[Effect of recombinant human thrombin for hemostasis in liver resection: a randomized controlled phase â ¢ clinical trial].

Objective: To evaluate the hemostatic efficacy, safety and immunogenicity of recombinant human thrombin in the treatment of liver wounds that still ooze after conventional surgical hemostasis. Methods: A multicenter, stratified randomized, double-blind, placebo-controlled phase Ⅲ trial with a planned enrollment of 510 subjects at 33 centers, with a 2∶1 randomization to the thrombin group versus the placebo group. An interim analysis will be conducted after approximately 70% of the subjects have completed the observation period. The primary efficacy endpoint was the rate of hemostasis within 6 minutes at the point of bleeding that could be evaluated. Safety analysis was performed one month after surgery, and the positive rates of anti-drug antibody (ADA) and neutralizing antibody were evaluated. Results: At the interim analysis, a total of 348 subjects had been randomized and received the study drug (215 were male and 133 were female). They were aged 19-69 (52.9±10.9)years. Among them, 232 were in the thrombin group and 116 were in the placebo group, with balanced and comparable demographics and baseline characteristics between the two groups. The hemostasis rate at 6 minutes was 71.6% (95%CI:65.75%-77.36%) in the thrombin group and 44.0% (95%CI: 34.93%-53.00%) in the placebo group, respectively (P<0.001). No grade≥3 drug-related adverse events and no drug-related deaths were reported from the study.No recombinant human thrombin-induced immunologically-enhanced ADA or immunologically-induced ADA was detected after topical use in subjects. Conclusion: Recombinant human thrombin has shown significant hemostatic efficacy and good safety in controlling bleeding during liver resection surgery, while also demonstrating low immunogenicity characteristics.

[Analysis of fast-growing culturable bacteria and pathogenic bacteria in the surface water of the northeast coast of Hainan Island in China].

Objective: To obtain the diversity and abundance of fast-growing bacteria in the surface water of the northeast coast of Hainan Island in China, different cultivation methods were employed. This study also aims to provide a reference for isolating bacterial samples from seawater sources and preventing marine-derived pathogens. Methods: Based on the principles of taxonomic design, surface seawater samples were collected from six locations along the northeast coast of Hainan Island in China in March, June, October, and December 2021. Then, bacterial enrichment was performed based on traditional cultivation methods for Salmonella, Vibrio, Burkholderia pseudomallei, Actinomycetes, and general marine bacteria. After that, bacterial species identification was conducted by 16S rDNA amplicon sequencing and metagenomic sequencing. Results: A total of 1 151 fast-growing cultivable bacteria belonging to 66 genera and 213 species were identified using five different culture protocols. In different cultivation protocols, Bacillus and Klebsiella demonstrated extensive discriminatory advantages and ranked among the top genera in terms of abundance. Protocol 1 had Escherichia, Klebsiella, and Citrobacter as dominant genera. Pathogenic bacteria detected by protocol 1 included Klebsiella pneumoniae and Escherichia coli, with 37 and 29 strains respectively, while Salmonella enterica was uniquely detected with seven isolates. Proteus, Enterococcus, and Providencia were the dominant genera in protocol 2, and Proteus mirabilis was the most abundant pathogenic bacteria detected with 66 isolates. Vibrio cholerae was uniquely detected with six isolates at a higher abundance. Klebsiella, Escherichia, and Acinetobacter were the dominant genera in protocol 3, and Klebsiella pneumoniae was the most abundant pathogenic bacteria detected with 53 isolates, while Acinetobacter nosocomialis was uniquely detected with seven isolates. Vibrio and Pseudoalteromonas were the dominant genera in protocol 4, and they showed advantages in isolating and cultivating Marine-derived Vibrio. Exiguobacterium, Staphylococcus, and Bacillus were the dominant genera in protocol 5. Bacillus cereus and Lactococcus lactis were the most abundant pathogenic bacteria detected with 20 and 15 isolates, respectively, while Lactococcus lactis was uniquely detected at higher abundance. Metagenomic sequencing showed that Klebsiella pneumoniae was significantly dominant with a gene abundance of 51.11%, followed by Alcanivorax sp. at 12.57%. Conclusion: The surface water of the northeast coast of Hainan Island in China exhibits a rich diversity of bacteria, with Klebsiella pneumoniae being highly abundant in the studied area. Different cultivation methods demonstrate distinct selective advantages in culturing bacterial genera and pathogens. Therefore, it is necessary to optimize cultivation conditions for specific marine bacteria.

