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Malunion is a common complication following a calcaneal fracture which was not treated or treated inappropriately.It is a therapeutic target and a great challenge as well to relieve pain, correct deformity and restore the function of the affected foot in clinical treatment of calcaneal malunion. As a result of researches by scholars at home and abroad focusing on the biomechanical mechanisms underlying the symptoms caused by calcaneal malunion, a variety of corrective calcaneal osteotomy has been widely applied in clinical practice to specifically correct the calcaneal deformity and restore normal calcaneal morphology. This review expounds on the techniques, outcomes, indications and complications of corrective calcaneal osteotomies commonly used in clinic.
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Mesenchymal stem cells (MSCs) are a class of pluripotent cells that can self-renew and differentiate. Numerous studies have shown that MSCs have important roles in areas such as regenerative medicine and tissue engineering. However, it is worth noting that MSCs will gradually age during long-term in vitro expansion with decreased stemness such as weakened migration ability, slowed proliferation rate and decreased differentiation potential, which greatly hinders the application of MSCs. Currently, the microenvironment for cell growth is recognized as one of the factors causing senescence in MSCs. Recent studies point out that the latest technologies such as exogenous administration, oxygen concentration regulation and extracellular matrix (ECM) construction can delay stem cell senescence by simulating or regulating the microenvironment. Here, we review the current knowledge of the characteristics and molecular mechanisms of senescent MSCs and microenvironment strategies to maintain MSCs stemness, which can provide a reference for future large-scale application of MSCs preparations in tissue engineering and clinical studies.
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Cell Differentiation , Cell Proliferation , Cells, Cultured , Cellular Senescence , Extracellular Matrix , Mesenchymal Stem CellsABSTRACT
Objective:To observe the therapeutic efficacy and prognosis of daratumumab combined with chemotherapy bridging to allogeneic hematopoietic stem cell transplantation (allo-HSCT) followed by daratumumab and lenalidomide maintenance treatment for primary plasma cell leukemia (PCL).Methods:The clinical data of a patient with primary PCL admitted to the First People's Hospital of Yunnan Province in January 2020 were retrospectively analyzed, and relevant literatures were reviewed.Results:The patient was diagnosed with primary PCL and treated with daratumumab combined with BD (bortezomib + dexamethasone) for 1 course and BCDD (bortezomib + cyclophosphamide + liposomaldoxorubicin + dexamethasone) for two courses. The patient was treated with daratumumab combined with allo-HSCT after complete remission. The donor cells were successfully implanted and the chimerism rate of donor cells was 94.36% without acute graft-versus-host disease reaction. And then the patient received intermittent maintenance therapy of daratumumab combined with low dose lenalidomide after transplantation, and the current remission period after transplantation reached 4 months.Conclusions:Daratumumab combined with chemotherapy bridging to allo-HSCT followed by daratumumab and lenalidomide may improve the prognosis of primary PCL and prolong survival time.
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OBJECTIVE：To evaluate the pharmacoec onomics of Enalapril folic acid tablet and Enalapril tablet for stroke prevention in patients with hypertension. METHODS ：Markov model was constructed by using Excel 2016 software. Patients with essential hypertension were selected as the research object with 1 year cycle and 20 years horizon. From the perspective of health system，the pharmacoeconomics of Enalapril folic acid tablets versus Enalapril tablets for stroke prevention in patients with hypertension was compared by cost-effectiveness analysis ，and the stability of the research results was verified by sensitivity analysis. RESULTS ：Compared with Enalapril tablet ，the incremental cost-effectiveness ratio of Enalapril folic acid tablet was 221 323 yuan/QALY，which was higher than three times of China ’s per capita GDP in 2020（217 341.04 yuan）. The results of single factor sensitivity analysis and probabilistic sensitivity analysis were consistent with that of basic analysis. CONCLUSIONS ： Compared with Enalapril tablet ，Enalapril folic acid tablet doesn ’t have a better economy for patients with hypertension.
