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Background: Although China accounts for 7.8% of worldwide new prostate cancer (PCa) cases and 14.5% of new deaths according to GLOBOCAN 2020, the risk of PCa associated with germline mutations is poorly defined, hampered in part by lack of nationwide evidence. Here, we sequenced 19 PCa predisposition genes in 1,836 Chinese patients with PCa and estimated disease risk associated with inherited mutations. Patients and Methods: Patients were recruited from 4 tertiary cancer centers (n=1,160) and a commercial laboratory (n=676). Germline DNA was sequenced using a multigene panel, and pathogenic/likely pathogenic (P/LP) mutation frequencies in patients with PCa were compared with populations from the gnomAD (Genome Aggregation Database) and ChinaMAP (China Metabolic Analytics Project) databases. Clinical characteristics and progression-free survival were assessed by mutation status. Results: Of 1,160 patients from hospitals, 89.7% had Gleason scores ≥8, and 65.6% had metastases. P/LP mutations were identified in 8.49% of Chinese patients with PCa. Association with PCa risk was significant for mutations in ATM (odds ratio [OR], 5.9; 95% CI, 3.1–11.1), BRCA2 (OR, 15.3; 95% CI, 10.0–23.2), MSH2 (OR, 15.8; 95% CI, 4.2–59.6), and PALB2 (OR, 5.9; 95% CI, 2.7–13.2). Compared with those without mutations, patients with mutations in ATM, BRCA2, MSH2, or PALB2 showed a poor outcome with treatment using androgen deprivation therapy and abiraterone (hazard ratio, 2.19 [95% CI, 1.34–3.58] and 2.47 [95% CI, 1.23–4.96], respectively) but similar benefit from docetaxel. Conclusions: The present multicenter study confirmed that a significant proportion of Chinese patients with PCa had inherited mutations and identified predisposition genes in this underreported ethnicity. These data provide empirical evidence for precision prevention and prognostic estimation in Chinese patients with PCa.

At present, the deficiency of β-cell function is progressive in patients with type 2 diabetes mellitus. Exenatide cannot only control blood glucose well, but also promotes the regeneration and proliferation of islet β-cells and improves the function of β cells. However, it needs to be given twice a day, and there are many adverse reactions such as nausea. PEGylated exenatide (study code: PB-119) needs to be administered only once a week. The purpose of this experiment was to evaluate the safety, pharmacokinetics and pharmacodynamics of an escalating dose regimen of subcutaneous PEGylated exenatide injections in healthy subjects. Twelve healthy young adult subjects in each group received once-weekly subcutaneous injections of 165 μg, 330 μg, and 660 μg PEGylated exenatide for 6 weeks. Plasma drug concentration was determined in venous blood collected across selected time points. Safety and tolerability were evaluated by monitoring adverse events, laboratory parameters, and electrocardiogram. Blood glucose, insulin, glucagon and C peptide were monitored at different time points to evaluate the pharmacodynamics of PEGylated exenatide. A total of 11, 10, and 12 subjects completed the study in 165 µg, 330 µg, and 660 µg dose groups, respectively. After 6 consecutive weeks of administration, the t1/2 in the 165 μg, 330 μg, and 660 µg dose groups was 55.67 ± 11.03 h, 56.99 ± 21.37 h, and 54.81 ± 13.87 h, respectively. The Cavg was 4.22 ± 0.78 ng/ml, 6.03 ± 1.43 ng/ml, and 10.50 ± 3.06 ng/ml, respectively. AUCss was 708.59 ± 131.87 h•ng/ml, 1012.63 ± 240.79 h•ng/ml, and 1763.81 ± 514.50 h•ng/ml, respectively. The accumulation index was 1.15 ± 0.07, 1.17 ± 0.11, and 1.14 ± 0.07. The CLss/F was 241.25 ± 51.13 ml/h, 341.53 ± 73.62 ml/h, and 450.06 ± 313.76 ml/h, respectively. A total of 10 of 36 (27.78%) subjects in the three dose groups developed specific antibodies after consecutive subcutaneous injections of PEGylated exenatide. The Cavg and Cmax were higher than those of antibody-negative subjects. Furthermore, in antibody-positive subjects, CLss/F, t1/2, AUCτ, accumulation index, MRT(0–inf) and other parameters were lower than those of antibody-negative subjects. In the 165 μg dose group, two subjects (16.67%) experienced 4 adverse events. In the 330 μg dose group, no subjects reported adverse events. In the 660 μg dose group, 8 subjects (66.67%) reported 16 adverse events, which were mostly gastrointestinal. There were no significant changes in the pharmacodynamic parameters except the glucagon level at day 36 in the 660 µg dose group, the 2h postprandial insulin and C peptide levels at day 36 and day 50 in the 165 μg dose group compared with baseline (− 1 day). A once-weekly subcutaneous injection of 165 µg and 330 µg PEGylated exenatide is safe. No significant effects on blood glucose or pancreatic hormone levels were observed in the subjects within these dose groups. The pharmacokinetic parameters of PEGylated exenatide may be affected by immunogenicity. The study is registered at clinicaltrials.gov (No. NCT03062774).

BACKGROUND Aortic dissection (AD) is a life-threatening condition with a high mortality rate without immediate medical attention. Early diagnosis and appropriate treatment are critical in treating patients with AD. In the emergency department, patients with AD commonly present with classic symptoms of unanticipated severe chest or back pain. However, it is worth noting that atypical symptoms of AD are easily misdiagnosed. CASE SUMMARY A 51-year-old woman was first diagnosed with scapulohumeral periarthritis due to left shoulder pain. After careful examination of her previous medical history and contrast-enhanced computed tomography angiography, the patient was diagnosed with a new type A AD after chronic type B dissection in the ascending aorta. The patient was successfully treated with surgical replacement of the dissected aortic arch and remains in good health. CONCLUSION New retrograde type A AD after chronic type B dissection is relatively rare. It is worth noting that a physician who has a patient with suspected AD should be vigilant. Both patient medical history and imaging tests are crucial for a more precise diagnosis.