[Years of potential life lost due to premature death of cardiovascular diseases among residents in Suzhou from 1987 to 2017].

From 1987 to 2017, cardiovascular disease (CVD) had been ranking the first cause of death in Suzhou, and the mortality rate showed an upward trend annual percentage changes (APC=0.62%, P=0.001), while the standardized mortality rate showed a downward trend (APC=-2.65%, P<0.001). The probability of premature death of CVD declined consistently from 7.06% in 1987 to 2.00% in 2017 (APC=-4.45%, P<0.001). When the life expectancy was set at 70, the potential years of life lost rate (PYLLR) decreased from 6.35‰ in 1987 to 3.30‰ in 2017, and the standardized PYLLR decreased from 7.30‰ to 2.68‰. When the life expectancy was set at 75, the PYLLR decreased from 10.12‰ to 5.19‰, and the standardized PYLLR decreased from 11.44‰ to 3.88‰. With the increase of years, all PYLLR and standardized PYLLR showed a significantly downward trend (APC=-2.51%--3.89%, P<0.001).

Final kissing balloon inflation for coronary bifurcation lesions treated with single-stent technique : A meta-analysis.

BACKGROUND: The efficacy of final kissing balloon (FKB) inflation in one-stent techniques for bifurcation lesions is controversial. The goal of the present study was to investigate the impact of FKB on long-term clinical outcomes in one-stent strategies. METHODS: A literature search of the PubMed, Embase, and Cochrane Library databases was undertaken through August 2017. The primary outcome was major adverse cardiac events (MACE), defined as the composite of cardiac death, myocardial infarction, and target lesion revascularization. Overall hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using the random-effects model. RESULTS: Ten studies comprising 7364 patients treated with a one-stent technique were included in the analysis. Overall, FKB did not demonstrate a significant reduction in MACE compared with non-FKB in both randomized trials (HR: 1.13; 95% CI: 0.65-1.98) and observational studies (HR: 0.86; 95% CI: 0.61-1.20). The risk of cardiac death (HR: 0.89; 95% CI: 0.53-1.49), myocardial infarction (HR: 0.76; 95% CI: 0.53-1.09), and target lesion revascularization (HR: 0.96; 95% CI: 0.74-1.23) was also similar in both groups. CONCLUSION: FKB may not be mandatory and a selective FKB strategy might be more justified in one-stent techniques for bifurcation lesions.

[Clinical significance of CTP combined with ABIC score in predicting the short-term prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure].

Objective: To investigate the risk factors affecting the short-term prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF), and establish a new scoring model to predict the short-term prognosis of patients. Methods: This study enrolled 222 patients with HBV-ACLF. According to their clinical outcomes during hospitalization and 90 days after discharge, they were divided into survival and death group. Clinical data were collected to calculate the Child-Turcotte-Pugh (CTP), model for end-stage liver disease (MELD), albumin-bilirubin (ALBI), and age-bilirubin-international normalized ratio-creatinine (ABIC) scores for prognosis. Multivariate logistic regression analysis was used to analyze the independent risk factors affecting 90-day mortality in HBV-ACLF patients. Cox regression model was used to establish a new prediction model. Area under the receiver operating characteristic curve was used to calculate short-term prognostic value of the models. K-M survival curve was used to predict the prognosis of patients. Results: CTP and ABIC scores were independent risk factors for 90-day mortality in HBV-ACLF patients, and the risk of death from liver failure had increased with increase of score. Cox regression model established a new predictive model CTP-ABIC = 0.551 × CTP + 0.297 × ABIC. Area under the receiver operating characteristic curve of all three scoring models (CTP, ABIC and CTP-ABIC) were 0.878, 0.829, 0.927, respectively. CTP-ABIC score was superior to the CTP and ABIC score (P value < 0.001). Patients with CTP-ABIC score ≥9.08 had higher mortality rate than patients with CTP-ABIC score < 9.08, and the difference was statistically significant (P < 0.001). Conclusion: All three scoring systems can predict short-term prognosis in patients with HBV-ACLF, but the accuracy of CTP-ABIC is superior.

