Objective To explore and verify the active components of Dachengqi decoction in regulating autophagy and its mechanism of protecting the intestinal mucosal barrier through network pharmacology and animal experiments.Methods The chemical components and autophagy-related target points of Dachengqi decoction were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database Analysis Platform(TCMSP)and GeneCards databases.The intersection of the drug target points and disease target points was taken and analyzed.The Cytoscape 3.10.2 software's Network Analyzer tool was used to analyze the drug components and target points,and the core target points were screened out to construct a traditional Chinese medicine compound regulatory network.The drug active component target point-disease network model and protein-protein interaction(PPI)network were visualized.Then,30 C57BL/6J mice were randomly divided into the Dachengqi decoction group,the intestinal infection group,and the control group,with 10 mice in each group.The intestinal infection group was given 200 μL/d of Klebsiella pneumoniae strain by gavage for 5 consecutive days,with a colony count of 109 CFU/mL,to create an intestinal infection model.The control group was given 200 μL/d of sterile normal saline by gavage.The Dachengqi decoction group(drug composition:Rhubarb 12 g,Aurantii Fructus 12 g,Magnolia Officinalis 24 g,Mirabilite 9 g,the drugs were dissolved in boiling distilled water to make a 1 kg/L solution)was given by gavage at a dose of 8 g·kg-1·d-1 for 3 consecutive days,and then given Klebsiella pneumoniae by gavage for 5 consecutive days on the 4th day.Detection indicators and methods:after the experiment,the mice were sacrificed and the terminal ileum tissues were collected.The tissues were stained with hematoxylin-eosin(HE),and the pathological changes of the intestinal mucosa were observed under a light microscope;immunofluorescence staining was used to observe the positive expressions of junction proteins ZO-1,Claudin-2,light chain 3-Ⅱ(LC3-Ⅱ),and Beclin-1 and the intestinal mucosal autophagy;the mRNA expression levels of autophagy genes were determined by polymerase chain reaction(PCR).Results The intersection of the obtained drug targets and disease targets yielded 111 potential autophagy-related targets for drug treatment of diseases.Key targets included β2-adrenergic receptor(ADRB2),heme oxygenase-1(HO-1),etc.,and the signaling pathways involved included AMP-activated protein kinase(AMPK)pathway,mammalian target of rapamycin(mTOR)pathway,etc.Animal experiments confirmed that the intestinal mucosal barrier function in the Dachengqi decoction group was better than that in the intestinal infection group,and the positive expression of microtubule-associated protein 1 lingt chain 3-Ⅱ(LC3-Ⅱ)and autophagy gene Beclin1 was significantly higher than that in the intestinal infection group.Transcriptome sequencing results showed that the key genes associated with autophagy and oxidative stress included ADRB2,HO-1,etc.The mRNA expression levels of ADRB2 and HO-1 in the Dachengqi decoction group were significantly higher than those in the intestinal infection group[HO-1 mRNA expression(FPKM):11.20±0.80 vs.6.63±0.53,ADRB2 mRNA expression(FPKM):6.98±0.54 vs.3.98±0.32,both P<0.01],verifying some of the predictions from network pharmacology.Conclusions Dachengqi decoction regulates autophagy through multiple components,multiple targets and multiple pathways,protecting the intestinal mucosal barrier function and reducing the translocation of intestinal microbiota.This lays a certain foundation for further in-depth research on the mechanism of reducing intestinal bacterial translocation by Dachengqi decoction.

