Objective To investigate the anti-inflammatory action of Celastrol in the ocular tissues of mice with ex-perimental autoimmune uveitis(EAU)and its effect on microglia polarization.Methods A total of 36 healthy B10.RⅢmice at 6-8 weeks of age were selected and randomly divided into the normal control group,EAU solvent control group and Celastrol intervention group,with 12 mice in each group.The interphotoreceptor retinoid-binding protein(IRBP)161-180 and Freund's complete adjuvant were mixed by thorough emulsification and injected subcutaneously into the bilateral thighs and tails of mice in the EAU solvent control group and the Celastrol intervention group with a total volume of 200 μL and 50 μg IRBP 161-180 in each mouse.On 7-14 days after immunization,mice in the Celastrol intervention group received a daily intraperitoneal injection of 0.5 mg·kg-1 Celastrol,and mice in the EAU solvent control group were injected with an equivalent dose of sterile Phosphate Buffered Saline solution.On the 14th day after immunization,the anterior segment of mice in each group was observed by slit-lamp microscope and Hematoxylin and Eosin(HE)staining of tissue sections was performed;the clinical and histopathological scores of mice in each group were obtained by reference to the Caspi grading standards;immunofluorescence staining was used to observe the activation of microglia in the eyes of mice;Western blot was used to detect the protein expression levels of inducible nitric oxide synthase(iNOS)and arginase-1(Argl)in the reti-na;quantitative real-time PCR was used to detect the relative mRNA expression of inflammatory factors in the retina,such as tumor necrosis factor(TNF)-α,interleukin(IL)-1β and IL-6.GraphPad Prism 9.0 was used for data analysis.Results On the 14th day after immunization,it was observed by the slit-lamp microscope that the anterior segment of mice in the EAU solvent control group was markedly congested with dilated iris blood vessels,corneal edema,and anterior chamber exudation;the inflammation in the anterior segment of mice in the Celastrol intervention group was markedly at-tenuated,and the iris blood vessels were seen to be mildly congested.Compared with the normal control group,the clini-cal scores of mice in the EAU solvent control group and the Celastrol intervention group were significantly elevated(both P＜0.05);the clinical scores of mice in the Celastrol intervention group were lower than those in the EAU solvent control group(P＜0.05).HE staining results showed that on the 14th day after immunization,mice in the EAU solvent control group showed severe retinal folds and detachment with diffuse infiltration of inflammatory cells,while mice in the Celastrol intervention group showed slight structural damage to the retina and a small amount of inflammatory cell infiltration.Com-pared with the normal control group,the histopathological scores of mice in the EAU solvent control group and the Celas-trol intervention group were significantly elevated(both P＜0.05);the histopathological scores of mice in the Celastrol in-tervention group were lower than those in the EAU solvent control group(P＜0.05).The intraocular Iba1+cell densities of mice in the normal control,EAU solvent control and Celastrol intervention groups were(1.00±0.12)％,(36.07± 4.57)％,and(1.83±0.36)％,respectively.Compared with the normal control group,the number of Iba1+cells in the eyes of mice in the EAU solvent control group and the Celastrol intervention group significantly increased(both P＜0.05);compared with the EAU solvent control group,the number of Iba1+cells in the eyes of mice in the Celastrol intervention group was significantly reduced(P＜0.05).Compared with the normal control group,the expression levels of iNOS and Arg1 proteins in the retinas of mice in the EAU solvent control group were significantly elevated(both P＜0.01);compared with the EAU solvent control group,the expression of iNOS protein in the retinas of mice in the Celastrol intervention group was significantly reduced(P＜0.01).Compared with the normal control group,the relative mRNA expressions of TNF-α.IL-1β,and IL-6 in the retinas of mice in the EAU solvent control group was significantly elevated(all P＜0.05);compared with the EAU solvent control group,the relative mRNA expressions of TNF-α,IL-1 β,and IL-6 in the retinas of mice in the Celastrol intervention group significantly decreased(all P＜0.05).Conclusion Celastrol inhibits Ml microglia activation and reduces the production of retinal inflammatory factors TNF-α,IL-1 β and IL-6 in EAU mice,thereby attenuating the in-flammatory reaction.

