Objective To elucidate the bidirectional causal relationship between lipid profiles and colorectal cancer(CRC)by using the two-sample and two-step Mendelian randomization(MR)methods,and to explore the mediating role and proportion of immune cells as intermediary factors.Methods The pooled statistical data related to the study were screened,and 179 lipids and CRC were analyzed using two-sample and two-step MR with the inverse variance weighted method.Simultaneously,the causal effect was verified via Bayesian weighted MR.Two-step MR analysis was conducted to determine whether a mediated effect was exerted on immune cell traits.Sensitivity,heterogeneity,and pleiotropy analyses were performed to verify the reliability of the study results.Results The causal relationship between nine lipid traits and CRC was preliminarily identified,and no reverse causal effect was found(P>0.05).The validity of the results was verified via Bayesian weighted MR(P<0.05).Twenty-seven types of immune cells were suggested to exert a causal effect on CRC.The causal effect of phosphatidylcholine(O-18:2_20:4)on CRC was determined via mediation analysis(OR:0.8579,95% CI=0.7395-0.9952,P=0.0429).The CD127-mediated proportion on CD45RA+CD4+T cells was 9.14% (β=-0.1052,P=0.0155).Conclusion A causal relationship exists between lipid traits and CRC,and the intervention of CD127 on CD45RA+CD4+T cell helps phosph-atidylcholine reduce the risk of CRC.

ObjectiveThis study aimed to evaluate the clinical efficacy of Ruyi Zhenbaowan（RYZBW）in the treatment of initial and early knee osteoarthritis （KOA） through a prospective multicenter，randomized，double-blind，and placebo-parallel controlled trial. MethodFrom October 13^th， 2021 to December 25^th， 2021， 240 KOA subjects meeting the acceptance criteria were enrolled in 15 sub-centers including Wangjing Hospital， Chinese Academy of Chinese Medical Sciences， and they were randomly divided into observation group and control group， with 120 cases in each group. The intervention measures for the observation group were RYZBW + health education， and the intervention measures for the control group were RYZBW placebo + health education. The intervention period in both groups was four weeks， and they were followed up for four weeks after the intervention. The primary outcome measure was the total score of Western Ontario and McMaster University Osteoarthritis Index score （WOMAC score）， and the secondary outcome measures were the response rate of visual scale （VAS） pain score， WOMAC sub item scores （joint pain， joint stiffness， and joint function）， quality of life （SF-12） score， and traditional Chinese medicine （TCM） syndrome score. Result（1） Efficacy evaluation. The marginal model results showed that the observation group was better than the control group in improving the WOMAC total score and WOMAC pain score in the treatment of KOA with RYZBW， and the difference was statistically significant （P<0.05）. There was no significant difference between the two groups in improving VAS score response rate， WOMAC function score， WOMAC stiffness score， SF12-PCS （quality of life-physical health） score， SF12-MCS （quality of life-mental health） score， and TCM syndrome score. （2） Subgroup analysis. ① In terms of VAS score response rate， the response rate of the observation group was higher than that of the control group for subjects with baseline VAS score of （4， 5］， and the difference was statistically significant （P<0.05）. ② In terms of TCM syndrome score， for subjects aged ［56， 60］ and ［61， 65］， the decrease in total TCM syndrome score in the observation group was better than that in the control group， and the difference was statistically significant （P<0.05）. ConclusionTibetan medicine RYZBW has good clinical efficacy in improving WOMAC total score， VAS score response rate， WOMAC pain score， WOMAC function score， and TCM syndrome score for patients with initial and early KOA， which can fill the lack of Tibetan medicine RYZBW in the treatment of KOA and make a demonstration study for the inheritance and development of ethnic medicine.