Objective To explore the value of CT radiomics analysis in predicting the curative effect of extracorporeal shock wave lithotripsy(ESWL)in ureteral calculus(UC)patients.Methods A total of 126 UC patients who underwent ESWL from January 2018 to December 2023 were selected,and randomly divided into training group and validation group at a ratio of 7∶3.Forty-five UC patients from January 2024 to September 2024 were selected as external validation group and divided into two groups according to whether the residual stones were less than 4 mm after operation.There were 81 cases in the successful lithotripsy group and 45 cases in the failed lithotripsy group.The 3D Slicer software was used to outline the stone layer by layer to obtain region of interest(ROI),and 851 radiomics features were extracted.After the observer consistency test,maximum relevance and minimum redundancy(mRMR)algorithm and least absolute shrinkage and selection operator(LASSO),the radiomics features were selected,and the logistic regression model was established.The diagnostic efficiency of the model was analyzed by receiver operating characteristic(ROC)curve.Results The six optimal features were obtained from the radiomics features.The combined clinical-radiomics model showed the best prediction efficiency with area under the curve(AUC)of 0.908,0.906 and 0.908 in the training,validation and external validation groups respectively.Conclusion CT radiomics model can be used to predict the curative effect of UC patients after ESWL,and provide a basis for assisting UC patients in individualized treatment.

Objective To explore the value of CT radiomics analysis in predicting the curative effect of extracorporeal shock wave lithotripsy(ESWL)in ureteral calculus(UC)patients.Methods A total of 126 UC patients who underwent ESWL from January 2018 to December 2023 were selected,and randomly divided into training group and validation group at a ratio of 7∶3.Forty-five UC patients from January 2024 to September 2024 were selected as external validation group and divided into two groups according to whether the residual stones were less than 4 mm after operation.There were 81 cases in the successful lithotripsy group and 45 cases in the failed lithotripsy group.The 3D Slicer software was used to outline the stone layer by layer to obtain region of interest(ROI),and 851 radiomics features were extracted.After the observer consistency test,maximum relevance and minimum redundancy(mRMR)algorithm and least absolute shrinkage and selection operator(LASSO),the radiomics features were selected,and the logistic regression model was established.The diagnostic efficiency of the model was analyzed by receiver operating characteristic(ROC)curve.Results The six optimal features were obtained from the radiomics features.The combined clinical-radiomics model showed the best prediction efficiency with area under the curve(AUC)of 0.908,0.906 and 0.908 in the training,validation and external validation groups respectively.Conclusion CT radiomics model can be used to predict the curative effect of UC patients after ESWL,and provide a basis for assisting UC patients in individualized treatment.

Objective To explore and verify the active components of Dachengqi decoction in regulating autophagy and its mechanism of protecting the intestinal mucosal barrier through network pharmacology and animal experiments.Methods The chemical components and autophagy-related target points of Dachengqi decoction were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database Analysis Platform(TCMSP)and GeneCards databases.The intersection of the drug target points and disease target points was taken and analyzed.The Cytoscape 3.10.2 software's Network Analyzer tool was used to analyze the drug components and target points,and the core target points were screened out to construct a traditional Chinese medicine compound regulatory network.The drug active component target point-disease network model and protein-protein interaction(PPI)network were visualized.Then,30 C57BL/6J mice were randomly divided into the Dachengqi decoction group,the intestinal infection group,and the control group,with 10 mice in each group.The intestinal infection group was given 200 μL/d of Klebsiella pneumoniae strain by gavage for 5 consecutive days,with a colony count of 109 