抗生素的降阶梯治疗（de-escalation therapy）是近年来提出的用于治疗重症肺部感染的一个策略，在临床研究和实践中能够有效地提高重症感染治疗的成功率，降低病死率，同时降低住院时间和费用，是感染治疗策略的一大进展。本文就这一策略的概念演变和应用时机作一介绍
In order to promote the responsible development of precision medicine in China, the current situation of precision medicine in three major fields (clinical, research and commercial) was briefly introduced, and key ethical issues or disputes in each field (including informed consent, return of incidental findings, and allocation of medical resources in the clinical field; informed consent, return of research results, and data use and sharing in the research field; genetic counseling, clinical utility of genetic testing, and use of data in the field of direct-to-consumer genetic testing) were discussed. It is necessary to actively meet these ethical challenges for the development of precision medicine in China.
Objective To investigate whether Chlamydia pneumoniae alters the expression of TLR2 mRNA and p38 MAPK mRNA in mice with Chlamydia pneumoniae infection in TLR2-p38 MAPK-dependent pathway, subsequently leading to the release of cytokines. Methods Seventy-two male C3H/HeJmice were randomly divided into three groups as follow: a normal control group, a C. pneumoniae-inoculated group, and a C. pneumoniae-inoculated with SB203580 treatment group. The mice in the three groups were sacrificed on 1st, 4th, 7th, 14th day separately, and lung tissues were sampled for measurement. The expression changes of TLR2 mRNA and p38 MAPK mRNA in the mice lung tissue were measured by semi-quantitative RT-PCR. The concentrations of TNF-αin the lung tissue were measured by ELISA.Results Compared with those in the normal group, the expressions of TLR2 mRNA and p38MAPK mRNA in the lung tissue increased quickly after C. pneumoniae infection, which was especially obvious on day 4 and on day 7, the expression level of TLR2 mRNA on day 7 was markedly higher than that of the normal group [ ( 7. 24 ±1. 78) mg/L vs.( 0. 64 ±0. 14) mg/L, P lt;0. 05] ; The expression level of p38 MAPK mRNA on day 4 was markedly higher than that of the normal group [ ( 9. 267 ±1. 813) mg/L vs. ( 3. 734 ±0. 946) mg/L, P lt;0. 05] . After 14 days, C. pneumoniae infection of mice was attenuated, the concentration of TNF-α in the lung tissue increased, and was clearly higher than that of the normal control group, peaking on day 4 [ ( 77. 29 ±9. 66) pg/mg] . Treatment with SB203580 could effectively inhibit TLR2 mRNA and p38 MAPK mRNA expression in lung, which was especially obvious on day 4 and on day 7. The expression level of TLR2 mRNA on day 7 was ( 0. 269 ±0. 09) mg/L, and the expression level of p38 MAPK mRNA on day 7 [ ( 0. 002 ±0. 001) mg/L] was even more obviously attenuated, the concentration of TNF-α in the lung tissue markedly decreased when compared with that in the infected group, and its concentration on day 4 [ ( 25. 76 ±3. 49) pg/mg] lowered more clearly. Conclusions The alteration of TLR2-p38 MAPKdependent signal pathway in lungs is closely connected with Chlamydia pneumoniae infection. SB203580 treatment can effectively controll the elevation of TLR2 mRNA and p38 MAPK mRNA expressions in lung. It can effectively control the TLR2-MAPK signal transduction pathway.
