Objective:To investigate the effect of tranexamic acid combined with rivaroxaban on perioperative blood loss in patients undergoing posterior lumbar interbody fusion and its potential benefits.Methods:This is a retrospective study. The clinical data of 90 patients who underwent posterior lumbar interbody fusion for lumbar spinal stenosis or spondylolisthesis at Affiliated Hospital of Jining Medical University between September 2019 and September 2021 were analyzed. These patients were divided into two groups: group A ( n = 46) and group B ( n = 44) based on their medication. Patients in group A received an intravenous infusion of 0.5 g tranexamic acid and 100 mL of 5% glucose injection 15 minutes before the surgical incision. The incision wound was soaked externally with 1 g of tranexamic acid solution for 5 minutes before the surgical incision was closed, and it was suctioned before its closure. Patients in group B received the same procedure, except that oral rivaroxaban was administered 10 mg, once daily, after surgery till 35 days after surgery. The operative time, intraoperative blood loss, and the amount of drainage were recorded. Total blood loss, occult blood loss, incidence of lower extremity deep vein thrombosis, incidence of pulmonary embolism and epidural hematoma, and C-reactive protein levels were determined. Results:There were no significant differences in operative time, intraoperative blood loss, the amount of drainage, total blood loss, and occult blood loss between the two groups (all P > 0.05). Postoperative C-reactive protein levels in group A [29.94 (15.75, 50.25) mg/L] were significantly higher than those in group B [7.89 (4.94, 11.10) mg/L, Z = -5.68; P < 0.05]. Lower extremity deep vein thrombosis, pulmonary embolism, or epidural hematoma did not occur in either group. In group A, one patient was infused with 200 mL of leucodepleted red blood cell suspension, while the other patient received 150 mL of autologous blood transfusion. In group B, two patients were infused with 525 mL and 200 mL of leucodepleted red blood cell suspensions, respectively, while the rest did not require blood transfusion. Conclusion:The combined use of tranexamic acid and rivaroxaban after posterior lumbar interbody fusion does not increase perioperative bleeding, and it has additional anti-inflammatory effects without increasing the incidence of lower extremity deep vein thrombosis and pulmonary embolism, as well as the formation of epidural hematomas and the need for blood transfusion.

Objective:To investigate the risk factors for preoperative hypoxemia in geriatric patients with hip fracture.Methods:A case-control study was used to analyze the clinical data of 99 geriatric patients with hip fracture admitted to Zhongda Hospital affiliated to Southeast University between November 2020 and August 2021. There were 29 males and 70 females, aged 67-96 years [(82.6±6.2)years]. The patients were divided into hypoxemia group ( n=51) and non-hypoxemia group ( n=48) using partial arterial partial pressure of oxygen (PaO 2)<80 mmHg while breathing room air at emergency as the reference standard. The two groups were compared in terms of sex, age, fracture types, body mass index (BMI), American Society of Anesthesiologists (ASA) classification, pulmonary diseases diagnosed by preoperative chest CT [atelectasis, pleural effusion, chronic obstructive pulmonary disease (COPD)], time from injury to visit, New York Heart Association (NYHA) classification, Barthel index, KATZ index, modified Medicine Research Council (mMRC) dyspnea scale, numeric rating scale (NRS), smoking, drinking, comorbidities (hypertension, diabetes mellitus, Parkinson′s disease, Alzheimer′s disease, cerebral infarction, coronary atherosclerotic heart disease), body temperature, blood routine test at first examination (erythrocyte count, leukocyte count, C-reactive protein, hemoglobin), biochemistry (serum albumin, blood glucose, blood creatinine, blood urea nitrogen), electrolyte (serum potassium, serum sodium), and other related examinations [D-dimer, brain natriuretic peptide (BNP), lactic acid]. Univariate analysis was performed to the correlation of those indicators with preoperative hypoxemia. Multivariate Logistic regression analysis was used to identify the independent risk factors for preoperative hypoxemia in geriatric patients with hip fracture. Results:Differences in sex, age, fracture types, BMI, pulmonary diseases diagnosed by preoperative chest CT, time from injury to visit, Barthel index, KATZ index, NRS, smoking, drinking, comorbidities, body temperature, first laboratory results of erythrocyte count, biochemistry, electrolyte and other related examinations were not statistically significant between the two groups (all P>0.05). The two groups showed statistical differences in ASA classification, NYHA classification, mMRC dyspnea scale, leukocyte count at first examination, C-reaction protein and hemoglobin (all P<0.05). Univariate analysis indicated that ASA classification, NYHA classification, mMRC dyspnea scale, leukocyte count at first examination and C-reaction protein were correlated with the occurrence of preoperative hypoxemia in geriatric patients with hip fracture (all P<0.05). Multivariate Logistic regressions analysis indicated that higher mMRC dyspnea scale ( OR=2.30, 95% CI 1.10-4.81, P<0.05), higher leukocyte count at first examination ( OR=1.24, 95% CI 1.05-1.45, P<0.05), higher level of C-reaction protein ( OR=1.02, 95% CI 1.01-1.03, P<0.05) and higher level of hemoglobin ( OR=1.04, 95% CI 1.01-1.07, P<0.05) were significantly correlated with the occurrence of preoperative hypoxemia in geriatric patients with hip fracture. Conclusion:Higher mMRC dyspnea scale, higher leukocyte count, higher level of C-reaction protein and higher level of hemoglobin are independent risk factors for preoperative hypoxemia in geriatric patients with hip fracture.