Objective To establish and verify the microscopic review rules of Dirui GMD-S600 gynecologi-cal secretion analysis system.Methods A total of 2 619 samples of vaginal secretions were collected and test-ed for tangible components and dry chemistry items using the Dirui GMD-S600 gynecological secretions analy-sis system.All samples were subjected to manual microscope examination using a double blind method,and the results of instrument testing,manual image review of instrument testing,and manual microscope examina-tion were recorded separately.Using the results of manual microscope examination as the standard,the false negative rates and the false positive rates of instrument testing results and tangible component results after manual image review of instrument testing were analyzed.At the same time,the false negative rates and the false positive rates of instrument detection dry chemistry items and their corresponding tangible components were analyzed,and the review rules were derived based on this.Subsequently,344 samples were selected to verify the effectiveness of the review rules.Results The false positive rates of white blood cells,fungi,trichomonas and clue cells detected by the instrument were 28.77%,14.71%,20.09%and 2.30%,and the false negative rates were 0.28%,15.06%,4.35%and 10.34%.After manual image review and correction,the false positive rates of white blood cells,fungi,trichomonas and clue cells were 28.77%,7.06%,8.67%,0.66%,and the false negative rates were 0.28%,3.35%,4.35%and 10.34%.The false positive rates of white blood cell esterase(LE)for white blood cells,N-acetylhexylglucosidase(NAG)for fungi,NAG for trichomonas,hydrogen peroxide(H2O2)for bacteria,lactic acid(LA)for bacteria,sialidase(SNA)for clue cells,and proline aminopeptidase(PIP)for clue cells were 13.83%,22.47%,24.10%,95.52%,2.52%,12.92%and 5.54%,and the false negative rates were 28.17%,48.12%,0.00%,23.55%,78.82%,0.00%and 74.14%.The false positive rate of 260 validation samples was 1.68%,the false negative rate was 4.22%,and the review rate was 45.38%.Conclusion The review rules of the Dirui GMD-S600 gynecological secretion analysis system are as follows(1)All specimens need to be reviewed with images,and the following rules are based on this rule.(2)When the result of white blood cell shows positive,then the microscopic exam-ination is required.(3)When the result of fungi shows positivity,then the microscopic examination is re-quired.(4)When the result of trichomonas shows positive,then the microscopic examination is required.(5)When the result of SNA does not match the positive result of clue cells,then the microscopic examination is required.

Pharmacometabolomics has been already successfully used in toxicity prediction for one specific adverse effect. However in clinical practice, two or more different toxicities are always accompanied with each other, which puts forward new challenges for pharmacometabolomics. Gastrointestinal toxicity and myelosuppression are two major adverse effects induced by Irinotecan (CPT-11), and often show large individual differences. In the current study, a pharmacometabolomic study was performed to screen the exclusive biomarkers in predose serums which could predict late-onset diarrhea and myelosuppression of CPT-11 simultaneously. The severity and sensitivity differences in gastrointestinal toxicity and myelosuppression were judged by delayed-onset diarrhea symptoms, histopathology examination, relative cytokines and blood cell counts. Mass spectrometry-based non-targeted and targeted metabolomics were conducted in sequence to dissect metabolite signatures in predose serums. Eventually, two groups of metabolites were screened out as predictors for individual differences in late-onset diarrhea and myelosuppression using binary logistic regression, respectively. This result was compared with existing predictors and validated by another independent external validation set. Our study indicates the prediction of toxicity could be possible upon predose metabolic profile. Pharmacometabolomics can be a potentially useful tool for complicating toxicity prediction. Our findings also provide a new insight into CPT-11 precision medicine.

