Objective:To evaluate direct and indirect costs for schizophrenia,major depressive disorder(MDD)and bipolar disorder,and to compare their differences of cost composition,and to explore the drivers of the total costs.Methods:A total of 3 175 inpatients with schizophrenia,MDD,and bipolar disorder were recruited.In-patient's self-report total direct of medical costs outpatient and inpatient,out-of-pocket costs,and direct non-medical costs were regarded as direct costs.Productivity loss and other loss caused by damaging properties were defined as indirect costs.The perspectives of this study included individual and societal levels.Multivariate regression analysis was applied for detecting the factors influencing disease costs.Results:The total cost of schizophrenia was higher than those of MDD and bipolar disorder at individual and societal levels.The indirect costs of three mental disorders were higher than the direct costs,and the indirect cost ratio of bipolar disorder was higher than those of schizophre-nia and MDD.Age,gender,working condition and marital status(P＜0.05)were the important drivers of total costs.Conclusion:The economic burden of the three mental disorders is relatively heavy.Schizophrenia has heaviest disease burden,and the productivity loss due to mental disorders is the driving force of the soaring disease cost

Objective:To construct a value evaluation framework for high-value medical consumables,providing a guidance for medical insurance access and hospital access management scenarios in China.Methods:It conducted literature review,qualitative in-terviews and quantitative surveys.A total of 12 experts were invited for qualitative interviews,while 100 experts from four fields of health technology assessment,medical insurance,hospital management,and clinical practice participated in the quantitative survey.Through those process,it generated the composition of the value framework and the scoring of each item.Differences in ratings be-tween different scenarios and experts were analyzed through chi-square tests.The recommendation level for each item was graded.Re-sults:A comprehensive value evaluation framework for high-value medical consumables was established,which included 6 core dimen-sions,comprised 16 items for secondary dimensions and 50 items for tertiary dimensions.It showed significant differences between the medical insurance access and hospital access scenarios,as well as among different fields of experts in the same scenario.furthermore,grading the items in two scenarios.The medical insurance access scenario had 8 highly recommended items,and the hospital access scenario had 24 highly recommended items.Conclusion:Value evaluation should encourage multi-dimensional assessments and inter-disciplinary participation,continually improving the management of high-value medical consumables in medical insurance and hospital access.

Iodine accumulation represents a differentiation marker of thyroid cancer (TC) and a cornerstone of benefits from 131I therapy. However, dedifferentiation phenotypes occur in nearly 70% of recurrent or metastatic TCs driven by oncogenic mutations such as B-Raf proto-oncogene, serine/threonine kinase (BRAF), telomerase reverse transcriptase (TERT) promoters, and tumor proten p53 (TP53). Beyond genetic alterations, epigenetics, autophagy, tumor microenvironment and other pathways are also involved in the dedifferentiation of TC and the tolerance to 131I therapy. Targeting the above-mentioned pathways has potential to improve the malignant phenotype of TC and restore sensitivity to 131I therapy, which is of great clinical significance. Based on the relevant mechanisms of dedifferentiation, this paper elaborates on the progress of preclinical experiments and clinical studies related to differentiation therapies of TC.

Objective    To evaluate the early and mid-term safety of transcatheter aortic valve replacement via transfemoral (TF), transapical (TAp) and transsubclavian (TSc) approaches by meta-analysis. Methods    We systematically searched the clinical comparative trials published from inception to June 2019 from PubMed, Web of Science, EMbase and The Cochrane Library, to evaluate the safety of transcatheter aortic valve replacement through TF, TAp or TSc approaches. The information of all-cause mortality at 30 days, 1 year, 2 years and the incidence of common complications at 30 days after operation (including pacemaker-dependent block, major vascular complications, severe bleeding events, acute renal injury and stroke) were exacted, and a meta-analysis was conducted by RevMan 5.3 software. Results    This study included 11 literatures, with a total of 7 833 patients, among whom 5 348 patients were treated by TF TAVR, 1 796 patients by TAp TAVR and 689 patients by TSc TAVR. The results of the meta-analysis were as follows: (1)  at 30 days after operation, the mortality of TF and TSc approaches were lower than that of the TAp approach (TF vs. TAp:OR=0.57, 95%CI 0.39-0.84, P=0.004; TSc vs. TAp: OR=4.12, 95%CI 1.93-8.79, P=0.000 3). There was no statistical difference between the TF and TSc approaches (TF vs. TSc: OR=0.98, 95%CI 0.38-2.51, P=0.97); at 1 year, there was no statistical difference in mortality among the three approaches (P>0.05); at 2 years, there was no statistical difference between TSc and TF or TAp approaches (TF vs. TSc: OR=1.21, 95%CI 0.95-1.54, P=0.13; TSc vs. TAp: OR=1.02, 95%CI 0.76-1.36, P=0.91). (2) The incidence of acute kidney injury after TF approach was lower than that of the TAp approach (OR=0.30, 95%CI 0.22-0.41, P<0.000 01). (3) There was no statistical difference in major vascular complications between TSc and TF or TAp approaches (TF vs. TSc: OR=0.75, 95%CI 0.38-1.49, P=0.41; TSc vs. TAp: OR=1.37, 95%CI 0.56-3.32, P=0.49). (4) There was no statistical difference in severe bleeding events between TF and TSc (OR=0.97, 95%CI 0.53-1.76, P=0.92). (5) There was no statistical difference in the incidence of postoperative stroke, pacemaker dependent block among the three approaches (P>0.05). Conclusion    TAp and TSc approaches are safe and effective. They are not only an alternative to TF approach, but also the first choice in some patients with poor condition of iliofemoral artery.

