Esophageal cancer is one of the malignant tumors that poses a threat to human health, with both high incidence and malignancy. Currently, surgery following neoadjuvant chemoradiotherapy is the standard treatment for locally advanced esophageal cancer; however, the long-term prognosis remains unsatisfactory. In recent years, inhibitors of programmed death protein-1 (PD-1) and its ligand (programmed death ligand-1, PD-L1) have achieved breakthrough progress in other solid tumors, and research on esophageal cancer is gradually being conducted. With the demonstration of good efficacy of PD-1/PD-L1 inhibitors in the first-line and second-line treatment of advanced unresectable esophageal cancer, their incorporation into neoadjuvant treatment regimens has become a hot topic. Therefore, this article reviews the mechanism of action of PD-1/PD-L1 inhibitors and their application in the neoadjuvant treatment of esophageal cancer.

BACKGROUND:Soft tissue damage induced by cobalt nanoparticles is currently the most noticeable complication in patients with artificial joint prostheses.Therefore,an effective therapeutic strategy is needed to limit the toxicity of cobalt nanoparticles.OBJECTIVE:To investigate the protective effect of a ferroptosis inhibitor on cobalt nanoparticles-induced cytotoxicity.METHODS:To evaluate the detoxification effect of ferroptosis inhibitor on mouse fibroblasts(Balb/3T3),Balb/3T3 cells were treated with cobalt nanoparticles and ferroptosis inhibitor for 24 hours.The cell viabilities were measured by cell viability assay.Based on the results of the cell viability assay,the concentrations of cobalt nanoparticles and deferiprone were determined.The experiment was divided into four groups:the cobalt nanoparticles group(400 μmol/L cobalt nanoparticles),the cobalt nanoparticles+deferiprone group(400 μmol/L cobalt nanoparticles and 25 μmol/L deferiprone),the deferiprone group(25 μmol/L deferiprone),and the control group.The expressions of glutathione peroxidase 4 and solute carrier family 7 member 11 protein were examined by western blot assay.RESULTS AND CONCLUSION:(1)The cell viability assay results showed that as the exposure time or the drug concentration increased,cell viability decreased further,indicating that the cytotoxic effect of cobalt nanoparticles was time-and dose-dependent.Additionally,after 24 hours of exposure,cobalt nanoparticles significantly reduced cell viability and glutathione levels compared with the control group(P＜0.05).At the same time,compared with the control group,there was an increase in reactive oxygen species production,intracellular iron levels,and the expression of inflammatory cytokines such as tumor necrosis factor α,interleukin-1β,and interleukin-6.After the addition of deferiprone,compared with the cobalt nanoparticles group,cell viability significantly improved,and reactive oxygen species production,intracellular iron levels,and the expression of inflammatory cytokines(tumor necrosis factor α,interleukin-1β,and interleukin-6)significantly decreased(P＜0.05).This demonstrated that deferiprone had a protective effect on cells exposed to cobalt nanoparticles.(2)Western blot assay results showed that cobalt nanoparticles reduced the expression of glutathione peroxidase 4 and solute carrier family 7 member 11 protein(P＜0.05),while deferiprone inhibited this effect(P＜0.05).(3)The above findings verify that cobalt nanoparticles are highly cytotoxic and ferroptosis inhibitor deferiprone has a detoxification effect on cytotoxicity induced by cobalt nanoparticles.Ferroptosis plays an important role in the process by which cobalt nanoparticles induce cytotoxicity.The inhibitory effect of ferroptosis inhibitors on the toxicity of cobalt nanoparticles may provide valuable insights for further research into the mechanisms of cobalt nanoparticle toxicity and potential detoxification strategies.