[Microbiology analysis of periprothetic joint infection post total hip and knee arthroplasty of 9 centers in Beijing between 2014 and 2016].

Objective: To investigate the microbiological test, antibiotic sensitivity and surgical treatment of periprosthetic joint infection(PJI) cases in post total hip arthroplasty (THA) and total knee arthroplasty (TKA) patients. Methods: A retrospective cross-sectional survey was conducted on 318 patients who underwent THA or TKA in 9 clinical centers in Beijing from January 2014 to December 2016.The data of microbiology, antibiotic sensitivity and surgical treatment were collected.The average age of patients was (62.3±13.1) years old (range: 21-86 years old), including 145 males and 173 females.The body mass index was (25.6±3.8) kg/m (2) (range: 15.6-38.1 kg/m(2)). Results: In total, 318 patients had microorganisms detected by periprosthetic tissue culture or synovial fluid culture, 209 cases (65.7%) had Gram-positive bacteria, 29 cases (9.1%) had Gram-negative bacteria, 10 cases (3.1%) had fungi, 3 cases (0.9%) had non-tuberculous mycobacteria, 72 cases (22.6%) were negative, 69 cases (21.7%) had methicillin-resistant bacteria. The antibiotic sensitivity results showed that the overall resistance rate of penicillin, cefuroxime, amoxicillin+clavulanic acid was 79.9%, 69.9%, and 68.1%, respectively; meropenem, vancomycin, and linezolid resistance rate was 0. For the treatment methods of hip and knee PJI, two-stage revision surgery acounted for 72.9% (108/148) and 64.1% (109/170), respectively. One-stage revision surgery accounted for 21.6% (32/148) and 7.6% (13/170), and open debridement surgery accounted for 4.7%(7/148) and 26.4% (45/170). Conclusions: Gram-positive bacteria was still the main pathogen of PJI.The methicillin-resistant bacteria and rare bacteria should be payed attention to. The Majority of hip and knee PJI cases were treated by two-stage revision surgery.

[Clinical study on topography-guided laser ablation combined with accelerated corneal collagen cross-linking for early keratoconus].