Objective With the epidemic of coronavirus disease 2019 (COVID-19), the healthcare workers (HCWs) require proper respiratory personal protective equipment (rPPE) against viral respiratory infectious diseases (VRIDs). It is necessary to evaluate which type of mask and manner of wearing is the best suitable rPPE for preventing the VRID. Study design A Bayesian network meta-analysis was performed to comprehensively analyze the protective efficacy of various rPPE. Methods This network meta-analysis protocol was registered in an international prospective register of systematic reviews (CRD42020179489). Electronic databases were searched for cluster randomized control trials (RCTs) of comparing the effectiveness of rPPE and wearing manner in preventing HCWs from VRID. The primary outcome was the incidence of laboratory-confirmed viral respiratory infection reported as an odds ratio (OR) with the associated 95% credibility interval (CrI). The secondary outcome was the incidence of clinical respiratory illness (CRI) reported as an OR with the associated 95% CrI. Surface under the cumulative ranking curve analysis (SUCRA) provided a ranking of each rPPE according to the primary outcome and the secondary outcome as data supplement. Results Six studies encompassing 12,265 HCWs were included. In terms of the incidence of laboratory-confirmed viral respiratory infection, the continuous wearing of N95 respirators (network OR, 0.48; 95% CrI: 0.27 to 0.86; SUCRA score, 85.4) showed more effective than the control group. However, in terms of reducing the incidence of CRI, there was no rPPE showing superior protective effectiveness. Conclusions There are significant differences in preventive efficacy among current rPPE. Our result suggests that continuous wearing of N95 respirators on the whole shift can serve as the best preventive rPPE for HCWs from the VRID., Highlights • First network meta-analysis of respiratory personal protective equipment (rPPE). • Wearing manner is important for susceptible healthcare workers. • Continuous wearing of N95 respirators on the whole shift can serve as the best preventive rPPE for healthcare workers from the VRIDs.

Background The purpose of this study was to investigate the safety, tolerability and pharmacokinetics of tetramethylpyrazine nitrone (TBN) in healthy Chinese volunteers. Methods A single-ascending-dose (SAD) study where 68 subjects were randomized to a single dose of placebo or TBN (50, 100, 200, 400, 700, 1,000, 1,400, or 1,800 mg) through IV infusion over 30 min. A multiple-ascending-dose (MAD) study where 24 subjects received TBN twice daily (with 12 hr interval) for total 6.5 days at doses of either 700 or 1,400 mg. Adverse events were recorded and pharmacokinetic samples were collected during the whole study period. Results No serious adverse events were found in the study. All of the observed adverse events, including increased white blood cell (4.4% subjects) and neutrophil counts (4.4% subjects), and decreased hemoglobin levels (4.2% subjects), were laboratory test abnormalities. All the adverse events were mild and tolerable, and returned to normal without any intervention. In the SAD study, linear Cmax values were observed in the dose interval of 50-1,800 mg. In the MAD study, the average steady-state concentrations (Cavg.ss ) of TBN in the 700 and 1,400 mg dose group were 2,407 and 5,837 ng/ml, respectively. No drug accumulation was observed in this study. Conclusions TBN is well tolerated in healthy volunteers. Linear Cmax values were observed in the interval of 50-1,800 mg, and target exposures of TBN were achieved without accumulation after twice daily administration to subjects. (This study has been registered at ChiCTR.org.cn. Identifier: ChiCTR1800016225 and ChiCTR1800019627.).

Acute heart failure (AHF) is a severe complication after cardiac surgery with cardiopulmonary bypass (CPB). Although some AHF biomarkers have been used in clinic, they have limitations when applied in the prediction and diagnosis of AHF after cardiac surgery with CPB, and there are still no effective and specific biomarkers. We and other researchers have shown that circulating microparticles (MPs) increased in a variety of cardiovascular diseases. However, whether the concentration of circulating MPs could be a new biomarker for AHF after cardiac surgery remains unknown. Here, 90 patients undergoing cardiac surgery with CPB and 45 healthy subjects were enrolled. Patients were assigned into AHF (n=14) or non-AHF (n=76) group according to the diagnosis criteria of AHF. The concentrations of circulating MPs were determined before, as well as 12 h and 3 days after operation with nanoparticle tracking analysis technique. MPs concentrations in patients before surgery were significantly higher than those of healthy subjects. Plasma levels of MPs were significantly elevated at 12 h after surgery in patients with AHF, but not in those without AHF, and the circulating MPs concentrations at 12 h after surgery were higher in AHF group compared with non-AHF group. Logistic regression analysis indicated that MPs concentration at postoperative 12 h was an independent risk factor for AHF. The area under receiver operating characteristic curve for MPs concentration at postoperative 12 h was 0.81 and the best cut-off value is 5.20×108 particles mL-1 with a sensitivity of 93% and a specificity of 10%. These data suggested that the concentration of circulating MPs might be a new biomarker for the occurrence of AHF after cardiac surgery with CPB.

To evaluate the use of real-time shear wave elastography (SWE) in the assessment of renal elasticity and the efficacy of steroid treatment in adult idiopathic nephrotic syndrome (INS). This study included 120 patients with INS. Patients were divided into steroid-sensitive and steroid-resistant groups. Renal biopsy was performed. Thirty healthy subjects were recruited as controls. Young’s modulus (YM) of the renal parenchyma was measured by SWE. The YM values in each group were compared using glomerular sclerosis index (GI) and renal interstitial fibrosis (RIF). The YM values were significantly different between the INS and control groups, as well as between the steroid-sensitive and steroid-resistant groups (P