BACKGROUND:Soft tissue damage induced by cobalt nanoparticles is currently the most noticeable complication in patients with artificial joint prostheses.Therefore,an effective therapeutic strategy is needed to limit the toxicity of cobalt nanoparticles.OBJECTIVE:To investigate the protective effect of a ferroptosis inhibitor on cobalt nanoparticles-induced cytotoxicity.METHODS:To evaluate the detoxification effect of ferroptosis inhibitor on mouse fibroblasts(Balb/3T3),Balb/3T3 cells were treated with cobalt nanoparticles and ferroptosis inhibitor for 24 hours.The cell viabilities were measured by cell viability assay.Based on the results of the cell viability assay,the concentrations of cobalt nanoparticles and deferiprone were determined.The experiment was divided into four groups:the cobalt nanoparticles group(400 μmol/L cobalt nanoparticles),the cobalt nanoparticles+deferiprone group(400 μmol/L cobalt nanoparticles and 25 μmol/L deferiprone),the deferiprone group(25 μmol/L deferiprone),and the control group.The expressions of glutathione peroxidase 4 and solute carrier family 7 member 11 protein were examined by western blot assay.RESULTS AND CONCLUSION:(1)The cell viability assay results showed that as the exposure time or the drug concentration increased,cell viability decreased further,indicating that the cytotoxic effect of cobalt nanoparticles was time-and dose-dependent.Additionally,after 24 hours of exposure,cobalt nanoparticles significantly reduced cell viability and glutathione levels compared with the control group(P＜0.05).At the same time,compared with the control group,there was an increase in reactive oxygen species production,intracellular iron levels,and the expression of inflammatory cytokines such as tumor necrosis factor α,interleukin-1β,and interleukin-6.After the addition of deferiprone,compared with the cobalt nanoparticles group,cell viability significantly improved,and reactive oxygen species production,intracellular iron levels,and the expression of inflammatory cytokines(tumor necrosis factor α,interleukin-1β,and interleukin-6)significantly decreased(P＜0.05).This demonstrated that deferiprone had a protective effect on cells exposed to cobalt nanoparticles.(2)Western blot assay results showed that cobalt nanoparticles reduced the expression of glutathione peroxidase 4 and solute carrier family 7 member 11 protein(P＜0.05),while deferiprone inhibited this effect(P＜0.05).(3)The above findings verify that cobalt nanoparticles are highly cytotoxic and ferroptosis inhibitor deferiprone has a detoxification effect on cytotoxicity induced by cobalt nanoparticles.Ferroptosis plays an important role in the process by which cobalt nanoparticles induce cytotoxicity.The inhibitory effect of ferroptosis inhibitors on the toxicity of cobalt nanoparticles may provide valuable insights for further research into the mechanisms of cobalt nanoparticle toxicity and potential detoxification strategies.

Objective To observe the effect of the supine-posture ripple wood training in preventing motion sickness caused by linear acceleration.Methods Totally 61 motion sickness sensitive males were screened by a vertical oscillation simulator and divided into mildly sensitive group(Graybiel score 1-15,n=28)and severely sensitive group(Graybiel score 16,n=33).The participants in the 2 groups received 5-d ripple wood training,30 min/d.The movement frequency of the ripper wood was maintained at 0.25-0.35 Hz,with an acceleration of 0.15-0.25 g.Graybiel score during the training period was recorded.The static balance function test was conducted before and after training on the 1st and 5th day.Results During the training period,the Graybiel scores and motion sickness incidence in the severely sensitive group were decreased with the increase of training days,and all participants achieved complete acclimatization on the 4th day.The Graybiel scores of the mildly sensitive group were low during the whole period,and the complete acclimatization period was 2 d.There was no significant difference in the sway area of the severely sensitive group in static balance function test before and after training(P＞0.05).The mean velocity of the severely sensitive group in static balance function test was significantly increased after training versus before training on the 1st day(P＜0.01),and there was no significant difference before and after training on the 5th day(P＞0.05).There were no significant differences in the sway area or mean velocity of the mildly sensitive group during the whole training period(all P＞0.05).The validation experiment showed that the motion sickness incidence and the symptom severity were significantly decreased in both groups;the motion sickness incidence of the mildly sensitive group decreased from 100.00％(28/28)to 35.71％(10/28);the incidence of severe symptoms in the severely sensitive group decreased from 100.00％(33/33)to 6.06％(2/33)and the vomiting incidence decreased from 96.97％(32/33)to 6.06％(2/33).Conclusion The supine-posture ripple wood training has great effect in preventing motion sickness,with widespread use and simple operation.