Objective: To study the safety and efficacy of topography-guided customized excimer laser subepithelial ablation combined with accelerated collagen cross-linking technique in treatment of early keratoconus. Methods: Ninteen patients(20 eyes) (13 males 14 eyes, and 6 females 6 eyes), aged 12 to 44 years (24.7±8.0) were diagnosed as keratoconus by three-dimensional corneal topography and tomography, clinical history and examinations, and classified as KC1~KC3. Based on the classical excimer laser subepithelial keratomileusis (LASEK) method, topography guided laser ablation was performed with an excimer laser system (WaveLight EX500). After laser ablation, the corneal stromal bed was immersed with 0.1% riboflavin for 10 minutes, and then was irradiated by ultraviolet light (Avedro KXL) at 30 mW/cm(2) for 4 minutes. All the patients were followed up for more than 12 months. The uncorrected visual acuity (UCVA), diopter, best corrected visual acuity (BSCVA), corneal topography, central corneal endothelial cell density (ECD), hexagonal cell percentage (HEX), coefficient of variation (CV) and other indicators were observed. For normal distribution variables, Dunnett-t test was used before and after operation, and Wilcoxon test was used for variables with abnormal distribution. And the complications were recorded. Results: There was no loss of BSCVA at 12 months postoperatively, 20% of the eyes had no change of BSCVA, and 15% of the eyes gained 1 line of BSCVA, 15% of the eyes gained 2 lines of BSCVA, 50% of the eyes gained 3 lines and more of BSCVA. There was no significant difference in UCVA, BSCVA, manifest refractive spherical equivalent (MRSE) and the cylinder at 3 months postoperatively (P>0.05). The BSCVA were significantly improved at 6 and 12 months postoperatively compared with those before operation (t=3.095, 3.079, <0.05). Although there was no significant difference in UCVA and MRSE, the cylinder was significantly reduced at 6 and 12 months postoperatively (t=-2.890, -2.435, P<0.05). Apex curvature (Kapex) and mean pupil power (MPP) within 4.5mm of central cornea decreased significantly (Z=-2.903, P<0.01; Z=-2.667, P<0.01). Even though the thinnest corneal thickness decreased from pre-operational (461.9±31.1) µm to post-operational (416.6±27.0) µm (Z=-3.059, P<0.01), the cornea became regular with keratometric asymmetry index of anterior corneal surface decreased (Z=-2.667, P<0.01). The corneal optical quality parameters were improved. There was no significant difference in ECD, HEX and CV at 12 months postoperatively (P>0.05). Twelve months after operation, grade 0, 0.5, 1 and 2 haze were seen on 20%, 55%, 20% and 5% corneas respectively. Conclusions: The topography guided excimer laser ablation combined with accelerated corneal collagen cross linking is safe and effective in treatment of early stage keratoconus. It can significantly improve corneal regularity while preventing keratoconus progression, so as to improve the best corrected visual acuity postoperatively. (Chin J Ophthalmol, 2019, 55: 904-910).

Serum hepatitis B surface antigen correlates with fibrosis and necroinflammation: A multicentre perspective in China.

The kinetics of serum hepatitis B surface antigen (HBsAg) during the natural history of hepatitis B virus (HBV) infection has been studied, but the factors affecting them remain unclear. We aimed to investigate the factors affecting HBsAg titres, using data from multicentre, large-sized clinical trials in China. The baseline data of 1795 patients in 3 multicentre trials were studied, and the patients were classified into 3 groups: hepatitis B early antigen (HBeAg)-positive chronic HBV infection (n = 588), HBeAg-positive chronic hepatitis B (n = 596), and HBeAg-negative chronic hepatitis B (n = 611). HBsAg titres in the different phases were compared, and multiple linear progression analyses were performed to investigate the implicated factors. HBsAg titres varied significantly in different phases (P = .000), with the highest (4.60 log10 IU/mL [10%-90% confidence interval: 3.52 log10 IU/mL-4.99 log10 IU/mL]) in patients with HBeAg-positive chronic HBV infection. In all phases, age and HBV DNA were correlated with serum HBsAg level. In HBeAg-positive chronic hepatitis B patients, a negative correlation between HBsAg titres and fibrosis stage was observed. Alanine amonitransferase or necroinflammatory activity was also correlated with HBsAg titres in HBeAg-negative chronic hepatitis B patients. In conclusion, decreased HBsAg titres may be associated with advancing fibrosis in HBeAg-positive chronic hepatitis B patients or increased necroinflammation in those with HBeAg-negative chronic hepatitis B. Our findings may help clinicians better understand the kinetics of HBsAg and provide useful insights into the management of this disease.

Very high external quantum efficiency and wall-plug efficiency 527 nm InGaN green LEDs by MOCVD.

