Objective To evaluate the mode of referral by response time for inter-hospital transfer of critically ill pediatric patients,and subsequently some measures taken for minimizing the response time in referral process.Methods A total of 9231 patients (≤14 years) transferred from primary hospital were included in a cross-section study.Information about age,sex,referral radius,the seasonal variation for inter-hospital transport of critically ill pediatric patients,time of referral telephone call and response time were collected.All computations were performed using the Statistic Package for Social Sciences for Windows version 18.0.Differences between groups were assessed by x2 tests or Wilcoxon test or Kruskal-Wallis for categorical data.Results Among all critically ill pediatric patients for the inter-hospital transfer,male to female ratio was 2.24:1,and the majority of patients were neonates and infants.Median retrieval mobilization time was 30 min (interquartile range,20-50 min).This study has demonstrated that referral time,age categories,referral radius,different years and seasons were associated with response time.Conclusions With the improvement of technologies and management mechanism,the response time was apparently minimized since the beginning of interhospital transportation.But there is still plenty of room for shortening rsponse time compared with advanced Westem countries.

Objective To investigate the adrenal histopathology damage in critically ill non-survival children,and the incidence of adrenal damage,and to explore the risk factors for the adrenal hemorrhage and necrosis in critically ill children.Methods A total of 141 critically ill non-survival children was admitted in this study in Hunan Children's Hospital from January 1,2005 to December 30,2012.Clinical data in children were systematically collected,including age,sex,sodium,potassium,blood gas analysis,liver and kidney function,blood clotting function,etiology,treatment and pediatric clinical illness score (PCIS) or neonatal critical illness score (NCIS),and pathological data.All data were analyzed by SPSS 18.0.Results Logistic regression analysis showed the factors of adrenal hemorrhage and necrosis of critically ill non-survival children were sepsis,PCIS score ＜ 80 critically ill children are risk factors for adrenal hemorrhage necrosis (P ＜ 0.05),ORwas 3.659 (95％ CI:1.344-9.965),and 2.325 (95％ CI:1.028 -5.258).Intravenous corticosteroids were protective factors for critically ill non-survival children with adrenal hemorrhage necrosis (P ＜ 0.05),and ORwas 0.377 (95％ CI:0.163-0.875).Conclusions There were two significant risk factors of adrenal hemorrhage and necrosis:sepsis and critical illness score less than 80 points.Intravenous corticosteroid is a protective factor in critically ill children.

Objective To introduce the clinical experience of 4 cases of left atrial decompression via minithoracotomy technique in pediatric application under venoarterial extracorporeal membrane oxygenation (VA‐ECMO) in pediatric fulminant myocarditis treatment. Methods The clinical data of 4 patients with VA‐ECMO support for fulminant myocarditis admitted in Zhengzhou Children′s Hospital and Bayi Children′s Hospital Affiliated to the Seventh Medical Center of PLA General Hospital from July 2017 to October 2018 were reviewed. Results A total of 4 patients with fulminant myocarditis supported by VA‐ECMO received left ventricular decompression,and left atrial decompression was performed by left atrial intubation with a small incision near the left sternum. Left heart ultrasound showed that left heart function improved after de‐compression. One case with ventilator was still Ⅲ degree atrioventricular block after weaning,and installed permanent pacemaker postoperative 1 month. One case had more pleural drainage and improved after adjus‐ting anticoagulation. One case died due to the termination of treatment by the guardian. A total of 3 cases sur‐vived,and the recent follow‐up results were satisfactory. Conclusion Left artrial decompression of this mini‐mally invasive technique can improve left ventricular function in children with fulminant myocarditis suppor‐ted by VA‐ECMO. It is safe, feasible with small trauma and bleeding controlled.