Objective:To explore potential predictors of refractory Mycoplasma pneumoniae pneumonia (RMPP) in early stage. Methods:The prospective multicenter study was conducted in Zhejiang, China from May 1 st, 2019 to January 31 st, 2020. A total of 1 428 patients with fever >48 hours to <120 hours were studied. Their clinical data and oral pharyngeal swab samples were collected; Mycoplasma pneumoniae DNA in pharyngeal swab specimens was detected. Patients with positive Mycoplasma pneumoniae DNA results underwent a series of tests, including chest X-ray, complete blood count, C-reactive protein, lactate dehydrogenase (LDH), and procalcitonin. According to the occurrence of RMPP, the patients were divided into two groups, RMPP group and general Mycoplasma pneumoniae pneumonia (GMPP) group. Measurement data between the 2 groups were compared using Mann-Whitney U test. Logistic regression analyses were used to examine the associations between clinical data and RMPP. Receiver operating characteristic (ROC) curves were used to analyse the power of the markers for predicting RMPP. Results:A total of 1 428 patients finished the study, with 801 boys and 627 girls, aged 4.3 (2.7, 6.3) years. Mycoplasma pneumoniae DNA was positive in 534 cases (37.4%), of whom 446 cases (83.5%) were diagnosed with Mycoplasma pneumoniae pneumonia, including 251 boys and 195 girls, aged 5.2 (3.3, 6.9) years. Macrolides-resistant variation was positive in 410 cases (91.9%). Fifty-five cases were with RMPP, 391 cases with GMPP. The peak body temperature before the first visit and LDH levels in RMPP patients were higher than that in GMPP patients (39.6 (39.1, 40.0) vs. 39.2 (38.9, 39.7) ℃, 333 (279, 392) vs. 311 (259, 359) U/L, both P<0.05). Logistic regression showed the prediction probability π=exp (-29.7+0.667×Peak body temperature (℃)+0.004×LDH (U/L))/(1+exp (-29.7+0.667×Peak body temperature (℃)+0.004 × LDH (U/L))), the cut-off value to predict RMPP was 0.12, with a consensus of probability forecast of 0.89, sensitivity of 0.89, and specificity of 0.67; and the area under ROC curve was 0.682 (95% CI 0.593-0.771, P<0.01). Conclusion:In MPP patients with fever over 48 to <120 hours, a prediction probability π of RMPP can be calculated based on the peak body temperature and LDH level before the first visit, which can facilitate early identification of RMPP.

Objective:To conduct data mining on hospital accreditation results for inspirations and clues in hospital management.Methods:The Apriori function contained in the arules package of R software was used to extract the association rules. This practice aimed to analyze association rules of the accreditation results of 56 tertiary hospitals which were made based on tertiary hospital accreditation standard(2011)and Detailed Rules from 2017 to 2019; to explore the correlation between the clauses, and analyze the inspirations for hospital management.Results:A total of 6 566 138 and 247 rules were generated for all clauses and core clauses, receptively. The top 10 rules sorted by lift were selected as strong association rules. Among them, the minimum lift of all clauses and core clauses was 1.41 and 1.53, respectively. There was a strong correlation between the establishment of a quality and safety management team in the hospital and the development & implementation of relevant regulations by the hospital. There were strong correlations among emergency service procedure and regulations, patient rights to know, responsibility system by the first one to receive a complaint, medical safety(adverse)event reporting, development & implementation of antimicrobial management system, as well as training for prevention of multi-drug resistance infection measures, and multi-drug resistance infection hospital infection control system.Conclusions:This study suggested that hospital management should highlight the correlation between regulations development and staffing, that between indicator systems and monitoring feedback systems, and that between indicators in different sectors in the medical process. These correlations can be used as management clues and inspirations for hospital management.

Objective To analyze the 14 indicators of on-site evaluation at 18 hospitals under Beijing hospital authority in 2016 , and to provide technical support and reference for further optimization of medical quality and service .Methods According to the "Beijing Municipal Administration of Hospital 2016 On-site Evaluation Indicators", the results were analyzed using the fuzzy combined method of TOPSIS and rank sum ratio , and the ranking of the indicators was sorted .Results TOPSIS method and rank sum ratio weighted fuzzy joint analysis showed that the top three indicators from high to low were medical technology management , patient identification and verification system , clinical care service management;and the last three indicators were hospital-acquired infection monitoring , medical malpractice reporting and management , critical value report and disposal .Conclusions Hospitals are recommended to strengthen their exchange , popularize the concept of continuous improvement , the use of management tools to solve practical problems , and further improve the hospital medical quality and service quality .

