Construction of Lung Adenocarcinoma Prognosis Model and Drug Sensitivity Analysis Based on Cuproptosis Related Genes / 中国肺癌杂志

BACKGROUND@#Lung cancer is one of the most common malignant tumors in the world, and the current lung cancer screening and treatment strategies are constantly improving, but its 5-year survival rate is still very low, which seriously endangers human health. Therefore, it is critical to explore new biomarkers to provide personalized treatment and improve the prognosis. Cuproptosis is a newly discovered type of cell death, which is due to the accumulation of excess copper ions in the cell, eventually leading to cell death, which has been suggested by studies to be closely related to the occurrence and development of lung adenocarcinoma (LUAD). Based on The Cancer Genome Atlas (TCGA) database, this study explored the association between cuproptosis-related genes (CRGs) and LUAD prognosis, established a prognostic risk model, and analyzed the interaction between CRGs and LUAD immune cell infiltration.@*METHODS@#The RNA-seq data of LUAD tissue and paracancerous or normal lung tissue were downloaded from the TCGA database; the RNA-seq data of normal lung tissue was downloaded from the Genotype-tissue Expression (GTEx) database, and the data of 462 lung adenocarcinoma cases were downloaded from the Gene Expression Omnibus repository (GEO) as verification. T the risk score model to assess prognosis was constructed by univariate Cox and Lasso-Cox regression analysis, and the predictive ability of the model was evaluated by receiver operating characteristic (ROC) curve and calibration curve. Immune-related and drug susceptibility analysis was further performed on high- and low-risk groups.@*RESULTS@#A total of 1656 CRGs and 1356 differentially expressed CRGs were obtained, and 13 CRGs were screened out based on univariate Cox and Lasso-Cox regression analysis to construct a prognostic risk model, and the area under the curves (AUCs) of ROC curves 1-, 3- and 5- year were 0.749, 0.740 and 0.689, respectively. Further study of immune-related functions and immune checkpoint differential analysis between high- and low-risk groups was done. High-risk groups were more sensitive to drugs such as Savolitinib, Palbociclib, and Cytarabine and were more likely to benefit from immunotherapy.@*CONCLUSIONS@#The risk model constructed based on 13 CRGs has good prognostic value, which can assist LUAD patients in individualized treatment, and provides an important theoretical basis for the treatment and prognosis of LUAD.

Comparative analysis of MR imaging findings of perianal fistulas in patients with and without Crohn disease / 中华放射学杂志

Objective To investigate the differences in magnetic resonance imaging characteristics between perianal?fistulas of Crohn disease (P?FCD) and perianal?fistulas of non?Crohn disease (P?FNCD). Methods A retrospective analysis was made of 109 patients with perianal fistula who were confirmed by clinical examinations and surgery and had complete preoperative pelvic MRI data from sir run run shaw hospital affiliated to Zhejiang University from June 2015 to March 2017. Patients were divided into P?FCD and P?FNCD groups according to whether the patient was clinically diagnosed with Crohn disease (CD). There were 59 cases in group P?FCD and 50 cases in group P?FNCD. All patients underwent pelvic MRI plain scan and enhanced scan. the classifications of perianal fistula (St. James University Hospital classification and improved Parks classification) were evaluated. The number of branches, the number of abscesses, the number of internal opening, the height of the internal opening were measured and recorded. The incidence of proctitis and anal inflammation were recorded. Van Assche score was evaluated. Measured data between patients in the P?FCD and P?FNCD groups were compared using independent sample t test (normal distribution) or non?parametric test (skewed distribution).The quantitative data were compared using cross?sectional Pearson χ2 test. Results There were significant differences in the number of branches, the number of abscesses, the number of internal opening, the height of the internal opening, the positive rate of proctitis, the positive rate of anal canalitis, and the Van Assche score between the P?FCD group and the P?FNCD group (all P<0.05). There was no significant difference in the modified Parks classification between the P?FCD group and the P?FNCD group (P>0.05).There was significant difference in the classification of St. James University Hospital between the P?FCD group and the P?FNCD group (P<0.05). Conclusions P?FCD is mainly composed of high complex anal fistula, which is significantly different from P?FNCD. We used St. James University Hospital classification and Van Assche score to diagnose perianal fistula in combination with clinical examinations, which was helpful for the diagnosis of P?FCD.

