Objective To discuss the feasibility and effect of labeled antibody on targeting therapy of systemic lupus erythematosus(SLE) associated thrombocytopenia.Methods MTX-IVIG conjugate was prepared by indirect and direct cross linking,and the binding ability of it to Fc fragment was detected by indirect immunofluor-escence.The killing activity of the conjugate was detected by MTT method using murine macrophage with Fc receptor and strain U937 of human monocytic leukemia cell as targets.Results Conjugation showed stronger cytotoxicity upon target cells than free MTX,and it showed less cytotoxic effect on Fc receptor negative cells compared with the positive ones.IVIG-HSA-MTX restrained the phagocyte of macrophage.The killing effect of IVIG-HSA-MTX was significantly stronger than that of IVIG-MTX.Conclusion The conjugation can show a highly specific cytotoxicity upon mononuclear-macrophage in vitro.

Dexmedetomidine is an α2-adrenergic receptor agonist that exhibits a protective effect on ischemia-reperfusion injury of the heart, kidney, and other organs. In the present study, we examined the neuroprotective action and potential mechanisms of dexmedetomidine against ischemia-reperfusion induced cerebral injury. Transient focal cerebral ischemia-reperfusion injury was induced in Sprague-Dawley rats by middle cerebral artery occlusion. After the ischemic insult, animals then received intravenous dexmedetomidine of 1 μg/kg load dose, followed by 0.05 μg/kg/min infusion for 2 h. After 24 h of reperfusion, neurological function, brain edema, and the morphology of the hippocampal CA1 region were evaluated. The levels and mRNA expressions of interleukin-1β, interleukin-6 and tumor nevrosis factor-α as well as the protein expression of inducible nitric oxide synthase, cyclooxygenase-2, nuclear factor-κBp65, inhibitor of κBα and phosphorylated of κBα in hippocampus were assessed. We found that dexmedetomidine reduced focal cerebral ischemia-reperfusion injury in rats by inhibiting the expression and release of inflammatory cytokines and mediators. Inhibition of the nuclear factor-κB pathway may be a mechanism underlying the neuroprotective action of dexmedetomidine against focal cerebral I/R injury.
Animals ; Brain Edema ; CA1 Region, Hippocampal ; Cyclooxygenase 2 ; Cytokines ; Dexmedetomidine* ; Heart ; Hippocampus ; Infarction, Middle Cerebral Artery ; Inflammation* ; Interleukin-6 ; Kidney ; Neuroprotection* ; Nitric Oxide Synthase Type II ; Rats* ; Rats, Sprague-Dawley ; Reperfusion ; Reperfusion Injury* ; RNA, Messenger

Dexmedetomidine is an α2-adrenergic receptor agonist that exhibits a protective effect on ischemia-reperfusion injury of the heart, kidney, and other organs. In the present study, we examined the neuroprotective action and potential mechanisms of dexmedetomidine against ischemia-reperfusion induced cerebral injury. Transient focal cerebral ischemia-reperfusion injury was induced in Sprague-Dawley rats by middle cerebral artery occlusion. After the ischemic insult, animals then received intravenous dexmedetomidine of 1 μg/kg load dose, followed by 0.05 μg/kg/min infusion for 2 h. After 24 h of reperfusion, neurological function, brain edema, and the morphology of the hippocampal CA1 region were evaluated. The levels and mRNA expressions of interleukin-1β, interleukin-6 and tumor nevrosis factor-α as well as the protein expression of inducible nitric oxide synthase, cyclooxygenase-2, nuclear factor-κBp65, inhibitor of κBα and phosphorylated of κBα in hippocampus were assessed. We found that dexmedetomidine reduced focal cerebral ischemia-reperfusion injury in rats by inhibiting the expression and release of inflammatory cytokines and mediators. Inhibition of the nuclear factor-κB pathway may be a mechanism underlying the neuroprotective action of dexmedetomidine against focal cerebral I/R injury.
Animals ; Brain Edema ; CA1 Region, Hippocampal ; Cyclooxygenase 2 ; Cytokines ; Dexmedetomidine* ; Heart ; Hippocampus ; Infarction, Middle Cerebral Artery ; Inflammation* ; Interleukin-6 ; Kidney ; Neuroprotection* ; Nitric Oxide Synthase Type II ; Rats* ; Rats, Sprague-Dawley ; Reperfusion ; Reperfusion Injury* ; RNA, Messenger