Objective To summarize the long-term outcomes and safety of childhood Hodgkin lymphoma (HL) with protocol ABVD. Methods The clinical data of 20 children with HL admitted to the Union Hospital of Fujian Medical University from July 2010 to June 2017 were retrospectively analyzed. Among the 20 children with HL, 15 were male and 5 were female. The median age of initial diagnosis was 6.5 years old (3-12 years old). The pathological types were as follow: 1 case was nodular lymphocyte-predominant HL (NLPHL) and 19 cases were classical HL (cHL), including 9 cases of mixed cell type, 9 cases of nodular sclerosis type and 1 case of lymphocyte rich type. Basing on Ann Arbor staging system, 1 patient was evaluated as stage Ⅰ, 4 patients were stage Ⅱ, 10 patients were stage Ⅲ, and 5 patients were stage Ⅳ. There were 3 patients in the low-risk group, 7 patients in the intermediate-risk group, and 10 patients in the high-risk group. There were 9 patients with B symptoms. All patients were treated with the ABVD regimen. Results All the 20 patients completed all chemotherapy courses. After 2 courses, the effective rate was 100％(20/20), including 12 cases of complete remission (CR) and 8 cases of partial remission (PR). After the treatment, 19 cases achieved CR, and at the end of the 6 courses, the evaluation showed that 1 case had residual lesions. Follow-up to February 2018, clinical symptoms of 18 cases achieved CR, 2 cases relapsed (all high-risk group); the median follow-up time was 42 months (10.1-87.9 months), the overall survival rate was 100 ％ (20/20), the estimated 5-year rate of freedom from treatment failure (FFTF) was (89.1 ±7.3) ％.Conclusions According to the risk stratification, ABVD regimen has good safety and long-term efficacy for children with cHL. Even the patients in low-risk or intermediate-risk group do not achieve CR after 2 courses and do not receive radiotherapy, the prognosis of them is still good.

The credibility of the third-party mediation agencies in medical disputes lies in their own advantages of efficiency,neutrality,professionalism and objectivity.However,because of the differences of actual operation,the credibility of the third-party mediation agencies often is questioned by both doctors and patients and the public.Aiming at these,this paper would study the status and the pushing approach of the third-party mediation agencies credibility from the perspective of professionalism and neutrality,legislation,fundraising channels and supervision.

Objective To evaluate the effect of silencing ACAT1 gene on colon cancer cells proliferation,migration,invasion and colon cancer development by using the small interference RNA (siRNA) in colon cancer cell line HT-29.Methods Acyl coenzyme A cholesterol acyltransferase 1 (ACAT1) gene was silenced in HT-29 cell lines using Hiperfect transfection reagent.The expression level of ACAT1 was detected by real time PCR.CFSE and transwell assays were used to evaluate the effect of ACAT1 gene interfering on cells proliferation,mi gration and invasion.Result ACAT1 mRNA expression decreased obviously after siRNA interference.Compared with pre-transfection,proliferation,migration and invasion of colon cancer cells have been significantly inhibited (P ＜ 0.05).Conclusion ACAT1 gene interference reduced proliferation,migration and of invasion of HT29 cells,which provide a new potential target for colon cancer treatment.

Objective To compare the efficacy and safety of vitrectomy combined with internal limiting membrane flap and vitrectomy combined with internal limiting membrane peeling for the treatment of idiopathic macular hole with different sizes.Methods A total of 127 consective patients (127 eyes)were divided into two groups according to the size of the hole diameter of the smallest split points by less than or equal to 500 μm (small diameter macular hole group) and more than 500 μm (huge diameter macular hole group).According to different surgical methods the patients were divided into non ILM flap coverage group (peeling 1 group and peeling 2 group) and ILM flap cover group (covering 1 group and covering 2 group).All the patients underwent vitrectomy combined with internal limiting membrane peeling or vitrectomy combined with limiting membrane flap.Preoperative and postoperative best correct visual acuity,closure ratio of macular hole and postoperative major complications were observed and followed up.Results The postoperative best correct visual acuity improved in all the groups,there was no significance difference between small diameter macular hole group and huge diameter macuiar hole group (t =0.112 2,0.750 8;all P ＞0.05).The closure ratio of peeling 1 group and covering 2 group at postoperative 6 months were all 100％,there was no statistical difference (P ＞ 0.05),which in peeling 2 group and covering 2 group were 84.85％ and 100.00％,there was statistical difference (x2 =13.292,P ＜ 0.05).There was no statistical difference in preoperative defect diameter of the inner and outer junction between peeling 2 group and covering 2 groups (P ＞0.05),there was also no statistical difference between peeling 2 group and covering 2 groups at postoperative 1 months (P ＞ 0.05),but there were statistical differences at postoperative 3 months,6 months and 12 months (all P ＜ 0.05),the covering 2 group were less than the peeling 2 group.Conclusion ILM flap coverage helps to heal macular holes greater than 500 μm diameter,and has no extra effect on healing of diameter less than 500 μm.