Objective:To analyze the risk factors of subdelirium syndrome in Intensive Care Units (ICU) patients, build a risk prediction model and verify the prediction performance of the model.Methods:From July 2021 to February 2022, 443 ICU patients who were admitted to the Affiliated Hospital of Zunyi Medical University were selected by convenient sampling. The patients were divided into subdelirium syndrome group ( n=151) and non-subdelirium syndrome group ( n=292) according to whether they had subdelirium syndrome. The binomial Logistic regression was used to screen out independent influencing factors to construct a risk prediction model of subdelirium syndrome in ICU. The prediction effect of the model was tested by the area under the curve ( AUC) of receiver operating characteristic curve. According to the same standard, 147 ICU patients admitted to the Affiliated Hospital of Zunyi Medical University from March to April 2022 were selected for external validation of the model. Results:The risk prediction model of subdelirium syndrome in ICU was Y=-4.126+1.569×Acute Physiology and Chronic Health Evaluation (APACHE) Ⅱ score+1.261×pain score+1.643×total leukocyte+1.276×albumin +1.530 × operation or not. The internal validation of the model showed that the AUC was 0.878 [95% confidence interval (0.844, 0.912) ], the maximum Youden index was 0.614, the sensitivity was 74.8%, and the specificity was 86.6%. Hosmer-Lemeshow goodness of fit test showed that χ 2=2.743, P>0.05. The external validation of the model showed that the sensitivity was 92.6% and the specificity was 95.7%. Conclusions:This risk prediction model of subdelirium syndrome in ICU has good prediction performance, which can help medical and nursing staff identify high-risk patients with subdelirium syndrome in ICU as soon as possible.

Objective To analyze the impact of canceling drug price markup policy on hospitalization expenses of urban public hospitals in Sichuan province and provide decision-making basis. Methods Data of hospitalization expenses of the top 50 diseases among inpatients discharged in 2016 and 2017 were collected, totaling 2 732 022 inpatient cases. Based on hospitalization expenses, these disease were divided into seven categories ( A-G) using dynamic clustering analysis, which represent respectively dominant diseases of different expense makeups, to compare such indicators as hospitalization expenses and composition ratios of these diseases before (2016) and after the reform (2017). Results The study found drastic changes among the medical expenses of different categories of dominant diseases. For example, per-hospitalization cost of categories E ( featuring high drug and examination expenses ) and G ( featuring balanced expenses distribution) diseases decreased since the reform, while the other categories rose instead. The proportion of drugs of different disease categories decreased to various extents. For example, category A ( high drug ratio of 5.60% ) and category E (5.15% ) diseases of which were found with the sharpest drop. Proportion of service expenses, on the other hand, rose to different extents. For example, the proportion of service expenses of all disease categories increased to varying degrees, among which category E (3.46% ), category F (3.37% ) and category D (3.36% ) accounted for the largest share of increase.Conclusions The reform is moving the cost structure of dominant diseases in Sichuan towards a rational level, yet with significant differences among disease categories. The authorities should target various categories to adjust their reimbursement policies, minimize financial burden on patients, strengthen their supervision on drug use and medical behavior, prevent such misbehaviors as the inducing demands and transferring drug markups.

Objective:To explore the clinical effect of antibiotic bone cement combined with delayed lateral supramolleolar perforator fascial flap in the treatment of diabetic foot(DF).Methods:From April 2020 to July 2021, a total of 6 patients with DF were treated with antibiotic bone cement combined with delayed lateral supramolleolar perforator fascial flap. The patients were 5 males and 1 female, aged from 45 to 67 years old with an average of 56.2 years old. The wounds were all located in dorsal foot, 4 in right foot and 2 in the left. The wound area was 2.4 cm×5.0 cm-6.5 cm×10.0 cm. The depth of wound were: 3 cases up to tendon layer, and 3 cases up to metatarsal bone. Two of the wound were complicated with metatarsal osteomyelitis. The wounds at Wagner grade 3 in 4 patients and grade 4 in 2 patients. The flap size was 3.0 cm×6.0 cm-8.0 cm×11.0 cm. All of the wounds were repaired with delayed supramolleolar perforator fascia flap after debridement, application of antibiotic bone cement and fumigation with Sanhuang decoction(a traditional Chinese medicine). The affected limbs were externally fixed with plaster and raised after surgery, and the colour, temperature, tension and capillary reaction of the flaps were closely observed. Stitches were removed 2 weeks after surgery and rehabilitation of the affected limb was performed. Regular follow-up was made postoperatively. The appearance of flaps and the scar of donor and recipient sites were observed. The foot and ankle function were evaluated by the American Orthopaedic Association foot and Ankle Surgery(AOFAS) score scale.Results:Six cases of DF had no recurrence of wound infection. All flaps survived well. The average follow-up time was 6(3-14) months. The postoperative follow-up revealed satisfactory appearance of the flap, only linear scars remained in the donor and recipient sites. The function of foot and ankle recovered well with full weight-bearing and normal walk. AOFAS scores ranged from 81 to 95.Conclusion:It is an effective method to treat DF by applying antibiotic bone cement combined with delayed superior lateral malleolus perforator fascial flap. The operation is simple, safe and can cut down the time of treatment, quickly control the wound infection. It deserves further trials.