Objective To construct Raji-Luc lymphoma cells with CD19 knockout using CRISPR/Cas9 technology and preliminarily validate their immune escape ability.Methods PB-CRISPR-CD19 small guide RNA(sgRNA)plasmids was constructed,the optimal sgRNA sequence was screened,and Raji-Luc cells with pCAG-PBase,PB-CD19 sgRNA,and PB-CRISPR-Cas9 were co-transfected.Stable knockout monoclonal cell lines were screened by flow sorting and limit dilution method and the knockout effect was verified through gene sequence testing.The expression of luciferase on the surface of the cell line was detected by microplate reader,CD19 CAR-T and CD38 CAR-T previously constructed in the laboratory were used as effector cells,and the immune escape ability of Raji-Luc CD19 KO cell line was verified by universal luciferase chemiluminescence method.Results The transfection efficiency of Raji-Luc CD19 KO cells prepared by electro transfection was high,and the knockout efficiency of the two monoclonal cells was more than 99%.There was no significant difference in luciferase expression compared to the original Raji-Luc cells,and CD19 CAR-T cells could not be activated to the kill them.Conclusion Successfully constructed Raji-Luc CD19 KO lymphoma cell line.

Eucommiae Folium(EF),a traditional Chinese medicine,has been used to treat secondary hypertension,including renal hypertension and salt-sensitive hypertension,as well as hypertension caused by thoracic aortic endothelial dysfunction,a high-fat diet,and oxidized low-density lipoprotein.The antihyperten-sive components of EF are divided into four categories:flavonoids,iridoids,lignans,and phenyl-propanoids,such as chlorogenic acid,geniposide acid and pinoresinol diglucoside.EF regulates the occurrence and development of hypertension by regulating biological processes,such as inhibiting inflammation,regulating the nitric oxide synthase pathway,reducing oxidative stress levels,regulating endothelial vasoactive factors,and lowering blood pressure.However,its molecular antihypertensive mechanisms are still unclear and require further investigation.In this review,by consulting the relevant literature on the antihypertensive effects of EF and using network pharmacology,we summarized the active ingredients and pharmacological mechanisms of EF in the treatment of hypertension to clarify how EF is associated with secondary hypertension,the related components,and underlying mechanisms.The results of the network pharmacology analysis indicated that EF treats hypertension through a multi-component,multi-target and multi-pathway mechanism.In particular,we discussed the role of EF tar-gets in the treatment of hypertension,including epithelial sodium channel,heat shock protein70,rho-associated protein kinase 1,catalase,and superoxide dismutase.The relevant signal transduction path-ways,the ras homolog family member A(RhoA)/Rho-associated protein kinase(ROCK)and nicotinamide adenine dinucleotide phosphate(NADPH)oxidase/eNOS/NO/Ca2+pathways,are also discussed.

Objective In view of the controversy over radiotherapy target volume for patients with limited-stage small cell lung cancer ( SCLC), a prospective randomized controlled trial was conducted to compare the impact of different radiotherapy target volumes on prognosis. Methods After 2 cycles of EP chemotherapy,patients without progressive disease were randomly assigned to receive thoracic radiotherapy (TRT) to either the post-or pre-chemotherapy primary tumour extent as study arm or control. Involved field radiotherapy (IFRT) to the entire metastatic lymph node regions was applied for both arms. TRT consisted of 45 Gy/30Fx/19 d administered concurrently with cycle 3 chemotherapy. Prophylactic cranial irradiation was administered to patients achieved complete or partial remission. Kaplan-Meier method was used for survival analysis. Results Between June 2002 and December 2017,159 and 150 patients were randomly assigned to study arm and control respectively. The 1-,2-,and 5-year local/regional control rates were 79. 4%,61. 5% and 60. 1% respectively in the study arm versus 79. 8%,66. 5%,and 57. 3% in the control arm (P=0. 73). The median OS time was 22. 1 months in the study arm (95%CI,18. 2-26. 0 months) and 26. 9 months (95%CI,23. 5-30. 3 months) in the control arm,the 1-,3-,5-,and 7-year OS rates were 81. 1%,31. 6%, 23. 9% and 22. 2% respectively in the study arm versus 85. 3%,36. 6%,26. 1% and 20. 0% in the control arm (P=0. 51).Grade 2-3 acute esophagitis was developed in 32. 9% and 43. 2% of patients respectively in study arm and control arm (P=0. 01),while grade 2-3 pulmonary fibrosis was observed in 2. 0% and 10. 9% of patients ( P= 0. 01 ) respectively. Conclusions For patients with limited-stage SCLC who received induction chemotherapy,thoracic radiotherapy can be limited to post-chemotherapy tumour extent and IFRT can be routinely applied.

