Objective To evaluate the preliminary mechanisms of endovenous laser treatment (EVLT) for lower extremity varicose vein.Methods Laser energy was endovenously administered to observe its biological effects on greater saphenous vein (GSV) segments with different conditions.Some great saphenous vein that was surgically removed after EVLT was examined by means of histopathology.Cruor status was tested after EVLT.Results Histopathologic examination found the vein wall treated by EVLT showed reddening,carbonization,or even perforation,denudation of the intima,loss of cellular contours,and fibrin deposition.Additionally,some areas showed marked vacuolization of cells or even spongiosis,swelling and waxy homogenization of collagen,focal coagulation necrosis within the intima.In saline-filled veins,EVLT-induced vessel wall injury was confined to the site of direct laser impact.In contrast,blood-filled veins exhibited thermal damage in more remote areas including the vein wall opposite to the laser impact.D-dimer was significantly changed after EVLT.Conclusions EVLT laser induced indirect local heat injury of the inner vein wall by steam bubbles originating from boiling blood is proposed as the pathophysiological mechanism of action of EVLT.Intravascular blood plays a key role for homogeneously distributed thermal damage of the inner vein wall during EVLT.No significant difference could be detected between the two laser wavelengths.Continuous emission mode is better than pulse emission mode.

Objective To study the influence of body mass index on ambulatory venous pressure of chronic venous insufficiency of lower extremity.Methods One hundred and two consecutive patients with chronic venous insufficiency of lower extremity were enrolled in this study.Ambulatory venous pressure and body mass index were assessed and compared.Normal body weight group had 28 cases,over weight group had 43 cases,obesity group had 31 cases.Resets The complication of pigmentation,eczema,skin sclerosis and ulcer were more in obesity group and over weight group than those in normal body weight group.The resting pressure (P0) in obesity group,over weight group and normal body weight group were (118.0 ± 11.5),(113.0 ± 9.7),(101.0 ± 10.6) mm Hg (1 mm Hg =0.133 kPa),the pressure after unclamp 4 s (4SP)were (75.00 ± 2.99),(71.00 ± 3.01),(65.00 ± 2.17) mm Hg,the percentage of decreased pressure(pd)were (35.0 ± 5.4)％,(39.0 ± 4.3)％,(43.0 ± 5.1)％,the time of P0 recovered 50％ (RT50) were(7 ± 1),(9 ± 2),(12 ± 3) s.The P0 and 4SP in obesity group,over weight group were significantly higher than those in normal body weight group (P ＜0.05).The Pd,RT50 in obesity group,over weight group were significantly lower than those in normal body weight group (P＜0.05).Conclusion With the increasing of body mass index,the chronic venous insufficiency of lower extremity is more severity.

Retrievable vena cava filters can be used to prevent pulmonary embolism. The advantage of the retrievable vena cava filters is that they can either be removed or be remained in the vena cava permanently if needed. This article describes the current status of retrievable vena cava filters including indications, outcomes, patient management, time of filter removal, and the management of thrombus in the filter.

Background and Objective Previous study showed tenecteplase and alteplaxe were equovalent for 30-day mortality in the treatment of acute myocardial infarction. The purpose of this open-label, randomized, multi-center, angiographic trial was to assess the efficacy and safety of tenecteplase compared with alteplase in Chinese patients with acute myocardial infarction. Methods We recruited patients with acute ST-elevation myocardial infarction presenting within 6 hours of symptom onset from October, 2002 to March,2004, in 5 hospitals in Beijing. After giving informed consent, patients were randomly assigned a single-bolus injection of tenecteplase (30-50 mg according to body weight) or front loaded alteplase (100 mg), and underwent coronary angiography at 90 min after starting the study drug. All patients received aspirin and heparin (target activated partial thromboplastin time 50-70 s). The primary efficacy end point was the rate of TIMI grade 3 flow at 90 minutes. Other efficacy end points included TIMI grade 2/3 flow at 90 minutes. Safety end points included all stroke, intracranial hemorrhage (ICH), moderate/severe hemorrhage (except for ICH), all-cause mortality at 30-days, and major non-fatal cardiac events at 30 days. Results Overall 110 patients were eligible for statistical analysis, with 58 patients assigned to receive tenecteplase and 52 patients to alteplase. Tenecteplase produced a rate of TIMI grade 3 flow at 90 minutes after the start of thrombolysis(68.4%) similar to that of alteplase (66.7%, P=1.0); the rates of TIMI grade 2 or 3 were similar for patients treated with tenecteplase versus alteplase (89.5% versus 80.4%, respectively, P=0.278). At 30 days, rates for all strokes were similar for the two groups (5.17% for tenecteplase and 1.92% for alteplase, P=0.62); rates of ICH were 3.45% and 1.92% (tenecteplase and rt-PA,P=1.00) respectively. The rate of moderate/severe hemorrhage was 8.62% with tenecteplase and 5.77% with alteplase (P=0.72); total mortality was almost identical in the two groups (13.8% versus 9.6%, respectively, P=0.565) while the rates of non-fatal cardiac complications were 10.35% and 11.54% (tenecteplase and alteplase, P=1.0). Conclusions The efficacy of a single-bolus, weightadjusted tenecteplase fibrinolytic regimen is equivalent to front-loaded alteplase in terms of the rates of TIMI grade 3 flow, and TIMI 2 or 3 flow, but the 30-day mortality and ICH in both groups was so high that the use of tenecteplase is not permitted in China. These negative safety results might be due to the high rate of percutaneous coronary intervention (PCI) and high dose of bolus heparin and suboptimal concomitant medical therapy during hospitalization, so further studies are needed to confirm the safety for tenecteplase in Chinese patients.