Computed tomography and magnetic resonance imaging features of IgG4-related pancreatitis / 中华消化外科杂志

Objective To summarize the computed tomography (CT) and magnetic resonance imaging (MRI) features of IgG4-related pancreatitis.Methods The retrospective and descriptive study was conducted.The clinical data of 23 patients with IgG4-associated pancreatitis who were admitted to Sir Run Run Shaw Hospital of Zhejiang University School of Medicine from November 2012 to May 2018 were collected.There were 21 males and 2 females,aged from 45 to 83 years,with an average age of 63 years.Patients underwent upper abdominal enhanced CT and enhanced MRI examinations.Observation indicators:(1) imaging examination of the patients;(2) imaging characteristics on CT and MRI examinations;(3) follow-up.Follow-up using outpatient examination including laboratory and imaging examination was performed to detect clinical symptoms and signs once a month within 3 months postoperatively,once every 3 months within 3 months to 1 year postoperatively,once every 6 months with 1-2 years postoperatively,and once a year after 2 years postoperatively up to August 2018.Measurement data with skewed distribution were represented as M (range).Count data were described as absolute numbers.Results (1) Imaging examination of the patients:19 of 23 patients underwent upper abdominal enhanced CT combined with upper abdominal enhanced MRI scanning,3 underwent upper abdominal enhanced CT combined with upper abdominal MRI plain scanning,and 1 underwent only upper abdominal enhanced MRI scanning.(2) Imaging characteristics on CT and MRI examinations:pancreatic manifestations included 7 aspects.① Location of lesion and morphological classification:of 23 patients,17 were diffuse type,showing sausage-like appearance;4 were focal type,including 2 with mass in the pancreatic head and 2 with mass in the pancreatic body and tail;2 were multiple type,including 1 with mass in the pancreatic head,body and tail,and 1 with mass in the pancreatic body and tail.② Density of lesions on CT examination:of 23 patients,22 received CT plain scanning,including 10 with equal density and 12 with slightly low density;1 didn't receive CT plain scanning.③ Signal of lesions on MRI examination:on T1 weighted imaging,16 of 23 patients showed homogeneous slightly low signal,4 showed isointensity signal,2 showed mixed slightly low signal,and 1 showed slightly high signal.On T2 weighted imaging,21 of 23 patients showed homogeneous slightly high signal,1 showed isointensity signal,and 1 showed mixed slightly high signal.Of 23 patients,19 underwent diffuse weighted imaging (DWI) and 4 didn't undergo DWI.There were 17 patients with slightly high signal and 2 with high signal on DWI.On apparent diffusion coefficient imaging,10 patients showed slightly low signal,and 9 showed low signal intensity.④ Calcification:of 23 patients,2 had multiple calcifications including 1 of diffuse type with calcification located at pancreatic head,and 1 of focal type with calcification located at pancreatic body and tail;20 had no calcification;1 without CT plain scanning cannot be judged calcification.⑤ Enhancement pattern:23 patients showed progressive delayed enhancement of pancreatic lesions on enhancement scanning,homogeneous or heterogeneous enhancement in the arterial phase,and further enhancement in the portal venous phase and delayed phase (enhancement degree of focal type and multiple type was basically consistent with that of normal pancreas).⑥ Halo sign surrounding lesions:of 23 patients,7 had no halo sign,including 2 of diffuse type,3 of focal type,and 2 of multiple type;16 had halo sign (15 of diffuse type and 1 of focal type),including 11 with halo sign surrounding pancreatic body and tail,3 with halo sign surrounding whole pancreas,and 1 with halo sign posterior pancreatic body and tail,and 1 with halo sign anterior pancreatic head.⑦ The main pancreatic duct:14 of 23 patients had irregular stenosis of the main pancreatic duct,7 had mild dilatation of the main pancreatic duct,and 2 had no dilatation of the main pancreatic duct.Extra-pancreatic manifestations included 3 aspects.① Bile duct dilatation:10 of 23 patients had simple intra-hepatic and extra-hepatic bile duct dilatation,8 had no intrahepatic or extra-hepatic bile duct dilatation,and 5 had intra-pancreatic common duct stenosis with upstream bile duct dilatation.② Extra-pancreatic organ involvement:18 of 23 patients had extra-pancreatic organ involvement (5 with gall bladder involvement,4 with intra-hepatic and extra-hepatic bile duct and gall bladder involvement,3 with intra-hepatic and extra-hepatic bile duct involvement,1 with lung involvement,1 with spleen involvement,1 with common duct involvement,1 with kidney involvement,1 with lung and intra-hepatic and extra-hepatic bile duct involvement,1 with fibrosis of mesenteric root),and 5 had no extra-pancreatic organ involvement.③ Retroperitoneal lymph nodes:2 of 23 patients had enlarged retroperitoneal lymph nodes,21 had no enlarged retroperitoneal lymph nodes.(3) Follow-up:of 23 patients,19 were followed up for 3-74 months,with a median time of 22 months.Sixteen of 19 patients had various degrees of improvement in clinical symptoms,laboratory and imaging manifestations after standardized hormonotherapy,and 3 had no response to hormonotherapy.Conclusions CT and MRI examinations have important diagnostic value for IgG4-related pancreatitis.The pancreas mainly show diffuse swelling and halo sign surrounding lesions is a typical imaging characteristic.