Osteoporotic thoracolumbar fracture in the elderly will seriously reduce their quality of life and life expectancy. For osteoporotic thoracolumbar fracture in the elderly, spinal reconstruction is necessary, which should comprehensively consider factors such as the physical condition, fracture type, clinical characteristics and osteoporosis degree. While there lacks relevant clinical norms or guidelines on selection of spinal reconstruction strategies. In order to standardize the concept of spinal reconstruction for osteoporotic thoracolumbar fracture in the elderly, based on the principles of scientificity, practicality and progressiveness, the authors formulated the Clinical guideline for spinal reconstruction of osteoporotic thoracolumbar fracture in elderly patients ( version 2022), in which suggestions based on evidence of evidence-based medicine were put forward upon 10 important issues related to the fracture classification, non-operative treatment strategies and surgical treatment strategies in spinal reconstruction after osteoporosis thoracolumbar fracture in the elderly, hoping to provide a reference for clinical treatment.

We retrieve and analyze the articles on body surface temperature of acupoints in the recent 50 years. Surface temperatures have been compared between acupoints and nonacupoints, and among acupoints in different states. The impacts of interventions for acupoint temperature are explored, including acupuncture,moxibustion and cupping, etc. We summarize the features and the rules of acupoint skin temperature. It is considered that there exists distribution rule for healthy people's acupoint skin temperature. That means acupoints have higher surface temperature than nonacupoints. In the same meridian the nearer acupoints close to the head and trunk, the higher the temperature is. The difference in symmetrical acupoints temperatures between the left and right side is about 0.5℃. In the different meridians the skin temperatures of adjacent acpoints are similar. The changes of acupoint's skin temperature in illness can be used as the auxiliary diagnosis. Acupuncture, moxibustion and cupping can produce acupoints stimulating, metabolism improving,balance, acupoint temperature regulating. Thus,diseases are relieved. The specificity and regularity that acupoint's skin temperature presents may be one of the manifestations of the acupoint specificity, also it is an important starting point of the research on acupoint sensitization. The further studies should consider different diseases and modern biological engineering techniques, so that more rules of acupoints temperature can be found by more sensitive and objective temperature measurements as well as experimental and the mathematical models.

Objective: To investigate the epidemiological data of ventilator-associated pneumonia(VAP) occurred in adults after cardiac surgery and exploring the relationship between ventilator-associated pneumonia related factors, and all purpose is to provide strong theoretical advice and technical guidance for prevent the occurrence of ventilator-associated pneumonia in post-cardiac surgery patients. Methods: Using literature research method to determine 55 VAP related factors, and 21 nursing experts were selected to conduct 2 rounds of enquiries. Based on the results of the consultation, a retrospective questionnaire was formed. A total of 150 patients who underwent ICU mechanical ventilation after cardiac surgery from September 2016 to August 2017 were retrospectively selected. The related factors of VAP and its etiological characteristics were retrospectively observed. Results: Delphi experts consultation results: the response rate two rounds were 86.4% and 100.0% respectively; the coefficient of reliability ascertained the authority of evaluation was 0.857 and 0.903 respectively; Kendall’s W were 0.406 and 0.304 respectively (P all < 0.01). The average incidence of VAP was 25.10/1 000 ventilation days. In the VAP infection group, a total of 84 strains were detected, in which gram-negative bacteria accounted for 69.05% (58/84), fungi 26.19% (22/84), and gram-positive bacteria 4.76% (4/84).The most of them were Acinetobacterbaumannii 27.38% (23/84). Multiple infections were more than the proportion of 48%. Univariate analysis showed that there were 26 statistically significant items (P all < 0.01). Non-conditional binary logistic regression analysis showed that there were 4 independent risk factors with statistical significance: length of ventilator using> 5 days, length of cardiopulmonary ≥2h, perioperative blood transfusion >1 200 ml and perioperative using of acid inhibitors. Conclusions The study showed that most of the predictable VAP factors cannot be artificially intervened. Basing on the occurrence and development of VAP and the status of nursing interventions, Medical staff should take enhanced measures to prevent the occurrence of VAP and improve the quality of medical care

The integrity of lysosomes is of vital importance to survival of tumor cells. We demonstrated that LW-218, a synthetic flavonoid, induced rapid lysosomal enlargement accompanied with lysosomal membrane permeabilization in hematological malignancy. LW-218-induced lysosomal damage and lysosome-dependent cell death were mediated by cathepsin D, as the lysosomal damage and cell apoptosis could be suppressed by depletion of cathepsin D or lysosome alkalization agents, which can alter the activity of cathepsins. Lysophagy, was initiated for cell self-rescue after LW-218 treatment and correlated with calcium release and nuclei translocation of transcription factor EB. LW-218 treatment enhanced the expression of autophagy-related genes which could be inhibited by intracellular calcium chelator. Sustained exposure to LW-218 exhausted the lysosomal capacity so as to repress the normal autophagy. LW-218-induced enlargement and damage of lysosomes were triggered by abnormal cholesterol deposition on lysosome membrane which caused by interaction between LW-218 and NPC intracellular cholesterol transporter 1. Moreover, LW-218 inhibited the leukemia cell growth