The resolution of single molecule localization imaging techniques largely depends on the precision of localization algorithms. However, the commonly used Gaussian function is not appropriate for anisotropic dipoles because it is not the true point spread function. We derived the theoretical point spread function of tilted dipoles with restricted mobility and developed an algorithm based on an artificial neural network for estimating the localization, orientation and mobility of individual dipoles. Compared with fitting-based methods, our algorithm demonstrated ultrafast speed and higher accuracy, reduced sensitivity to defocusing, strong robustness and adaptability, making it an optimal choice for both two-dimensional and three-dimensional super-resolution imaging analysis.
Alcohol Oxidoreductases ; analysis ; genetics ; metabolism ; Algorithms ; Animals ; COS Cells ; Cercopithecus aethiops ; Cytochrome P-450 Enzyme System ; analysis ; genetics ; metabolism ; HeLa Cells ; Humans ; Imaging, Three-Dimensional ; Microscopy, Fluorescence ; Normal Distribution ; Plasmids ; metabolism

Objective:To explore early-onset gout and related risk factors in Shandong Province, and provide decision-making information on prevention.Methods:Data from electronic medical records and face-to face interview were collected from 8 393 patients with gout who first visited the gout clinic of the Affiliated Hospital of Qingdao University from September 2016 to December 2021. Data included demographics, comorbidity and biochemical examinations. The dynamic changes of onset age from 2002 to 2021 were statistically analyzed. The clinical characteristics and related risk factors of patients with early-onset and late-onset gout were statistically analyzed.Results:The age of onset of gout decreased significantly from 2002 to 2021. Compared with 2002, the average age of onset in 2021 decreased by 2.3 years [(41.9±10.6 vs 39.6±14.0) years]. The median age of onset decreased by 3 years in 2012-2021 compared with 2002-2011(37 vs 40 years, P<0.001). The proportion of gout patients with onset age<40 years old increased significantly, from 45.1% in 2002 to 57.8%, and increased by 12.7% in 20 years( P<0.001). The constituent ratios of 20-29 years old group( Ptrend<0.001) and≤19 years old group( Ptrend=0.011) increased by 9.3%( P<0.001) and 4.2%( P=0.002) over 20 years, which was the highest increase among all age groups with onset age<40 years old. Multivariate stepwise linear regression analysis showed that positive family history, blood uric acid level, metabolic syndrome and smoking were independent risk factors for early onset of gout. Conclusion:The age of gout onset in tends to be younger. The increase of the proportion of patients younger than 30 years old is probably the key factor leading to the early-onset gout in Shandong Province. Early and effective intervention on the risk factors related to early-onset gout is essential to prevent the early-onset gout as well as to reduce the prevalence of gout and complications.

