Background and purpose: Tumor vasculature is increasingly recognized as a target for cancer therapy. In recent years, a fusion protein consisting of the extra cellular domain of tissue factor (truncated tissue factor, tTF) was fused to the antibody selectively binding to tumor vasculature. Antibody-truncated tissue factor(Ab-tTF) fusion protein specifically induced thrombotic occlusion of tumor vessels resulting in tumor growth retardation or regression in some types of solid tumors. However, there were still some disadvantages in the above approach. We constructed and expressed that the (RGD)_3-tTF fusion protein with peptides arginine-glycine-aspartic acid (GRGDSP, abbr. RGD)as the carrier of tTF to explore whether it bad the capability of targeting to tumor vasculature in the colonic carcinoma model. Methods: The (RGD)_3-tTF fusion gene consisting of the tTF was fused to three series-wound peptides RGD. The (RGD)_3-tTF construct was expressed in Escherichia coil BL21(DE_3). The fusion protein was purified through Nickel affinity chromatography column. The activity of inducing blood coagulation was detected by clotting assay and coagulation factor X (FX) activation assay. The specific binding to integrins α_vβ_3 was analyzed by indirect enzyme linked immunosorbent assay (ELISA). All these were compared with the fusion protein RGD-tTE Colonic nude mice models were randomly divided into 3 groups (1 nude mice per group).Tumors were stained by the (RGD)_3-tTE RGD-tTF fusion protein and tTF which were labeled with Fluorescein Isothiocyanate(FITC). The location of the (RGD)_3-tTF fusion protein in the colonic carcinoma bearing nude mice tissue was analyzed by immunofluorescence assay. Results: The (RGD)_3-tTF fusion protein retained tissue factor thrombogenic activities. With increasing concentration, the clotting time was shortened correspondingly. Under the conditions of Ca~(2+), the clotting time was 9.96±0.56 min when the concentration was 6 μmol/L(P<0.01). The (RGD)_3-tTF fusion protein could activise F X above 6 μmol/L concentration, which was similar to RGD-tTF fusion (F=0.147, P>0.05). The ability of the (RGD)_3-tTF fusion protein binding specifically to integrins α_vβ_3 was stronger than that of the RGD-tTF fusion protein in the same concentration (F=164.81, P<0.01), which was apparently indicated by the A_(405nm) 1.25 and 0.95 when the concentration was 0.24 μmol/L. Immunofluorescence assay showed that the (RGD)_3-tTF fusion protein was assembling in the tumor vasculature of the colonic carcinoma bearing nude mice. Conclusion: The (RGD)_3-tTF fusion protein which retained tissue factor thrombogenic activities could bind specifically and efficiently to tumor vasculature in the colonic carcinoma bearing mice through binding to the tumor marker integrins α_vβ_3. It might be a promising foundation for further studies on the colon cancer molecular targeted therapy with tTF as an effective factor.

Objective To analyze whether β1,4-galactosyltransferase-Ⅰ(β1,4-GaiT-Ⅰ)expression correlates with the expression of tumor necrosis factor(TNF)-α in osteoarthritis(OA).Methods Synovial tissue samples from eight OA patients and eight healthy people were obtained as the experimental group and controls respectively.The mRNA levels of β1,4-GalT-Ⅰ and TNF-α were measured by reverse transcriptionpolymerase chain reaction(RT-PCR)and real-time PCR.Enzyme linked immunosorbent assay(ELISA)was used to test the expression of TNF-α in the protein level.Cellular colocalization of β1,4-GalT-Ⅰ and TNF-α was analyzed by double immunofluorescence.ANOVA and t-test was used for statistical analysis.Results ①Compared with the control group[β1,4-GalT-Ⅰ(0.48±0.09),TNF-α(0.46±0.07)],the expression of β1,4-GalT-Ⅰ(0.94±0.16)and TNF-α(1.19±0.19)were significantly increased in OA synovial tissue(t=3.47,t=4.06,P＜0.01)and there was colocalization between β1,4-GalT-Ⅰ and TNF-α;② Lipopolysaccharide (LPS)could induce fibroblast-like synoviocytes(FLSs)β1,4-GalT-Ⅰ[11.2±0.9 vs 2.9±0.5(dose effect),22.3±2.3 vs 4.4±0.9(time effect),F=83.03,F=157.58,P＜0.05]overexpression;③ LPS could induce FLSs TNF-α[(1256±96)vs(101±7)pg/ml,F=431.96,P＜0.01]overexpression;④ Not only endogenous TNF-α,but exogenous TNF-α could induce FLSs β1,4-GalT-Ⅰ[23.2±1.9 vs 8.4±1.3(dose effect),23.9±1.8 vs 11.5±1.3(time effect),F=124,F=93.6,P＜0.05]overexpression.Conclusion It is possible that FLSs mayuse TNF-αto control β1,4-GalT-Ⅰ functions during inflammation in OA.