We demonstrate very high luminous efficacy InGaN-based green light-emitting diodes (LEDs) grown on c-plane patterned sapphire substrates (PSS) using metal organic chemical vapor deposition (MOCVD). The 527 nm green LEDs show a peak external quantum efficiency (EQE) of 53.3%, a peak wall-plug efficiency (WPE) of 54.1% and a peak luminous efficacy of 329 lm/W, respectively. A high EQE of 38.4%, a WPE of 32.1% and a very low forward voltage of 2.86 V were obtained at a typical working current density of 20 A/cm2. By operating low cost green LEDs at a low current density, our devices (0.5 mm2) demonstrating an EQE and a WPE higher than 50% and an efficacy of 259 lm/W at 4 A/cm2 with an output power of 24 mW. High crystal quality of the InGaN/GaN MQWs was characterized by X-ray diffraction (XRD) and the advantage of the epitaxy design was investigated by APSYS software simulation. These results provide a simple way to achieve very high efficiency InGaN green LEDs.

Childhood asthma clusters reveal neutrophil-predominant phenotype with distinct gene expression.

BACKGROUND: Childhood asthma comprises different phenotypes with complex pathophysiology. Different asthma phenotypes evoke various clinical symptoms and vary in their responses to treatments. METHODS: We applied k-means clustering algorithm of twelve objective laboratory tests among 351 asthmatic children enrolled in the Taiwanese Consortium of Childhood Asthma Study (TCCAS). We constructed gene expression profiles of peripheral blood mononuclear cells (PBMC) from children with different asthma phenotypes. RESULTS: Five distinct phenotypes of childhood asthma were identified and can be characterized by either eosinophil-predominant or neutrophil-predominant inflammatory characteristics. In the gene expression profile analysis, significant differences were noted for neutrophil-predominant asthma, compared with samples from all the other asthma phenotypes. The vast majority of the differentially expressed genes in neutrophil-predominant asthma was associated with corticosteroid response. From an independent inhaled corticosteroid (ICS) response cohort, we also found neutrophils could be activated in this severe asthma phenotype and neutrophil-predominant asthma may be associated with corticosteroid nonresponsiveness. CONCLUSION: Phenotype clustering of childhood asthma can be helpful to identify clinically relevant patients and reveal different inflammatory characteristics in asthmatic children. Neutrophil-predominant asthma is the most severe asthma phenotype with poor corticosteroid response. Gene expression profile of different asthma phenotypes not only improve our knowledge of childhood asthma, but also can guide asthma precision medicine.

[Value of serum matrix metalloproteinase 3 in the assessment of early rheumatoid arthritis].

OBJECTIVE: To investigate the expression level of serum matrix metalloproteinase 3 (MMP3) in early rheumatoid arthritis (ERA) patients with normal C-reaction protein (CRP) or erythrocyte sedimentation rate (ESR), and the significance in disease assessment. METHODS: In the study, 133 cases of early RA patients, 25 osteoarthritis (OA) patients and 60 healthy controls in Peking University People's Hospital from 2011 to 2015 were included. The RA patients were further divided into 4 groups according to levels of CRP and ESR: 88 patients with increased CRP and increased ESR, 15 patients with normal CRP and normal ESR, 17 patients with normal CRP but increased ESR, and 13 patients with increased CRP but normal ESR. All the clinical information of the patients was collected, and the serum MMP3 levels of both patients and healthy controls were detected by enzyme-linked immune sorbent assay (ELISA). RESULTS: The serum MMP3 level of RA patients with normal CRP and/or normal ESR [(72.89±6.34) µg/L] was obviously higher than that of OA patients [(42.87±4.14) µg/L] (P=0.002) and healthy controls [(31.62±2.88) µg/L] (P<0.001). The serum MMP3 levels of the patients with normal CRP and normal ESR [(47.04±9.64) µg/L] were higher than those of the healthy controls, and there was statistical significance between the two groups (P<0.05). The serum MMP3 levels of the patients with increased CRP but normal ESR [(94.18±9.11) µg/L] and the patients with normal CRP but increased ESR [(79.42±10.60) µg/L] were both higher than those of the OA patients and healthy controls, and there was obvious statistical difference (P<0.05). In the early RA patients with normal CRP and/or normal ESR, the serum MMP3 level was positively correlated with the CRP level (r=0.336, P=0.024). The positive rate of MMP3 in the patients with normal CRP and/or normal ESR was 44.44%, higher than the positive rate of CRP (28.89%) and the positive rate of ESR (37.78%). In these early RA patients, the positive rate was 52.94% in the patients with normal CRP but increased ESR and 53.85% in the patients with increased CRP but normal ESR. CONCLUSION: The detection of the serum MMP3 level was significant in the assessment of early RA patients within 2-year duration who had normal CRP or ESR value.

