Objective:To analyze the relationship between preoperative deep vein thrombosis (DVT) and parameters of conventional coagulation tests (CCTs) and thromboelastography (TEG) in patients with acute trauma, and to establish a prediction model to screen out high-risk patients with preoperative DVT.Methods:The clinical data of patients with acute traumatic fracture admitted to the Emergency Intensive Care Unit of Shanghai Sixth People’s Hospital from January 2021 to June 2021 were retrospectively collected. According to whether preoperative DVT occurred, the patients were divided into the DVT group and non-DVT group. The differences of CCTs and TEG parameters at the same time were compared between the two groups. Logistic regression analysis was applied to identify independent risk factors for DVT after trauma. The receiver-operating characteristic curve analysis was employed to analyze the clinical value of those parameters to predict preoperative DVT.Results:Among 123 patients with acute traumatic fracture, 101 patients were treated with anticoagulation before operation, and 51 patients were diagnosed with DVT. There were significant differences in activated partial thromboplastin time, fibrinogen (Fib), D-Dimer, fibrinogen degradation products (FDPs), reaction time, clotting time, α angle, maximum amplitude (MA) and coagulation index between the DVT and non-DVT groups. D-Dimer and MA were independent risk factors for preoperative DVT in patients with traumatic fracture. Logistic regression equation was used to establish a prediction model: the predicting index = 0.101×D-Dimer +0.241×MA + (-18.190). The α angle (AUC=0.833, P<0.001), MA (AUC=0.904, P<0.001), coagulation index (AUC=0.914, P<0.001) of TEG versus Fib (AUC=0.684, P=0.001), D-Dimer (AUC=0.685, P<0.001) and FDPs (AUC=0.656, P=0.003) of CCTs had a higher diagnostic efficacy in developing DVT of lower extremity in patients with traumatic fracture, and of all the coagulation index was the best. However, the predictor of D-Dimer combined with MA had a better predictive value (AUC=0.926, P<0.001), and the best cut-off value was 0.32 with a sensitivity and specificity of 90.2% and 79.8%, respectively. Conclusions:Compared with CCTs, TEG has more advantages in predicting preoperative DVT in patients with traumatic fracture, and the predictor of D-Dimer combined with MA can screen out patients with high risk of DVT, which can be recommended for clinical application.

Objective To investigate the relationships between serum osteocalcin (OC) levels and glycometabolism markers in nondiabetic post-traumatic male patients.Methods Populaitons were selected at the Department of Emergency Medicine of Shanghai Jiao Tong University Affiliated Sixth People's Hospital from October 2017 to February 2019.The age,injury severity score (ISS),and characteristic indicators were recorded.The inclusion criteria were age ≥ 18 years and blood collection time ＜ 24 h after the injury.The exclusion criteria were emergency surgery,acute brain trauma,and hemoglobin A1c (HbA1c) ≥ 6.0％.The patients were divided into two groups by fasting plasma glucose (FPG):stress hyperglycemia (SH) (FPG＞7.8 mmol/L) and nonstress hyperglycemia (NO-SH) (FPG ≤ 7.8 mmol/L) groups.The fasting venous blood samples were collected and examined.The characteristics and biochemical indicators in the two groups were compared statistically by LSD-t test,rank sum test and ANOVA,and the relationships between serum OC levels and glycometabolism markers were analyzed by partial correlation analysis.Results A total of 395 traumatic patients were enrolled and divided into the SH group (n=182) and NO-SH group (n=213).There were no differences in ISS,fasting insulin (FINS),and C-peptide (C-P) levels between groups.Age,HbAlc and FPG were higher (P=0.041,P=0.037,P＜0.01),while the OC level was lower (P=0.023),in the SH group than those in the NO-SH group.The serum OC level did not correlate with HbAlc,FPG,and FINS,but negatively correlated with C-P by partial correlation analysis (r=-0.262,P=0.008).The multivariate linear regression analysis showed that C-P was an independent factor affecting serum OC levels after trauma (β=-0.655,P=0.043).Conclusion A correlation existed between the serum OC level and glycometabolism markers in nondiabetic post-traumatic male patients.