Objective:To evaluate the effect of ozone preconditioning on splenic natural killer (NK) cells in septic mice.Methods:Twenty-four SPF-grade male C57BL/6 mice, aged 6-8 weeks, weighing 18-22 g, were divided into 4 groups ( n=6 each) according to the random number table method: control group (group C), lipopolysaccharide (LPS)group, ozone+ LPS group (O 3+ LPS) and air+ LPS group (Air+ LPS). The sepsis was induced by intraperitoneal injection of LPS 10 mg/kg. Ozone preconditioning was started at 5 days before developing the model: ozone 1 mg/kg was intraperitoneally injected once a day for 5 consecutive days, the equal volume of air was injected in Air+ LPS group. The survival was observed within 72 h after LPS injection, and sepsis score and ear temperature (once every 2 h, an average was calculated) were recorded. The posterior orbital venous blood samples were taken at 6 and 24 h after LPS injection for determination of serum interferon-γ (IFN-γ) and interleukin-10 (IL-10) concentrations using enzyme-linked immunosorbent assay. The spleen was then taken, and a single cell suspension of the spleen was prepared for measurement of the percentage of NK cells in the spleen by flow cytometry. Results:Compared with C group, the ear temperature, sepsis score and 72-h survival rate were significantly decreased, serum IFN-γ and IL-10 concentrations were increased at each time point after LPS injection, and the percentage of splenic NK cells was increased at 6 h after LPS injection and decreased at 24 h after LPS injection in LPS, Air+ LPS and O 3+ LPS groups ( P<0.05). Compared with LPS group, the ear temperature, sepsis score and 72-h survival rate were significantly increased, serum IFN-γ concentrations were decreased at each time point after LPS injection, serum IL-10 concentrations were increased at each time point after LPS injection, and the percentage of splenic NK cells was decreased at 6 h after LPS injection and increased at 24 h after LPS injection in O 3+ LPS group ( P<0.05), and no significant change was found in the parameters mentioned above in Air+ LPS group ( P>0.05). Conclusions:The mechanism by which ozone preconditioning reduces sepsis may be related to reduction of inflammatory responses and regulation of splenic NK cell levels in septic mice.

OBJECTIVE To systematically review the efficacy and safety of tranexamic acid （TXA） for hemostasis in cancer patients before and during surgery， and to provide evidence-based reference for clinical drug use. METHODS Retrieved from PubMed， Embase， the Cochrane Library， CNKI， VIP and Wanfang databases， randomized controlled trials （RCTs） about tranexamic acid （trial group） versus 0.9% Sodium chloride injection， Lactated Ringer’s solution， Compound electrolyte solution or placebo （control group） for cancer surgery were electronically searched from the inception to June 9， 2022. After literature screening and data extraction， the quality of included RCTs were evaluated by bias risk assessment tool recommended by Cochrane system evaluator manual 5.1.0. RevMan 5.3 software was used for meta-analysis or descriptive analysis， sensitivity analysis and publication bias analysis. RESULTS A total of 2 032 patients in 22 RCTs were included for meta-analysis. Results of meta-analysis showed that the blood transfusion rate [RR＝0.59， 95%CI （0.50， 0.69）， P＜0.000 01] and the volume of erythrocyte suspension infusion [MD＝－0.53， 95%CI （－0.92， －0.14）， P＝0.007] in trial group were significantly lower than control group； there was no statistical significance in the incidence of thromboembolic events [RR＝0.44， 95%CI （0.16， 1.17）， P＝0.10] or post-operative mortality [RR＝1.27， 95%CI（0.32，5.08）， P＝0.73] between two groups. Results of descriptive analysis showed that the total blood loss and postoperative drainage volume were still controversial between two groups. The results of sensitivity analysis showed that the results were basically stable. The results of publication bias analysis showed that there was little possibility of publication bias in this study. CONCLUSIONS TXA can significantly decrease the blood transfusion， reduce the volume of erythrocyte suspension infusion， whereas does not increase the incidence of thromboembolic events and post-operative mortality in cancer surgery.

Objective:To investigate the value of net water uptake (NWU) in predicting malignant edema (ME) in large hemispheric infarction (LHI).Methods:Fifty-six patients suffering from LHI in the General Hospital of Northern Theater Command from September 2017 to July 2018 were retrospectively analyzed, and their NWU was calculated separately. Patients were divided into two groups according to the occurrence of ME, which was defined as space-occupying infarct requiring decompressive craniectomy or death resulting from cerebral hernia in seven days from onset. The clinical characteristics were analyzed, and receiver operating characteristic (ROC) curve and respective area under curve (AUC) were used to assess the value of NWU and other factors.Results:After adjusting for atrial fibrillation, National Institutes of Health Stroke Scale scores at admission, and time from onset to imaging, multivariable analysis showed that NWU was an independent predictor of ME ( OR=1.226，95% CI 1.040-1.446, P=0.015). According to the ROC curve, NWU≥13.08% identified ME with great predictive power (AUC=0.813;sensitivity 0.64, specificity 0.94). Conclusions:NWU is an important predictor of ME in patients with LHI. It can help identify patients at risk of ME.

