Objective The aim of this study was to explore the predictive value of the systemic inflammatory immune nutri-tion score(SIINS)for the prognosis of immunotherapy for advanced gastric cancer.Methods A retrospective analysis was conducted on the clinical data of 202 patients with advanced gastric cancer who received treatment with programmed death-1(PD-1)inhibitors at the Harbin Medical University Cancer Hospital from October 2018 to July 2022.The LASSO regression analysis was used to screen prognostic indicators,construct SIINS indicator,determine the optimal cutoff value for predicting prognosis using subject operating characteristic curves,and divide patients into the high SIINS and low SIINS groups.Independent prognostic factors for overall survival(OS)were determined using univariate and multivariate Cox regression analyses.Results Four indicators,including lymphocyte count,lactate dehydrogenase,and neutrophil lymphocytes,were selected to construct the SIINS index.The prognosis of patients in the high SIINS group was significantly lower than that in the low SIINS group(P<0.05).The results of the multifactorial Cox regression a-nalysis showed that the Eastern Cooperative Oncology Group(ECOG)score,Geriatric Nutritional Risk Index(GNRI),SIINS,treatment regimen,and number of treatment lines(P<0.05)could serve as the independent predictive prognosis of immunotherapy for advanced gastric cancer.Conclusion SIINS can predict the prognosis of patients with advanced gastric cancer treated with PD-1 inhibitors.

Endothelial dysfunction is a pivotal contributor to atherosclerosis(As)pathogenesis.A comprehensive understanding of the mechanisms of endothelial dysfunction would provide novel insights into effective treatment of As.Recent advances in genome and transcripome technology have enabled researchers to further explore the molecular mecha-nisms of endothelial dysfunction.It has been found that the regulatory network of competitive endogenous RNA(ceRNA)mediated by long non-coding RNA(lncRNA)plays a key role in endothelial dysfunction.lncRNA acts as a"molecular sponge"for microRNA(miRNA)to block the post-transcriptional repression of miRNA on downstream target gene messen-ger RNA(mRNA)by binding to miRNA,thereby regulating the function and phenotypic conversion of endothelial cell(EC)lncRNA-miRNA-mRNA interactions are widely involved in play an essential role EC inflammatory responses,apopto-sis,autophagy,angiogenesis,and endothelial-mesenchymal transition(EndMT).Which suggests that it may be a poten-tial therapeutic targets for As.

Endothelial dysfunction is a pivotal contributor to atherosclerosis(As)pathogenesis.A comprehensive understanding of the mechanisms of endothelial dysfunction would provide novel insights into effective treatment of As.Recent advances in genome and transcripome technology have enabled researchers to further explore the molecular mecha-nisms of endothelial dysfunction.It has been found that the regulatory network of competitive endogenous RNA(ceRNA)mediated by long non-coding RNA(lncRNA)plays a key role in endothelial dysfunction.lncRNA acts as a"molecular sponge"for microRNA(miRNA)to block the post-transcriptional repression of miRNA on downstream target gene messen-ger RNA(mRNA)by binding to miRNA,thereby regulating the function and phenotypic conversion of endothelial cell(EC)lncRNA-miRNA-mRNA interactions are widely involved in play an essential role EC inflammatory responses,apopto-sis,autophagy,angiogenesis,and endothelial-mesenchymal transition(EndMT).Which suggests that it may be a poten-tial therapeutic targets for As.