Study on the Pharmacokinetics of Arotinoid Ethylester in Beagle Dogs / 中国药房

OBJECTIVE:To study the pharmacokinetic characteristics of arotinoid ethyl ester (RO) in Beagle dogs in vivo. METHODS:18 Beagle dogs were randomly divided into high-dose,medium-dose,low-dose groups (40,20,10 mg/kg),6 in each group. Rats were intragastrically administrated related doses of RO. Blood sample 1 mL was taken after 0.5,1.0,2.0,4.0, 6.0,8.0,12.0,24.0,36.0,48.0,60.0,72.0 h of administration,and plasma was separated. RP-HPLC was used to determine the concentrations of RO and its metabolite arotinoid acetic acid(RA)in plasma. Using DAS 2.0 software for fitting,pharmacokinetic parameters were calculated. RESULTS:Both RO and RA showed a distribution in one-compartment model in dogs in vivo. The cmax of RO high-dose,medium-dose,low-dose groups in dogs in vivo were (0.42 ± 0.87),(0.54 ± 0.09),(0.31 ± 0.05)μg/mL;t1/2z were(1.20±0.33),(1.14±0.45),(1.90±0.65)h;AUC0-72 h were(3.55±0.90),(0.87±0.50),(0.92±0.31)μg·h/mL;and CL/F were(11.99±4.01),(19.87±10.79),(12.29±7.57)L/(kg·h). The cmax of RA high-dose,medium-dose,low-dose groups in dogs in vivo were (32.51 ± 4.04),(19.87 ± 2.78),(16.55 ± 4.06)μg/mL;t1/2z were (7.27 ± 4.20),(7.17 ± 4.20),(10.18 ± 4.01) h;AUC0-72 h were (408.14 ± 96.61),(333.39 ± 61.28),(286.55 ± 30.96)μg·h/mL;and CL/F were (1.30 ± 0.53)、(0.76 ± 0.87)、(0.54±0.10)L/(kg·h). CONCLUSIONS:Orally taking RO is easy to absorb with rapid elimination. Its active metabolite RA has longer accumulation time in vivo.

