-localized in the cytoplasm of human gallbladder cancer NOZ cells. However, YAP1 with obvious fluorescence was localized in the nucleus of human gallbladder SGC996 cells and NF1 showed weak fluorescence. (3) Expression of NF1 protein in different human gallbladder cancer cell lines. Western blot results showed that with the expression level of NF1 protein in HELA cell line as the standard, the relative expression levels of NF1 protein in EH-GB1, GBC-SD, NOZ, SGC996, ZJU0428 cell lines were 1.28, 0, 1.01, 0, 0, respectively. Conclusion:NF1 affects the gallbladder cancer by directly acting on YAP1 protein.

Objectives:To evaluate the role of pancreas multidisciplinary team(MDT) clinic in the diagnosis of pancreatic diseases,patient compliance with MDT advice,and the impact of MDT on the postoperative survival of patients with pancreatic cancer.Methods:The study included 927 patients(554 males,373 females,aged (58.1±13.3)years (range: 15 to 89 years)) that had visited the pancreas MDT clinic of Zhongshan Hospital from May 2015 to December 2021,and 677 patients(396 males, 281 females, aged (63.6±8.9)years(range: 32 to 95 years)) who underwent radical surgery and with pathologically confirmed pancreatic adenocarcinoma from January 2012 to December 2020,of whom 79 patients had attended the pancreas MDT. The clinical and pathological data were collected and analyzed retrospectively. Diseases were classified in accordance with 2010 WHO classification of tumors of the digestive system and usual clinical practices. The Kaplan-Meier method was used for drawing the survival curve and calculating the survival rate. The univariate analysis was done by Log-rank test and the multivariate analysis was done by COX proportional hazards model. Survival rates were compared using χ 2 test. Results:Among the 927 patients that had visited the MDT clinic,233 patients(25.1%) were referred due to undetermined diagnosis. A direct diagnosis was made in 109 cases (46.8%,109/233) by the MDT clinic, of which 98 were consistent with the final diagnosis,resulting in an accuracy of 89.9%(98/109). The direct diagnosis rate in the recent years(36.6%(41/112),from June 2019 to December 2021) decreased compared to that in the previous years(56.2%(68/121),from May 2015 to May 2019),yet the accuracy in the recent years(90.2%,37/41) was basically the same as before (89.7%,61/68). The rate of compliance of the entire cohort was 71.5%(663/927), with the compliance rate in the recent two and a half years(81.4%,338/415) remarkably higher than that in the previous four years(63.4%,325/512). Patients with pancreatic cancer that attended the MDT exhibited a trend toward longer median postoperative survival than patients that did not attend the MDT,but the difference was not statistically significant(35.2 months vs.30.2 months, P>0.05). The 1-year and 3-year survival rates of patients that attended the MDT were significanly higher than patients that did not attend the MDT(88.6% vs. 78.4%, P<0.05;32.9% vs. 21.9%, P<0.05,respectively),but the 5-year survival rate was not statistically different(7.6% vs. 4.8%, P>0.05). Conclusions:The pancreas MDT clinic is an accurate and convenient way to diagnose intractable pancreatic diseases,and in the recent years the patients′ compliance rate with MDT advice has increased. Pancreatic cancer patients that have attended the MDT have higher 1-year and 3-year postoperative survival rates,but the long-term survival benefits of MDT still needs to be proved by clinical studies on a larger scale.