Optically pumped lasing with a Q-factor exceeding 6000 from wet-etched GaN micro-pyramids.

We report the observation of room-temperature optically pumped lasing modes from a single GaN pyramid microcavity on a metallic mirror. The mode at 367.2 nm exhibits a low threshold (0.4-0.5 MW/cm2) and a narrow linewidth (0.054 nm), by which the quality factor can be estimated to be >6000. These lasing behaviors can be attributed to the specific wet-etching approach by selectively etching away defects and pyramid geometry with bottom Ag reflectors for better light confinement. Optical resonances in these pyramids are further investigated in combination with three-dimensional finite-difference time-domain simulations.

[Precision of three-dimensional printed brackets].

OBJECTIVE: This study was based on digital orthodontic diagnosis work flow for indirect bonding transfer tray model design and three-dimensional (3D) printing, and the aim of this paper was to inspect the dimensional accuracyof 3D printed brackets, which is the foundation of the follow up work and hoped that will illuminate the clinical application of the digital orthodontics work flow. METHODS: The samples which consisted of 14 cases of patients with malocclusion from Department of Orthodontics Peking University were selected, including 8 cases with tooth extraction and 6 cases without tooth extraction. All the 14 patients were taken intra-oral scan (Trios 3Shape, Denmark) and cone-beam computed tomography (CBCT, NewTom 3G volumetric scanner, Aperio Service,Italy)shooting after periodontal treatment. STL data and DICOM data were obtained from intraoral scans and CBCT images.Data segmentation, registration, fusion, automatic tooth arrangement, virtual positioning of orthodontic appliance and conversion the coordinates of malocclusion model were all done with self-programming software. The data of 3D printing model with brackets on it were output finally and printed out with EDEN260V (Objet Geometries, Israel) to make indirect bonding transfer tray. Digital vernier caliper was used to measure the length and width of upper and lower left brackets and buccal tubes on those 3D models after removal of surrounding supporting material by ultrasonic vibration and water-spray. Intra-examiner reliability was assessed by using intra-class correlation coefficients (ICC), and one-sample T test was used to compare the measurements with the standard dimensional data of the brackets. RESULTS: There were significant differences which range in 0.04-0.17 mm between the 13 items out of the 19 measurement items. Except for the length of the lower left premolars'brackets, mean values of the other items were greater than the test value. CONCLUSION: Although the measurement results in the width of brackets and the width and length of the buccal tubes obtained experimentally were slightly larger than the test value,this may not reduce the accuracy of indirect bonding procedure in clinic necessarily. Whether the differences which range in 0.04-0.17 mm would actually affect the retention and positioning of brackets needs to be confirmed by further studies.

Cloning and expression analysis of cysteine protease gene (MwCP) in Agropyron mongolicum Keng.