Objective:To explore the effects of miRNA-373-3p (miR-373-3p) on the proliferation of nephroblastoma G401 cells through targeted regulation of CD44 expression.Methods:Bioinformatic method was used to predict the possible targeted genes of miR-373-3p based on bioinformatic databases including miRDB, miRanda, PITA and DIANA-microT. G401 cells were taken and transfected with miR-373-3p mimic, mimic negative control, miR-373-3p inhibitor or inhibitor negative control, respectively. Cell proliferation ability was detected by using CCK-8 assay. The number of clones was detected by using clone formation assay. The relative expression level of CD44 mRNA was detected by using real-time fluorescent quantitative polymerase chain reaction (qRT-PCR), and the expression level of CD44 protein was detected by using Western blotting. The dual luciferase gene reporter assay was carried out in HEK-293T cells to vertify the target gene of miR-373-3p.Results:Bioinformatic analysis indicated that CD44 was a targeted gene of miR-373-3p. After 24 h transfection, the proliferation activity of G401 cells in miR-373-3p mimic group was decreased compared with that in mimic negative control group (all P < 0.05). After 48 h transfection, the proliferation activity of tumor cells in miR-373-3p inhibitor group was increased compared with that inhibitor negative control group (all P < 0.05). The formed number of clones in miR-373-3p mimic group was reduced compared with that in the mimic negative control group (55.3±2.5 vs. 90.7±2.9), and the difference was statistically significant ( t = 14.57, P < 0.01). The formed number of clones in miR-373-3p inhibitor group was more than that in inhibitor negative control group (115.0±2.7 vs. 92.0±2.4), and the difference was statistically significant ( t = 8.86, P < 0.01). The dual-luciferase gene reporter assay showed that CD44 was a direct targeted gene of miR-373-3p. The relative expression levels of CD44 mRNA in miR-373-3P mimic and mimic negative control group were 0.62±0.03 and 1.00±0.01, respectively, and the difference was statistically significant ( t = 11.28, P < 0.01). The relative expression levels of CD44 mRNA in miR-373-3p inhibitor and inhibitor negative control group were 1.31±0.02 and 1.00±0.00, respectively, and the difference was statistically significant ( t = 12.65, P < 0.01). The CD44 protein expression was decreased in miR-373-3p mimic group, while increased in miR-373-3p inhibitor group. Conclusion:miR-373-3p can inhibit tumor cell proliferation by targeting CD44 in nephroblastoma.

Objective To analyze the interaction between voriconazole(VRC)and immunosuppressants such as tacrolimus and cyclosporine and the effect of CYP2C19 gene polymorphism on the interaction and adverse reactions(ADR)based on the results of CYP2C19 gene polymorphism and therapeutic drug monitoring,so as to provide a basis for the development of individualized VRC combined with immunosuppressants.Methods Two-dimensional liquid chromatography and pyrosequencing was used to detect the concentration of VRC and the CYP2C19 gene pol-ymorphism,respectively.And the concentration of immunosuppressants was detected at the same time.The rela-tionship among CYP2C19 gene polymorphism,the concentration of VRC and immunosuppressant and ADR was an-alyzed.Results A total of 61 patients were enrolled in this study,and the mutation rates of CYP2C19*2 and CYP2C19*3 were 54.1％(33/61)and 9.84％(6/61),respectively.The concentrations of VRC in patients with extensive metabolism(EMs),intermediate metabolism(IMs)and poor metabolism(PMs)were(4.44±3.46),(3.62±3.02)and(10.05±1.46)μg/ml(P＜0.05),respectively.The concentration of tacrolimus af-ter combined with VRC significantly increased compared to tacrolimus alone[(13.4±9.2)ng/ml vs(6.5±3.6)ng/ml;P=0.002],and the concentration of tacrolimus increased along with an increasing of VRC concentration.The concentration of VRC in patients combined with tacrolimus was lower than that in patients without immunosup-pressants[(3.81±3.48)μg/ml vs(5.84±3.71)μg/ml;P=0.032].The concentration of VRC inpatients with cyclosporine significantly decreased(P＜0.01),while tacrolimus and mycophenolate mofetil had no signifi-cant effect on the concentration of VRC.45.90％(28/61)of the patients had adverse reactions,the concentration of VRC in patients with ADR was significantly higher than that in patients without ADR[(7.07±3.43)μg/ml vs(3.06±2.90)μg/ml;P＜0.001].And the concentration of VRC in patients with ADR was higher than patients without ADR with based on CYP2C19 genotype.Conclusion CYP2C19 gene polymorphism can significantly affect the concentration and adverse reactions of VRC,and VRC has significant interaction with immunosuppressants such as tacrolimus.CYP2C19 gene polymorphism combined with therapeutic drug monitoring can improve the individual-ized treatment of tacrolimus and voriconazole,and is expected to minimize toxicity and improve treatment effects.