Objective To investigate the effects of human dendritic cells ( DCs) infected by bovine Mycobacterium tuberculosis attenuated live bacteria ( BCG) on differentiation of CD4 +naive T cells from neonate cord blood .Methods After infected with BCG , human DCs were cultured with CD 4 +naive T cells from neonate cord blood, the expression of miRNA-99b in DCs and the expression of Foxp3, ROR-γt, IFN-γand IL-10 mRNAs in CD4+ T cells were detected by qRT-PCR.DCs were transfected with miRNA-99b antisense oligonucleotides and co-cultured with neonatal cord blood CD 4 +naive T cells , and the transcription level of CD4 +T cell-related genes was detected .SPSS 15.0 was used to analyze the data .Results The transcriptional activity of miRNA-99b gene in BCG-infected DCs was significantly higher than that in uninfected DCs (t=7.06,P<0.01).Compared with CD4 +T cells co-cultured with uninfected DCs, the mRNA expression of IFN-γ(45.61 ±4.46 vs.3.54 ±1.73, t=32.32, P<0.01), IL-10 (4.17 ±1.06 vs.1.26 ±0.67, t=2.24, P<0.05) in CD4 +T cells co-cultured with BCG-infected DCs was significantly increased, while the mRNA expression of ROR-γt was significantly decreased ( 0.08 ±0.02 vs.0.63 ± 0.10, t=0.42, P<0.01).Compared with CD4 +T cells co-cultured with DCs transfected with NC-siRNA, the miRNA-99b expression was blocked , the mRNA expression of Foxp3 (0.12 ±0.01 vs.1.57 ±0.90, t=1.06, P<0.05), IFN-γ(0.03 ±0.01 vs.0.64 ±0.35, t =0.44, P<0.05), IL-10(0.03 ±0.01 vs. 0.76 ±0.09, t=0.54,P<0.01) in CD4 +T cells was significantly decreased , while the expression ROR-γt mRNA was significantly increased (17.03 ±5.51 vs.1.32 ±0.14, t=11.54,P<0.01).Conclusion BCG induces the imbalance of initial CD 4 +T lymphocytes into Th17/Treg by regulating the expression of miRNA-99b in DCs, leading to the occurrence and development of infection .