In this study, a cysteine protease gene (MwCP) from Agropyron mongolicum Keng was isolated using RACE. Sequence analysis indicated that MwCP was 1473 bp, and it contained a 1134-bp open reading frame, which encoded 377 amino acids with a 24-amino acid N-terminal signal peptide. The results indicated that the MwCP protein was a new member of the papain C1A family, and it was predicted to be an extracellular, secretory stable hydrophilic protein. The secondary structure of MwCP was mainly composed of α-helices and random coils, and the space structure primarily contained α-helices, ß-sheets, and ß-turns. Homology analyses showed the 98% homology between MwCP amino acids and a cysteine protease found in Triticum aestivum (GenBank accession No. AAW21813.1). Analysis of mRNA using semi-quantitative RT-PCR indicated that during a 48-h drought stress period, MwCP was expressed during the 4th hour, and the expression level peaked during the 6th hour before declining to the original level. The results revealed that MwCP was involved in drought-resistant physiological processes of A. mongolicum. Moreover, the MwCP expression levels were highest in leaves, intermediate in roots, and lowest in stems.

[Inhibitory effect of imrecoxib combined with lobaplatin on tumor growth and lymph node metastasis of human lung cancer xenografts in nude mice].

OBJECTIVE: To evaluate the inhibitory effect of imrecoxib combined with lobaplatin on tumor growth and lymph node metastasis of human lung adenocarcinoma xenografts in nude mice, and to explore its possible mechanisms. METHODS: Human lung cancer A549 cells were injected into Bal B/c nude mice subcutaneously. Twenty-eight healthy male nude mice were randomly divided into 4 groups: the control group, imrecoxib group, lobaplatin group and imrecoxib combined with lobaplatin group. Each group was treated with appropriate drugs and the tumor size was measured every five days. The expression of ezrin and E-cadherin protein was detected by immunohistochemistry and flow cytometry. Ezrin and E-cadherin mRNA were detected by real-time PCR. RESULTS: The tumor inhibition rates of imrecoxib group, lobaplatin group and combination group were 36.7%, 54.6% and 69.2%, respectively. The tumor volumes of imrecoxib group [(905.33±113.31) mm(3)] and combination group [(507.74±77.50) mm(3)] were significantly lower than that of the control group (1355.33±189.04) mm(3) (P<0.05), and the tumor weights were significantly reduced [(1.13±0.14) g, (0.63±0.10) g respectively] vs. (1.69±0.24) g (P<0.05). The expressions of ezrin protein and mRNA in the imrecoxib group and combined treatment group were significantly lower than that of the control group (136.53±35.52, 74.72±19.48 vs. 175.62±21.16 for protein expression level; 0.54±0.03, 0.36±0.03 vs. 1.02±0.02 for mRNA expression level, respectively, P<0.05 for both), while the expression of E-cadherin protein and mRNA in the imrecoxib group and combined treatment group was significantly higher than that of the control group (253.78±38.87, 308.94±24.67 vs. 213.66±30.31 for protein expression level; 2.19±0.02, 3.02±0.02 vs. 1.05±0.03 for mRNA expression level, respectively, P<0.05 for both). There was a significant negative correlation between ezrin protein and E-cadherin protein (r=-0.737, P<0.01), as well as between ezrin mRNA and E-cadherin mRNA (r=-0.977, P<0.01). CONCLUSIONS: Administration of imrecoxib combined with lobaphatin has inhibitory effects on the growth of non-small cell lung cancer xenografts and lymph node metastasis via down-regulated ezrin and upregulated E-cadherin. Imrecoxib and lobaplatin have a synergistic antitumor effect.

Implication of polymorphisms in DNA repair genes with an increased risk of hepatocellular carcinoma.

We explored the association between 4 XRCC1 (Arg194Trp and Arg399Gln) and XPD (Asp312Asn and Lys751Gln) polymorphisms with the development and prognosis of hepatocellular carcinoma (HCC). A total of 218 cases with HCC and 277 healthy controls were included in the study. Genotyping of the XRCC1 (Arg194Trp and Arg399Gln) and XPD (Asp312Asn and Lys751Gln) polymorphisms was performed in a 384-well plate format on the Sequenom MassARRAY platform. We found that individuals with the XRCC1 399AA genotype had a higher risk of HCC compared with the GG genotype (odds ratio, OR = 1.85, 95% confidence interval, CI = 1.03-3.23). Similarly, individuals carrying the XPD 751GG genotype showed a greatly increased risk of HCC (OR = 2.97, 95%CI = 126- 7.38). Cox regression analysis showed that individuals carrying XPD 751Gln/Gln genotypes had a 0.30-fold increased risk of death from HCC. These results suggest that polymorphisms in XRCC1 and XPD may have functional significance in HCC.