Objective To evaluate the effect of nutritional risk screening and interventions on postoperative nutritional status in patients with oral cancer. Methods A total of 83 oral cancer patients with mild or moderate nutritional risk rated by patient-generated subjective global assessment(PG-SGA) from January 2015 to June 2017 were randomized into an experimental group(43 cases) and a control group (40 cases). The patients in the experimental group received 2-week nutritional intervention before the operation,while the patients in the control group received routine preoperative treatment and diet guidance. The biochemical measurements of postoperative nutritional indicators, peripheral blood immunoglobulin indicators, postoperative complications and hospital stays were compared between the two groups. Results The levels of prealbumin, retinol- binding protein, total lymphocyte count and transferrin were (218.5±34.6) mg/L, (23.5±4.3)μg/L, (1.82±0.45)×109/L, (2.07±0.63 )μg/L on the day of admission in the experimental group, and at 1 day before the operation were (237.3±36.5) mg/L, (27.7±4.8)μg/L, (2.02±0.39)×109/L, (2.43±0.54)μg/L, there was no significant difference(P<0.05). IgM, IgG, IgA at 1 day before the operation were significantly higher than those on the day of admission in the experimental group(P<0.05), and the levels of prealbumin, retinol-binding protein, total lymphocyte count,transferrin, IgM, IgG, IgA and body mass index at 8 days after the operation in the experimental group were significantly higher than those in the control group(t=1.574-3.418, P<0.05). The total rate of postoperative complications was 11.6％(5/43) in the experimental group, 30.0％(12/40) in the control group, and there was significant difference between the two groups (χ2=6.840, P<0.01). The incidence of infection-associated complications such as pneumonia and incision infection was 7.0％(3/43) in the experimental group, 20.0％(8/40) in the control group, and there was significant difference between the two groups (χ2=5.096, P<0.05). Conclusions Preoperative nutritional support can effectively improve the perioperative nutritional status,decrease postoperative complications and operative risk in esophageal cancer patients with mild or moderate nutritional risk.

Trauma can trigger systemic pathological states, including coagulation disorders, tissue damage and metabolic disturbances, in which immune responses are extensively involved and play an important role. As an important component of innate immunity, the complement system is known to be implicated in the bactericidal process of lysis in vivo and can also induce immune inflammation in the body, but its role in trauma is not clear. The authors summarize the interaction between complement system activation and immune system, and the clinical translation of complement system intervention after trauma from the aspects of posttraumatic innate immunity, acquired immunity as well as there internal bridging, in order to provide more ideas for clinical trauma treatment.