Objective To investigate the treatment,outcomes and disease burden of severe hand-foot-and mouth diseases(HFMD),and to evaluate the compliance to the 2011 guideline for treatment in regions with a high in-cidence of HFMD.Methods A collaborative study group was established including Children's Hospital of Fudan Uni-versity,Jiangxi Provincial Children's Hospital,Anhui Provincial Children's Hospital,Linyi People's Hospital and the Second People's Hospital of Fuyang City.Clinical manifestation,treatment,prognosis and other data of severe HFMD pa-tients were prospectively collected by filling out a survey form in real time from April 2014 to October 2016. Results Two hundred and twenty-six severe HFMD cases were collected during the research time,including 114 ca-ses in stage 2,75 cases in stage 3,and 37 cases in stage 4.Two hundred and twenty-one cases(97.8%)were given mannitol,with a mortality of 6.2%;91 cases(40.3%)were given mannitol and glycerol fructose,with a mortality of 3.3%;the combined use of mannitol and glycerol fructose might have a better result than the single use of mannitol. One hundred and ninety-eight cases(87.6%)were given intravenous immunoglobulin(IVIG).One hundred and ninety cases(84.1%)were given antiviral drugs.One hundred and forty-five cases(64.2%)were given hormone therapy,and the use of hormone could reduce temperature,but did not reduce the mortality.One hundred and fifty cases (66.4%)needed vasoactive agent,including milrinone,dobutamine,phentolamine and sodium nitroprusside. The vasoactive agent use in stage 3 and 4 were 88.0%(66/75 cases)and 91.9%(34/37 cases),respectively.Sixty-nine cases(30.5%)received continuous positive airway pressure(CPAP),91 cases(40.3%)with mechanical ventila-tion,peak inspiratory pressure(PIP)≥20 cmH2O(1 cmH2O=0.098 kPa)accounted for 61.6%(53/86 cases),po-sitive end-expiratory pressure(PEEP)≥10 cmH2O accounted for 36.3%(33/91 cases).The mean mechanical ven-tilation time was(125.9 ± 101.8)h.Eleven cases(4.86%)died or died after giving up treatment,in which the mortality in stage 3 was 6.7%(5/75 cases),and the mortality in stage 4 was 16.2%(6/37 cases).The death causes were respiratory failure,pulmonary hemorrhage,and circulatory failure. The average time from onset to death was (5.91 ± 5.26)(1-15)d.Length of stay in hospital was(9.18 ± 5.16)(1-37)d in which length of stay in hospi-tal in stage 3 and 4 were(11.3 ± 6.35)d,(11.4 ± 6.62)d,respectively,which were significantly longer than that in stage 2[(7.50 ± 3.04)d],and the difference was statistically significant(P <0.05). The cost was(19 136 ± 12 556)CNY,of which the cost in stage 3 and 4 was(23 121 ± 13 846)CNY,(29 849 ± 16 015)CNY,respectively, which were significantly higher than that in stage 2[(12 961 ± 4 272)CNY],and the difference was statistically sig-nificant(P<0.05). Multivariate analysis found that respiratory rhythm abnormality,capillary refill time more than 3 seconds were risk factors for the deaths in the severe HFMD.Conclusion The 2011 edition of guidelines for treat-ment of children with severe HFMD was well executed.Hormone,IVIG,antiviral drugs did not significantly reduce the mortality of severe HFMD in children.

Objective To investigate the clinical features of severe hand,foot and mouth disease (HFMD) in recent three years,and to analyse the risk factors of severe HFMD.Methods A multicenter collaborative research group was set up,including five children's hospitals(pediatric department)with high incidence of HFMD.Prospective epidemiologic approaches were adopted.After training,staffs from the col-laborative center executed the study by filling up the record forms.Results We collected 114 HFMD cases in stage 2,75 cases of HFMD in stage 3,37 cases of HFMD in stage 4 from April 2014 to October 2016.The age ranged from 2 months to 13 years old,the median age was 2 years old,younger than 3 years accounted for 86.3%.Fever was observed in all the severe HFMD,mean temperature was (39.2 ± 0.7) ℃,fever lasted for (4.54 ± 2.89)d.The mean heart rates in stage 2,3,4 were (128.2 ± 13.3,176.1 ± 22.2,184.2 ± 27.5) times/min,respectively.The mean arterial pressure was (84.4 ± 14.6) mmHg(1 mmHg=0.133 kPa),the mean respiratory rate was (39.0 ± 8.4)times/min,the mean respiratory rates in stage 2,3,4 were (37.8 ± 7.36,38.7 ± 8.13,43.4 ± 10.7) times/min,respectively. Respiratory rhythm abnormality in stage 2,3,4 were 9.6%,14.9% and 56.8%,respectively.The blood glucose increased gradually in 2,3 and 4 stages,the mean blood glucose in stage 4 was(12.4 ± 4.74)mmol/L.The incidence of coma in stage 4 was higher than those in stage 2 and 3. Multivariate Logistic regression analysis found that tachycardia,drowsiness,coma, respiratory rate increase,respiratory rhythm abnormality,capillary refilling time more than 3 seconds were risk factors for severe HFMD.Conclusion The incidence of severe HFMD is still high in children under 3 years of age in last three years.The severe patients have obvious changes in the nervous,respiratory and circulatory system. Tachycardia,drowsiness,coma,respiratory rate increase,respiratoy rhythm abnormality,capillary refilling time more than 3 seconds are risk factors for severe HFMD.