OBJECTIVE： To investigate the potential pharmacological mechanism of the seed of Draba nemorosa， and to provide reference for further development， utilization and clinical application. METHODS： Effective components and related target proteins of D. nemorosa were screened and identified by using TCMSP and STRING database. Cytoscape 3.7.0 software was used to construct a visual network of effective components and target proteins for the seed of D. nemorosa， and the network topology analysis was performed. The targeting protein-protein interaction （PPI） network was constructed and analyzed by STRING database and Cytoscape 3.7.0 software. KEGG pathway enrichment of target proteins was analyzed by DAVID bioinformatics resource database. RESULTS： A total of 9 effective components were screened from the seed of D. nemorosa， including quercetin， kaempferol， β-sitosterol， etc. Totally 174 target proteins were obtained， mainly including PTGS2， NCOA2， PGR， etc. Among them， JUN and MAPK1 were core proteins in PPI network. KEGG enrichment pathway included PI3K/Akt signaling pathway， TNF-α signaling pathway， HIF-1 signaling pathway， Toll-like receptor signaling pathway and thyroid hormone signal pathway， etc. CONCLUSIONS： Effective components from the seed of D. nemorosa such as quercetin， kaempferol and β-sitosterol may act on PTGS2， JUN and MAPK1 target proteins through PI3K-Akt signaling pathway and TNF-α signaling pathway， thus exert the effects of purging lung， relieving asthma， promoting edema and reducing edema.

Objective To explore the immunopathological mechanism for the imbalance between the positive signal mediated by inducible costimulator (ICOS) and the negative signal mediated by programmed death-1 (PD-1) in patients with myasthenia gravis (MG).Methods Eighty-two patients with MG,56 healthy controls (HC) and 20 non-MG (NMG) patients,collected in the First Affiliated Hospital of Suzhou University from February 2014 to December 2016,were chosen to participate in the study.The expression of ICOS and PD-1 on peripheral blood mononuclear cells was detected by immuno-fluorescence staining and flow cytometry.The levels of soluble programmed death-1 (sPD-1),soluble programmed death ligand 1 (sPD-L1),IL-4 and other cytokines were detected by enzyme-linked immunosorbent assay.Results (1) Flow cytometry analysis:The co-expression of PD-1,ICOS on CD4 + T cells from MG group (9.64％ (8.82％)) was higher than in HC (1.81％ (2.10％),Z =-7.389,P ＜0.05) and NMG group (2.86％ (1.49％),Z =-4.636,P ＜ 0.05).The expression of ICOS on CD4 + T cells,ICOS ligand (ICOSL) on CD14+ monocytes and CD19+ B cells were increased in MG group comparing with that of the control groups.The proportion of PD-1 + CD4 + T cells (MG group 16.82％ (10.66％),HC 9.34％ (9.18％),Z =-4.345,P＜0.05;NMG group 7.07％ (3.40％),Z=-4.594,P＜0.05) and PD-1 Ligand (PD-L1) + CD14+ monocytes was higher in MG patients.All of these were detected by flow cytometry.(2) ELISA analysis:Serum sPD-1 expression significantly increased in MG group compared with that in the control groups (MG group (1.87 ± 0.64) ng/ml,NMG group (1.49 ± 0.70) ng/ml,t =2.04,P ＜ 0.05;HC (1.05 ± 0.50)ng/ml,t =2.08,P ＜ 0.05),while for serum sPD-L1,there was no significant difference between MG and control groups.(3) Serum cytokines detection:The expression of IL-4 was increased in MG patients (MG group (61.88 ±5.15) pg/ml,HC (32.03 ±1.84) pg/ml,t=2.50,P＜0.05;NMG group (42.62± 3.31) pg/ml,t =2.34,P ＜0.05),and there was a negative correlation between the expression of sPD-1 and the concentration of IL-4.Conclusions The increased expression of PD-1 + ICOS + CD4 + T cells suggested the subset involved in the pathological progress of MG.sPD-1 might disturb the ligation of PD-1 on T cells and PD-L1 on antigen presenting cells,while the ligation of ICOS and ICOSL passed positive signal,leading to over activity of the subsets and the progression of disease.