Exenatide promotes insulin secretion and inhibits postprandial glucagon secretion. Polyethylene glycolated exenatide injection (PB-119), a derivative obtained by modification of exenatide, is more stable in metabolic behavior than exenatide in vivo. Our study aimed to evaluate the safety, tolerability and pharmacokinetic characteristics of polyethylene glycolated exenatide as a single subcutaneous injection in healthy volunteers. Seventy subjects were randomly assigned to 8 incremental dosage groups (2, 5, 10, 25, 50, 100, 200 and 400 µg). The 2- to 50-µg groups had 8 subjects in each group (the ratio of test preparation to placebo was 3:1), and the 100- to 400-µg groups had 10 subjects in each group (the ratio of test preparation to placebo was 4:1). All the subjects received a single subcutaneous injection of polyethylene glycolated exenatide and placebo according to the dosage groups. The tolerability test was conducted in the 2- to 10-µg groups. The pharmacokinetic test was carried out in the 25- to 400-µg groups, and plasma samples were collected to determine the pharmacokinetics of polyethylene glycolated exenatide. After medication, the vital signs of the subjects were monitored, and laboratory tests and electrocardiogram tests were carried out regularly in all the subjects. All 70 subjects completed the experiment. Except for the 5-µg and 10-µg groups, the safety and tolerability tests showed no adverse reactions in the 2-µg to 50-µg groups. Several subjects in the 100-µg and 200-µg groups had tolerable gastrointestinal tract reactions, and all subjects in the 400-µg group experienced adverse reactions, mainly gastrointestinal tract reactions and liver dysfunction. The pharmacokinetics of polyethylene glycolated exenatide was studied in 36 subjects, which showed slow absorption, a mean peak time of 20–40 h, and a mean elimination half-life of 51–64 h. The administration of polyethylene glycolated exenatide injection at a single dose of 2–200 µg is safe and tolerable for healthy volunteers. Once-weekly polyethylene glycolated exenatide injection can be recommended. The study was registered at clinicaltrials.gov (No. NCT02084251).

In order to strengthen the prevention and management in the geriatric department during the pandemic of COVID-19 and to explore how to implement nursing measures to control the spread of COVID-19 to elderly patients, our geriatric department established a leading group for epidemic prevention to train the medical staffs, the patients and caregivers and implemented a set of measures such as controlling the source of infection, cutting off the transmission route, and rehabilitation nursing of Chinese medicine, thus achieved zero infection of medical staff and elderly patients.

Background: Femoral neck fractures are the worst consequence of osteoporosis (OP), and its early prevention and treatment have become a public health problem.This study aims to investigate the relationship of bone-related biomarkers,femoral neck bone mineral density (BMD) and maximum load (Lmax),selecting the indicator which can reflect femoral neck bone loss and reduced bone strength. Methods: A total of 108 patients were recruited from January 2017 to December 2019. Femoral neck BMD, femoral neck Lmaxand bone-related biomarkerswere all measured and analyzed.Results: The expression of femoral neck type I collagen (COL-I)were significantly decreased, whereas other markers were all significantly increased with the decreasing of femoral neck BMD and Lmax(Pindependent factorsof femoral neck BMD and Lmax, whereasCOL-I was independent factor affectingLmax(P< 0.05). Moreover, CTX was the independent risk factor of OPN and COL-I(PConclusions: Bone-related biomarkersdo reflect decreased femoral neck bone mass and bone strength. Of them, the CTX increases most significantly in the process of bone loss, and can be used as a surrogate markerof OPN and COL-I for bone loss and reduced bone strength.Early measurement of CTXcouldfacilitate the diagnosis of osteopenia and provide a theoretical basis for delaying the occurrence of femoral neck OP and fragility fractures.

Peng Su,1,2 Jun-lin Zhou,2 Cai Yun,1 Feng Liu,1 Yi Zhang1 1Department of Orthopaedics, Teaching Hospital of Capital Medical University, Beijing Shijingshan Hospital, Beijing, People’s Republic of China; 2Department of Orthopedics, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Jun-lin ZhouDepartment of Orthopedics, Beijing Chaoyang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing, 100020, People’s Republic of ChinaTel +86-13240718193Email zhoujunlin145@163.comObjective: This study aimed to directly and accurately measure the range of motion of the acromioclavicular joint through 3D reconstruction and image registration.Methods: Thirteen healthy volunteers participated in the study. Computerized tomography (CT) was used to measure the acromioclavicular joint in four different motion poses. The images were integrated using reconstruction and registration technology, and the rotation angle range of the acromioclavicular joint was measured using 3D reconstruction. The measurements were expressed by axial angle representation. The dominant and the non-dominant sides were compared, and the difference in the axial angle of the acromioclavicular joint was compared in different postures.Results: The difference between the dominant and non-dominant sides in acromioclavicular motion was not significant. In the sagittal motion of the upper limb, the rotation angle of the acromioclavicular joint was greatest in a resting horizontal position, with an average of 26.1°. In this position, 34.6% of flexion and extension movements of the upper limb were completed by the acromioclavicular joint, which was the highest level of engagement. The rotation angle was lowest in the resting posteroinferior position, with an average of 8.2°. In this position, 24.9% of the flexion and extension movements of the upper limb were completed by the acromioclavicular joint.Conclusion: Combining 3D reconstruction and image registration is a direct and accurate method of measuring the motion of the acromioclavicular joint. The rotational motions of the acromioclavicular joint are bilaterally symmetrical and can be used as a reference for comparative study. The maximum range of motion of the acromioclavicular joint during rotation was found in the resting horizontal position. The clinical examination and post-treatment evaluation of the acromioclavicular joint’s rotation function can therefore be targeted in this range.Keywords: image registration, axial angle representation, acromioclavicular joints

Background The cross-sectional area of three parallel screws might affect the stability of the internal fixation of femoral neck fractures. The screws fixed in the oblique-triangle configuration (OTC) were assumed to have a larger cross-sectional area, but the biomechanical stability has not yet been validated. In this study, finite element analyses were performed to compare the biomechanical properties of the internal fixation fixed by the OTC and the traditional Inverted Equilateral Triangle Configuration (IETC). Method Pauwels type III fracture was established on the three-dimensional femoral model and three cannulated screws with the OTC and traditional IETC methods were applied. The oblique-triangle configuration with the largest area inscribed the femoral neck isthmus by the three screws was determined, the area and circumference of the cross-section formed by the OTC and IETC model were compared. Stress, strain, and displacement peaks of the two configuration models under different loads were compared. Twelve pairs of nodes on the fracture ends were selected and the displacement of the fracture ends was evaluated through the displacement between these nodes. Results The area and circumference of the cross-section formed by the OTC were larger than those in the IETC model. The degree of stress dispersion around the screw holes in the OTC model was better than that of the IETC, but the stress distribution order of the three screws in the two models was consistent. The maximum stress, strain, displacement, and displacement of the fracture end in the OTC model were smaller than those in the IETC model. The stress, strain, displacement, and fracture end displacement peaks of the two fixed models gradually increase with the increase of loads. Conclusion The oblique-triangle configuration showed superior mechanical properties than the IETC in finite element analyses. This study suggests that when three screws are fixed in parallel method, the larger the cross-sectional area of the screw configuration, the better stability of the internal fixation might be obtained. Furthermore, the biomechanical properties of various spatial configurations and screw holes of the three parallel screws need to be considered before clinical practice.