Objective:To analyze the risk factors for postoperative one-year mortality in elderly patients with femoral intertrochanteric fracture following multidisciplinary treatment (MDT) by intramedullary nailing.Methods:The clinical data were retrospectively analyzed of the 158 elderly patients with femoral intertrochanteric fracture who had undergone MDT by proximal femoral intramedullary nailing between January 2018 and August 2020 at Department of Orthopedics, Trauma Center, Zhongda Hospital Affiliated to Southeast University. There were 41 males and 117 females with an average age of 82.5 years (from 65 to 95 years). By the modified Evans classification, there were 15 cases of type Ⅰ, 16 cases of type Ⅱ, 35 cases of type Ⅲ, 81 cases of type Ⅳ, and 11 cases of type Ⅴ. The one-year mortality was documented in the patients after surgery. To screen for risk factors, univariate analysis was conducted of gender, age, body mass index (BMI), modified Evans classification of fractures, time from injury to operation, American Society of Anesthesiologists (ASA) classification, Charlson comorbidity index (CCI) and comorbidities, as well as preoperative hemoglobin (Hb), serum albumin (ALB) and total lymphocyte count (TLC). The factors with P<0.05 were included in the multivariate logistic regression model analysis to determine the risk factors. Results:A total of 13 patients died within one year after surgery, yielding a mortality of 8.2% (13/158). Univariate analysis showed significant differences in age, body mass index, modified Evans classification of fractures, CCI and Hb between the surviving and dead patients ( P<0.05). Multivariate logistic regression analysis showed that age >85 years ( OR=0.122, 95% CI: 0.018 to 0.834, P=0.032), BMI>23.9 kg/m 2 ( OR=0.083, 95% CI: 0.013 to 0.510, P=0.007), CCI≥3 points ( OR=0.051, 95% CI: 0.090 to 0.275, P=0.001) and preoperative Hb<90 g/L ( OR=4.733, 95% CI: 1.036 to 21.624, P=0.045) were the independent risk factors for postoperative one-year mortality in the elderly patients with intertrochanteric fracture following MDT by proximal femoral intramedullary nailing. Conclusions:After MDT by proximal femoral intramedullary nailing of femoral intertrochanteric fractures, the geriatric patients with an age >85 years, BMI>23.9 kg/m 2, CCI≥3 points and Hb<90 g/L are likely to die. Therefore, special care should be taken for them.

Chimeric antigen receptor (CAR) T cells have been indicated effective in treating B cell acute lymphoblastic leukemia and non-Hodgkin lymphoma and have shown encouraging results in preclinical and clinical studies. However, CAR T cells have achieved minimal success against solid malignancies because of the additional obstacles of their insufficient migration into tumors and poor amplification and persistence, in addition to antigen-negative relapse and an immunosuppressive microenvironment. Various preclinical studies are exploring strategies to overcome the above challenges. Mobilization of endogenous immune cells is also necessary for CAR T cells to obtain their optimal therapeutic effect given the importance of the innate immune responses in the elimination of malignant tumors. In this review, we focus on the recent advances in the engineering of CAR T cell therapies to restore the immune response in solid malignancies, especially with CAR T cells acting as cellular carriers to deliver immunomodulators to tumors to mobilize the endogenous immune response. We also explored the sensitizing effects of conventional treatment approaches, such as chemotherapy and radiotherapy, on CAR T cell therapy. Finally, we discuss the combination of CAR T cells with biomaterials or oncolytic viruses to enhance the anti-tumor outcomes of CAR T cell therapies in solid tumors.
Humans ; Immunotherapy, Adoptive ; Neoplasms/therapy* ; T-Lymphocytes ; Tumor Microenvironment

Cholangiocellular carcinoma (CCA) is a malignant tumor derived from the biliary epithelium, with a lack of effective therapeutic drugs and poor prognosis. Studies have shown that the development and progression of CCA are closely associated with angiogenesis, and a variety of angiogenic factors, including vascular endothelial growth factor (VEGF) and its receptor VEGFR, can regulate angiogenesis in CCA, participate in the development and progression of CCA, and affect its prognosis. Therefore, anti-angiogenic drugs targeting VEGF/VEGFR, such as monoclonal antibodies and small-molecule inhibitors, have gradually become research hotspots for the treatment of CCA. This article reviews the role of the VEGF/VEGFR pathways in the clinical features and prognosis of CCA, the advances in anti-angiogenic therapy for CCA, and related studies on drug resistance.