This phase I clinical trial (NCT01935843) is to evaluate the safety, feasibility, and activity of chimeric antigen receptor-engineered T cell (CART) immunotherapy targeting human epidermal growth factor receptor 2 (HER2) in patients with advanced biliary tract cancers (BTCs) and pancreatic cancers (PCs). Eligible patients with HER2-positive (>50%) BTCs and PCs were enrolled in the trial. Well cultured CART-HER2 cells were infused following the conditioning treatment composed of nab-paclitaxel (100-200 mg/m) and cyclophosphamide (15-35 mg/kg). CAR transgene copy number in the peripheral blood was serially measured to monitor the expansion and persistence of CART-HER2 cells in vivo. Eleven enrolled patients received 1 to 2-cycle CART-HER2 cell infusion (median CAR T cell 2.1 × 10/kg). The conditioning treatment resulted in mild-to-moderate fatigue, nausea/vomiting, myalgia/arthralgia, and lymphopenia. Except one grade-3 acute febrile syndrome and one abnormal elevation of transaminase (>9 ULN), adverse events related to the infusion of CART-HER2 cells were mild-to-moderate. Post-infusion toxicities included one case of reversible severe upper gastrointestinal hemorrhage which occurred in a patient with gastric antrum invaded by metastasis 11 days after the CART-HER2 cell infusion, and 2 cases of grade 1-2 delayed fever, accompanied by the release of C-reactive protein and interleukin-6. All patients were evaluable for assessment of clinical response, among which 1 obtained a 4.5-months partial response and 5 achieved stable disease. The median progression free survival was 4.8 months (range, 1.5-8.3 months). Finally, data from this study demonstrated the safety and feasibility of CART-HER2 immunotherapy, and showed encouraging signals of clinical activity.
Aged ; Biliary Tract Neoplasms ; immunology ; therapy ; Female ; Humans ; Immunotherapy, Adoptive ; Male ; Middle Aged ; Pancreatic Neoplasms ; immunology ; therapy ; Receptor, ErbB-2 ; immunology ; Receptors, Chimeric Antigen ; immunology ; T-Lymphocytes ; immunology

Cancer stem cells (CSCs), a subpopulation of tumor cells, have self-renewal and multi-lineage differentiation abilities that play an important role in cancer initiation, maintenance, and metastasis. An accumulation of evidence indicates that CSCs can cause conventional therapy failure and cancer recurrence because of their treatment resistance and self-regeneration characteristics. Therefore, approaches that specifically and efficiently eliminate CSCs to achieve a durable clinical response are urgently needed. Currently, treatments with chimeric antigen receptor-modified T (CART) cells have shown successful clinical outcomes in patients with hematologic malignancies, and their safety and feasibility in solid tumors was confirmed. In this review, we will discuss in detail the possibility that CART cells inhibit CSCs by specifically targeting their cell surface markers, which will ultimately improve the clinical response for patients with various types of cancer. A number of viewpoints were summarized to promote the application of CSC-targeted CART cells in clinical cancer treatment. This review covers the key aspects of CSC-targeted CART cells against cancers in accordance with the premise of the model, from bench to bedside and back to bench.
Humans ; Molecular Targeted Therapy ; methods ; Neoplasms ; immunology ; pathology ; therapy ; Neoplastic Stem Cells ; pathology ; Receptors, Chimeric Antigen ; metabolism ; T-Lymphocytes ; immunology ; metabolism ; Translational Medical Research