Traditional Chinese medicine (TCM) has been used successfully to treat rheumatoid arthritis (RA). Qingre Huoxue treatment (Qingre Huoxue decoction (QRHXD)/Qingre Huoxue external preparation (QRHXEP)) is a therapeutic scheme of TCM for RA. To date, there have been few studies comparing the efficacy and safety of QRHXD and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) for the treatment of active RA. This was investigated in a multicenter, double-blind, randomized controlled trial involving 468 Chinese patients with active RA [disease activity score (DAS)-28 > 3.2] treated with QRHXD/QRHXEP (TCM group), methotrexate plus hydroxychloroquine [Western medicine (WM) group], or both [integrative medicine (IM) group]. Patients were followed up for 24 weeks. The primary outcome measure was the change in DAS-28 from baseline to 24 weeks. The secondary outcome measures were treatment response rate according to American College of Rheumatology 20, 50, and 70% improvement criteria (ACR-20/50/70) and the rate of treatment-related adverse events (TRAEs). The trial was registered at ClinicalTrials.gov (NCT02551575). DAS-28 decreased in all three groups after treatment (p < 0.0001); the score was lowest in the TCM group (p < 0.05), while no difference was observed between the WM and IM groups (p > 0.05). At week 24, ACR-20 response was 73.04% with TCM, 80.17% with WM, and 73.95% with IM (based on the full analysis set [FAS], p > 0.05); ACR-50 responses were 40.87, 47.93, and 51.26%, respectively, (FAS, p > 0.05); and ACR-70 responses were 20.87, 22.31, and 25.21%, respectively, (FAS, p > 0.05). Thus, treatment efficacy was similar across groups based on ACR criteria. On the other hand, the rate of TRAEs was significantly lower in the TCM group compared to the other groups (p < 0.05). Thus, QRHXD/QRHXEP was effective in alleviating the symptoms of active RA—albeit to a lesser degree than csDMARDs—with fewer side effects. Importantly, combination with QRHXD enhanced the efficacy of csDMARDs. These results provide evidence that QRHXD can be used as an adjunct to csDMARDs for the management of RA, especially in patients who experience TRAEs with standard drugs.Clinical Trial Registration: ClinicalTrials.gov, identifier NCTNCT025515.

AIM: To compare the effect of myopia and astigmatism correction and postoperative change in higher-order aberration as results of receiving small-incision lenticule extraction (SMILE) and femtosecond laser-assisted in situ keratomileusis (FS-LASIK). METHODS: A prospective and non-randomized controlled study was conducted. The subjects are divided into two groups according to different operations received: 229 eyes of 116 patients in the SMILE group and 168 eyes of 86 patients in the FS-LASIK group. All subjects were followed up for 3mo by monitoring their uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), spherical equivalent, higher-order aberrations, and the preoperative and postoperative complications. RESULTS: At 1wk, 1, and 3mo post-surgery, 224 eyes (97.8%), 227 eyes (99.1%) and 229 eyes (100%) had UCVA≥20/20 in the SMILE group, while 165 eyes (98.2%), 167 eyes (99.4%) and 167 eyes (99.4%) had UCVA≥20/20 in the FS-LASIK group, respectively (χ2=0.146, 2.135, and 1.124; all P>0.05). BCVA reduction was not observed in both groups at 1 and 3mo of post-surgery (χ2=0.734 and 1.898, P>0.05). There was no statistically significant difference in the spherical equivalent between the two groups at 1 and 3mo post-surgery, though the percentage of the spherical equivalent within ±0.50 D at 3mo post-surgery was 98% in the SMILE group, which was higher than that of the FS-LASIK group (92%, χ2=1.872, P>0.05). The root mean square (RMS) values of total high-order aberration, coma, and spherical aberration of the two groups increased significantly in the early postoperative period and decreased after 3mo, but the values were still higher than the preoperative levels (P0.05). The incidence of complications in the SMILE group was lower than that in the FS-LASIK group (χ2=14.52, P

Objective: The aim of this study is to develop automatic methods of geometric coordination registration (GCR) for the virtual planning and evaluation of implant surgery. Methods: The target modalities of the image to be registered are cone-beam computed tomography (CBCT) or optical surface (OS) scan. Several geometric fiducial markers, cubic corners (CC) and discs, are fabricated on the patient's oral stent and digitized into a 3D mesh model. By analyzing the distribution of vertices and normal vectors of the mesh model, a novel descriptor is proposed to detect the position of the geometric fiducial markers. CC edges and disc centers are then used to find the transformation matrix to align the input point cloud to the target Cartesian axes. Results: CBCT and OS scans of the plaster models with implants of 29 patients were collected. The implant positions found by using the proposed algorithm were compared to the Gold standard developed with a coordinate measuring machine (CMM). Experimental results show that the target registration error (TRE) of the proposed method was 0.43mm. Conclusion: The proposed method performs better than existing manual or semi-automatic GCR (TRE 0.52mm).

OBJECTIVE Fracture is a common consequence of osteoporosis and is associated with high morbidity and mortality. Recently, increasing evidence has suggested that polymorphisms in tumor necrosis factor-α (TNF-α) gene were associated with osteoporosis risk and bone mineral density (BMD), but results remain conflicting. We herein performed a meta-analysis based on evidence currently available from the literature to make a more precise estimation of these relationships. METHODS The PubMed, EMBASE, Cochrane Library, CNKI (China National Knowledge Infrastructure) and Wan Fang databases were searched for eligible studies. Articles meeting the inclusion criteria were comprehensively reviewed and all available data were accumulated. The pooled odds ratios (ORs) or mean differences (MDs) and corresponding 95% confidence intervals (CIs) were applied to assess the strength of the relationships. RESULTS A total of 15 studies involving 5273 subjects were included in our meta-analysis. The GG genotype of TNF-α G308A was associated with an increased risk of osteoporosis under a mutant model (GG vs GA+AA: OR = 0.63, 95% CI: 0.51-0.77, P