Objective To explore the satisfaction of tertiary hospital employees, and to offer a basis for human resources management and decision-making improvement in hospitals.Methods The total area of China was divided into eastern, central and western areas by stratification sampling, and totally 15716 employees from 104 university hospitals and provincial hospitals in the three areas were selected by convenience sampling and investigated. This study was conducted online, and the time of sample return was from October 1st to November 30th, 2015. The employees were investigated for their satisfaction with the status of hospital management with the National Monitoring of Employees' Satisfaction Scale, which took into consideration such characteristics as position, sex, age, marital status, education, income, labor relations, working years and title.Results As for the position, the employees specialized in nursing showed the highest degree of satisfaction (91.10 points), while the employees working on medical positions had the lowest degree of satisfaction (85.34 points). Female employees had a higher degree of satisfaction than male ones, and married employees had a slightly lower degree of satisfaction than unmarried employees. Medical employees at different levels showed different degrees of satisfaction. Clinical front-line employees had lower satisfaction with their give and take than the employees on other positions.Conclusions The HR department of hospitals should pay attention to the employees' real concerns, and take measures to improve medical and nursing staffs' job satisfaction.

OBJECTIVE:To explore the role of clinical pharmacists participating in anti-infective treatment for a child with complex infection. METHODS:Clinical pharmacists participated in treatment process of one child with pulmonary infection and brain abscess after a near-drowning incident,assisted physicians to adjust antibiotics therapy plan,and put several suggestions as the adjustment of anti-gram-positive and anti-gram-negtive bacterium drugs,the dosage adjustment of vancomycin,vancomycin-induced ADR and disposal,the selection of anti-Pasteurella pneumotropica drugs,the enhancement of anti-fungal infection therapy,accord-ing to pathogen characteristics,treatment effect and ADR. RESULTS:Physicians partly adopted the advice of clinical pharmacists, the child’s pulmonary and brain infection were controlled effectively and ADR disappeared after 5 times of adjusting anti-infective the rapy plan. CONCLUSIONS:Clinical pharmacists participate in the treatment process of one child with complex infection,and assist physicians to formulate safe and effective anti-infective plan according to the results of etiological examination;dispose ADR timely and carry out efficacy evaluation of antibiotics and pharmaceutical care,that can give positive effects on patient treatment.

Objective To generate HLA - A * 0201 and A * 2403 restricted HBcAg - specific cytotoxic T lymphocyte (CTL) clones. Methods Peripheral blood mononuclear cells (PBMCs) were derived from a HLA - A * 0201/2403 - positive patient with chron- ic hepatitis B . PBMCs were stimulated respectively using two synthetic peptides( HBc18 ～ 27 and HBc 117 ～ 125) , and epitope -specific CTL clones were generated by limiting dilution technique with PHA alone or combined with synthetic peptides. The cell clones were then characterized by IF staining,FCM and LDH release. Results After 2 weeks of in vitro stimulating PBMCs, specific CTL lines were established. 29 T clones were generated from those CTL lines using HBc18 ～27 stimulating. Among the 29 clones ,28 clones belonged to CD8~+ T cells and all displayed cytolytic activity. 12 CD8 +T clones were generated from those CTL lines using HBc117 ～ 125 stimulating. Specific cytotoxic activity was observed in 9 of those clones. The other three displayed less cytolytic activity. In the process of cloning, PHA was used alone or combined with synthetic peptides,and the achievement showed a rate of 15.62% and 14.58% . Conclusion HBc18 ～ 27 and HBc117 ～ 125 are capable of activating CD8~+ T cells in PBMCs of HLA - A * 0201 /2403 patient with chronic hepatitis B. In the process of CD8~+T cloning, synthetic peptides could not increase the rate of successful cloning.