ObjectiveTo observe the effect of vascular endothelial growth factor/polylactide-polyethyleneglycol-polylactic acid copolymer/basic fibroblast growth factor (VEGF/PELA/bFGF) mixed microcapsules in promoting the angiogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs) in vitro. MethodsThe BMSCs were isolated by the method of whole bone marrow adherent, and sub-cultured. The passage 3 BMSCs were identified by Wright-Giemsa staining and flow cytometry, and used for subsequent experiments. VEGF/PELA/bFGF (group A), PELA/bFGF (group B), VEGF/PELA (group C), and PELA (group D) microcapsules were prepared. The biodegradable ability and cytotoxicity of PELA microcapsule were determined, and the slow-released ability of VEGF/PELA/bFGF mixed microcapsules was measured. The passage 3 BMSCs were co-cultured with the extracts of groups A, B, C, and D, separately. At 1, 3, 7, 14, and 20 days after being cultured, the morphological changes of induced BMSCs were recorded. At 21 days, the induced BMSCs were tested for DiI-labeled acetylated low density lipoprotein (Dil-ac-LDL) and FITC-labeled ulex europaeus agglutinin I (FITC-UEA-I) uptake ability. The tube-forming ability of the induced cells on Matrigel was also verified. The differences of the vascularize indexes in nodes, master junctions, master segments, and tot.master segments length in 4 groups were summarized and analyzed. ResultsThe isolated and cultured cells were identified as BMSCs. The degradation time of PELA was more than 20 days. There was no significant effect on cell viability under co-culture conditions. At 20 days, the cumulative release of VEGF in the mixed microcapsules exceeded 95%, and the quantity of bFGF exceeded 80%. The morphology of cells in groups A, B, and C were changed. The cells in groups A and B showed the typical change of cobble-stone morphology. The numbers of double fluorescent labeled cells observed by fluorescence microscope were the most in group A, and decreases from group B and group C, with the lowest in group D. The cells in groups A and B formed a grid-like structure on Matrigel. Quantitative analysis showed that the differences in the number of nodes, master junctions, master segments, and tot.master segments length between groups A, B and groups C, D were significant (P<0.05). The number of nodes and the tot.master segments length of group A were more than those of group B (P<0.05). There was no significant differences in the number of master junctions and master segments between group A and group B (P>0.05). ConclusionVEGF/PELA/bFGF mixed microcapsules have significantly ability to promote the angiogenic differentiation of rat BMSCs in vitro.
ObjectiveTo explore the role of chest wall arteriovenous graft (CWAVG) for establishing hemodialysis access in patients with end-stage renal disease.MethodsA retrospective analysis was made on the clinical data of 12 patients with end-stage renal disease who underwent CWAVG for establishing hemodialysis access between January 2014 and June 2015. There were 3 males and 9 females with an average age of 63.6 years (range, 54-82 years). The renal disease causes were chronic glomerulonephritis in 2 cases, hypertensive renal damage in 4 cases, diabetic nephropathy in 1 case, both kidney resection because of urinary tract tumors in 3 cases, and causes unknown in 2 cases. Hemodialysis time ranged from 1 to 144 months, with an average of 38.4 months. The 12 patients all underwent 1-14 times (mean, 4.2 times) anterior pathway failure in CWAVG, all of which were caused by repeated occlusion of dialysis pathway or poor vascular condition of upper extremity, resulting in the exhaustion of vascular pathway in upper extremity.ResultsAll patients were followed up 30-48 months (mean, 35.4 months). Two patients died, including 1 case of digestive tract hemorrhage, 1 case of heart failure. The other 10 CWAVGs were functionally useful for hemodialysis access about 6 weeks after operations. The primary patency rates at 6, 12, 18, 24, and 30 months were 83.3%, 75.0%, 33.3%, 33.3%, and 16.7%, respectively, and the cumulative patency rates at 6, 12, 18, 24, and 30 months were 83.3%, 75.0%, 50.0%, 33.3%, and 16.7%, respectively. Among 8 cases of CWAVG dysfunction, 6 cases had thrombosis, 1 case had seroma, and 1 case had vertebral artery stealing. Among them, 4 patients underwent hemodialysis using tunneled-cuffed catheter, 3 patients using fistula or graft on other limbs, and 1 patient was not treated with hemodialysis.ConclusionAlthough the long-term patency rate of CWAVG is yet to be further increased by improvement of treatment strategies, but it is still a supplementary option for end-stage renal disease patients with inadequate upper extremity venous access sites.