Better understanding of esophageal precancerous lesions (EPL) can inform prevention strategies for esophageal squamous cell carcinoma (ESCC). Here, a cross-sectional epidemiologic study based on the Early Diagnosis and Early Treatment Project of Esophageal Cancer database from 2011 to 2017 was performed to fully investigate and characterize the epidemiology of EPL in rural Huai'an District. Data of 11,518 participants ages 35–75 years were collected through face-to-face interviews by questionnaire. Participants underwent a routine endoscopy examination, tissues were biopsied, and diagnosed according to the histologic criteria of dysplasia. Unconditional univariate and multivariate logistic regression analyses were performed to obtain crude and adjusted odds ratios and corresponding 95% confidence intervals, respectively. A total of 667 subjects were diagnosed with EPL. Factors associated with an increased risk of EPL included: drinking shallow well water and surface water, irregular diet, excessive smoking, exposure to secondhand smoke, consumption of corn, corn flour, pickled food, fried food, and hot food, and having a history of digestive system diseases. In addition, liquor use, but not other alcohol types, contributed to risk of EPL. Consumption of deep well water and vegetables, fruits, and animal livers were associated with lower EPL risk. This study suggested a completely distinct pattern that alcohol use plays only a minor role in EPL and excessive tobacco use shows a significant association in rural Huai'an District, while eating habits and environmental exposure may be the dominant factors. This work may be promising to provide scientific evidence to support primary prevention of ESCC in this region.

Radar emitter signal is interfered by various noises during the propagation process, and the signal-to-noise ratio varies widely. Therefore, the features that play a key role in sorting and classifying or identification signals are often difficult to find. In addition, the extracted features are usually subjective and speculative, so it is necessary to select the features that can characterize the maximum difference mode information between the modulated signal categories and the changes in the signal-to-noise ratio. That is, the selected features also have good separability at low SNR. In this paper, based on rough set theory the feature selection method is studied, which lays a foundation for the feature selection of radiation source signals by rough set theory.

With the rapid application of the new radar system, radar signal sorting based on conventional parameters has not achieved the desired results. Therefore, new features need to be extracted for signal sorting. In response to this problem, the paper proposes to use the entropy theory to extract the fuzzy entropy characteristics of the radar signal to determine the uncertainty of the radar source signal. Experiments with test signals show that the fuzzy entropy characteristics are less affected by noise over a wide range of SNR.

Scannerless time-of-flight three-dimensional imaging, the successor to raster scanning three-dimensional imaging, relies on large-scale detector arrays to obtain high pixel resolution; however, manufacturing limitations lead to a bottleneck in imaging resolution. Here, we report a methodology for laser imaging using code division multiple access, which involves three key steps. Optical encoding is carried out for a pulsed laser to generate space-time encoded beams for projection. Optical multiplexing subdivides the backscattered light signals and multiplexes them to a downscaled avalanche-photodiode array. Subpixel decoding decodes the digitized encoded full waveforms and decomposes the features of all subpixels. Accordingly, we design a prototype based on a 64-order encoder and a 4-element avalanche-photodiode array and conduct an outdoor experiment. We demonstrate that the system is capable of obtaining 256 pixels per frame in push-broom mode and reconstruct a three-dimensional image with centimetre-level lateral resolution and range precision at a distance of ∼112 m. Scannerless time of flight three-dimensional devices can produce high-quality images from the ground or in space and provide information on light detection and ranging. The authors design and demonstrate a downscaled subpixel 3D laser imaging device which uses pulse-encoded illumination to encode the pixels.

The development of the Internet has provided firms with the ideal opportunity to make up for the knowledge gap for achieving internal knowledge generation (IKG) and external knowledge acquisition (EKA). It is worth exploring how Internet resources can be used to satisfy organizational knowledge needs efficiently to adapt to dynamic environments. Thus, according to the resource-based view, knowledge-based view, and contingency theory, we study the impact of different types of Internet resources on the two modes of knowledge creation (IKG and EKA), as well as the moderating effect of environmental dynamism (ED) on this relationship. The hypothesized relationships were tested using the hierarchical regression analysis method with survey data collected from 399 Chinese firms. We found that Internet relationship resource and Internet human resource can simultaneously facilitate IKG and EKA, while Internet infrastructure resource positively affects IKG but has no significant impact on EKA. Furthermore, ED positively moderates the relationship between Internet relationship resource and IKG and EKA, but negatively moderates the relationship between Internet human resource and EKA.

S100 calcium binding protein P (S100P) and miR‐495 are aberrantly expressed and exert essential roles in cancers. However, the mechanisms of miR‐495‐S100P in pancreatic cancer are yet to be illustrated. Thus, we explored the regulatory functions of miR‐495‐S100P axis in pancreatic adenocarcinoma cells growth and invasion. In this study, we identified that S100P was upregulated in pancreatic adenocarcinoma by bioinformatics analysis of the GEO (Gene Expression Omnibus database) microarray dataset (GSE16515). Western blotting and luciferase reporter gene analysis exhibited that miR‐495 negatively determined the level of S100P via binging to its 3′‐untranslated regions (3′‐UTRs). A series of functional experiments indicated that upregulation of miR‐495 or S100P knockdown suppressed pancreatic adenocarcinoma cells proliferation, invasion, and promoted apoptosis. Furthermore, the expression of S100P was negatively associated with the level of miR‐495 in The Cancer Genome Atlas (TCGA) pancreatic adenocarcinoma case‐cohort. Besides, reintroduction of S100P debilitated the anti‐cancer action of miR‐495 in pancreatic adenocarcinoma cells. Our data indicated that miR‐495 performed suppressive roles in pancreatic adenocarcinoma through targeting S100P.

