Objective To investigate the value of preoperative risk assessments and countermeasures on ultrasound-guided radiofrequency ablation for benign thyroid nodules.Methods The preoperative risk assessments of 311 benign solid thyroid nodules in 274 patients were divided into level 0-Ⅳ,among which 38 nodules on level 0,69 nodules on level Ⅰ,36 nodules on level Ⅱ,59 nodules on level Ⅲ,109 nodules on level Ⅳ.Treatments were performed by moving shot technique or multiplanar shot technique,using Leverage Displacement or Hydrodissection to prevent the adjacent vital structures from thermal injuries.Results 311 thyroid nodules were completely ablated.In ablating the 59 nodules on risk level Ⅲ,thermal injuries were effectively avoided in 30 cases by using Leverage Displacement,while recurrent laryngeal nerve injuries happened in 2 cases using Hydrodissection for 29 nodules.The difference between these two methods on risk level Ⅲ had no statistical significance(P =0.237).To avoid thermal injuries during ablation for 109 nodules on risk level Ⅳ,using Leverage Displacement for 102 nodules,recurrent laryngeal nerve injuries happened in 1 case,while using Hydrodissection for 7 nodules,recurrent laryngeal nerve injuries happened in 2 cases.The difference between the two methods on risk level Ⅳ had statistical significance(P =0.010).No thermal injury happened during ablation for 143 nodules on risk level 0-Ⅱ.Conclusions Preoperative risk assessment on thyroid nodules is helpful in preventing potentially avoidable complications.Proper use of Leverage Displacement can protect adjacent vital structures from thermal injuries during ablation for nodules,which is easy and simple to handle and has a certain practical application value.

Objective To observe the efficacy and adverse effect of IHDA [Idarubicin(IDA) + high-dose Cytarabine(HD-Ara-C)] as a remedy regimen in the treatment of pediatric patients with refractory acute lymphoblastic leukemia(ALL).Methods Twelve children with refractory ALL were treated by IHDA regimen as follows:IDA,10 mg/(m2·d),d1-3;Ara-C,1.0g/m2,q12h,d1-3.The children who achieved complete remission(CR)could get into the following sequential regimens or allogeneic hematopoietic stem cell transplantation (allo-HSCT).The same regimen was given to the children who didn't achieve CR when WBC ＞2.0×109/L.The efficacy and hematology or non-hematology adverse effect were evaluated.Results CR/partial remission (PR)/non-remission (NR) were respectively 4/3/5 cases after giving the first regimen,and CR/PR/NR were 5/3/4 cases after giving the second regimen,respectively.The overall remission was 66.7％ (8/12 cases),of which 5 cases(41.7％) achieved CR,3 cases (25.0％) reached PR and 4 cases(33.3％) reached NR.Grade Ⅳ myelosuppression occurred in all patients,but no severe infection and hemorrhage happened after the application of granulocyte colony stimulating factor (G-CSF),platelet transfusion and anti-infection treatment.Some reversible side effects like liver toxicity,myocardial damage and nerve injury were observed in some patients.There was no chemotherapy related mortality in all the patients.Two cases relapsed again followed up to October 2015.One achieved CR after applying chimeric antigen receptor T-cell immunotherapy and was receiving allo-HSCT now.Another was dead after applying FLAG (Prednisone+Fludarabine+Ara-C+G-CSF) save regimen.The time of the other 3 cases achieving CR was 26,10,4 months,respectively.Among the remaining 7 cases,3 cases were forced to receive hematopoietic stem cell transplantation,2 cases abandoned treatment and 2 cases failed to follow up.Conclusions The IHDA regimen is a well-effective and tolerated treatment for pediatric patients with refractory ALL,and could create an opportunity for the application of allo-HSCT.

Objective To investigate susceptibility and antibacterial activity of cationic porphyfin derivative mediated photodynamic antimicrobial chemotherapy (CPD-PACT) against Pseudomonas aeruginosa,to provide experimental evidence for its high efficiency antibacterial activity.Methods The impacts of culture environments on minimum inhibitory concentration (MIC) were measured by double dilution method.The formation of inhibition zone was determined by diffusion plate method.The postantibiotic effect was analyzed by colony forming units.The viability and morphology of Pseudomonas aeruginosa were observed by confocal laser scanning microscopy (CLSM).Results The inoculum size of bacterial had a certain effect on the MIC.The MIC values increased as the pH of medium rose.When the calf serum content of culture medium increased,the MIC rose in light reaction and dropped in dark reaction.The diameter of inhibition zone mainly depended on the laser energy density,but not the concentration of photosensitizer.Though CPD possessed strong antimicrobial activity and persistent suppression on bacterial growth,the surviving Pseudomonas aeruginosa would soon continue to proliferate after PACT.The fluorescence images captured by CLSM showed that CPD-PACT could destroy the membrane integrity,leak the cytoplasmic component,decrease the bacterial activity and finally lead Pseudomonas aeruginosa to death.Conclusions CPD has strong inhibitory activity and obvious postantibiotic effect on Pseudomonas aeruginosa,which is suitable to be developed as an drug candidate for PACT.