Objective:To evaluate the value of synthetic MRI combined with three dimensional-arterial spin labeling (3D-ASL) imaging in the grading of diffuse glioma and its correlation with tumor cell proliferative activity (Ki-67).Methods:This study was prospective. The clinical and imaging manifestations of 66 patients with diffuse glioma who underwent synthetic MRI combined with 3D-ASL imaging from August 2020 to June 2021 in General Hospital of Ningxia Medical University were analyzed. Among 66 patients, there were 36 males and 30 females, aged 4-76 years, and divided into low grade glioma (LGG) group ( n=25) (WHO Ⅱ) and high grade glioma (HGG) group ( n=41) (WHO Ⅲ and vⅣ). T 1, T 2, proton density (PD) and cerebral blood flow (CBF) of tumor parenchyma were measured by GE ADW4.7 postprocessing software. The Ki-67 label index (Ki-67 LI) in postoperative pathological sections was detected by immunohistochemistry. Independent sample t test or Mann-Whitney U test was used to compare the differences of quantitative parameters between HGG group and LGG group. Receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy of T 1, PD, CBF and the combination. Spearman test was used to analyze the correlation between the parameters and Ki-67 label index (LI). Results:T 1[(1 573±173)ms], PD[(86.2±2.4)pu] and CBF[(129±48)ml·100 g -1·min -1] in HGG group were significantly higher than those in LGG group [(1 376±134)ms, (83.0±2.5)pu and (77±49)ml·100g -1·min -1 respectively], and difference had statistical significance ( t=-4.86, -5.08, -4.24, P<0.01). ROC confirmed that the area under curve (AUC) of T 1, PD and CBF in differentiating HGG from LGG were 0.847, 0.843 and 0.777, respectively. In multi-parameter analysis, the combination of three parameters had the best diagnostic efficiency (AUC=0.973) and the sensitivity and specificity were 87.8% and 100%, respectively. In LGG and HGG groups, there was no correlation between T 1, T 2, PD, CBF and Ki-67 LI. In the overall cohort, T 1, PD and CBF had slight positive correlation with Ki-67 LI ( r=0.394, 0.411 and 0.406, respectively, all P<0.01). There was no correlation between T 2 and Ki-67 LI ( r=-0.100, P=0.423). Conclusion:Synthetic MRI and 3D-ASL can noninvasively evaluate the pathological grade of glioma and predict the expression of Ki-67, among which T 1 and PD are novel imaging marks.

Two cases of pregnant women with lumbar disc herniation causing neurologic deficits are reported. The first case received percutaneous endoscopic discectomy following the cesarean section; and the second case underwent micro-discectomy in the left lateral position under local anesthesia at 23-week gestation. After surgery, satisfactory outcomes were obtained in both cases. The management of these two cases indicates that the disc surgery is a safe procedure for patients during pregnancy.

Objective To observe the effect of ultrasound-guided iliopsoas plane block(IPB)on the quality of postoperative recovery in patients undergoing hip arthroplasty.Methods Sixty patients who underwent hip arthroplasty were selected,37 males and 23 females,aged 40-79 years,BMI 18-30 kg/m2,ASA physical status Ⅰ-Ⅲ.The patients were divided into two groups by random number table method:the iliopsoas plane block group(group IPB)and the femoral nerve block(FNB)group(group FNB),30 pa-tients in each group.Before anesthesia induction,IPB was performed with 0.5%ropivacaine 10 ml and lat-eral femoral cutaneous nerve block was performed with 0.5%ropivacaine 5 ml in group IPB.And FNB was performed with 0.5%ropivacaine 10 ml and lateral femoral cutaneous nerve block was performed with 0.5%ropivacaine 5 ml in group FNB.The dosages of propofol,remifentanil,and cis-atracurium during operation were recorded.The quality of recovery-15(QoR-15)scale was evaluated preoperatively and postoperatively 1 day,2 and 3 days.The max VAS(VASmax)pain score and manual muscle test(MMT)score of quadri-ceps muscle were recorded 12,24,and 48 hours after surgery.The time of getting out of bed for the first time,opioid dosage,and patient satisfaction were recorded.The incidence of nerve injury,vascular injury,puncture site infection,and local anesthetic poisoning were recorded.The postoperative complications of diz-ziness,nausea and vomiting,deep vein thromboses,and elirium were also recorded.Results There was no significant difference in the dosage of propofol,remifentanil,and cis-atracurium between the two groups.Compared with group FNB,the QoR-15 scale score in group IPB was significantly higher 1 day,2 and 3 days after operation(P＜0.05).Compared with group FNB,the MMT scores of quadriceps muscle was sig-nificantly higher in group IPB 12 and 24 hours after surgery(P＜0.05),and the first time of getting out of bed was shortened in group IPB(P＜0.05).However,there were no significant differences in the VASmax pain score,MMT score of quadriceps muscle 48 hours after surgery,opioid dosage,and patient satisfaction between the two groups.No nerve block related complications were found in both groups.There were no sig-nificant differences in postoperative complications between the two groups.Conclusion The iliopsoas plane block can improve the quality of postoperative recovery and accelerate the recovery of patients with hip re-placement,and the effect is better than that of femoral nerve block.