CFU/mL,to create an intestinal infection model.The control group was given 200 μL/d of sterile normal saline by gavage.The Dachengqi decoction group(drug composition:Rhubarb 12 g,Aurantii Fructus 12 g,Magnolia Officinalis 24 g,Mirabilite 9 g,the drugs were dissolved in boiling distilled water to make a 1 kg/L solution)was given by gavage at a dose of 8 g·kg-1·d-1 for 3 consecutive days,and then given Klebsiella pneumoniae by gavage for 5 consecutive days on the 4th day.Detection indicators and methods:after the experiment,the mice were sacrificed and the terminal ileum tissues were collected.The tissues were stained with hematoxylin-eosin(HE),and the pathological changes of the intestinal mucosa were observed under a light microscope;immunofluorescence staining was used to observe the positive expressions of junction proteins ZO-1,Claudin-2,light chain 3-Ⅱ(LC3-Ⅱ),and Beclin-1 and the intestinal mucosal autophagy;the mRNA expression levels of autophagy genes were determined by polymerase chain reaction(PCR).Results The intersection of the obtained drug targets and disease targets yielded 111 potential autophagy-related targets for drug treatment of diseases.Key targets included β2-adrenergic receptor(ADRB2),heme oxygenase-1(HO-1),etc.,and the signaling pathways involved included AMP-activated protein kinase(AMPK)pathway,mammalian target of rapamycin(mTOR)pathway,etc.Animal experiments confirmed that the intestinal mucosal barrier function in the Dachengqi decoction group was better than that in the intestinal infection group,and the positive expression of microtubule-associated protein 1 lingt chain 3-Ⅱ(LC3-Ⅱ)and autophagy gene Beclin1 was significantly higher than that in the intestinal infection group.Transcriptome sequencing results showed that the key genes associated with autophagy and oxidative stress included ADRB2,HO-1,etc.The mRNA expression levels of ADRB2 and HO-1 in the Dachengqi decoction group were significantly higher than those in the intestinal infection group[HO-1 mRNA expression(FPKM):11.20±0.80 vs.6.63±0.53,ADRB2 mRNA expression(FPKM):6.98±0.54 vs.3.98±0.32,both P<0.01],verifying some of the predictions from network pharmacology.Conclusions Dachengqi decoction regulates autophagy through multiple components,multiple targets and multiple pathways,protecting the intestinal mucosal barrier function and reducing the translocation of intestinal microbiota.This lays a certain foundation for further in-depth research on the mechanism of reducing intestinal bacterial translocation by Dachengqi decoction.

From October 2021 to February 2023, we retrospectively analyzed the clinical and laboratory data of six patients (three male and three female, median age: 54 years, age range: 29-73 years) with mast cell leukemia (MCL) diagnosed in the First Affiliated Hospital of Soochow University (The Mastocytosis Collaborative Network of China). All patients had acute MCL, with at least one C-finding present. The main clinical presentations were hypoalbuminemia ( n=4), fatigue ( n=3), fever ( n=2), abdominal discomfort ( n=2), osteolytic lesions ( n=2), dizziness ( n=1), skin flushing ( n=1), and weight loss ( n=1). Splenomegaly and lymphadenopathy were noted in six and three patients, respectively. Six patients were strongly positive for CD117, five were positive for CD30 and CD25, and four were positive for CD2. Four patients had a normal karyotype and two patients had an abnormal karyotype. Gene mutations were detected in 4/6 cases. The median serum tryptase level was 24.9 (range: 20.1-171.9) μg/L. Two patients were treated with venetoclax and azacitidine for induction (one patient achieved partial remission by combination with afatinib, while there was no remission after combination with dasatinib in the other patient). Two patients did not achieve complete remission despite treatment with cladribine and imatinib, respectively. One patient treated with interferon combined with glucocorticoids was lost to follow-up, and one patient abandoned treatment. The follow-up time ranged from 1.1 to 21.7 months. Three patients died and two survived. Overall, MCL is a rare subtype of systemic mastocytosis with heterogeneous clinical course, and these patients have poor outcome. A better understanding of the clinical characteristics, treatment, and prognosis of MCL is urgently needed.