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@#Objective To explore the factors that affect the accuracy of percutaneous thermal ablation of lung metastases and coping strategies. Methods We retrospectively analyzed the clinical data of 31 patients who met the conditions for thermal ablation of lung metastases in Ninth People’s Hospital affiliated to Shanghai Jiao Tong University School of Medicine between October 2019 and December 2020. There were 19 males and 12 females with a mean age of 40-81 (62.8±10.3) years. A total of 33 metastases tumors were thermally ablated, 12 were radiofrequency ablation and 19 were microwave ablation. Results Of the 33 metastatic tumors, 5 targets showed significant puncture deviation, 4 of them completed the ablation after adjustment and 1 failed. The result of the univariate logistic regression showed the distance within the lung parenchyma (P=0.043) and the maximum diameter of the tumor (P=0.025) were independent risk factors for the accuracy of percutaneous thermal ablation. In terms of correlation, there was a positive correlation between the accuracy of percutaneous thermal ablation and the distance within the lung parenchyma (P=0.033), and a negative correlation between the maximum diameter of metastases tumor (P=0.004) and hemoptysis (P=0.015). Complete ablation rate was 87.8% (29/33). Conclusion When we perform CT-guided percutaneous thermal ablation of lung metastases, we must fully prepare the deviation plan for the small diameter tumor, the long travel distance in the lung parenchyma, and hemoptysis during puncture. Complete ablation can be achieved by fully identifying the anatomical features of the tumor and its surrounding structures, shortening the travel distance in the lung parenchyma and increasing the ablation range.
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OBJECTIVE：To pr ovide reference for the future pharmacoeconomic evaluation. METHODS ：Four typical cases of pharmacoeconomic evaluation showed the special situation that “not cost-effective at a zero price ”，defined the concept of “net value”to assist in theoretical analysis ，and summarized the possible causes of this situation . RESULTS & CONCLUSIONS ：The system（ATPS）：an overview and advances in its applica background treatment cost other than the target drug was too high ，the patient ’s quality of life during survival was too low ，the threshold of willingness to pay of incremental cost-effectiveness ratio was too low ，the cost of risk events during extended survival was too high or the health loss was too high ，and the price of the control scheme was too low ，which might affect the results of economic evaluation ，and even le d to the dilemma of pharmacoeconomic evaluation of “not cost-effective at a zero price ”. Pharmacoeconomic evaluation discusses the economy of intervention programs rather than the economy of drugs. The uneconomic results caused by various reasons need to be treated objectively ；theoretically，all“relevant”and“irrelevant”costs should be included in the calculation category in pharmacoeconomic evaluation ；pharmacoeconomics mainly solves the problem of “cost performance”comparison among several treatment schemes ，and the medical and health field often needs to face problems such as ethics and fairness. Therefore ，researchers may need to jump out of the framework of pharmacoeconomics analysis and conduct in-depth discussion from a higher and broader perspective.
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OBJECTIVE：To provide reference for the selection of more economical programmed death- 1（PD-1）/programmed death-ligand 1（PD-L1）inhibitors for National Medical Insurance List and the quality improvement of related economic evaluation. METHODS：Retrieved from CNKI ，VIP，Wanfang database ，PubMed，Web of Science and Ovid Embase ，economic evaluation studies including listed PD- 1/PD-L1 inhibitors of China were collected during the inception to Oct. 2020. CHEERS checklist was used to evaluate the quality of the included literatures ，and the methodological characteristics and economic evaluation results of the included studies were analyzed systematically. RESULTS ：A total of 14 literatures were included ，all of which were model-based and with moderate or high quality. However ，there were still some deficiencies in the included literatures ，mainly manifesting as the insufficient reports on the reasons for setting or selecting model parameters ，as well as the great uncertainty of clinical effect data and utility value. Only 3 of the 8 PD-1/PD-L1 inhibitors listed in China were involved in the included literatures. Compared with chemotherapy or targeted therapy plan ，9 literatures（64.29％）showed that the therapy plan containing PD- 1/PD-L1 inhibitors was not cost-effective. CONCLUSIONS ：The economic evidence of domestic PD- 1/PD-L1 inhibitors is lacking ，the higher price of imported PD- 1/PD-L1 inhibitors lead to poor economic performance. The existing economic evaluations has some shortcomings in methodological application and parameter selection. Pharmaceutical enterprises should fill in the data gaps and adjust the pricing strategy，researchers should improve the standardization of research ，and medical insurance decision-making departments should improve the judgment on the quality of economic evidences ，so as to promote more economical drugs to be included in the National Medical Insurance List.