Objective To analyze the urine trace albumin(mALb)/creatinine(Cr) ratio and blood uric acid(UA),and other various metabolic index level in patients with diabetic nephropathy(DN),combined with clinical data such as patients' age,body mass index(BMI),course of diseases,to explore the related mechanism of occurrence and development of DN.Methods 76 DN patients were selected.The microalbuminuria group(urinary mALb/Cr<300μg/mg) had 46 cases,the clinical albuminuria group(urinary mALb/Cr≥300μg/mg) included 30 cases,another 49 diabetic patients without kidney damage were seleted as control group.The urinary mALb/Cr,blood UA,fasting blood glucose(FBG),triacylglycerol(TG),total cholesterol(TC),high-density lipoprotein(HDL),low density lipoprotein(LDL),glycosylated hemoglobin(HbA1c) levels were determined.The BMI and the length of the course of the disease calculate.Results The patients' age,course of the disease,urinary mALb/Cr,blood UA,FBG,TC,TG,LDL,HbA1c and BMI level in the clinical albuminuria group and microalbuminuria group were significantly higher than those in the control group,the differences were statistically significant (F=6.18,12.48,141.43,12.48,8.49,4.98,6.18,3.89,3.17,3.89,all P<0.05).The high uric acid hematic disease rates of the clinical albuminuria group and microalbuminuria group were 26.09% and 26.09%,which were significantly higher than 10.20% of the control group,the differences were statistically significant(x2=4.074,24.833,all P<0.05).Urinary mALb/Cr was positively correlated with age,duration,BMI,UA,TG,TC,LDL,FBG,HbA1c(r=0.120,0.299,0.148,0.340,0.157,0.149,0.103,0.487,0.103).Multiple linear stepwise regression analysis suggested that duration,blood UA,FBG were independent risk factors of urinary mALb/Cr;TG,BMI,urinary mALb/Cr were independent risk factors for blood UA.Conclusion Urinary mALb/Cr and blood UA are the independent risk factors,high uric acid hematic disease may participate in the development process of DN,and diabetes duration,UA,BMI,TG,TC,LDL,FBG,HbA1C associated with increased urinary mALb/Cr excretory DN patients,the effective monitoring can improve the symptoms of DN and quality of life.

AIM: To observe the effects of berberine (Ber) on enterocyte apoptosis in septic mice and its pos-sible mechanism.METHODS: Male C57BL/6 mice (8 ~10 weeks old) were randomly divided into sham group, cecal ligation and puncture (CLP) group, CLP +Ber group and sham +Ber group.The mice in CLP group underwent CLP ope-ration, and the mice in sham groups suffered a similar operation except the ligation and puncture.After the sham or CLP operation, the mice were administered intragastrically with distilled water or berberine (50 mg/kg) within 2 h.After 20 h, the mice were killed with excess pentobarbital sodium and the ileum tissues were removed.The histological changes of the intestine were observed and the enterocyte apoptosis was examined by determining the protein level of cleaved caspase-3. Furthermore, mitochondrial Bax, cytoplasm cytochrome C (Cyt C) and the total proteins of Bcl-2, Fas, FasL and Fas-as-sociated protein with death domain (FADD) were examined by Western blot.The mRNA expression of tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH) was measured by real-time PCR.RESULTS: The extensive ileum injuries, including remarkably increased leukocytes and necrosis of intestinal villus were observed 20 h after CLP.In CLP group, the protein levels of cleaved caspase-3, cytoplasm Cyt C, as well as Fas, FasL were significantly increased, but the Bcl-2 level was decreased.Bax translocation into mitochondria was promoted.However, FADD was not changed significantly.The mRNA expression of TH and DBH was also increased sharply in CLP group.On the contrary, treatment with berberine made a considerable alleviating alteration in the ileum of the septic mice.CONCLUSION: Treatment with berberine pro-vides protective effects on intestinal injury in septic mice by reducing enterocyte apoptosis, and its possible mechanism may be involved in the inhibition of the endogenous and exogenous apoptosis pathways.