Background::Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s dementia. Mitochondrial dysfunction is involved in the pathology of PD. Coiled-coil-helix-coiled-coil-helix domain-containing 2 (CHCHD2) was identified as associated with autosomal dominant PD. However, the mechanism of CHCHD2 in PD remains unclear.Methods::Short hairpin RNA (ShRNA)-mediated CHCHD2 knockdown or lentivirus-mediated CHCHD2 overexpression was performed to investigate the impact of CHCHD2 on mitochondrial morphology and function in neuronal tumor cell lines represented with human neuroblastoma (SHSY5Y) and HeLa cells. Blue-native polyacrylamide gel electrophoresis (PAGE) and two-dimensional sodium dodecyl sulfate-PAGE analysis were used to illustrate the role of CHCHD2 in mitochondrial contact site and cristae organizing system (MICOS). Co-immunoprecipitation and immunoblotting were used to address the interaction between CHCHD2 and Mic10. Serotype injection of adeno-associated vector-mediated CHCHD2 and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration were used to examine the influence of CHCHD2 in vivo.Results::We found that the overexpression of CHCHD2 can protect against methyl-4-phenylpyridinium (MPP+)-induced mitochondrial dysfunction and inhibit the loss of dopaminergic neurons in the MPTP-induced mouse model. Furthermore, we identified that CHCHD2 interacted with Mic10, and overexpression of CHCHD2 can protect against MPP +-induced MICOS impairment, while knockdown of CHCHD2 impaired the stability of MICOS. Conclusion::This study indicated that CHCHD2 could interact with Mic10 and maintain the stability of the MICOS complex, which contributes to protecting mitochondrial function in PD.

Previous studies suggest that the reduction of SMAD3 (mothers against decapentaplegic homolog 3) has a great impact on tumor development, but its exact pathological function remains unclear. In this study, we found that the protein level of SMAD3 was greatly reduced in human-grade IV glioblastoma tissues, in which LAMP2A (lysosome-associated membrane protein type 2A) was significantly up-regulated. LAMP2A is a key rate-limiting protein of chaperone-mediated autophagy (CMA), a lysosome pathway of protein degradation that is activated in glioma. We carefully analyzed the amino-acid sequence of SMAD3 and found that it contained a pentapeptide motif biochemically related to KFERQ, which has been proposed to be a targeting sequence for CMA. In vitro, we confirmed that SMAD3 was degraded in either serum-free or KFERQ motif deleted condition, which was regulated by LAMP2A and interacted with HSC70 (heat shock cognate 71 kDa protein). Using isolated lysosomes, amino-acid residues 75 and 128 of SMAD3 were found to be of importance for this process, which affected the CMA pathway in which SMAD3 was involved. Similarly, down-regulating SMAD3 or up-regulating LAMP2A in cultured glioma cells enhanced their proliferation and invasion. Taken together, these results suggest that excessive activation of CMA regulates glioma cell growth by promoting the degradation of SMAD3. Therefore, targeting the SMAD3-LAMP2A-mediated CMA-lysosome pathway may be a promising approach in anti-cancer therapy.

Objective: To investigate the change of hepatitis B surface antibody (HBsAb) titer and its long-term protection and infection rates between 1 and 3-year-old children whose mothers were chronic hepatitis B pregnant woman with HBeAg positive and high viral load after successful blocking of mother-to-child transmission. Methods: One-year-old children whose mothers were hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) positive, with HBV DNA≥10⁶IU/ml were enrolled, then were followed up till 3 years old, and tested the five serological markers of hepatitis B and biochemical parameters at the age of one and three years respectively, and analyzed HBsAb titer, positive rate, negative rate and infection rate of 1 to 3-year-old children without enhanced vaccination; meanwhile, data of HBsAb titers at the age of 7 months were collected HBsAb titer, positive rate, and negative rate were analyzed. Results: Totally 264 1-year-old children were enrolled into the study, including 178 children without enhanced vaccination between seven months and 1 year of age, and 114 children without enhanced vaccination between 1 year and 3 years of age. Our result showed that there were no infected children at the age between 1 and 3 years. HBsAb titer decreased from 7 months to 1 year old and dropped from 1 000 IU/L to 509.43 IU/L (P<0.05), and the antibody was still protective. From 1 year to 3 years old, HBsAb titer dropped from 466.72 IU/L to 67.3 IU/L (P< 0.05); at the age of 3 years, 60.52 % children were either weakly positive or negative, but still protective, but significantly less than those who had the reinforced vaccination. As a result , the children without the enhanced vaccination between 1 and 3 years of age were still at high risk. Conclusions If the antibody was protective at 7 months, children were not easily infected between 1 year and 3 years of age. At the age of 3, the antibody dropped to low or no responsive levels, and the children were still at high risk. It is necessary to take protective measures and supplement the vaccine.