ObjectiveTo investigate the effect of nicotinamide adenine dinucleotide on vascular endothelial injury in hypertension and its molecular mechanism. MethodsC57BL/6J mice were randomly divided into saline group （Saline） and hypertension group （Ang Ⅱ， which were infused with Ang Ⅱ via subcutaneously implanted osmotic pumps）， and supplemented daily with nicotinamide mononucleotide （300 mg/kg）， a precursor of NAD⁺. Blood pressure， endothelial relaxation function and pulse wave velocity were measured after 4 weeks. Wound healing assay and adhesion assay were used to evaluate the function of endothelial cells in vitro. mtROS levels were detected by immunofluorescence staining. RT-PCR was used to detect the mRNA expression of mtDNA， SIRT3 and isocitrate dehydrogenase 2 （IDH2）. 8-hydroxy-2'-deoxyguanosine levels were detected by enzyme-linked immunosorbent assay. The protein expression levels of p-eNOS， eNOS， SIRT3 and IDH2 were detected by Western blot. ResultsNMN supplementation reduced blood pressure （P<0.001） and improved endothelial function and arterial stiffness （P<0.001） in hypertensive mice. In vitro， NMN improved endothelial function in AngII-stimulated endothelial cells （P<0.05） and attenuated mitochondrial oxidative stress levels （P<0.001）. Mechanistically， NMN elevated SIRT3 activity （P<0.001）， which subsequently enhanced IDH activity （P<0.001） and reduced oxidative stress levels in endothelial cells. Conversely， knockdown of IDH2 would reverse the effect of SIRT3 in improving endothelial function （P<0.001）. ConclusionNAD⁺ lowers blood pressure and enhances vascular function in hypertension by reducing the level of oxidative stress in endothelial cells through activation of the SIRT3/IDH2 signal pathway.

BACKGROUND: The HELIOS stent is a sirolimus-eluting stent with a biodegradable polymer and titanium oxide film as the tie-layer. The study aimed to evaluate the safety and efficacy of HELIOS stent in a real-world setting. METHODS: The HELIOS registry is a prospective, multicenter, cohort study conducted at 38 centers across China between November 2018 and December 2019. A total of 3060 consecutive patients were enrolled after application of minimal inclusion and exclusion criteria. The primary endpoint was target lesion failure (TLF), defined as a composite of cardiac death, non-fatal target vessel myocardial infarction (MI), and clinically indicated target lesion revascularization (TLR) at 1-year follow-up. Kaplan-Meier methods were used to estimate the cumulative incidence of clinical events and construct survival curves. RESULTS: A total of 2998 (98.0%) patients completed the 1-year follow-up. The 1-year incidence of TLF was 3.10% (94/2998, 95% closed interval: 2.54-3.78%). The rates of cardiac death, non-fatal target vessel MI and clinically indicated TLR were 2.33% (70/2998), 0.20% (6/2998), and 0.70% (21/2998), respectively. The rate of stent thrombosis was 0.33% (10/2998). Age ≥60 years, diabetes mellitus, family history of coronary artery disease, acute myocardial infarction at admission, and device success were independent predictors of TLF at 1 year. CONCLUSION: The 1-year incidence rates of TLF and stent thrombosis were 3.10% and 0.33%, respectively, in patients treated with HELIOS stents. Our results provide clinical evidence for interventional cardiologists and policymakers to evaluate HELIOS stent. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, NCT03916432.
Humans ; Middle Aged ; Sirolimus/therapeutic use* ; Drug-Eluting Stents/adverse effects* ; Prospective Studies ; Cohort Studies ; Treatment Outcome ; Risk Factors ; Time Factors ; Percutaneous Coronary Intervention/adverse effects* ; Cardiovascular Agents/therapeutic use* ; Coronary Artery Disease/therapy* ; Myocardial Infarction/etiology* ; Thrombosis/complications* ; Polymers ; Registries

Oral squamous cell carcinoma (OSCC) become a heavy burden of public health, with approximately 300 000 newly diagnosed cases and 145 000 deaths worldwide per year. Nucleotide metabolism fuel DNA replication and RNA synthesis, which is indispensable for cell proliferation. But how tumor cells orchestrate nucleotide metabolic enzymes to support their rapid growth is largely unknown. Here we show that expression of pyrimidine metabolic enzyme dihydroorotate dehydrogenase (DHODH) is upregulated in OSCC tissues, compared to non-cancerous adjacent tissues. Enhanced expression of DHODH is correlated with a shortened patient survival time. Inhibition of DHODH by either shRNA or selective inhibitors impairs proliferation of OSCC cells and growth of tumor xenograft. Further, loss of functional DHODH imped de novo pyrimidine synthesis, and disrupt mitochondrial respiration probably through destabilizing the MICOS complex. Mechanistic study shows that transcriptional factor SOX2 plays an important role in the upregulation of DHODH in OSCC. Our findings add to the knowledge of how cancer cells co-opt nucleotide metabolism to support their rapid growth, and thereby highlight DHODH as a potential prognostic and therapeutic target for OSCC treatment.
Carcinoma, Squamous Cell ; Cell Proliferation ; Head and Neck Neoplasms ; Humans ; Mouth Neoplasms ; Oxidoreductases Acting on CH-CH Group Donors ; SOXB1 Transcription Factors ; Squamous Cell Carcinoma of Head and Neck