BACKGROUND:Elderly patients with hip surgery in the department of orthopedics are often associated with a variety of diseases, and easily suffer from complications after implantation.
OBJECTIVE:To analyze the characteristics and the factors of complications and mortality of the elderly patients with hip disease by different orthopedic implants.
METHODS:249 patients accepted total hip arthroplasty, femoral head replacement, proximal femoral nail, Gamma nail, and holow screw fixation. We analyzed patients’ age, sex, hip disease type, anesthesia risk assessment, psychological and psychiatric factors, admission hemoglobin, preoperative albumin, Charlson comorbidity index, ways of anesthesia, orthopedic implants, operation time, intraoperative bleeding, length of stay, postoperative complications, mortality and survival.
RESULTS AND CONCLUSION:Hip disease in the elderly was repaired with five kinds of implants. (1) There were significant differences in age, anesthesia risk assessment, hemoglobin on admission and preoperative albumin, length of stay, duration and intraoperative bleeding. No significant difference in complications and death was found. (2) The most significant indicators affecting complications were length of stay and albumin on admission and preoperative Charlson comorbidity index. The most significant
indicators affecting death were age and hemoglobin on admission and preoperative Charlson comorbidity index. (3) Significance of comprehensive assessment of patients before placement: during hip operation, implants were not the factors that affected the complications and mortality after placement, patients with artificial joint replacement could get out of bed early, and complications and mortality could be reduced. Elderly patients with anemia, hypoalbuminemia and Charlson comorbidity index≥3 should be given a high degree of attention. We should assess Charlson comorbidity index as early as possible, positively treat complications, correct anemia and hypoproteinemia, prevent the occurrence of complications, shorten the length of hospital stay, and reduce the mortality after placement.

AIM:To observe the effect of B-HT933, a selective α2-adrenoceptor agonist, on lipopolysaccha-ride ( LPS )-induced TNF-αproduction in neonatal rat cardiomyocytes and to explore the underlying mechanisms . METHODS:The neonatal rat cardiomyocytes were cultured .The localization of α2A-adrenoceptor in the cardiomyocytes was examined by immunofluorescence staining .The cardiomyocytes were exposed to LPS or/and B-HT933 for different time.The level of TNF-αin the supernatants and the mRNA expression of TNF-αwere detected by ELISA and real-time PCR, respectively.In addition, LPS-associated signal molecules in the cardiomyocytes were also examined by Western blotting.RESULTS: Immunofluorescence staining showed that α2A-adrenoceptors were localized in the cardiomyocytes . LPS stimulated TNF-αproduction in the cardiomyocytes in a dose and time-dependent manner .B-HT933 pretreatment sig-nificantly inhibited the expression of TNF-αat mRNA and protein levels in LPS-treated cardiomyocytes .Furthermore, LPS exposure induced IκBαand p38 phosphorylation in cardiomyocytes and only IκBαphosphorylation was prevented by B-HT933 treatment.CONCLUSION:α2A-adrenoceptors are present in neonatal rat cardiomyocytes and its agonist B -HT933 inhibits LPS-induced TNF-αproduction in cardiomyocytes via suppressing IκBαphosphorylation .

Objective To explore the relationship between insluin resistance(IR)and plasma fibrinogen, blood lipids levels in patients with gestational diabetes mellitus (GMD).Methods Totally 127cases pregnant women in their 24 -28 gestational weeks were divided into GDM group(n =37),gestational impaired glucose tolerance test (GIGT)group(n =30)and normal glucose tolerance(NGT)group(n =60)based on the American Diabetes Associ-ation(ADA)2009 GDMdiagnostic standards.All selected cases's height,weight,fasting blood glucose (FBG),fasting insulin (FIN),blood lipids and fibrinogen(FIB)level were tested,and their body mass index(BMI)and IR index (HOMA -IR)were calculated.Results During the mid -trimester,the levels of BMI,FIB,HOMA -IR,FBG,FIN, triglyceride (TG),cholesterol(TC),low density lipoprotein -cholesterol (LDL -C)in the GDM group were signifi-cantly higher than the GIGT and NGT groups.However,high density lipoprotein -cholesterol (HDL -C)was signifi-cantly lower (F =69.29,98.15,70.32、141.43、61.92,106.06,157.06,90.59,25.25,all P <0.01).FIB was sig-nificantly positively correlated with BMI,FBG,FIN,HOMA -IR,TC,TG,LDL - C (r =0.441,0.682,0.506, 0.599,0.493,0.591,0.633,all P <0.01 ),and negatively correlated with HDL -C(r =-0.419,P <0.01 ).Multiple stepwise regression analysis indicated that BMI,LDL -C,FBG and TG were independent risk factors affect-ing FIB(t =7.683,2.678,3.184,3.844,all P <0.01);FIB,BMI,FBG,FIN and TC were independent risk factors influencing HOMA -IR(t =68.784,3.201,29.702,58.100,2.904,all P <0.01).Conclusion Pregnant women have IR and blood lipid disorders during the mid -trimester,the overexpression of FIB is closely related to it.