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Type 1 diabetes mellitus(T1DM)is a chronic, immune-mediated disease characterised by the destruction of insulin-producing cells.The specific pathogenesis of T1DM has not been clarified.It is mainly believed that the occurrence of T1DM is caused by the joint action of genetic and environmental factors.The occurrence, development, treatment and prevention of T1DM are urgent problems to be solved.A number of studies have found that vitamin D is involved in the pathological process of many autoimmune diseases and is related to cell proliferation, differentiation, apoptosis and other mechanisms.Vitamin D may play a key role in the pathological mechanism of T1DM.Here we review the relationship between the incidence, prevention and treatment of T1DM and vitamin D.
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Ischemic stroke is the second leading cause of death worldwide with limited medications and neuroinflammation was recognized as a critical player in the progression of stroke, but how to control the overactive neuroinflammation is still a long-standing challenge. Here, we designed a novel SIRT6 activator MDL-811 which remarkably inhibited inflammatory response in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and primary mouse microglia, which were abolished by silencing SIRT6. RNA-seq screening identified the forkhead box C1 (
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Objective:To investigate the correlation between concomitant diabetes mellitus and clinical features in patients with COVID-19.Methods:Fifty patients with COVID-19 admitted to the Sixth People′s Hospital of Shenyang were divided into 2 groups with and without diabetes mellitus. Indexes such as hospitalization days, duration of positive virus-PCR result, secondary infection, duration of fever, rate of liver dysfunction, and rate of cardiac injury were compared between 2 groups.Results:The average hospitalization durations of diabetes group and control group were(24.0±6.8) and(18.4±5.9) days, respectively, and the duration of positive virus-PCR testing results were(16.0±4.5) and(12.3±4.4) days respectively, suggesting longer hospital stay and longer time for virus clearance in the diabetes group than those in the control group(both P<0.05). The rates of secondary infection, severe subtype, liver dysfunction and cardiac injury in the diabetes group increased, though without significant difference( P>0.05). Conclusion:Prolonged duration of positive virus-PCR result and average days of hospitalization in patients with COVID-19 may be associated with diabetes mellitus.
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Macrophages play an important role in inflammation, and excessive and chronic activation of macrophages leads to systemic inflammatory diseases, such as atherosclerosis and rheumatoid arthritis. In this paper, we explored the anti-inflammatory effect of broussonin E, a novel phenolic compound isolated from the barks ofBroussonetia kanzinoki, and its underlying molecular mechanisms. We discovered that Broussonin E could suppress the LPS-induced pro-inflammatory production in RAW264.7 cells, involving TNF-α, IL-1β, IL-6, COX-2 and iNOS. And broussonin E enhanced the expressions of anti-inflammatory mediators such as IL-10, CD206 and arginase-1 (Arg-1) in LPS-stimulated RAW264.7 cells. Further, we demonstrated that broussonin E inhibited the LPS-stimulated phosphorylation of ERK and p38 MAPK. Moreover, we found that broussonin E could activate janus kinase (JAK) 2, signal transducer and activator of transcription (STAT) 3. Downregulated pro-inflammatory cytokines and upregulated anti-inflammatory factors by broussonin E were abolished by using the inhibitor of JAK2-STAT3 pathway, WP1066. Taken together, our results showed that broussonin E could suppress inflammation by modulating macrophages activation statevia inhibiting the ERK and p38 MAPK and enhancing JAK2-STAT3 signaling pathway, and can be further developed as a promising drug for the treatment of inflammation-related diseases such as atherosclerosis.