Objective: To establish the methods for extraction and isolation of punicalagin from pomegranate peel, and further study the purification and quantification of punicalagin. Methods: Using an ultrasonic-assisted extraction method, punicalagin in pomegranate peel was extracted at room temperature by 50% ethanol with 20-fold volume of raw material. The content of punicalagin in the crude extract was determined by HPLC. To optimize the purification process of punicalagin, static adsorption and desorption experi-ments were employed to study five kinds of macroporous adsorbent resins (D101, A8-8, NKA-9, HPD-100 and HPD-500) for the one with the highest purification efficacy of punicalagin. In addition, the technical parameters of the macroporous adsorbent resin were opti-mized to obtain punicalagin with higher purity. Punicalagin was further separated and purified by using a reverse phase MCI GEL CHP20P column. Results:HPD500 resin showed the best ability to absorb and separate punicalagin in among five kinds of macro-porous adsorbent resins. The best technical parameters were as follows:the mass concentration of sample solution was 15 mg·ml-1 , the loading amount was 2BV, the pH was 2 and the eluting solvent was 8BV of 30% ethanol. With the best process as described a-bove, the content of punicalagin extracted from pomegranate peel increased from 10. 3% to 30. 7%. The obtained punicalagin could be further purified to 61. 3% from 30% in ethanol eluate by the reverse phase MCI GEL CHP20P column. Conclusion:HPD500 resin is the most effective in the purification of punicalagin from pomegranate peel, and the content of punicalagin can be dramatically increased after the purification by a reverse phase MCI GEL CHP20P column. The optimized process shows good reproducibility and stability.

Objective To study the incidence and risk factors ofdefecatory dysfunction in acute minorischemic strokepatientsandexplore the influence of the risk factors onprognosis.Methods Clinical data of 274 patients with acute minor ischemic strokewere reviewed and analyzed retrospectively.According to the presence of poststroke defecatorydysfunction,they were divided into defecatory dysfunction group and non-defecatory dysfunction group.The factors associated withdefecatory dysfunctionwere analyzed by univariate analysis and multivariatelogisticanalysis respectively,followed by investigating their effects on the prognosis.Results 74 patients of them with acute minor ischemic stroke had defecatory dysfunction.The univariate analysis indicated that4 factors including baseline NIHSS scorewere the risk factors.Multivariate logistic analysis showed that female,age,diabetes mellitus and baseline NIHSS score were independent risk factors for defecatory dysfunction.The scores of modified Rankin Scale (mRS) after 3 months in minor stroke patients with defecatory dysfunction wassignificantly higher(P ＜ 0.05).Baseline NIHSS score was a predictive factor for the prognosis of post-stroke defecatorydysfunctionpatients.Conclusions Defecatory dysfunction in acute minor stroke patients may increase the risk of poor prognosis.The female,elderlypatients as well those with diabetes mellitus and serious neurologicalfunction deficits are more likely to suffer post-stroke defecatory dysfunction.

Objective To discuss the clinical significance of programmed cell death-1 (PD-1) in neuromyelitis optica spectrum disorder (NMOSD) patients by analyzing PD-1 and programmed death 1-1igand (PD-L1) expressions.Methods Sixteen patients with NMOSD,16 patients with longitudinally extensive transverse myelitis (LETM),13 patients with opticneuritis (ON),20 with other diseases of the central nervous system (OTH) and 16 health controls (CONs) were chosen in our hospital from April 2015 to July 2016;their peripheral blood was separately collected.The PD-1 expression in the CD4+r lymphocytes,and PD-L1 expressions in the CD14+ mononuclear leucocytes and CD19+B lymphocytes of peripheral blood were detected by flow cytometry.ELISA was performed to analyze the levels of soluble PD-1 and soluble PD-L1 in plasma samples.Results The PD-1 level from the peripheral blood of NMOSD patients was significantly higher than that from LETM,ON,and OTH patients and CONs (P＜0.05).The PD-L1 level of NMOSD patients was significantly higher than that of the other 4 groups (P＜0.05).ELISA indicated that levels of soluble PD-1 and soluble PD-L1 in plasma samples from NMOSD patients were significantly higher than those in LETM,ON,and OTH patients and CONs (P＜0.05).Conclusion The PD-1/PD-L1 pathway is an important immune response approach and takes part in the earlier stage of the NMOSD pathological process.