Objective:To investigate the safety of minimally invasive liver resection for resectable hepatocellular carcinoma (HCC) complicated with portal hypertension.Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 807 patients with resectable HCC who underwent minimally invasive liver resection in 8 medical centers, including Sir Run Run Shaw Hospital, Affiliated with the Zhejiang University School of Medicine et al, from June 2011 to November 2022 were collected. There were 670 males and 137 females, aged 58(50,66)years. Of the 807 patients, 173 cases with portal hypertension were divided into the portal hypertension group, and 634 cases without portal hypertension were divided into the non-portal hypertension group. Observation indicators: (1) propensity score matching and comparison of general data of patients between the two groups after matching; (2) intraoperative and post-operative situations; (3) subgroup analysis. Propensity score matching was done by the 1:1 nearest neighbor matching method, with the caliper setting as 0.001. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the rank sum test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was constructed using the non-parameter rank sun test. Results:(1) Propensity score matching and comparison of general data of patients between the two groups after matching. Of the 807 patients, 268 cases were successfully matched, including 134 cases in the portal hypertension group and 134 cases in the non-portal hypertension group. The elimination of the tumor diameter and robot-assisted surgery confounding bias ensured comparability between the two groups after propensity score matching. (2) Intraoperative and postoperative situations. The occlusion time of porta hepatis, cases with intraoperative blood transfusion, cases with postoperative complication, cases with complication >Ⅱ grade of Clavien-Dindo classification, cases of Clavien-Dindo classification as Ⅰ grade, Ⅱ grade, Ⅲ grade, Ⅳ grade, cases with liver related complication were 27.0(15.0,43.0)minutes, 33, 55, 15, 13, 29, 14, 1, 37 in the portal hypertension group, versus 35.0(22.0,60.0)minutes, 17, 25, 5, 14, 9, 4, 1, 13 in the non-portal hypertension group, showing significant differences in the above indicators between the two groups ( Z=-2.15, χ2=6.30, 16.39, 4.38, 20.72, 14.16, P<0.05). (3) Subgroup analysis. Results of subgroups analysis showed that in cases with major live resection, the operation time, volume of intraoperative blood loss, duration of postoperative hospital stay were 243.5(174.6,296.3)minutes, 200.0(150.0,600.0)mL, 7.5(6.0,13.0)days in the portal hypertension group, versus 270.0(180.0,314.5)minutes, 200.0 (75.0,450.0)mL, 7.0(5.5,10.0)days in the non-portal hypertension group, showing no significant difference in the above indicators between the two groups ( Z=-0.54, -1.73, -0.92, P>0.05). In cases with non-major live resection, the operation time, volume of intraoperative blood loss, duration of postoperative hospital stay were 170.0(120.0,227.5)minutes, 100.0(50.0,200.0)mL, 8.0(5.0,10.0)days in the portal hypertension group, versus 170.0(120.0,227.5)minutes, 100.0(50.0,200.0)mL, 7.0(5.5,9.0)days in the non-portal hypertension group, showing no significant difference in the above indicators between the two groups ( Z=-1.39, -0.10, 1.05, P>0.05). In cases with anatomical liver resection, the operation time, volume of intraoperative blood loss, duration of postoperative hospital stay were 210.0(150.0,285.0)minutes, 150.0(50.0,200.0)mL, 8.0(6.0,9.3)days in the portal hypertension group, versus 225.5(146.3,306.8)minutes, 100.0(50.0,250.0)mL, 7.0(6.0,9.0)days in the non-portal hypertension group, showing no significant difference in the above indica-tors between the two groups ( Z=-0.75, -0.26, -0.91, P>0.05). In cases with non-anatomical liver resection, the operation time, volume of intraoperative blood loss, duration of postoperative hospital stay were 173.5(120.0,231.5)minutes, 175.0(50.0,300.0)mL, 7.0(5.0,11.0)days in the portal hyper-tension group, versus 186.0(123.0,262.5)minutes, 100.0(50.0,200.0)mL, 7.0(5.0,9.5)days in the non-portal hypertension group, showing no significant difference in the above indicators between the two groups ( Z=-0.97, -1.12, -0.98, P>0.05). Conclusion:Minimally invasive liver resection or even major liver resection is safe and feasible for screened HCC patients complicated with portal hyper-tension, but attention should be paid to the prevention and treatment of postoperative complications.