OBJECTIVE:To establish the method for simultaneous determination of berberine hydrochloride and baicalin in Jianpi zhixiening granules. METHODS:HPLC switching walvelength method was adopted. The determination was performed on Hypersil BDS C18 column with mobile phase consisted of methanol-0.45％ phosphoric acid solution-triethylamine(50:49:1,V/V/V) at the flow rate of 1.0 mL/min. The detection wavelength was set at 265 nm(berberine hydrochloride)and 280 nm(baicalin). The column temperature was set at 30 ℃,and sample size was 10 μL. RESULTS:The linear range of berberine hydrochloride and baicalin were 60.3-312.8 ng(r=0.9997)and 81.5-368.9 ng(r=0.9999). The limits of quantitation were 0.6668,0.7740 ng,andthe limits of detection were 0.2226,0.2580 ng,respectively. RSDs of intermediate precision,stability and repeatability tests were all lower than 1.0％. The recoveries were 96.48％-99.30％(RSD=1.06％,n=6) and 95.20％-99.39％(RSD=1.66％,n=6), respectively. RSDs of durability test were all lower than 2.0％. CONCLUSIONS:The method is simple, precise, stable, reproducible,accurate and durable. It can be used for simultaneous determination of berberine hydrochloride and baicalin in Jianpi zhixiening granules.

Objective To investigate the relationships between serum osteocalcin levels of fasting plasma glucose(FPG),fasting serum insulin(FINS),insulin resistance,β-cell function as well as lipid metabolism in male traumatic patients.Methods A prospective cohort study was carried out in the Emergency Room of Shanghai Sixth People's Hospital from April to October of 2015.The male adult traumatic patients without traumatic brain injury,shock and the medical history such as the fractures,diabetes were enrolled as trauma group,and then patients' age,body mass index(BMI),injury severity score(ISS), admission time after trauma and fluid resuscitation volume before testing(FRVT) were recorded.A total of 80 heathly male adult subjects were enrolled from the physical examination center as control group with matched age and BMI.Comparison of biochemical characteristics were carried out between two groups, and relationships between serum osteocalcin levels and glycolipid metabolism in trauma group were analyzed.Insulin resistance and β-cell function were calculated by Homeostasis model assessment-insulin resistance(HOMA-IR)and Homeostasis model assessment of β-cell function(HOMA-β).Results A total of 102 male adult traumatic patients mostly subjected to traffic accident (56.9%) with FRVT (208.78±98.68)mL and ISS(9.30±3.67)were enrolled in trauma group.Serum OC levels,HOMA-β,total cholesterol(TC),high density lipoprotein(HDL-c)and low density lipoprotein(LDL-c) were lower,but FPG,FINS,C-peptide(C-P),HOMA-IR were higher compared with control group(P<0.05).Serum OC levels wer were negatively correlated with FPG and TC(P<0.05),and positively correlated with FINS,HOMA-IR,and HOMA-β(P<0.05),but there were no correlation of OC with FRVT and ISS.By multiple linear regression analysis after adjusting for age,BMI,FRVT and ISS,serum osteocalcin levels were significantly related to TC in traumatic patients (β=-0.812,P=0.024).Conclusion The glycolipid metabolism may be impacted by the serum level of osteocalcin after trauma.

Objective To describe the association between age and the sex-based outcome difference and analyze the potential mechanism responsible for sex-based outcome difference in severe trauma patients.Methods A retrospective analysis derived from the Emergency Intensive Care Unit of the acute trauma center of the Shanghai Municipal Sixth People's Hospital during the 2010-2013 period was performed to identify sex-based outcome differences after severe blunt trauma.The study cohort of patients was then stratified by age:(1) 18 years ≤ age ＜45 years,(2) 45 years ≤ age ≤ 55 years,and (3) age ＞55 years.Crude and adjusted odds ratios (ORs) were calculated to evaluate the association between gender and the hospitalized mortality,both overall and subgroups according to age categories.Results A total of 987 severe trauma patients met our inclusion criteria were enrolled in this study.Crude mortality was higher in male severe trauma patients (male 9.1％ vs.female 5.0％,P ＜ 0.05).Multiple logistic regression revealed that females had a 79％ decrease in hospitalized mortality compared with males (OR =0.21,95％ CI:0.07-0.64,P =0.006).This difference was most distinct in patients with age ＜ 45 years,(OR =0.15,95％ CI:0.04-0.67,P =0.012).There is no significant difference between genders in mortality of trauma patients with 45 years ≤ age ≤ 55 years and age ＞ 55 years.Conclusions The present study revealed a statistical significant association between gender and mortality among severe blunt trauma patients,particularly in patients with age ＜ 45 years.These results may highlight the importance of sex hormones in outcomes of severe trauma.