Objective To evaluate the effect of pulse dye-densitometry by indocyanine green test (PDD-ICG)on the assessment of hepatic function reserve. MethodsSeventy-five hepatic carcinoma patients aimed to accept hepatectomy from March 2007 to February 2008 at West China Hospital were prospectively included in this study.Patients were grouped by dysfunction grade of hepatic function and the indexes before operation were compared.Furthermore, patients were grouped by K and R15 value to compare the moderate and severe liver dysfunction ratio, respectively. ResultsSixty cases manifested slight liver dysfunction,12 cases manifested moderate liver dysfunction,and 3 cases manifested severe liver dysfunction(the latter was took into moderate group due to the cases were too few).The difference of Child-Pugh score and common liver function examination indexes such as PT and INR before operation was not significant betweentwo groups(P＞0.05).ButPDD-ICG experiment indexes(K and R15)were remarkable different betweentwo groups(P＜0.05).The patients were divided into two groups according to K and R15 value,respectively.The rate of moderate and severe liver dysfunction was significant different between K＜0.158/min groupand K≥0.158/min group(47.1% vs. 12.1%,P＜0.05),and likewise moderate and severe liver dysfunction was significant different between R15≤10% group and R15＞10% group(15.9% vs.41.7%,P＜0.05）. ConclusionPDD-ICG is an effective and easyto evaluate hepatic function reserve of patient undergone hepatectomy.Therefore,it may give clinical instruction to predict and avoid the liver dysfunction after operation.
Coronary microcirculation dysfunction (CMVD) is an important risk factor for the prognosis of re-perfused ischemic heart. Recent studies showed that the evaluation of CMVD has significant impact on both the early diagnosis of heart diseases relevant to blood supply and prognosis after myocardial reperfusion. In this review, the definition of CMVD from the perspective of pathophysiology was clarified, the principles and features of the state-of-the-art imaging technologies for CMVD assessment were reviewed from the perspective of engineering and the further research direction was promoted.
Objective To investigate the dynamic changes of postoperative liver reserve function and laboratory liver function as well as liver volume regeneration, and their potential relationship with short-term clinical outcomes after adult-to-adult living donor liver transplantation (LDLT). Methods The data of 30 recipients underwent LDLT were prospectively collected. The plasma clearance (K) by indocyanine green (ICG) excretive test, liver function test by laboratory methods, liver volume by CT and shortterm (lt;3 months) complications were analyzed. Results The graft recipient body weight ratio (GRBW) was 0.63%-1.43%. The hepatic volume of the recipients in the operation was (638±103) ml, which was smaller than that day 7, 30, and 90 after operation (Plt;0.001), but the hepatic volume at subsequent time point was not different from that at the former time point (Pgt;0.05). The KICG values of recipients among the day 3 〔(0.177±0.056)/min〕, 7 〔(0.183±0.061)/min〕, 30 〔(0.200±0.049)/min〕, and 90 〔(0.209±0.050)/min〕 after operation gradually increased, which was respectively higher than that of recipients before operation (P=0.006, P=0.002, Plt;0.001, and Plt;0.001). Compared with the baseline KICG 〔(0.228±0.036)/min〕 of the donors, the KICG of recipients showed significant variation on day 3 and 7 after operation (P=0.004 and P=0.015), and the KICG of recipients on day 30 and 90 after operation approached the baseline KICG (P=0.355 and P=0.915). The recipients were divided into good liver function group (n=23) and poor liver function group (n=7) according to total serum bilirubin on day 14 after operation. The KICG significantly dropped compared with the recipients of good liver function group on day 3 after operation (P=0.001). Conclusions The liver volume regenerates dramatically on day 7 after operation for the recipients. The ICG excretivetest shows that volume recovery occurs much more gradually than the recovery of function in the recipients. The ICG excretive test is a more reliable indicator of graft function and subsequent graft outcome early after LDLT.