OBJECTIVE To introduce a case of interstitial pneumonia induced by vedolizumab （VDZ）， summarize and analyze the characteristics of the occurrence of VDZ-associated lung toxicity， and provide a reference for the clinically safe use of drugs. METHODS From the perspective of clinical pharmacists， the diagnosis and treatment of a case of VDZ-induced interstitial pneumonia were retrospectively analyzed， and the association of adverse drug reactions （ADR） was analyzed. Retrieving from Chinese and English databases such as CNKI， VIP， PubMed and Web of Science， case reports of VDZ-associated lung toxicity were summarized and analyzed. RESULTS The patient developed interstitial pneumonia during the use of VDZ and empirical anti- infective therapy with antibiotics was ineffective. After withdrawal of VDZ and treatment with methylprednisolone， symptoms and imaging examinations improved， but interstitial pneumonia still existed. According to Naranjo’s ADR evaluation scale and based on China Adverse Drug Reaction Reporting and Monitoring Manual， the association between VDZ and interstitial pneumonia was “very likely”. Results of the literature analysis showed that among 29 involved patients （including the patient reported in this article）， there were 19 males and 10 females， with an average age of （49.24±17.06） years. Lung toxicity mainly included VDZ- associated pneumonia， eosinophilic pneumonia， pulmonary granulomas or necrobiotic nodules， interstitial lung injury， etc.， which mostly occurred ≤24 weeks after medication （58.62%）. The main clinical manifestations included cough， dyspnea and fever. The vast majority of patients improved or recovered after drug withdrawal and/or glucocorticoid treatment， but one patient died of respiratory failure. CONCLUSIONS Lung toxicity is a rare ADR of VDZ with insidious onset and nonspecific symptoms. Once patients experience symptoms such as cough and dyspnea， early diagnosis，timely drug withdrawal，and symptomatic treatment measures such as glucocorticoid should be taken to ensure medication safety.

Objective:To evaluate the clinical characteristics and prognosis of gallbladder cancer (GBC) patients in China.Methods:This retrospective multicenter cohort study enrolled 3 528 consecutive GBC patients diagnosed between January 2010 to December 2017 in 15 hospitals from 10 provinces. There were 1 345 (38.12%) males and 2 183 (61.88%) females.The age of diagnosis was (63.7±10.8) years old (range: 26 to 99 years old) .There were 213 patients (6.04%) in stage 0 to Ⅰ, whereas 1 059 (30.02%) in stage Ⅱ to Ⅲ, 1 874 (53.12%) in stage Ⅳ, and 382 (10.83%) unavailable. Surgery was performed on 2 255 patients (63.92%) . Three hundred and thirty-six patients received chemotherapy or radiotherapy (9.52%; of which 172 were palliative); 1 101 (31.21%) received only supportive treatment.The patient source, treatment and surgery, pathology, concomitant gallstone, and prognosis were analyzed.Results:Among the 3 528 GBC patients, 959 (27.18%) were from East China, 603 (17.09%) from East-North China, 1 533 (43.45%) from Central China, and 433(12.27%) from West China. Among the 1 578 resectable tumor, 665 (42.14%) underwent radical surgery, 913 (57.86%) underwent surgery that failed to follow the guidelines.Eight hundred and ninety-one (56.46%) patients were diagnosed before surgery, 254 (16.10%) during surgery, and 381 (24.14%) after surgery (time point of diagnosis couldn′t be determined in 52 patients) .Among the 1 578 patients with resectable tumor, 759 (48.10%) had concomitant gallstone.Among the 665 patients underwent radical surgery, 69 (10.4%) showed positive resection margin, 510 (76.7%) showed negative resection margin, and 86 (12.9%) unreported margin status.The 5-year overall survival rate (5yOS) for the 3 528-patient cohort was 23.0%.The 5yOS for patients with resectable tumor was 39.6%, for patients with stage ⅣB tumor without surgery was 5.4%, and for patients with stage ⅣB tumor underwent palliative surgery was 4.7%.Conclusions:More than half GBC patients in China are diagnosed in stage Ⅳ.Curative intent surgery is valuable in improving prognosis of resectable GBC.The treatment of GBC needs further standardization.Effective comprehensive treatment for GBC is in urgent need.