Objective To investigate the incidence and risk factors of deep vein thrombosis (DVT) in a cohort of Chinese patients with traumatic spinal cord injury (TSCI),and in addition,to evaluate the effect of injury types and concomitant injuries of other parts of body.Method Records of 143 casualties admitted to our institute for TSCI were analyzed retrospectively.Both lower extremities of all casualties were examined routinely with color Doppler ultrasonography (CDUS) before major surgical treatment.None of these casualties received any thromboprophylaxis before CDUS.Logistic regression was used to analyze risk factors of DVT.Results Of the 143 patients,32.2％ (n =46) suffered from DVT (proximal n =15,distal n =31).All casualties were diagnosed within one week after injury (mean 3.35 ± 1.65 days).Risk factors associated with DVT induced complete motor paralysis (odds ratio [OR] 5.05,95％ CI 1.70-14.90),concomitant fracture of lower extremities (OR 4.30,95％ CI 1.34-17.64),and lumbar vertebra injury (OR 4.29.95％ CI 1.50-10.83).Conclusions Clinically detectable DVT in TSCI are not uncommon in the Chinese population.Casualties with multiple risk factors may be benefited from early administration of thromboprophylaxis.

Objective To explore the influence of hematopoietic growth factors on the TBI patients in the conditioning regimen for stem cell transplantation,and to evaluate the effect of cytokines on treatment of acute radiation disease.Methods The usage of hematopoietic growth factors,implantations and the side-effects of the patients and donors of TBI in the conditioning regimen for stem cell transplantation were retrospectively analysed from 1990 to 2012,and the effect and side-effects of cytokines on the hematopoietic function recovery and stem cell mobilization were observed.Results All patients recovered from their hematopoietic function except one died due to the side-effecs.The median time of white blood cell recover was 10 d in auto-SCT and 12 d in allo-SCT in the G-CSF group.The median day of platelet recovery was 11.67 ± 1.53 in rhIL-11 arm and 13.70 ±6.27 in no rhIL-11 arm in the auto-SCT group.The incidence rates of dental ulcer and diarrhea in the TBI patients were 48％ and 44％,respectively.The occurrence of side-effect was rare in the period of cytokines treatment,but was over 50％ during stem cell mobilization.Conclusions Cytokines play very important roles in the hematopoietic function recovery and stem cell mobilization in the TBI patients.

Objective To explore the value of fluorescence in situ hybridization (FISH) and multiplex RT-PCR in the detection of mixed lineage leukemia (MLL) gene rearrangement in acute leukemia (AL) patients. Methods Dual-color MLL probe, multiplex RT-PCR and R or G banding techniques were used to detect the MLL gene rearrangement in 189 cases of AL.Results MLL gene rearrangements were detected in 9 cases (5.03 ％) by FISH,and 16 cases (8.47 ％) by multiplex RT-PCR,including MLL/AF9,MLL/AF10,MLL/AF6, MLL/AF7, MLL/ELL, MLL/PTD. R or G banding techniques could find 11q23 in 5 out of 189 patients (2.65 ％). There was no statistic difference in the incidence of 6 common MLL gene rearrangements between ALL (73 cases) and AML patients (116 cases) (P ＞ 0.05).Conclusion Multiplex RT-PCR is a powerful technique in the detection of MLL gene rearrangement for tentatively diagnosed AL.It could not only confirm translocation detected by conventional cytogenetic method, but also detect MLL partial tandem duplication which could not been detected by cytogenetic examination or FISH. It plays an important role in guiding therapy and predicting prognosis for AL.