Conditional forebrain-specific presenilin-1 and presenilin-2 double knockout mice (dKO mice) exhibit several neurodegenerative phenotypes of Alzheimer's disease (AD) pathology, such as tau hyperphosphorylation, neuron loss, forebrain cortical shrinkage and memory impairment. By using capillary electrophoresis assay, monoamine neurotransmitters in forebrain cortex, hippocampus and other forebrain region of dKO mice aged at 6, 9 and 12 months were measured to illustrate the relationship among presenilins function deficiency, neurodegenerative phenotypes and monoamine neurotransmitters. Data showed that levels of monoamine neurotransmitters in forebrain cortex of dKO mice were significantly decreased at 6 months when compared to controls, while as mice getting older, levels of monoamine neurotransmitters increased to that of controls, or even higher. In hippocampus, 5-hydroxytryptamin and epinephrine in dKO mice had a significant increase at 6 months, followed with a significant increase of each monoamine neurotransmitter at 12 months age. In other forebrain region, 5-hydroxytryptamin and dopamine had a similar level between control and dKO mice at 6 and 9 months but a significant decrease at 12 months; however, level of norepinephrine and epinephrine were significantly decreased at 6 and 12 months except epinephrine of 6 months. These results demonstrated that knockout of presenilins genes could lead to the variation of monoamine neurotransmitters, and the variation profiles were different among forebrain cortex, hippocampus and other forebrain region. However, whether presenilins deficiency caused the variation of monoamine neurotransmitter directly or not, and how about the effects of variation of monoamine neurotransmitters on AD-like pathology need to be further analyzed.

Objective:To investigate the efficacy and safety of programmed death-1 (PD1) inhibitor combined with transcatheter arterial chemoembolization (TACE) in the treatment of huge primary liver cancer.Methods:From June 2016 to December 2019, the clinical data of 31 patients with huge primary liver cancer enrolled in the Central Hospital of Lishui were retrospectively collected and analyzed. The tumor size ranged from 10.1 to 18.8 cm, with an average of (14.2±2.3) cm. The patients were divided into TACE group (TACE treatment, 18 cases) and combined group (one week after TACE, patients receiving a dose of 200 mg PD1 inhibitor administration every 21 days, 13 cases), according to whether patients receiving PD1 inhibitors. The patients were followed up. The disease control rate (DCR) were compared between the two groups using Mann-Whitney U test. The median overall survival (OS) and progression free survival (PFS) were calculated by Kaplan-Meier method. Results:The DCR in combined group (53.8%, 7/13) was higher than that in TACE group (22.2%, 4/18), and the difference was statistically significant ( Z=-2.13, P=0.04). The median PFS (5.0 months) in combined group was longer than that in TACE group (3.0 months), the difference was statistically significant (χ2=4.39, P=0.04). The median OS (15 months) in combined group was longer than that in control group (9 months), and the difference was statistically significant (χ2=5.51, P=0.02). Conclusion:The combine PD1 inhibitors with TACE is an effective and safe therapy for huge primary liver cancer.

This paper systematically summarized the core problems in the field of medical and health services and did the root analysis.It is concluded that the current domestic and international related medical service modes deviated from the essence of health services and led to difficulties in the idea and method,bringing people to new problems and new crises.KY3H health care service model,set innovative ideas,innovative technical methods,innovative products,innovative processes,standards and standards into one,by providing a full range and the whole cycle of people-oriented,self-help,"diagnosis and treatment of security" integration of health careservice,improve people's health status,fundamentally change the traditional passive "seeking medical treatment" service mode,to active "seeking one's own" health service mode,so as to achieve "health status continues to rise,the medical costs continue to decline,"which is the social development aims.The paper systematically analyzes the idea,operational logic,goal,mode structure,characteristics of the model,and its significance to individuals,industries,society,countries and even the international community in order to make a positive contribution to the healthy development strategy in China and provide a Chinese case for global Health.