Background: Behçet’s disease (BD) is associated with an increased risk of cancer. Few reports have been published on the relationship between drug exposure and the risk of cancer in patients with BD. Herein, we explored the relationship between pharmacologic interventions for BD and the risk of cancer.Methods: we carried out a retrospective nested case-control study in a cohort of BD patients from attending our institution. Among 1,148 patients, 22 cancer patients were individually 1:2 matched to 44 cancer-free controls. The following biochemical indicators were evaluated: routine blood analysis, liver and kidney function tests, inflammatory indexes, blood gas analysis, blood electrolyte and previous pharmacologic interventions to manage BD including systemic glucocorticoids, methotrexate, cyclosporine-A, azathioprine, cyclophosphamide (CYC), and thalidomide, which are considered the primary medicines used for the management of BD.Results: Among the 22 BD patients with cancers, myelodysplastic syndrome (MDS) (22.72%) was the most common type. Furthermore, CYC administration was significantly higher in BD patients with cancer compared with the cancer-free matched control group. Further, we observed that complement 4 (C4) (odds ratio [OR] = 0.0001, 95% confidence interval [CI]: 0.001–0.065) and hemoglobin (Hb) (OR = 0.891, 95% CI: 0.795–0.998) levels were independent protective factors for predicting cancer risk in BD patients on multivariate analyses.Conclusion: Our study revealed that CYC was associated with a high risk of cancer in BD patients. Furthermore, C4 and Hb are independent protective factors for oncogenesis in BD patients. These findings may provide references and suggestions for clinicians to select appropriate treatments and for the early recognition of high-risk patients to reduce cancer incidence in BD patients.

Background. Cutaneous melanoma (CM) is one of the most life-threatening primary skin cancers and is prone to distant metastases. A widespread presence of posttranscriptional modification of RNA, 5-methylcytosine (m5C), has been observed in human cancers. However, the potential mechanism of the tumorigenesis and prognosis in CM by dysregulated m5C-related regulators is obscure. Methods. We use comprehensive bioinformatics analyses to explore the expression of m5C regulators in CM, the prognostic implications of the m5C regulators, the frequency of the copy number variant (CNV), and somatic mutations in m5C regulators. Additionally, the CM patients were divided into three clusters for better predicting clinical features and outcomes via consensus clustering of m5C regulators. Then, the risk score was established via Lasso Cox regression analysis. Next, the prognosis value and clinical characteristics of m5C-related signatures were further explored. Then, machine learning was used to recognize the outstanding m5C regulators to risk score. Finally, the expression level and clinical value of USUN6 were analyzed via the tissue microarray (TMA) cohort. Results. We found that m5C regulators were dysregulated in CM, with a high frequency of somatic mutations and CNV alterations of the m5C regulatory gene in CM. Furthermore, 16 m5C-related proteins interacted with each other frequently, and we divided CM patients into three clusters to better predicting clinical features and outcomes. Then, five m5C regulators were selected as a risk score based on the LASSO model. The XGBoost algorithm recognized that NOP2 and NSUN6 were the most significant risk score contributors. Immunohistochemistry has verified that low expression of USUN6 was closely correlated with CM progression. Conclusion. The m5C-related signatures can be used as new prognostic biomarkers and therapeutic targets for CM, and NSUN6 might play a vital role in tumorigenesis and malignant progression.

Background This study aims to assess current evidence of ultrasound in diagnosis of hydatidiform mole (HM) in early pregnancy (EP). Methods This study will incorporate case-control study on investigating the impact of ultrasound in diagnosis of HM in EP. Potential articles will be retrieved in electronic databases of Cochrane Library, MEDLINE/PUBMED, EMBASE, PsycINFO, WANGFANG, and CNKI from inception to the present. Conference proceeding, website of clinical trial registry, and reference list of key articles will be examined for additional studies. Two independent researchers will scan and select studies, collect and manage data, and appraise methodological quality of all eligible studies. We will carry out summary effect size, statistical heterogeneity, synthesize, and analyze outcome data. Results This study will summarize present evidence to assess the accuracy of ultrasound in diagnosis of HM in EP. Conclusion This study may provide evidence for ultrasound in diagnosis of HM in EP, which may benefit both patients and clinicians. Study registration INPLASY202080080.

Atherosclerosis is the leading cause of morbidity and mortality worldwide. The underlying pathogenesis involves multiple metabolic disorders, endothelial dysfunction and a maladaptive immune response, and leads to chronic arterial wall inflammation. Numerous normal physiological activities exhibit daily rhythmicity, including energy metabolism, vascular function and inflammatory immunoreactions, and disrupted or misaligned circadian rhythms may promote the progression of atherosclerosis. However, the association between the circadian rhythm and atherosclerosis remains to be fully elucidated. In the present review, the effects of the circadian rhythm on atherosclerosis progression are discussed.

Background The impact of HER2 somatic mutations in colorectal carcinoma (CRC) has not been well studied and its relationship with microsatellite instability‐high (MSI‐H) is yet to be fully elucidated. Materials and Methods From February 2017 to February 2020, the data of patients with CRC who underwent next‐generation sequencing and had detailed record of clinicopathological information were investigated. HER2 alteration and its relationship with MSI‐H were analyzed. Results Among 731 patients who underwent sequencing, 55 patients (7.5%) had HER2 alteration, including 29 (4.0%) with HER2 somatic mutations, 24 (3.3%) with HER2 gene amplification, and 2 patients (0.2%) with both HER2 mutations and amplification. R678Q was the most common mutated kinase domain, and no HER2 kinase domain in‐frame insertions/deletions were found in HER2 mutated cases. MSI‐H was found in 5.2% of our cohort and 36.8% of MSI‐H patients had HER2 mutation. For HER2 mutated cases, 48.3% were MSI‐H, whereas none of the HER2 amplification cases were MSI‐H. MSI‐H patients with HER2 mutation had significantly worse median progression‐free survival for programmed death‐1 (PD‐1) antibody than those without HER2 alteration (p = .036). Conclusion High MSI‐H rate was found in HER2 mutated cases, but no MSI‐H was found in HER2 amplification cases. MSI‐H patients with HER2 mutated had worse progression‐free survival for PD‐1 antibody than those without. Implications for Practice This study highlights the high microsatellite instability‐high (MSI‐H) rate in HER2 mutated cases but no MSI‐H in HER2 amplification cases. Moreover MSI‐H patients with HER2 mutated had worse progression‐free survival for programmed death‐1 antibody than those without. Further research to explore the internal relationship between HER2 alteration and MSI‐H is needed., The clinical significance of HER2 somatic mutations and its relationship with high microsatellite instability in colorectal cancer is not fully understood. This study investigated the relationship by analyzing data of patients with colorectal cancer who underwent next‐generation sequencing.