Construction of fluorescent fusion expression vector for rat LC3B and its application of autophagy detection in Osteosarcoma cells / 中华骨科杂志

Objective To monitor the autophagy in osteosarcoma cells by constructing three rLC3B fusion expression vectors,respectively.Methods Rat LC3B gene sequence was amplified by PCR and cloned into pEGFP-C 1 and pmCherry-C1 to construct the fusion expression vector of pEGFP-rLC3B and pmCherry-rLC3B.Subsequently,the EGFP-rLC3B sequence was obtained by PCR with the pEGFP-rLC3B as a template,and cloned into pmCherry-C 1,so the pmCherry-EGFP-rLC3B fusion expression vector was constructed.Three plasmids were transfected into U-2OS cells,and the starvation or Rapamycin was adopted to induce autophagy or the chloroquine or Baf-A1 was used to inhibit autophagy,to verify the above plasmids' function in autophagy detection by laser scanning confocal microscopy.Western blot was used to detect the endogenous LC3B and exogenous EGFPrLC3B,pmCherry-rLC3B and mCherry-EGFP-rLC3B,and to verify the correct expression of exogenous rLC3B and their function of autophagy detection.Finally,cleaved free EGFP was detected by western blot to evaluate the level of autophagic degradation.Results Three fusion expression vectors were constructed successfully through sequencing and restriction enzyme digestion validation.The starvation or Rapamycin was adopted to induce autophagy or the chloroquine or Baf-A 1 was used to inhibit autophagy in transfected U-2OS cells.Clear autophagosomes and autolysosomes were observed by laser scanning confocal microscopy.Endogenous LC3B and exogenous EGFP-rLC3B,pmCherry-rLC3B and mCherry-EGFP-rLC3B were detected through western blot.Finally,western blot verified that the expression of cleaved free EGFP was significantly up-regulated with the increase of starvation time.12 h group increased 1.05 times than the control group and 24 h group increased 1.56 times,showing that the levels of autophagic degradation increased.Conclusion EGFP-rLC3B can be used to detect autophagosome and evaluate the level of autophagic degradation.mCherry-rLC3B can be used to detect autophagosome and autolysosome,but can't distinguish autophagosome from autolysosome.The pmCherry-EGFP-rLC3B has an advantage in the detection of autophagic flux which can distinguish autophagosome from autolysosome.

Correlation Analysis of Serum Thyroid Hormone NT-proBNP in Older Adults / 现代检验医学杂志

Objective To discuss the aged people N-terminal pro-B-type natriuretic peptide (NT-proBNP)changes in thyroid function disorder and its correlation.Methods With electrochemical luminescence analyzer,detected serum NT-proBNP lev-el 38 patients with hyperthyroid heart disease,68 patients with hyperthyroidism,31 patients with hypothyroidism,and 43 ca-ses of healthy controls.Compared each groupserum NT-proBNP level of older population with middle-aged people,and anal-ysied the correlation.Results The serum NT-proBNP level of Hyperthyroidism heart group,hyperthyroidism,hypothyroid-ism group and normal control group were 827.61±626.13,107.18±54.46,162.94±134.14,68.76±39.21 pg/ml,respec-tively.The serum level of HT-pro BNP.Hyperthyroidism group,hyperthyroidism,hypothyroidism group compared with nor-mal control group,there were statistically significan(t = 7.458,4.312,3.794,P = 0.000,0.000,0.001).Hyperthyroidism heart,hypothyroidism with hyperthyroidism group serum level of NT-proBNP comparison there was statistical significance(t=7.078,2.232;P = 0.000,0.032).Hyperthyroidism heartgroup,hypothyroidism group and normal control group older population was higher than the level of serum NT-proBNP middle-aged,difference was statistically significant (t=-3.216,-2.510,-2.653;P =0.007,0.016,0.014).Hyperthyroidism group of elderly serum NT-proBNP level higher than that of middle-aged people,but there was no statistically significant difference (t=-0.140,P =0.890).Multiple regression analy-sis in hyperthyroidism group serum levels of NT-proBNP and FT4 had positive correlation (r=0.224,P =0.033)and hypo-thyroidismgroup serum levels of NT-proBNP and T3 had negative correlation (r=-0.363,P =0.022).Conclusion Thy-roid dysfunction in elderly people for the level of serum NT-proBNP had significant influence.Auxiliary disgnosis and cura-tive effect observation of the serum level of NT-proBNP in people with different thyroid functional status has certain clinical value.