Objective The aim of this study was to explore the predictive value of the systemic inflammatory immune nutri-tion score(SIINS)for the prognosis of immunotherapy for advanced gastric cancer.Methods A retrospective analysis was conducted on the clinical data of 202 patients with advanced gastric cancer who received treatment with programmed death-1(PD-1)inhibitors at the Harbin Medical University Cancer Hospital from October 2018 to July 2022.The LASSO regression analysis was used to screen prognostic indicators,construct SIINS indicator,determine the optimal cutoff value for predicting prognosis using subject operating characteristic curves,and divide patients into the high SIINS and low SIINS groups.Independent prognostic factors for overall survival(OS)were determined using univariate and multivariate Cox regression analyses.Results Four indicators,including lymphocyte count,lactate dehydrogenase,and neutrophil lymphocytes,were selected to construct the SIINS index.The prognosis of patients in the high SIINS group was significantly lower than that in the low SIINS group(P<0.05).The results of the multifactorial Cox regression a-nalysis showed that the Eastern Cooperative Oncology Group(ECOG)score,Geriatric Nutritional Risk Index(GNRI),SIINS,treatment regimen,and number of treatment lines(P<0.05)could serve as the independent predictive prognosis of immunotherapy for advanced gastric cancer.Conclusion SIINS can predict the prognosis of patients with advanced gastric cancer treated with PD-1 inhibitors.

The hypoxic microenvironment and inflammatory state of residual tumors caused by insufficient radio-frequency ablation(iRFA)are major reasons for rapid tumor progression and pose challenges for immu-notherapy.We retrospectively analyzed the clinical data of patients with hepatocellular carcinoma(HCC)treated with RFA and observed that iRFA was associated with poor survival outcomes and progression-free survival.Using an orthotopic HCC mouse model and a colorectal liver metastasis model,we observed that treatment with melatonin after iRFA reduced tumor growth and metastasis and achieved the best out-comes when combined with anti-programmed death-ligand 1(anti-PD-L1)therapy.In mechanism,melatonin inhibited the expression of epithelial-mesenchymal transitions,hypoxia-inducible factor(HIF)-1 α,and PD-L1 in tumor cells after iRFA.Flow cytometry revealed that melatonin reduced the proportion of myeloid-derived suppressor cells and increased the proportion of CD8+T cells.Transcriptomic analysis revealed an upregulation of immune-activated function-related genes in residual tumors.These findings demonstrated that melatonin can reverse hypoxia and iRFA-induced inflammation,thereby overcoming the immunosuppressive tumor microenvironment(TME)and enhancing the efficacy of immunotherapy.

Objective Animal experiment is indispensible for the progress of medicine and medical research.Experimental animals deserve basic respect and care.This paper reviewed the history and status of the experimental animal welfare nationally and internationally to identify the ethical problems existed in animal experiments,and finally discuss the establishing of ethical review system of experimental animals.Methods According to literature review,as well as summarizing the operating practice in the affiliated hospital of Chengdu university of TCM,this study analyzed the problems in the field of experimental animal welfare protection.Results Many countries,such as Britain,Germany and the United States,have legislation on the welfare of experimental animals.There are no such laws in China while departmental regulations has formulated.At present,the weak cognition of bioethics among medical personnel,lack of corresponding certification system,lack of the ethical review system of laboratory animal are still unsolved problems.This paper summarizes the principles of ethical review,the documents of review and the elements of review.Conclusions The protection of experimental animals is a systematic project,and ethical review as the first link of animal experiments can play a good role in promoting animal experiment.