We constructed the CS1-targeted second- and third-generation CAR-T cells with genetic engineered 4-1BB or/and ICOS as a costimulatory signaling molecule by use of lentiviral platform. The CS1-targeted second-generation CAR-T cells with ICOS or 4-1BB had similar anti-neoplastic activity. When effector/target ratio was 1:1, the CAR-T cells with ICOS showed better killing effect on IM9-lucgfp cells than those with 4-1BB. However, The CS1-targeted third-generation CAR-T cells exihibited lower cytolytic capacity against IM9-lucgfp cells than the CS1-targeted second-generation CAR-T cells when the ratio of effector/target was 1:1, 2:1 or 5:1. When the ratio of effector/target was 10:1, the killing efficacy of both the second- and third-generation CAR-T cells against IM9-lucgfp cells was more than 85%, significantly higher than that of the control T cells. Taken together, both the CS1-targeted second- and third-generation CAR-T cells with ICOS or/and 4-1BB could efficiently kill CS1-positive multiple myeloma cells, but the CS1-targeted second-generation CAR-T cells had more potent killing effect on CS1-positive multiple myeloma cells than the CS1-targeted third-generation CAR-T cells.
4-1BB Ligand/metabolism* ; Cell Line, Tumor ; Genetic Engineering ; Humans ; Inducible T-Cell Co-Stimulator Protein/metabolism* ; Multiple Myeloma/therapy* ; Signal Transduction ; T-Lymphocytes/chemistry* ; Xenograft Model Antitumor Assays

Objective To evaluate the therapeutic efficacy and safety of HIFU ablation for uterine fibroids in patients with abdominal surgical scars in acoustic pathway causing acoustic attenuation width ＜10 mm.Methods Totally 861 patients with uterine fibroids were referred for HIFU treatment and underwent contrast-enhanced MR scans before and after HIFU ablation.Among all patients,202 had abdominal surgical scars causing width ＜10 mm acoustic attenuation (abdominal scars group) and 659 had no abdominal surgical scars (without abdominal scars group).The outcomes,intra-operative adverse reactions and post-operative complications between the two groups were compared.Results HIFU ablation was successfully performed in all patients.The volume ablation rate was (80.31 ± 18.16)％ in abdominal scars group and (79.60±17.57)％ in without abdominal scars group (P＝0.620).The rate of ‘hot'skin sensation during HIFU procedure in abdominal scars group (52.97％ [107/202]) was higher than that in without abdominal scars group (41.58％ [274/ 659];P＝0.004).Anterior abdominal wall edema was found in 40 cases (40/202,19.80％) in abdominal scars group and 98 cases (98/659,14.87％) in without abdominal scars group on post-operation MRI (P＝ 0.095).Conclusion Prior abdominal surgical scars in acoustic pathway causing width ＜10 mm acoustic attenuation has not significantly influence on the efficacy and safety of HIFU treatment for uterine fibroid.