Assessment of effects of tutorial system on comprehensive clinical ability of undergraduates / 中华医学教育探索杂志

We implemented tutorial system by relying on young teachers in hospitals and taking undergraduates in Capital Medical University as the main body aiming at cultivating students' clinical and scientific research abilities.Practice has proved that tutor system method is of great value to cultivate students' comprehensive clinical ability,scientific research ability and innovation ability.Meanwhile,this method is effective in improving clinical teaching effect.

In vivo imaging of colon mucosa targeted gadolinium-loaded chitosan particles in mice with MRI / 中华放射学杂志

Objective To synthesize a novel vector of chitosan-particles loaded with gadolinium (Gd-CPs) and observe the adhesion and absorption of the particles in the colon wall of mice with MR imaging in-vivo.Methods Chitosan particles (CPs) with and without gadolinium loaded were synthesized with the emulsion-droplet coalescence method.Sixteen mice were randomly classified into two groups.The suspension with Gd-CPs or with CPs was infused into the rectum of the 8 mice of each group,respectively.MR scans were performed before,during and 40 minutes after infusion for each mouse.Samples of the colon correlated to the enhanced area were obtained for electron microscopy examination.Signal intensity (SI) of ROIs in the wall of rectum or colon,muscles of the pelvis near the rectum and background were measured and corresponding relative SIs were calculated.Relative SI values between the two groups and pre- and post- infusion were compared with pared t test.Results Dimension of the Gd-CPs was about 500 nm,and content rate was about 30%. Values of relative SI of the rectum for pre- and post- infusion in the Gd-CPs group were 0.84±0.06 and 0.98±0.09(t=4.327,P＜0.01),respectively,while those in CPs group were 0.83±0.04 and 0.84±0.05(t=0.658.P＞0.05). The medial value of signal increase rate for CPs group was 19.0%.Gd-CPs particles were found inside the mucosal cells under the electron microscopy.Conclusion MR imaging in-vivo can reveal the phenomenon of adhesion and absorption of mucosa targeted chitosan particle carriers. Clinical MR imaging based on small animal coil is a good method to monitor colon mucosa targeted particle vectors in-vivo.

DSA in digital replantations / 中华放射学杂志

ObjectiveTo assess revascularization and vessel anastomosis in digital replantations with DSA.MethodsTwelve cases of digital replantations underwent digital subtract angiography during 2 to 4 days after fingers reattachment. The vessel anastomosis,hemodynamics,stenosis and discontinuation were investigated.The unobstructed and smooth anastomosis was suggested as early stage survival of the reattached fingers,the spasm and stenosis of the reattached vessels were considered as mild vascular crisis,and the discontinuation of hemodynamics were indicated as severe vascular crisis.ResultsThe total 27 vessels were clearly displayed on DSA.Of these vessels,23 vessels were unobstructed and smooth,all digits were survived.Diagnosis coincidence of early stage survival was 100%(23/23). Two vessels were obstructed,which were testified having thrombus by operation research.The other 2 vessels were spasm,the digits were also survived ultimately by expectant treatment.All 4 abnormal vessel anatomosis were found by DSA.Conclusion DSA is important modality in assessing revascularization and blood circulation for digital replantations,guiding in dealing with the vascular crisis,and in predicting early stage survival of the reattached digits.

Advances on mechanisms of acetaminophen-induced hepatic injury / 中国临床药理学与治疗学

Acetaminophen(AAP)-induced hepatic injury is one of the common causes of drug-induced hepatic injury.Up to date,the mechanisms of AAP-induced hepatic injury are still incompletely understood.Recent advances suggest that reactive metabolite formation,glutathione depletion,alkylation of proteins,especially mitochondrial proteins and peroxynitrite formation are critical initiating events for the toxicity.This review will focus on more recent advances in mitochondrial dysfunction after AAP overdose.Additional,oxidative stress and inflammatory mediators are also important for the overall outcome.