[Epidemic characteristics and trend analysis of major injuries deaths among children and adolescents in Jiangsu Province from 2012 to 2021].

Objective: To understand the situation and epidemic characteristics of injury deaths among children aged 5 to 24 years in Jiangsu Province from 2012 to 2021 and the trend of annual changes. Methods: The main injury mortality data of children and adolescents was collected, and the crude and standardized mortality rates of road traffic accidents, drowning, suicide, and accidental falls among children and adolescents over a decade and the annual average percentage of change (AAPC) were calculated. The main injury mortality characteristics and trends of children and adolescents of different age groups and genders were analyzed. Results: The total number of injury deaths among 5 to 24 adolescents in Jiangsu Province was 16 052, with a standardized mortality rate of 9.58/100 000. There was no significant trend in the overall standardized mortality rate of injuries (AAPC=-3.450%, P=0.055). The standardized mortality rate of road traffic injuries among children and adolescents showed a decreasing trend over the past decade, with statistical significance (AAPC=-9.406%, P<0.001). The standardized suicide mortality rate showed an upward trend over the past decade, with statistical significance (AAPC=9.000%, P=0.001). The overall injury mortality rate showed an upward trend with age. Suicide rates in males and females were on the rise and both have statistical significance (AAPC=9.420% and AAPC=9.607%, both P<0.05). The standardized mortality rates of female traffic accidents, drowning, and male traffic accidents showed a decreasing trend and were statistically significant (AAPC for female traffic accidents=-7.364%, AAPC for female drowning=-5.352%, and AAPC for male traffic accidents=-10.242%, all P<0.05). The standardized mortality rate of urban and rural traffic accidents showed a decreasing trend and was statistically significant(AAPC=-7.899% and AAPC=-9.421%, both P<0.001). The standardized suicide mortality rate showed an upward trend and statistical significance (AAPC=11.009% and AAPC=7.528%, both P<0.05). Conclusions: The overall injury situation of children and adolescents in Jiangsu Province improved in the past decade from 2012 to 2021, but the suicide mortality rate was on the rise. It is necessary to focus on the mental health issues of this age group and to strengthen the prevention and control of suicide among children and adolescents, in Jiangsu.

Identification of human-selective analogues of the vascular-disrupting agent 5,6-dimethylxanthenone-4-acetic acid (DMXAA).

BACKGROUND: Species selectivity of DMXAA (5,6-dimethylxanthenone-4-acetic acid, Vadimezan) for murine cells over human cells could explain in part the recent disappointing phase III trials clinical results when preclinical studies were so promising. To identify analogues with greater human clinical potential, we compared the activity of xanthenone-4-acetic acid (XAA) analogues in murine or human cellular models. METHODS: Analogues with a methyl group systematically substituted at different positions of the XAA backbone were evaluated for cytokine induction in cultured murine or human leukocytes; and for anti-vascular effects on endothelial cells on matrigel. In vivo antitumour activity and cytokine production by stromal or cancer cells was measured in human A375 and HCT116 xenografts. RESULTS: Mono-methyl XAA analogues with substitutions at the seventh and eighth positions were the most active in stimulating human leukocytes to produce IL-6 and IL-8; and for inhibition of tube formation by ECV304 human endothelial-like cells, while 5- and 6-substituted analogues were the most active in murine cell systems. CONCLUSION: Xanthenone-4-acetic acid analogues exhibit extreme species selectivity. Analogues that are the most active in human systems are inactive in murine models, highlighting the need for the use of appropriate in vivo animal models in selecting clinical candidates for this class of compounds.