Objective:To determine the median effective dose (ED 50) of ciprofol inhibiting responses to insertion of laryngeal mask airway in the patients when combined with alfentanil. Methods:American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ patients of either sex, aged 40-64 yr, with body mass index of 20-30 kg/m 2, undergoing elective general anesthesia, were enrolled. Midazolam 0.025 mg/kg was intravenously injected for anesthesia induction, the baseline mean arterial pressure and heart rate were recorded 5 min later, and the average value of three times was considered as the baseline value. Ciprofol and alfentanil 10 μg/kg were intravenously injected in sequence, rocuronium 0.6 mg/kg was intravenously injected when BIS value < 60, 2 min later a laryngeal mask airway was placed, and mechanical ventilation was performed. Positive response was defined as increase in the maximum mean arterial blood pressure or heart rate more than or equal to 20% of the baseline value within 3 min after placement of the laryngeal mask airway or as the occurrence of body movement, bucking, frowning, mouth and face twitching, tearing, laryngospasm or the BIS value failing to drop below 60. The study was performed by the Dixon′s up-and-down method. The initial dose of ciprofol was 0.4 mg/kg, and the ratio between the two successive doses was 1.1. If a positive response occurred, the dose was increased in the next patient, otherwise the dose was reduced. The ED 50 and 95% confidence interval of ciprofol inhibiting responses to insertion of laryngeal mask airway were calculated by the probit method. Results:The ED 50(95% confidence interval) of ciprofol inhibiting responses to insertion of laryngeal mask airway was 0.291(0.231-0.318) mg/kg when combined with alfentanil 10 μg/kg. Conclusions:The ED 50 of ciprofol inhibiting responses to insertion of laryngeal mask airway is 0.291 mg/kg in the patients when combined with alfentanil 10 μg/kg.

The condition of critically ill patients changes rapidly, involving pathological changes in multiple systems and organs throughout the body. Exploring the causal relationship of mechanisms can further reveal etiology, treatment, and prognosis of diseases. However, traditional prospective studies in the field of critical care are still subject to numerous limitations. As an emerging research method, Mendelian randomization (MR) analysis uses genetic variation to provide causal evidence for instrumental variables, which is expected to provide clues in critical diseases. This article systematically describes the research progresson the application of MR analysis in critical care medicine from four aspects: the principle of MR analysis, the difference between MR analysis and randomized controlled trial (RCT), the use of MR analysis in the field of critical illness, and the possible methods of application, aiming to provide possible directions for the research in this field.
Humans ; Mendelian Randomization Analysis/methods* ; Genetic Variation ; Causality ; Research Design

45.7% of Chinese patients with advanced lung adenocarcinoma were reported to harbour sensitizing epidermal growth factor receptor (EGFR) mutations. Limited therapeutic options are left for non-small cell lung cancer (NSCLC) harbouring sensitizing EGFR mutations after failure of EGFR-tyrosine kinase inhibitor (TKI) therapy and chemotherapy, finding effective options for them is an unmet clinic need. Herein we reported a case that till January 12, 2021, an 82-year-old female with sensitizing EGFR-mutant advanced lung adenocarcinoma received a surprising progression-free survival (PFS) benefit of over 21 months from the combination therapy of pembrolizumab and anlotinib after her failure of treatments of osimertinib, chemotherapy and anlotinib-monotherapy.
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Adenocarcinoma of Lung/genetics* ; Aged, 80 and over ; Antibodies, Monoclonal, Humanized ; Antineoplastic Combined Chemotherapy Protocols ; Carcinoma, Non-Small-Cell Lung/genetics* ; ErbB Receptors/genetics* ; Female ; Humans ; Indoles ; Lung Neoplasms/genetics* ; Mutation ; Quinolines