The Study of Hepatic Perfusion Disorders with Multi-Slice Spiral CT / 实用放射学杂志

Objective To evaluate the various patterns of hepatic perfusion disorders with multi-slice spiral CT and to emphasize the significance of recognition for them . Methods In a period of 1 year, the all CT images of 1568 patients received multi-slice spiral CT examination of upper abdomen were analyzed retrospectively. The CT findings, etiologies and mechanisms of different pattens of hepatic perfusion disorders were investigated. Results 103 cases were demonstrated to have hepatic perfusion disorders. 69 cases were associated with tumors and the other 34 cases were non-tumor associated. The etiologies of various hepatic perfusion disorders were classified as (1)arterioportal fistulae(41.7%), (2) portal venous inflow obstruction(23.3%), (3) inflammartory hyperemic changes(17.5%), (4) steal phenomenon by hypervascular tumors(6.8%), (5) hepatic venous outflow obstruction(4.9%), (6) aberrant hepatic blood supply (3.9%) and (7) uncertain causes(1.9%). There was significant correlation between the CT images of perfusion disorders in shape and distribution and the causes of them. Conclusion Multi-slice spiral CT provides a new effective technique for demonstrating and understanding various hepatic perfusion disorders. Familiarity with the spiral CT appearances of these perfusion disorders will result in more accurate evaluation for various pathologic or physiologic states reflected by them.

CT and MRI manifestations of hepatic tuberculosis / 中华放射学杂志

Objective To assess CT, MR manifestations and diagnostic value in hepatic tuberculosis. Methods CT findings in 12 cases and MR findings in 4 cases with hepatic tuberculosis proved by surgery or biopsy were retrospectively analyzed. Results (1) CT findings: one case of serohepatic type of hepatic tuberculosis was multiple nodular lesions in the subcapsule of liver. Parenchymal type were in 10 cases, including multiple,miliary, micronodular and low density lesions with miliary calcifications in 2 cases, singular, low density mass with multiple flecked calcifications in 3 cases, multiple cystic lesions in 1 case, multiple micronodular and low density lesions fusing into multiloculated cystic mass or “cluster” sign in 3 cases, and singular, macronodular and low density lesion with multiple miliary calcifications in 1 case. One case of tuberculous cholangitis showed marked dilated intrahepatic duct with multiple flecked calcifications in the porta hepatis. (2) MR findings in 4 cases were hypointense on both T 1WI and T 2WI in one case, hypointense on T 1WI and hyperintense on T 2WI in 3 cases. Enhanced MR in 3 cases showed slightly peripheral enhancement or with multilocular enhancement. Conclusions Various types of hepatic tuberculosis had their different imaging findings. The typical CT and MR findings could suggest the diagnosis.

CT Diagnosis of Xanthogranulomatous Cholecystitis:A Report of 11 Cases / 实用放射学杂志

Objective To analyze CT features of xanthogranulomatous cholecystitis(XGC)so that to improve the accuracy of diagnosis.Methods The data of CT,clinic and operation in 11 cases with XGC proved pathologically were analysed.The following CT features were analyzed:the cholecystic wall thickness,intramural hypoattenuated nodules,inner wall,mucosal line,patterns of enhancement of thickened wall,involved liver tissue and the presence of stones.The changes around the gallbladder were also noticed.Results The gallbladder wall was thickened and intramural hypoattenuated nodules were seen in all patients.The inner wall of gallbladder was smooth in 9 patients,the mucosal line was observed in 6 cases,the size of gallbladder was enlarged in 3 while 4 gallbladders were smaller than normal.Stones were found in 4 gallbladders.There were hepatic involvement in 6,pericholecystic infiltration in 3 and dilatation of biliary tract in 6 cases.Conclusion CT features of thickened gallbladder wall with intramural hypoattenuated nodules(sandwich sign)and continuous mucosal line were characteristic of XGC.