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Objective To evaluate the efficacy of long-term treatment with infliximab in patients with moderate to severe psoriasis vulgaris.Methods Patients with moderate to severe psoriasis vulgaris,who started infliximab therapy in Department of Dermatology,Peking University Third Hospital between March 2016 and May 2018,were followed up.The patients treated with infliximab for more than 54 weeks were enrolled into this study.The patients were treated with infliximab at a weight-based dosage of 5 mg/kg,and the total dosage used per session was 200,300 and 400 mg for patients with the body weight of 40-59 kg,60-79 kg,and ＞ 80 kg respectively.The patients were treated at week 0,2,6,14,22,30,38,46 and 54,and the psoriasis area and severity index (PASI) score was determined before each treatment.Mauchly's test of sphericity,randomized block analysis of variance and Bonferroni method were used to analyze changes of PASI scores after 2-,6-,14-,22-,30-,38-,46-and 54-week treatment.Sequelae and adverse reactions were also recorded.Results Twelve patients received the treatment with infliximab,and 9 patients were treated for more than 54 weeks,whose clinical data were analyzed.Before the treatment,the PASI score (M[P25,P75]) of the 9 patients was 26.3 (23.4,27.7).There were significant differences in the PASI score among different time points (F =7.12,P =0.0004),and the PASI score of the patients showed a generally decreasing trend over time.After 30-week treatment,the PASI score was 4 (2.5,5.2),and the PASI improvement rate was 86.38％ ± 6.98％;of the 9 patients,8 achieved PASI50,7 achieved PASI75,and 2 achieved PASI90.After 54-week treatment,the PASI score was 8 (3.5,8.9),the PASI improvement rate was 64.23％ ± 17.32％,and the number of patients achieving PASI50,PASI75 and PASI90 was 8,4 and 1 respectively.Bonferroni method showed that the PASI score significantly increased at week 54 compared with that at week 30 (t =3.269,P =0.0048),but significantly decreased at weeks 30 and 54 compared with that before the treatment(week 30:t =18.49,P ＜ 0.0001;week 54:t =5.81,P =0.0004).Conclusion Infliximab is remarkably effective for moderate and severe psoriasis vulgaris in the 54-week treatment.
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Paridis Rhizoma is a traditional Chinese medicine, mainly distributed in Yunnan, Sichuan, Guizhou and other areas of China. Because of its analgesic, hemostatic, anti-tumor, anti-oxidant, immune regulation and other functions, it has been widely used in medicine and health products. Therefore, the quality evaluation of Paridis Rhizoma has become an urgent restriction on the development and utilization, which becomes one of the problems to be solved. In this study, the chemical constituents and pharmacological activities of Paris plants were systematically sorted out, and the quality markers of Paris plants were predicted and analyzed based on the specificity of chemical constituents, the correlation between chemical constituents and pharmacodynamics, the traditional medicinal properties and the measurability of chemical constituents, which provides scientific basis for the quality evaluation of the genus Paris.
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<p><b>OBJECTIVE</b>To better define the effect of JAK2V617F mutant allele burden on clinical presentation of patients with essential thrombo cythamia (ET), especially thrombosis.</p><p><b>METHODS</b>Two ml of heparin anti-coagulated bone marrow was collected from 229 ET cases, who were diagnosed and treated in the First People's Hospital of Yunnan Province during 2013.10 to 2016.12. and then the mononuclear cells were separated by Red Blood Cell Lysis Buffer, genomic DNA was extracted from mononuclear cells by using a commercial DNA isolation kit and amplified by allele specific polymerase chain reaction (PCR). According to the size of molecular weight, the amplified products were separated by electrophoresis on a 2% agarose gel to screen the JAK2V617F mutation, then the JAK2V617F mutation burden was detected by real-time polymerase chain reaction (RT-PCR) in 120 patients with JAK2V617F mutation. Meanwhile, these samples were sequenced in order to verify the accuracy of the PCR screewing.