Objective To investigate the effect of different appropriate modes of weaning from mechanical ventilation (MV) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods Patients with AECOPD and mechanically ventilated by orotracheal intubation, suitable for continuous positive airway pressure+proportional pressure support (CPAP+PPS) and CPAP+assisted spontaneous breath (ASB) ventilation mode for weaning from MV, admitted to intensive care unit (ICU) of Tianjin Third Central Hospital form January 1st, 2016 to December 31st, 2017 were enrolled. When the patients recovered to spontaneous respiration and down regulation of ventilator support frequency to 10 bpm, they were taken ventilator weaning in CPAP+PPS and CPAP+ASB mode according to the random number table method, respectively. Basic characteristics, ventilator parameters, the incidence of high man-machine confrontation (man-machine confrontation index > 10%) and clinical outcomes (ventilator weaning time, which was defined as the time from randomization to successful weaning from MV, ventilator weaning failure times, the duration of MV, the length of ICU stay and the length of hospital stay) were compared between the two groups. Results Eighty-seven AECOPD patients were selected, 44 in CPAP+ASB group and 43 in CPAP+PPS group. There was no significant difference in gender, age, acute physiology and chronic health evaluation Ⅱ(APACHEⅡ), sequential organ failure score (SOFA), Glasgow coma score (GCS), Charsen index and the highest arterial blood carbon dioxide partial pressure (PaCO2), the lowest arterial oxygen partial pressure (PaO2) and tidal volume (VT) at the time of onset between the two groups. Compared with CPAP+ASB group, incidence of high man-machine confrontation was significantly decreased in CPAP+PPS group [9.30% (4/43) vs. 27.27% (12/44), P =0.027], and the airway occlusion pressure (P0.1) was significantly decreased [cmH2O (1 cmH2O = 0.098 kPa): 2.21±0.83 vs. 2.63±0.94, P = 0.032], and the failure rate of the first spontaneous breathing trial (SBT) was significantly decreased [6.98% (3/43) vs. 22.73% (10/44), P = 0.039], ventilator weaning time, the length of ICU stay and the length of hospital stay were significantly shortened [ventilator weaning time (hours): 12.73±14.23 vs. 50.64±38.11, the length of ICU stay (hours): 254.53±108.06 vs. 344.93±124.95, the length of hospital stay (days): 18.53±7.59 vs. 26.64±11.22, all P < 0.05]. However, there was no significant difference in PaCO2, duration of MV, ICU mortality and hospital mortality between the two groups. Conclusion Compared with CPAP+ASB ventilation mode, CPAP+PPS ventilation mode can reduce respiratory muscle load, promote respiratory function recovery, and reduce the occurrence of man-machine confrontation, which is beneficial to AECOPD patients taking ventilator weaning, and can significantly shorten the ventilator weaning time of patients and further shorten the hospitalization time.

Objective To observe the efficacy ofvitrectomy combined with internal limiting membrane (ILM) peeling and scleral shortening for myopic foveoschisis (MF).Methods Prospective and non-randomized concurrent control study.A total of 35 MF patients (35 eyes) were enrolled in this study.The patients were divided into 2 groups according to surgery,including group A (18 eyes) and group B (17 eyes),all received vitrectomy combined with ILM peeling,but group A also received scleral shortening.The best corrective visual acuity (BCVA) examination using the Snellen vision chart was converted to the minimum resolution logarithm (logMAR).Ocular axis length (AL) was measured by Zeiss IOL-Master or A-scan ultrasound (Quantel Medical,France).The maximal value of retinal foveoschisis (MxFT) was measured by frequency-domain optical coherence tomography (Heidelberg,Germany).Multifocal electroretinogram (mfERG) responses were obtained with the RETIscan system (Roland Consult,Gemany).There was no statistically significant difference between the two groups (P＞0.05) in age (t=0.460),AL (t=1.520),diopter (t=0.020),logMAR BCVA (t=-2.280),MxFT (Z=-4.179) and b-wave ERG amplitude (Z=-0.198).The changes of BCVA,AL,MxFT and b wave amplitude were followed-up for 3-12 months.Results At the last follow-up,the height of MF was decreased in 18 eyes of group A,and MF was completely disappeared in 4 eyes.The logMAR BCVA (t=7.272,5.951),MxFT (Z=-3.724,-3.622) and b-wave ERG amplitude (Z=-3.223,-3.243) in both groups A and B were statistically improved (P=0.000,0.000,0.000,0.000,0.001,0.001) compared to pre-operational results.There was significant difference of logMAR BCVA (t=-2.280) and MxFT (Z=-4.179) between the two groups (P=0.029,0.000).But there was no significant difference in the amplitude of b-wave (Z=-0.198,P=0.843).The AL in group A was shortened after surgery,the difference was statistically significant (t=10.017,P=0.000).During the follow-up,there was no ocular hemorrhage,endophthalmitis and other complications.Conclusion PPV combined with ILM peeling and scleral shortening can shorten AL significantly for MF patients,and gain relative normal anatomical structure of the fovea,thus improve the vision.