OBJECTIVE: To prepare zedoary turmeric oil compound liposomes (ZTOC-LPS) and evaluate its quality.METHODS: The preparation method of liposome, the addition amount of soybean phosphatidylcholine (SPC), ratio of SPC to cholesterol (CH) in lipid, drug-lipid ratio of zedoary turmeric oil (ZTO), drug-lipid ratio of tretinoin in formulation, and water bath temperature were screened using encapsulation efficiency and drug-loading amount of ZTO (represented by germacrone) and tretinoin as investigation indexes. Quality evaluation and primary stability investigation were conducted for liposomes prepared by optimal preparation technology. RESULTS: The optimal preparation method was ethanol injection method; The optimal preparation technology were SPC 4 mg in 1 mL lipid, the mass ratio of SPC to CH 3:1, the ratio of ZTO to lipid 1:9, the ratio of tretinoin to lipid 1:70, water bath temperature of 55 ℃. Encapsulation efficiencies of ZTO and tretinoin were (64. 63 ± 1. 00)％ and (90. 33 土 0. 72)％ in 3 batches of ZTOC-LPS, respectively. Drug-loading amount of ZTO and tretinoin were (9. 09 ± 0. 14)％ and (1. 43 ± 0. 02)％, respectively. Particle size was (257. 41 ± 7. 58) nm, Zeta potential was (-38. 77 ± 0. 81) mV,PDI was 0. 10 ± 0. 04; the results of centrifugal acceleration test showed that the liposomes had good physical stability. No obvious change was found in each investigation index of ZTOC-LPS that stored at (4 ± 2) ℃ for 1 month. CONCLUSIONS: Established preparation technology is simple and feasible, the quality of the prepared ZTOC-LPS conforms to the requirements, and it can provide reference for the following research of ZTOC-LPS.

Objective To explore the feasibility and safety of visualization puncture combined with flexible ureteroscopy in the treatment of lower calyx stones.Method Visualization puncture combined with flexible ureteroscopy to treat the lower calyx stones was done in our center from January to August 2016 in our hospital.32 cases of patients were enrolled to have a retrospective analysis.There were 18 males and 14 females,aged from 25 to 65 years,with an average age of 43 years.The diameter of stone was 1.0-2.0 cm,with an average of (1.4 ± 0.6) cm.We used general anesthesia and then adjusted the surgery bed to operation side lateral elevation was 30 °-35.Flexible ureteroscopy with 200μm holmium laser was used firstly to break calculi as much as possible.Ultrasound-guided F4.8 visualization puncture system was used to establish F4.8 channel.The power option was 2001μm hohnium laser to crush calculus of the renal calculi to treat the calculus of the distal end of soft lens which still can not be touched by ureteroscopy.Routine nephrostomy tube was not placed.The soft ureter sheath F5 double-J tube,and indwelling balloon catheter were routinely placed.We removed the catheter after 1-2 days and the double J tube after 4 to 6 weeks.Results The flexible ureteroscopy lithotripsy operation time was 8-25 mins in all of the 32 patients.Visualization puncture channels were successfully established in 3-7 mins,and the visualized puncture stone search rate of 100％ (32/32).The success rate of first stage lithotripsy was 93.8％ (30/32).Two cases of lower calyx stones diverticulum diverted to PNCL due to poor visibility by bleeding.The operation time was 30-60 mins and the average of 45 mins.KUB review at day one after the surgery showed that there were residual stones in 5 cases.The stone free rate at one month after the surgery is 100.0％.The average postoperative hospital stay was (2.0 ± 1.5) days.There were uo bleeding,ureteral avulsion and perforation,septic shock,pleural effusion and intestinal injury and other serious complications.Conclusions Navigation ultrasound-guided visualization puncture combined with flexible ureteroscopy is safe and effective to treat lower calyx stones.

Objective To investigate the clinical efficacy and safety of visual standard channel combined with visual ultrafine channel PCNL precision puncture in treatment of complex renal calculi. Methods From June 2015 to October 2016, 48 cases of complicated renal calculi were treated with multi-channel lithotripsy with visual standard channel ultrasonic pneumatic lithotripsy combined with visual superfine channel PCNL precision puncture holmium laser lithotripsy. Including 10 cases of staghorn stone, 38 cases of multiple renal stones. Results 110 channels were established in 48 patients. 4 cases of preoperative renal insufficiency with infection in the puncture found in the pus and stones load larger, intraoperative diarrhea and PCNL simple treatment of obstruction site stones; 44 cases to complete one of the surgery: There were single channel established in every one of 5 cases, and double channels established in every one of 24 cases, three channels in established in every one of 15 cases; There were two cases of surgery in 8 cases and there were 12 new channels established. The average time of unilateral first operation was 75 (35 ~ 125) min. The first clearance rate was 79.2% (38/48), and the total clearance rate of postoperative stone was 87.5% (42/48). 6 cases of residual stone combined with ESWL and drug row of stone, followed up for 3 months, 6 cases of stone row net, the total stone clearance rate of 100.0% (48/48). Two consecutive postoperative no sepsis, bleeding, ureteral injury and other serious complications. Conclusions Visual standard channel combined with visual superfine channel PCNL precise puncture for the treatment of complex renal calculi is safe and effective, with high fruiting rate and low complication, which can be popularized in clinical practice.