【Objective】 To investigate the related factors of allogeneic blood transfusion (ALBT) in total hip arthroplasty. 【Methods】 Thebasic information, surgical details and laboratory data of 258 patients who underwent total hip arthroplasty in Orthopedics Department of our hospital were collectedfrom the electronic medical record system and laboratorytest system. The factors concerningALBT were obtainedby single factor and multivariate logistic regression analysis. 【Results】 The ALBT rate in this study was 19%, and the differencesin such important factors affecting ALBT as gender, age, intraoperative blood loss, drainage volume, operation duration, preoperative hemoglobin (Hb), preoperative activated partial thromboplastin time (APTT), preoperative prothrombin time (PT) andhypertension between the two groupswere notable (P<0.05). Multivariate regression analysisrevealed that the independent related factors ofALBT were age ≥ 60 years (OR3.577), intraoperative blood loss (OR1.003), drainage volume (OR1.004)and preoperative PT (OR1.888). Preoperative Hb (OR0.94) was a protective factor. 【Conclusion】 Specific and individualized evaluation of ALBT, aimed atreducingunnecessary blood transfusion, can be provided through the analysis of relevant factors.

Medical information registration of rare disease cases serves as scientific basis for development of population intervention strategy, improvement of medical service system, better patient medical support level, and higher medicine accessibility. Based on their hospital work, the authors introduced the development practice of an all-dimensional management system for such information registration, in terms of formulating policies, establishing organizational structure, organizing and publicizing policies for the medical service of rare diseases, maintaining registration data and so on, so as to provide the reference for the management of registration work of rare diseases.

BACKGROUND:In recent years, the application of stem cel s to treat autoimmune diseases has become a hot spot. But, studies on umbilical cord blood mesenchymal stem cel s transplantation for the treatment of polymyositis/dermatomyositis are rarely reported. OBJECTIVE:To explore the immunologic mechanism of Th cytokines on the occurrence and development of polymyositis/dermatomyositis by observing the changes in serum interferon-γ, interleukin-4 and interleukin-17 in patients after umbilical cord blood mesenchymal stem cel s transplantation. METHODS:Eighty-one polymyositis/dermatomyositis patients were selected and divided into conventional therapy group (n=44) undergoing glucocorticoid and immunosuppressants therapy and cel transplantation group (n=37) undergoing intravenous infusion of umbilical cord blood mesenchymal stem cel s at a density of (3.5-5.2 )×107 . Dosing regimen was same in the two groups. After fol ow-up of 1, 3, 6 months, the changes of creatine kinase and myodynamia were evaluated;after fol ow-up of 3 and 6 months, lung imaging was evaluated;in the cel transplantation group, interferon-γ, interleukin-4 and interleukin-17 levels were detected before treatment and at 3 and 6 months after treatment. RESULTS AND CONCLUSION:At 1, 3, 6 months after treatment, the creatine kinase level was significantly decreased, and the muscle force grade was significantly increased in both groups (both P<0.001). Compared with the conventional therapy group, the creatine kinase level was lower and the muscle force grade was higher in the cel transplantation group (both P<0.001). Results from lung imaging test showed a remarkable improvement after cel transplantation, and it indicated that umbilical cord blood mesenchymal stem cel s transplantation had good stability. At 6 months after transplantation, the level of interferon-γwas significantly increased, while the interleukin-4 level was decreased significantly (both P<0.01);at 3, 6 months after cel transplantation, the levels of interleukin-17 were significantly decreased (P<0.01). Levels of interleukin-4 and interleukin-17 were positively correlated with the level of creatine kinase at 6 months after cel transplantation (r=0.467, 0.488, both P<0.05), but there was no obvious correlation between the levels of interferon-γand creatine kinase (r=0.213, P>0.05). These findings indicate umbilical cord blood mesenchymal stem cel s transplantation combined with glucocorticoid and immunosuppressants therapy can adjust immune network effects and improve the immune tolerance in polymyositis/dermatomyositis patients, which is safe and effective.

Objective To compare of the clinical using effect of implantable venous -access port(VAP) among different methods and the postoperative complication.Methods From 2011 to 2014,a total of 359 patients with VAP were included in this study.All patients were divided into two groups according to the surgery approaches methods,307 cases were implanted through internal jugular vein,and other 52 cases were through subclavian vein intubation.Statistics of postoperative flow conditions and complication between the two groups were gathered and com-pared.Results There were 3 cases of postoperative infected,and 13 cases were not free of transfusion,while 2 cases catheter were shed and shifted in the 307 cases of implantation through internal jugular vein,the complication rate was 5.86%;In other group,which in total of 52 cases of implantation through subclavian vein,including 2 cases were post-operative infected,6 cases were not free of transfusion,2 cases are of catheter fracture and5 cases were local hemato-ma,the complication rate was 28.85%.There was difference in rate of catheter leakage,catheter tip dystopy and cath-eter related infection between two groups[the proportion of through internal jugular vein vs that the group through sub-clavian vein:5.86%(18 /307)vs 28.85%(15 /52),χ2 =28.140,P =0.000].Conclusion The study suggests that the two ways of different operation methods of VAP are safe and reliable for long term intermittent venous access.The internal jugular vein implanted group has a slight advantage over the group of subclavian vein implanted,when it comes to develop the patients′living quality.