Objective To investigate the clinical features,diagnosis,treatment and prognosis of disseminated aspergillosis in children with leukemia after chemotherapy.Methods The clinical features and treatment of 3 leukemia children after chemotherapy complicated with disseminated aspergillosis were retrospectively analyzed.Results The underlying diseases of all recruited cases were leukemia,which occurred many high-risk predisposing factors for invasive fungal diseases.The major clinical features of disseminated aspergillosis in children with leukemia were prolonged and antibiotics uncontrollable fever,subcutaneous solid nodules,nodules or cavities in pulmonary CT,spread low density lesions in hepatosplenic and kidney in abdominal MR(T2 weighted)and positive serum aspergillus galactomannan(GM).The diagnosis of invasive fungal disease was proven by histopathologic examination.Amphotericin B lipid complex was selected in antifungal therapy for 2 patients and the course of treatment was more than 4 weeks.Moreover,chemotherapy was advised for the 2 patients when clinical manifestations of disseminated aspergillosis improved significantly,neutrophil counts recovered and images did not deteriorate.The patients received voriconazole treatment with follow-up from 6 months to 12 months,and then disseminated aspergillosis was cured up to the standard.1 case received complete remission and was still alive until follow-up period,1 case was died of leukemia relapse because of suspension demand from the family members,and the other 1 case was died of no response or serious adverse drug reactions,uncontrolled infection,and leukemia relapse because of long-term chemotherapy suspension.Conclusions Patients with leukemia after chemotherapy may present with the following manifestations,including fever,subcutaneous solid nodules,pulmonary nodules or cavities,spread low density lesions in hepatosplenic and kidney and serum aspergillus GM antigen positive,which may indicate disseminated aspergillosis.The improvement of prognosis depends on effective and adequate antifungal treatment and chemotherapy for leukemia at the right time.

After several in -depth investigations on the third party mediation mechanism of "Guangdong mode" in Guangdong Harmony Medical Dispute Mediation Committee and combined with the analysis of the domes-tic and foreign medical dispute disposal experience , this paper summed up five points that successful construction of harmonious mediation mechanism should grasp .The five points include the fairness of harmonious mediation thoughts , the feasibility of harmonious mediation paths , the justice of harmonious mediation mechanism , the suita-bility of harmonious mediation environment and the success of harmonious mediation results .Only when grasp these five points, couldit create a gradually harmonious doctor -patient relationship .

Objective To evaluate the effect of bispectral index (BIS) and muscle relaxation monitoring on robot-assisted laparoscopic radical prostatectomy in elderly patients.Methods One hundred elderly patients (aged 65-80 years,ASA Ⅰ or Ⅱ) who underwent robot-assisted laparoscopic radical prostatectomy were randomly allocated into BIS and muscle relaxation monitoring group (group AA,n=50) and control group (group AC,n=50).In group AA,propofol was infused to achieve the BIS value of 45-55,and we monitored the muscle relaxation to conduct closed-loop infusion of cisatracurium.In group AC,we regulated the depth of anesthetic with the patients` vital signs according to anesthetists` experience.Mean arterial pressures (MAP),heart rates (HR),airway platform pressure (Pplat),and airway peak pressure (Ppeak) were recorded at following time points: before anesthesia induction (T0),after anesthesia induction (T1),10 min (T2),60 min (T3) after artificial pneumoperitoneum,and the end of operation (T4).We recorded dosage of propofol,cisatracurium,sufentanil,remifentanil,vasoactive agent,extubation time and PACU stay time.Results At T1,T2 and T4,the MAP and HR in group AC were significantly higher than those in group AA (P<0.05);at T3,MAP in group AC were apparently lower than those in group AA (P<0.05).Compared with T0,MAP and HR in group AC were significantly increased at T1,T2 and T4(P<0.05),MAP in group AC were obviously reduced at T3 (P<0.05),MAP and HR in group AC were also fluctuated obviously at different time points.MAP and HR in group AA at each point had no statistically significant difference.Compared with T1,Pplat and Ppeak in the two groups were significantly increased at T2-T4 (P<0.05).Pplat and Ppeak in grpup AC were higher than those in group AA at T2,T3 (P<0.05).Compared with group AC,the dosages of propofol and cisatracurium were less in group AA.The postoperative extubation time and PACU stay time were shorter in group AA.Conclusion BIS and muscle relaxation monitoring in robot-assisted laparoscopic radical prostatectomy can effectively stablize hemodynamics,reduce airway pressure fluctuation and the dosage of anesthetics.It also shortens the extubation time and the PACU stay time and improves the anesthesia recovery quality.