</p><p><b>RESULTS</b>ET patients with thrombotic events had significantly higher JAK2V617F allele burden than those without thrombosis (23.2% vs 14.2%) ( P<0.05). Meanwhile, ET patients showed increased JAK2V617F allele burden in the group with higher leukocytosis (WBC > 10×10/L) (P<0.001) and hemoglobin (> 150 g/L) (P<0.05). JAK2V617F mutation burden in 17 patients with splenomegaly was higher than that in 45 patients without splenomegaly (28.1% vs 11.8%) (P<0.05). but the JAK2V617F mutation burden was regatively correlated with platelet count (P<0.05). On the other hand, no correlation was found between JAK2V617F mutation burden and sex (P > 0.05). Univariate analysis showed that the JAK2V617F allele burden did not affect survival. Multivariable analysis showed that prognostic variable including WBC counts, hemoglobin level, age, sex, and splenomegaly not affected survival, (P > 0.05).</p><p><b>CONCLUSION</b>The clinical presentations of ET patients, such as WBC counts, hemoglobin level and splenomegaly, are influenced by the JAK2V617F mutation burden. ET patients with thrombotic events has significantly higher JAK2V617F allele burden than those in ET palients without thrombosis.JAK2V617F mutation burden has no relations with sex and age..</p>
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In this study, Paeonia suffruticosa roots and rhizospheric soil in five geographic regions which were harvested in October were utilized as experimental materials, then the diversity of endophytic and rhizospheric actinomycetes were investigated by High-throughput sequencing technique. The 1 754 operational taxonomic units (OTUs) were obtained from 129 954 high quality sequences, 1 311 OTUs were detected in rhizospheric actinomycetes and belonged to four classes, four orders, twenty-seven families and ninety-seven genera, thirty-three genera such as Ilumatobacter were found in the five regions rhizospheric soil while three genera such as Longispora were only detected in the Dao-di regions, the dominant genera were Mycobacterium, Nocardioides, Streptomyces. 443 OTUs were obtained in roots and distributed in three classes, three orders, twenty-four families and fifty genera, thirteen genera such as Cryptosporangium were found in the five regions roots while Planosporangium, Luteococcus were only detected in the Dao-di regions, the dominant genera were Nocardioides. Alpha diversity analysis showed that the Shannon and Chao1 index in rhizospheric actinomycetes in Bozhou, Tongling and Nanling region were higher than Heze and Luoyang. Based on principal co-ordinates analysis (PCoA) analysis, the rhizospheric actinomycetes formations were similar in Tongling and Nanling region, at the same in Tongling and Luoyang endophytic actinomycetes. According to heatmap analysis, Bozhou, Tongling and Nanling region rhizospheric actinomycetes showed a close similarity in actinomycetes community structures on phylogenetic analysis, while Tongling, Luoyang and Nanling endophytic actinomycetes showed the same. Our results not only suggested that the rich and diverse actinomycetes resources in P. suffruticosa roots and rhizospheric soil but also revealed rhizospheric actinomycetes in the Dao-di regions had high similarity.
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Actinobacteria , Paeonia , Phylogeny , Plant Roots , Soil MicrobiologyABSTRACT
OBJECTIVE: To compare randomized controlled trial (RCT) study and observational study systematically, and to provide reference for selecting suitable study design types for clinical researchers. METHODS: RCT study and observational study were compared in respects of study design and study report paradigm. Relevant literatures were retrieved from PubMed database and Chinese Journal Full-text Database. The differences of literature publication of RCT study and observational study were compared at home and abroad. RESULTS: There were differences in design principles, objectives, subjects, interventions and validity between RCT study and observational study. The requirements of CONSORT statemtnt and STROBE statement to the topics, abstracts, introduction, results and discussions of report paradigm of two studies were basically consistent, and main difference of them were in aspects of methods and other information. The number of literatures about RCT study and observational study had little gap at abroad, but had great gap at home, especially in cohort study with high-level evidence of evidence-based medicine. CONCLUSIONS: The observational study has developed rapidly in recent years, but RCT study is still a "gold standard" to evaluate the causal effect of clinical study. The researchers should choose the appropriate type of design according to the actual situation.