Objective:To observe and follow up the effect of transcatheter occlusion of the azygos/hemiazygos veins in patients with complex congenital heart diseases and venous stealing after bidirectional Glenn procedure, who had not meet the criteria of total cavopulmonary connection(TCPC) or corrective operation.Methods:This article analyzed retrospectively and followed up the effect of transcatheter occlusion of the azygos/hemiazygos vein in patients after bidirectional Glenn procedure hospitalized during February 2012 to September 2017.Results:Transcatheter occlusions of azygos veins were performed in 21 patients and left superior vena cava(LSVC) was occluded in one of patients meanwhile. Azygos veins and hemiazygos veins were both occluded in two patients. One patient had the hemiazygos vein occluded. Aortic-to-pulmonary collaterals were occluded in 6 patients in the meantime. Atrial septal defect occluders were applied in the transcatheter occlusions of azygos veins, hemiazygos veins and LSVC, except one patient with an azygos vein which was 5.5 mm in diameter. Saturation was increased from 0.78 to 0.85 through occlusion( P<0.05). The pressure of superior vena cava(SVC) did not elevate and the mean pressure of SVC was13.97mmHg and 14.22 mmHg before and after occlusion( P>0.05). No complications associated with interventional procedures occurred. There was no significant decrease in blood oxygen saturation. Facial and upper limb edema, varicose veins in the chest and abdominal wall, pleural effusion and peritoneal effusion did not happen during follow up of 2 years. Two patients underwent TCPC operation one year and five years after interventional occlusion separately. Conclusion:Transcatheter occlusion of azygos/hemiazygos vein or PLSVC was feasible in patients with complex congenital heart diseases and venous stealing after bidirectional Glenn procedure on the premise of choosing suitable indications. Suitable indications meant that the pressure of pulmonary artery and superior vena cava was less than 20 mmHg in the basal state, and the pressure of superior vena cava was also less than 20 mmHg before the release of the occluder. Occlusions may increase the oxygen saturation of patients, improve the quality of life, and even promote the development of pulmonary vascular bed, so as to achieve the indications of TCPC operation in some patients.

Objective: To investigate the clinical outcomes of arthroscopic bridging reconstruction of irreparable massive rotator cuff tears using autogenous fascia lata. Methods: From July 2015 to July 2017, a total of 10 cases (4 male and 6 female) who were treated with arthroscopic bridging reconstruction for irreparable massive rotator cuff tears using autogenous fascia lata were retrospectively analyzed. The age before surgery was 61.3±2.9 years (range 57-67 years). There were 7 patients with right shoulders and 3 with left shoulders. The dominate sides were involved in 7 cases. The trauma history was documented in 2 shoulders. The duration of preoperative symptoms was 14.0±13.5 months (1-48 months). The case with revision surgery was not included. The patients were examined with magnetic resonance imaging (MRI) to evaluate the healing of fascia lata patch bridging in the joint at one week, six months, one year and two years after operation. The motion range of shoulder and the clinical scores, including visual analogue scale (VAS), University of California Los Angeles (UCLA) score, Constant-Murley score and American Shoulder & Elbow Surgeons (ASES) score, were measured before surgery and at follow-up duration. Results: All cases were reconstructed the horizontal couple. No perioperative complication was occurred and all surgery were completed safely and successfully. At the end of two years, the score of ASES was 92.2±3.5 (range 88.3-98.3), UCLA 31.6±2.0 (range 28-34), Constant-Murley 85.2±5.4 (range 78-93) with significant difference (t=11.254, P=0.000; t=12.111, P=0.000; t=8.948, P=0.00) comparing with that before surgery. The VAS pain score was 0.6±0.5 (range 0-1) which was significantly lower than that preoperatively (t=11.326, P=0.000). At 2 years after operation, MRI shows that fascia lata patches healed well in 9 patients. However, one case was with re-tear and patch absorption. The range of motion of shoulder was significantly improved in all patients but with different degrees of weakness (3-4). Conclusion Arthroscopic bridging reconstruction using autogenous fascia lata could effectively improve shoulder function in patients with irreparable massive rotator cuff tears. The autogenous fascia lata patch can heal with the help of rotator cuff tissue through bridging reconstruction.