Objective To investigate the clinical effect of paraquat (PQ) detoxification recipe combined with continuous hemoperfusion (HP) in the treatment of patients with acute paraquat poisoning (APP) and clinical significance of soluble CD14 subtype (sCD14-st, Presepsin). Methods A prospective randomized controlled trial was conducted. 152 patients with moderate APP admitted to Department of Emergency Medicine of Harrison International Peace Hospital Affiliated to Hebei Medical University from July 2013 to June 2017 were enrolled, and they were randomly divided into three groups. The patients in HP group (group A, n = 35) only received 2-hour HP for 3 times, 8 hours each time, those in PQ detoxification recipe combined with HP group (group B, n = 50) received PQ detoxification recipe 1 (once per 2 hours until no PQ component was found in faeces) and 2 (3 times a day for 14 days) beside HP. The others in PQ detoxification recipe combined with persistent HP group (group C, n = 67) received continuous HP until the PQ component in serum was not detected. The parameters of organ function and inflammatory factor, and blood Presepsin and PQ contents were determined before and after treatment. The curative effect and 28-day mortality were recorded. The correlations between serum Presepsin level and PQ content as well as 28-day mortality were analyzed with Pearson correlation analysis. Receiver operating characteristic curve (ROC) was plotted to analyze the predictive value of Presepsin on prognosis. Results The total effective rate of group C was significantly higher than that of groups A and B [70.1% (47/67) vs. 34.3% (12/35), 54.0% (27/50)], and 28-day mortality was significantly lowered [29.8% (20/67) vs. 65.7% (23/35), 46.0% (23/50), both P < 0.05]. There was no significant difference in alanine aminotransferase (ALT), MB isoenzyme of creatine kinase (CK-MB), serum creatinine (SCr), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukins (IL-6 and IL-10) before treatment among the three groups. Five days after treatment, the above parameters in the three groups were increased as compared with those before treatment, but the increase degree in group C was the lowest. At 7 days after treatment, the parameters were decreased, especially in group C. There was no significant difference in serum Presepsin and PQ levels before treatment among the three groups. With the prolongation of treatment time, the Prespsin levels in groups A, B, and C were increased, and peaked at 12 hours (μg/L: 4.28±0.20, 3.87±0.25, 3.53±0.23), then gradually decreased,and the PQ contents were lower than those before treatment from 8 hours (mg/L: 1.76±0.12 vs. 2.12±0.17, 1.57±0.08 vs. 2.24±0.16, 1.25±0.10 vs. 2.14±0.18), with a time dependence pattern, especially in group C (all P < 0.05) . Correlation analysis showed that blood Presepsin level was positively correlated with PQ content and 28-day mortality (r1= 0.917, r2= 0.864, both P = 0.001), suggesting that the higher the PQ content was, the higher the Presepsin level, and the higher the 28-day mortality was. ROC curve analysis showed that the area under ROC curve (AUC) of Presepsin predicting 28-day mortality was 0.863; when the cut-off value was 1.22 μg/L, the sensitivity was 83.3%, the specificity was 81.4%, the positive predictive value was 77.46%, and the negative predictive value was 86.42%. Conclusions Early administration of PQ detoxification recipe combined with continuous HP treatment can effectively reduce Presepsin level, decrease the mortality of patients with moderate APP, improve the prognosis. Presepsin can assess the prognosis of patients with APP.