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Objective To study the best formulation and technology of quercetin-loaded polylactic-co-glycolic acid-D-α-tocopheryl polyethylene glycol 1000 succinate(PLGA-TPGS) nanoparticles(QPTN) with QT as model drug and PLGA-TPGS as polymer materials by orthogonal tests,and to investigate the in vitro stability of QPTN. Methods To ensure the best formula-tion and technology for preparing QPTN,single-factor test was established to determine the influence of the ratio of quercetin to PLGA-TPGS,the concentration of TPGS as emulsifiers,the ultrasonic power and ultrasonic time to the particle size,drug loading (DL) and entrapment efficiency(EE).According to single-factor test,the factor levels of nanoparticles were set to select the best prescription and technology of QPTN by orthogonal test.The stability of QPTN was examined using the effecting factor test,accel-eration test and long-term test. Results The best formulation and technology of QPTN was that the ratio of quercetin to PLGA-TPGS was 3:10 (W:W) with 0.05% TPGS as emulsifier,the mixed solution was sonicated for 6 min at 200 W.The average particle size,DL and EE of QPTN prepared under the conditions described above were (155.4 ± 2.7) nm,(21.6 ± 1.5)% and (93.7±2.9)% (n=6),respectively.In the in vitro stability test,QPTN showed a good stability at high temperature,high humidity and strong light condition. Conclusion The best formulation and preparation technology of QPTN was selected.QPTN got small particle size,high DL and EE,and good in vitro stability.
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Objective :To explore clinical application value of drug-coated balloon (DCB) in patients with coronary ar-tery small vascular disease (SVD).Methods :A total of 140 SVD patients treated in our hospital were selected .Ac-cording to therapeutic plan ,they were divided into DCB group (n＝60) and drug-eluting stent (DES) group (n＝80).Clinical features ,dual-antiplatelet treatment condition and clinical outcome after one year were recorded in de- tail .Multi-factor Logistic regression analysis was used to analyze influencing factors for major adverse cardiovascular events (MACE) in SVD patients on one year .Results :After one year ,there were no significant difference in inci-dence rates of all-cause death ,myocardial infarction ,target lesion revascularization ,cerebrovascular accident ,late lumen loss and target lesion restenosis between two groups , P＞0.05 all.Diabetes mellitus ,hyperlipidemia and acute coronary syndrome were independent risk factors for MACE in SVD patients after one year (OR＝1.093～1.125 , P＜0.05 or ＜0.1).There was no significant difference in cumulative survival rate between two groups during fol-low-up , P＞0. 05. Conclusion : DCB is a safe ,effective and feasible alternative method in the treatment of patients with coronary artery small vascular disease .
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Objective To evaluate the clinical safety and efficacy of percutaneous interventional therapy in pediatric patients with secundum atrial septal defect(ASD).Methods Clinical data of 40 patients(age≤2 years)with secundum atrial septal defect treated in our hospital from February 2014 to December 2017 were analyzed retrospectively. There were 13 males and 27 females in these patients.Ultrasound of heart showed that there were 37 patients with single ASD,3 patients with multiple ASDs.One associated with pulmonary stenosis(PS),and 1 associated with patent ductus arteriosus.There were 6 patients with pulmonary hypertension, and the diameter of ASD was (10.6 ± 2.0) mm. All patients were proved to have secundum atrial septal defect before intervention.In the intervention,the transport system was delivered along the femoral vein,inferior vena cava and right atrium through atrial septal defect to the left atrium,and the occluder was released there. Results Of the 40 patients, 38 cases were successfully implanted, and the other two patients were not satisfied with the location of occlusion.The diameter of the ASD occluder was(12.0±2.1)mm and the transport sheath 7-9 F.Plug2 occluder was implanted in the patient with patent ductus arteriosus.To the patient with PS,pulmonary valve balloon angioplasty was performed,and then the pressure gradient reduced obviously, after that ASD occlusion was performed. The total follow up period was from 2 months to 3 years.No residual shunt and unsatisfactory device position were found during the follow up period.The pulmonary pressure reduced to normal,and the right atrium and right ventricle were smaller in a different degree. All patients had no arrhythmia and other complications.Conclusion Transcatheter closure of ASD is safe,reliable,and has fewer complications.It is worthy of popularization and application.Appropriate occluder should be selected according to the size and edge of ASD to reduce complications,such as residual shunt and valve injury.
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The Micro-infusion syringe pump has been widely used in infusion of various vasoactive agents. There are several modes of syringe replacement with advantages or limitations respectively. It is important to maintain the stability of hemodynamic parameters during the syringe replacement. In the times of the reformation of medical and medical insurance payment, it is worth paying attention to monitor costs of medical consumables. The large sample multicenter study is needed to reveal the relationships between the hemodynamic parameters and the sorts and volume of various vasoactive agents. It will provide the basis for the clinical choice of syringe replacement modes.