Objective To compare the feasibility,effectivity and security of modified trabeculectomy in advanced stage angle-close glaucoma with cataract.Methods One hundred and forty-five patients (151 eyes) of advanced stage angle-close glaucoma with cataract were enrolled in this study.Among them,85 patients(91 eyes,observation group) were treated with modified trabeculectomy with the resection of deep scleral resection and 60 patients (60 eyes,control group) were treated with routine trabeculectomy.The visual acuity,intraocular pressure (IOP),type of filtering bleb and postoperative complication were compared.Results There was significant difference in the visual acuity ＜ 0.1,0.4-0.5,＞ 0.5 between after operation for 1 month and before operation in two groups (P ＜ 0.05).but there was no significant difference in the visual acuity 0.1-0.3 (P ＞ 0.05).The IOP before operation in observation group was (29.6 ± 4.1) mmHg (1 mmHg =0.133 kPa),12 months after operation was (13.1 ± 4.9) mmHg,the degree of decrease was (16.6 ± 5.0) mmHg.The IOP before operation in control group was (30.4 ± 6.3) mmHg,12 months after operation was (18.9 ± 3.0) mmHg,the degree of decrease was (10.4 ± 4.0) mmHg.The IOP after operation and the degree of decrease between two groups had significant difference (P ＜ 0.05).The functional filtering bleb(Ⅰ type and Ⅱ type) in observation group was 77 eyes(84.6％,77/91),and 51 eyes(85.0％,51/60) in control group,there was no significant difference (P ＞ 0.05).After operation for 1 month,there was 8 eyes appeared transient hypotony in observation group and 5 eyes in control group,there was no significant difference (P ＞ 0.05).Conclusion The modified trabeculectomy in advanced stage angle-close glaucoma with cataract can reduce IOP more effectively and not increase the intraoperative risk and postoperative complication.

Objective To evaluate the changes of platelet activity before and after anti-platelet treatment in pa?tients with coronary heart disease, and their responsiveness to clopidogrel through detecting the phosphorylation levels of va?sodilator stimulated phosphoprotein (VASP). Methods Twenty-eight cases of healthy people were selected as control group . Patients with chronic stable angina pectoris (CSA, n=95) were randomly divided into A (48 cases) group and B (47 cases) group,and were given clopidogrel 75 mg/d or 150 mg/d respectively;Patients with non ST segment elevation acute coronary syndrome (NST-ACS, n=67) were all given 300 mg loading dose of clopidogrel at the first time, then randomly divid?ed into C (33 cases) group and D (34 cases) group, and given clopidogrel 75 mg/d and 150 mg/d respectively. Blood were tak?en to examine the phosphorylation levels of serum VASP by ELISA before taking clopidogrel, at time point of loading dose and the fifth day of clopidogrel administration . Results Before treatment, phosphorylation levels of serum VASP were low?er in A, B, C, D groups than those in the normal control group(P<0.05). After treatment of clopidogrel for 5 days: ① In group A and group B ,phosphorylation levels of serum VASP did not change compared to that before treatment (P>0.05).②In group C and group D, phosphorylation levels of serum VASP were significantly increased at loading dose and the fifth day of clopidogrel administration than those before treatment (P<0.05), but there were no significant differences in phosphory?lation level of VASP was lower group between group C and group D after serum treatment (P > 0.05). Conclusion The phosphorylation level of serum VASP was lower in patients with coronary heart disease than that in normal control group. Clopidogrel can improve the phosphorylation level of serum VASP in NST-ACS patients .

Objective To assess under different vessel diameter ,the effect of the aspiration thrombectomy catheter in improving the myocardial reperfusion and clinical prognosis in patients with acute myocardial infarction (AMI)who were undergone primary percutaneous coronary intervention(PCI) .Methods 205 patients with AMI immediate implant stents after thrombus suction ,the TIMI flow grade(myocardial infarction thrombolysis treatment test flow classification ) ,postoperative ecg evolution ,incidence of no-reflow MACE in 30 days and MACE in 6 months were compared between conventional thrombus suction group and suction again group(blood vessels of <3 .0 mm and ≥3 .0 mm) .Results The level 3 blood flow rate ,MACE in 6 months in suction again group with blood vessels of ≥3 .0 mm had improved significantly ,but had no beneficial effects in blood vessels of ≥3 .0 mm .Conclusion In AMI patients treated with primary PCI ,application of aspiration thrombectomy catheter with blood vessels of ≥3 .0 mm may im-prove the flow condition before infarction related blood vessels ,reduce MACE .