A 57-year old woman with Alzheimer’s disease developed liver injury 4 days after starting GV-971 therapy. This woman had no history of drug allergy before her AD diagnosis. After started her GV-971 medication (150 mg bid) while taking donepezil and memantine hydrochloride, she presented with jaundice of the skin and sclera, loss of appetite and fatigue. Laboratory examination suggested that liver function was abnormal with serum levels of alanine transaminase (ALT) (737 U/L), aspartate transaminase (1006 U/L). And Magnetic Resonance Imaging (MRI) showed the interstitial edema of the portal vein and the thickened gallbladder wall, which suggested the possibility of active liver disease or liver injury. Our report showed that GV-971 may lead to liver injury and we suggest that clinicians should monitor liver functions when using GV-971 in AD patients.

BACKGROUND Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak in China, constitutes a Public Health Emergency of International Concern. It is well known that COVID-19 patients may have increased serum lactate dehydrogenase (LDH) levels in the early stage. The clinical changes in LDH may have predictive value in disease evolution and prognosis in critically ill COVID-19 patients. AIM To examine serum LDH and clinical characteristics in patients with COVID-19 and their predictive value for prognosis. METHODS This retrospective study analyzed the clinical data of forty-seven critical COVID-19 patients in the intensive care unit of the Third People's Hospital of Yichang City from January 27 to March 25, 2020 and divided them into survivors and non-survivors. The patients were diagnosed according to the World Health Organization interim guidance and critical cases met any one of the following criteria: Respiratory failure and required mechanical ventilation, the occurrence of shock, and the combined failure of other organs that required intensive care unit monitoring and treatments, according to the diagnostic criteria of critical COVID-19. Clinical data including symptoms, detection of SARS-CoV-2, chest computed tomography (CT) images, changes in serum LDH in different clinical phases, and prognosis were collected. Statistical analysis of the data was performed. Continuous variables were expressed as median (interquartile range) and compared with the Mann-Whitney U test. Categorical variables were compared with the Chi-square test. Survival data were analyzed using Kaplan-Meier survival curves and log-rank tests. RESULTS According to chest CT images, we observed the alveolitis and fibrosis stages in all critical patients in this study. Most non-survivors died in the fibrosis stage. Non-survivors had fewer days of hospitalization, shorter disease duration, shorter duration of alveolitis and fibrosis, and had dyspnea symptoms at disease onset (P = 0.05). Both first and lowest LDH values in the alveolitis stage were more pronounced in non-survivors than in survivors (449.0 U/L vs 288.0 U/L, P = 0.0243; 445.0 U/L vs 288.0 U/L, P = 0.0199, respectively), while the first, lowest and highest values of serum LDH in non-survivors were all significantly increased compared to survivors in the fibrosis phase (449.0 U/L vs 225.5 U/L, P = 0.0028; 432.0 U/L vs 191.0 U/L, P = 0.0007; 1303.0 U/L vs 263.5 U/L, P = 0.0001, respectively). The cut-off points of first LDH values in the alveolitis and fibrosis phase for distinction of non-survivors from survivors were 397.0 U/L and 263.0 U/L, respectively. In the fibrosis stage, non-survivors had more days with high LDH than survivors (7.0 d vs 0.0 d, P = 0.0002). Importantly, patients with high LDH had a significantly shorter median survival time than patients with low LDH in the alveolitis phase (22.0 d vs 36.5 d, P = 0.0002), while patients with high LDH also had a significantly shorter median survival time than patients with low LDH in the fibrosis phase (27.5 d vs 40.0 d, P = 0.0008). The proportion of non-survivors with detectable SARS-CoV-2 until death in the alveolitis stage was significantly increased compared with that in the fibrosis stage (100% vs 35.7%, P = 0.0220). CONCLUSION High LDH and dyspnea symptoms were positive predictors of an adverse outcome in critical COVID-19. The rapid progressive fibrosis stage was more perilous than the alveolitis stage, even if SARS-CoV-2 is undetectable.

Lung cancer, especially lung adenocarcinoma, is one of the most common neoplasms worldwide. However, the mechanisms underlying its initiation, development, and metastasis are still poorly understood. Destrin (DSTN) is a member of ADF/cofilin family. Its detailed biological function remains unknown, although it is reported that DSTN is involved in cytoskeleton remodeling and regulation of actin filament turnover. Recent evidence has shown that high expression of cofilin-1 is associated with invasion and poor prognosis of several types of human tumors, but the detailed mechanism is still entirely unclear, particularly in lung cancer tumorigenesis and malignancy. Here, we report that DSTN was highly expressed in a mouse lung cancer model induced by urethane and in clinical lung adenocarcinoma tissue samples. Its expression level was positively correlated with cancer development, as well as metastasis to the liver and lymph nodes. Consistently, it was directly associated with the poor prognosis of lung adenocarcinoma patients. Furthermore, we also found that DSTN promotes cell proliferation, invasion, and migration in vitro, and facilitates subcutaneous tumor formation and lung metastasis via intravenous injection in vivo. Mechanically, DSTN associates with and facilitates nuclear translocation of β-catenin, which promotes epithelial-to-mesenchymal transition (EMT). Taken together, our results indicated that DSTN enhances lung cancer malignancy through facilitating β-catenin nuclear translocation and inducing EMT. Combined with multivariate analyses, DSTN might potentially serve as a therapeutic target and an independent prognostic marker of lung adenocarcinoma. Implications: This finding indicates that DSTN facilitates β-catenin nuclear translocation and promotes malignancy in lung adenocarcinoma.