Objective To study the levels of plasma catecholamine( norepinephrine,epinephrine and dopamine) in children with severe hand,foot and mouth disease( HFMD) ,and to assess the influence of cate-cholamine on the pathogenesis of severe HFMD. Methods A collaborative study group was established, including Children′s Hospital of Fudan University, Jiangxi Provincial Children′s Hospital, Anhui Provincial Children′s Hospital,Linyi People′s Hospital and No. 2 People′s Hospital of Fuyang City. Blood samples from children with severe HFMD were collected from April 2014 to October 2016. The levels of blood epineph-rine,norepinephrine,dopamine were measured at 2 h,24 h and 48 h after diagnosis for HFMD. Results The level of epinephrine at 24 h after diagnosis was ( 213. 0 ± 139. 8 ) ng/L in children with pulmonary edema, which was significantly higher than that of children without pulmonary edema[(137. 8 ± 45. 5)ng/L)](P=0. 022). The level of epinephrine at 24 h after diagnosis was (373. 2 ± 298. 1)ng/L in the dead children,and was (144. 2 ± 42. 5)ng/L in the survival children. The concentration of norepinephrine at 24 h after diagnosis was (1935. 7 ± 1824. 1)ng/L in the dead children,and was (858. 3 ± 212. 7)ng/L in the survival children. The levels of epinephrine and norepinephrine of those who died from HFMD were significantly higher than those of survival children at 24 h after diagnosis. There were no significant differences in catecholamine con-centrations among stage 2,3,4 HFMDs at 2 h,24 h and 48 h after diagnosis. Sex and enterovirus 71 virus infection had no significant influences on plasma catecholamine concentrations in children with severe HFMD. Conclusion Plasma epinephrine levels increase in children with HFMD complicated with pulmonary edema. Epinephrine and norepinephrine may play an important role in the death of children with severe HFMD.

Objective:To explore the clinical pathological characteristics and improve the recognition in the diagnosis and treatment of incidental (stage T1a -T1b)prostate cancer.Methods:Seven hundred and seventy-one patients who underwent TURP from May 2004 to September 2013 were analyzed retro-spectively.In our institution,TURP specimens should be totally submitted in an extensive sampling method.The tumor area was outlined by estimation of an experienced genitourinary pathologist and calcu-lated by the image analysis system software (Image J 1.47 h).The tumor area was then multiplied by the thickness of tissue.The total sum of all tumor volume was the estimated tumor volume.The clinical and pathological factors,follow-up results were obtained and we aimed to collect information about the period of watchful waiting (WW),PSA progression status,intervention status during the follow-up,the reason for intervention on WW and the type of intervention.Results:The average age of 771 patients was (71.3 ±5.9)years old,and the average BMI was (23.9 ±3.1)kg/m2 ,preoperative average tPSA was (4.4 ±2.8)μg/L.Eighty-six (11.2%)cases of incidental prostate cancer were detected.The patients in T1a group (77 cases,89.5%)had tumor volumes of (12.3 ±12.6)mm3 ,and the patients in T1b group had tumor volumes of (105.1 ±41.8)mm3 .The range of tumor volume was 0.4 -180.2 mm3 . The volume of all the 86 cases was less than 500 mm3 as the threshold of insignificant cancer.All the pa-tients were managed by WW.The mean follow-up time was 88.9 (27.9 -150.1)months.The Gleason score was <7 in 79 patients,and ≥7 in 7 patients.There was no significant difference in age,preopera-tive tPSA,preoperative PSAD,postoperative tPSA,prostate volume and TURP resection between T1a group and T1b group (P >0.05).Among 84 patients without follow-up losts,PSA progression occurred in 5 patients.One T1a patient underwent radical prostatectomy (RP)as an intervention,and 3 patients underwent hormone therapy.One patient in T1b group underwent radiotherapy for PSA progression and one was treated because of patient preference without evidence of disease progression.There were no pa-tients who died due to prostate cancer.Conclusion:Eighty-six (11.2%)cases of incidental prostate cancer were detected.The tumor volume of all the cases was insignificant cancer.The clinical outcomes of IPCa were satisfactory with the initial treatment of WW in the Chinese population.

Objective To establish the core knowledge system of training orthopedics specialist nurses based on post competency.Methods 40 experts were consulted for two rounds using Delphi methods to establish the core knowledge system of training orthopedics specialist nurses.Results Two rounds of consultation were issued 40,37 questionnaires,37,35 valid questionnaires were recovered respectively. Authority coefficient of two rounds consulting was 0.85 and 0.88 respectively.Coordination coefficient of projects and contents for training was 0.62 and 0.35.Determined core knowledge systems for training orthopedics specialist nurses included theoretical knowledge,skills,professional attitude and other 29 items. Conclusions The established core knowledge system of training orthopedics specialist nurses is reliable and valid,which may provide guidance and reference for the training of orthopedics specialist nurse in future.