Objective To analyze the efficacy of entecavir (ETV) combined with Peg IFNα-2b in chronic hepatitis B ( CHB) patients with low levels HBsAg following initial ETV treatment.Methods Sixty-nine CHB outpatients achieving serum HBsAg ＜2 000 IU/mL and HBV DNA＜100 IU/mL following initial ETV treatment in Pujiang People's Hospital and the First Affiliated Hospital of Zhejiang University School of Medicine from January 2014 to January 2016 were enrolled.Patients were randomly assigned in two groups: 39 patients in combination group received ETV (0.5 mg/d ) and Peg IFNα-2b (1.5 μg· kg－1· week －1, hypodermic injection), and 30 patients in ETV group received ETV (0.5 mg/d) alone.Serum HBsAg quantification, negative conversion rate of HBsAg and HBeAg , and levels of aminotransferase (ALT) were measured at baseline , 12th, 24th, 48th, 72th and 96th week after treatment.Results The levels of HBsAg in the combination group decreased gradually with the prolongation of therapy , which were lower than those in ETV group 24 week after treatment (Z＝－2.566,P＜0.05),and at 48th, 72th and 96th week (Z＝－3.499,－3.825 and －3.864,P＜0.01).Clearance of HBsAg appeared in the combination group at 24th week,the clearance rates were 7.70%(3/39) and 28.20%(11/39) at 24th and 96th week, respectively;while the clearance of HBsAg occurred in ETV group at 96th week, the clearance rate was only 3.30%(1/30).The negative conversion rates of HBsAg in combination group were higher than those in ETV group at 48th,72th and 96th week (P＜0.05 or＜0.01).In the combination group, there were 11 cases of clinical cure , 11 cases of clinical efficacy and 17 cases of clinical effectiveness , while there were 1, 1 and 28 cases in ETV group,respectively.The treatment effect of the combination group was better than that of ETV group(χ2＝18.496,P＜0.01).Serological conversion rates of HBeAg were 30.00%(6/20) and 65.00%(13/20) in combination group at 12th and 96th week, while those were 11.11%(2/18) and 22.22%(4/18) in ETV group at 48th and 96th week.There were significant differences in the HBeAg serological conversion rates at 12th, 24th, 72th and 96th week between two groups (P＜0.05 or ＜0.01). The levels of ALT in combination group increased at 12th and 24th week, which had significant difference compared with ETV group (Z＝－1.236 and －2.658,P＜0.05), and the ALT levels gradually declined 48 week after treatment in combination group and there were no statistical differences between two groups at other time points.The ETV combined with Peg IFNα-2b and low baseline HBeAg levels were associated with the clearance rate of HBsAg (both P＜0.01).Conclusions CHB patients with low HBsAg levels following initial ETV monotherapy can achieve high negative conversion rate of HBeAg and HBsAg with the combination treatment of ETV and Peg IFN α-2b.

Objective To investigate the clinical value of probiotics in the treatment of patients with nonal -coholic fatty liver disease ( NAFLD) .Methods The clinical data of 100 patients with NAFLD were retrospectively analyzed.According to different treatment methods ,the patients were divided into two groups ,with 50 cases in each group.The control group received basic treatment ,the observation group received probiotics treatment on the basis of the control group .The treatment effects of the two groups were analyzed .Results The total effective rate in the obser-vation group (54.00%) was significantly higher than that in the control group (30.00%)(χ2 =5.911,P=0.015) .After treatment,the ALT,TG,HOMA-R,TNF-α,D-lactic acid,endotoxin levels in the observation group were significantly better than those in the control group (all P<0.05).The incidence rate of adverse reactions between the two groups had no statistically significant difference (4.00% vs.2.00%,χ2 =0.343,P =0.558).Conclusion Probiotics in the treatment of NAFLD can reduce the intestinal permeability ,improve the intestinal endotoxemia and the prognosis of the patients .

Objective To study the different oral compound polyethylene glycol electrolyte powder on the effect of bowel preparation before colonoscopy.Methods A total of 602 inpatients or outpatients were selected from department of gastroenterology,and they were randomly divided into tranditional group(n =288)and improvement group(n =314).All patients took a dose of two box of compound polyethylene glycol electrolyte powder 4 hours before colonoscopy.Endoscopic doctor investigated the antibiotic tolerance,adverse reactions,heart rate,blood pressure,blood electrolytes and blood glucose during treatment in form of questionnaire with single blind Bosdon bowel preparation scale (BBPS)score.Results The BBPS scores of the tranditional group and improvement group were (7.03 ± 1.24)points,(7.82 ±1.12)points,the score of the improvement group was significantly higher than the traditional group(t =2.259,P <0.05).The taste scores were (1.89 ±0.07)points,(1.25 ±0.09)points (t =2.624,P <0.05),the fully taking rates were 90.28%,95.86%(χ2 =7.375,P <0.05 ),and the second taking rates were 88.54%,93.95%(χ2 =5.566,P <0.05).In contract,the score of adverse reactions of the improvement group was significantly lower than that of the traditional group [(2.58 ±0.07)points vs(2.22 ±0.09)points,t =2.068,P <0.05].There was no significant difference of colonoscopy time between the two groups[(10.78 ±4.34)min vs (9.89 ± 1.77)min,t =1.766,P >0.05 ],althought the improvement group was shorter than the tranditional group. Conclusion The modified way of oral compound polyethylene glycol electrolyte powder not only can improve the qulity of intestinal cleaning,but also acts as a more effective method in preparation of colonoscopy due to its high tolerance, good comfort,less pain and high acceptance of patients.Therefore,it is worthy of clinical promotion and application.