Objective:To investigate the efficacy and safety of short-term transcatheter arterial chemoembolization （TACE）-radiofrequency ablation （RFA） sequential therapy for advanced hepatocellular carcinoma (HCC).Methods:The clinical data of 117 patients with advanced HCC enrolled in the Central Hospital of Lishui from March 2010 to January 2019 were retrospectively analyzed. All patients received TACE and RFA sequential therapy. The patients were divided into 2 groups including short interval group (interval≤7 d, 61 cases) and long interval group (interval>7 d, 56 cases) according to interval between TACE and RFA. The difference of response rate was analyzed by Wilcoxon test. Kaplan-Meier survival curve was used to calculate the overall survival (OS) time and progression free survival (PFS) time.The risk factors of TACE-RFA sequential therapy were tested using Cox multivariate analysis. The complications in the two groups were compared using χ 2 test. Results:The response rate in the short interval group (72.1%, 43/61) was significantly higher than that in the long interval group (41.1%，23/56) with significant difference ( Z=-2.50, P=0.01). The median PFS in the short interval group (14.9 months) was longer than that in the long interval group (9.1 months). The difference of PFS survival curve between the 2 groups was statistically significant (χ2 =5.90, P=0.01).The median OS in the short interval group (34.7 months) was longer than that in the long interval group (20.3 months). The difference of OS survival curve between the 2 groups was statistically significant (χ2 =6.60, P=0.01). Cox multivariate analysis showed that tumor size [hazard ratio (HR)=2.42, P<0.01], cirrhosis (HR=2.04, P<0.01), interval (HR=0.44, P<0.01), aspartate aminotransferase (HR=1.71, P=0.03) were the independent risk factors for advanced HCC.There were no significant differences in the complication incidence between the 2 groups ( P>0.05). Conclusion:Short-term interval TACE-RFA sequential therapy as a protective factor is efficient and safe for advanced HCC treatment.

OBJECTIVETo study the objective diagnostic mechanisms on Chinese medical (CM) syndrome patterns of rheumatoid arthritis (RA), and to research different titers of rheumatoid factor (RF)/citrullinated protein antibody (CCP) in CM syndrome patterns of RA.

METHODSTotally 230 early RA patients were assigned to five CM syndrome pattern groups, i.e., the dampness-heat blockage group (50 cases), the cold-dampness blockage group (50 cases), the Shen-qi deficiency-cold group (50 cases), the Gan-Shen yin deficiency group (40 cases), and the blood stasis blockage group (40 cases). Another 100 healthy subjects were recruited as the healthy control group. RF-IGM, RF-IGA, RF-IGG, and anti-CCP antibody were detected and compared.

RESULTSThe titers of RF-IGM, RF-IGA, RF-IGG, and anti-CCP antibody were higher in all groups than in the healthy control groups (P < 0.01). As for the 5 groups, RF-IGM, RF-IGA,RF-IGG, and anti-CCP antibody were higher in the RA active stage than in the nonactive stage. They were higher in the dampness-heat blockage group in the RA active stage than in the Shen-qi deficiency-cold group, the Gan-shen yin deficiency group, and the blood stasis blockage group.

CONCLUSIONTiters of RF-IGM, RF-IGA, RF-IGG, and anti-CCP antibody could be taken as judging indicators for differentiating objective lab indices of CM syndromes and assessing the active stage of RA.

Adult ; Aged ; Arthritis, Rheumatoid ; blood ; diagnosis ; immunology ; Autoantibodies ; blood ; Case-Control Studies ; Female ; Humans ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Peptides, Cyclic ; immunology ; Rheumatoid Factor ; immunology

Objective To study the stress distributions of mandible defect by reconstruction with polyetheretherketone (PEEK) and its composite reconstruction plate through three-dimensional finite element analysis. Methods The finite element models of reconstruction plate of titanium alloy, PEEK, carbon-fiber-reinforced polyetheretherketone (CFR)-PEEK with 30% endless carbon fibers and CFR-PEEK with 68% endless carbon fibers were established by CBCT scanning，Mimics software，SolidWorks, Geomagic Studio and ANSYS Workbench software, and titanium alloy served as control. Two occlusal situations were simulated in the mandible model. Loading I: anterior region loading with 300 N; loading II: left posterior region with 300 N. Results The ratio of the maximum Von Mises stress of the reconstructed plate to its yield strength under two load situations: PEEK system ＞ 30%CFR-PEEK system ＞ titanium alloy system ＞ 68% CFR-PEEK system; the maximum stress of the mandible: PEEK system ＞ 30% CFR-PEEK system ＞ titanium alloy system ＞ 68% CFR-PEEK system. In the PEEK system, the maximum Von Mises stress of reconstructed plate and mandibular exceeded its yield strength under loading I; in the other systems, the maximum Von Mises stresses of mandible and reconstruction plate were below the yield strength. Conclusions The reconstruction plate of CFR-PEEK with 68% endless carbon fibers distributed the stresses in a similar manner as the titanium reconstruction plate, which could meet the mechanical strength requirements of mandible defect reconstruction. The fracture risk of the reconstructed plate was lower than that of titanium alloy, but the incidence of stress shielding was slightly higher. The result can provide references for the selection of materials and clinical application of reconstruction plate for mandibular defects.

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.