Background Since non-alcoholic fatty liver disease (NAFLD) pathogenesis is multi-factorial, pharmacotherapy with a specific target commonly exhibits limited efficacy. Phytotherapy, whose therapeutic efficacy is based on the combined action of several active compounds, offers new treatment opportunity for NAFLD. As a representative, many natural polyphenols could be utilized in phytotherapy for NAFLD. Purpose In present work, we aimed to investigate the therapeutic effects and underlying mechanism of polyphenols in blueberry leaves (PBL) on NAFLD from a mitochondria-centric perspective since mitochondrial dysfunction could play a dominant role in NAFLD. Methods Identification and quantification of PBL were performed using liquid chromatography coupled with tandem mass spectrometry. The beneficial effects, especially improving mitochondrial function, and potential mechanism of PBL on NAFLD were studied by in vitro and in vivo study. Results Polyphenols were abundant in blueberry leaves making it advantaged in NAFLD phytotherapy. PBL effectively alleviated hepatic steatosis, oxidative stress and inflammation as indicated by both in vitro and in vivo study. Furthermore, PBL mediated improvement of mitochondrial dysfunction and antioxidant capability through activation of AMPK/PGC-1α/SIRT3 signaling axis. Conclusion Considering that mitochondrial dysfunction takes precedence over hepatic steatosis and induces NAFLD development, we conclude that PBL improve mitochondrial dysfunction and oxidative defense, subsequently alleviate hepatic steatosis, oxidative stress and inflammation, and eventually alleviate NAFLD.

Many marine microorganisms synthesize exopolysaccharides (EPSs), and some of these EPSs have been reported to have potential in different fields. However, the pharmaceutical potentials of marine EPSs are rarely reported. The EPS secreted by the Artic marine bacterium Polaribacter sp. SM1127 has good antioxidant activity, outstanding moisture-retention ability, and considerable protective property on human dermal fibroblasts (HDFs) at low temperature. Here, the effects of SM1127 EPS on skin wound healing and frostbite injury prevention were studied. Scratch wound assay showed that SM1127 EPS could stimulate the migration of HDFs. In the full-thickness cutaneous wound experiment of Sprague&ndash, Dawley (SD) rats, SM1127 EPS increased the wound healing rate and stimulated tissue repair detected by macroscopic observation and histologic examination, showing the ability of SM1127 EPS to promote skin wound healing. In the skin frostbite experiment of SD rats, pretreatment of rat skin with SM1127 EPS increased the rate of frostbite wound healing and promoted the repair of the injured skin significantly, indicating the good effect of SM1127 EPS on frostbite injury prevention. These results suggest the promising potential of SM1127 EPS in the pharmaceutical area to promote skin wound healing and prevent frostbite injury.

ObjectiveTo monitor trastuzumab resistance and determine the underlying mechanisms for the limited response rate and rapid emergence of resistance of HER2+ metastatic gastric cancer (mGC).DesignTargeted sequencing of 416 clinically relevant genes was performed in 78 paired plasma and tissue biopsy samples to determine plasma-tissue concordance. Then, we performed longitudinal analyses of 97 serial plasma samples collected from 24 patients who were HER2+ to track the resistance during trastuzumab treatment and validated the identified candidate resistance genes.ResultsThe results from targeted sequencing-based detection of somatic copy number alterations (SCNA) of HER2 gene were highly consistent with fluorescence in situ hybridisation data, and the detected HER2 SCNA was better than plasma carcinoembryonic antigen levels at predicting tumour shrinkage and progression. Furthermore, most patients with innate trastuzumab resistance presented high HER2 SCNA during progression compared with baseline, while HER2 SCNA decreased in patients with acquired resistance. PIK3CA mutations were significantly enriched in patients with innate resistance, and ERBB2/4 genes were the most mutated genes, accounting for trastuzumab resistance in six (35.3%) and five (29.4%) patients in baseline and progression plasma, respectively. Patients with PIK3CA/R1/C3 or ERBB2/4 mutations in the baseline plasma had significantly worse progression-free survival. Additionally, mutations in NF1 contributed to trastuzumab resistance, which was further confirmed through in vitro and in vivo studies, while combined HER2 and MEK/ERK blockade overcame trastuzumab resistance.ConclusionLongitudinal circulating tumour DNA sequencing provides novel insights into gene alterations underlying trastuzumab resistance in HER2+mGC.

This paper proposes a new hybrid HVDC system with the line-commutated converter (LCC) at the rectifier side and LCC and the modular multilevel converters (MMC) connected in series at the inverter side, where multiple MMCs are connected in parallel. Firstly, two receiver connection modes are discussed, including centralized access and distributed access. The simulation results show that distributed access is helpful to reduce the interaction between the inverter-side LCC and MMC under the receiving-end AC faults. Then, two control modes of parallel-connected MMCs are proposed and compared, which include the fixed DC voltage control and the fixed active power control. The simulation results show that the fixed DC voltage control helps the system recover quickly after the MMC AC-side fault, and the DC current balance control can eliminate the unbalanced current distribution caused by the potential deviation of device parameters.

OBJECTIVE To comprehensively compare the differences between major dietary patterns in improving glycemic control, cardiovascular risk, and weight loss for patients with type 2 diabetes. METHOD We systematically searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) to identify randomized controlled trials (RCTs) that compared the efficacy of Mediterranean, low-carbohydrate, and/or low-fat dietary patterns for patients with type 2 diabetes. Studies that compared any one of those diets with regular diet were also included. The risk of bias in eligible RCTs was evaluated according to the Cochrane Handbook. The primary outcome was glycemic control. Secondary outcomes included weight loss and cardiovascular risk factors. A network meta-analysis was performed using R-3.3.2. RESULTS Ten RCTs involving five dietary patterns met the eligibility criteria. The findings revealed that compared to low-fat diet, Mediterranean diet showed beneficial effects in glycemic control (HbA1c [%]: MD = -0.45, 95% CI = -0.55 to -0.34; fasting plasma glucose [mmol/L]: MD = -1.24 95% CI = -1.57 to -0.91, respectively; weight loss [kg]: MD =-1.18, 95% CI = -1.99 to -0.37; waist circumference [cm]: MD = -0.73, 95% CI = -1.26 to -0.19), and cardiovascular risk factors (HDL-cholesterol [mmol/L]: MD = 0.07, 95% CI = 0.04 to 0.11; total cholesterol [mmol/L]: MD = -0.17, 95% CI = -0.26 to -0.08; triglycerides [mmol/L]: MD = -0.21, 95% CI = -0.27 to -0.16). Network meta-analysis showed that high-carbohydrate diet improved HDL-cholesterol (mmol/l) (MD = 1.04, 95% CI = 0.39 to 1.68) when compared with regular diet. The differences were not statistically significant in other indirect comparison groups for other outcomes. CONCLUSIONS A mediterranean diet showed beneficial improvements in glycemic control, weight loss, and cardiovascular risk factors in people with type 2 diabetes.

In order to guide the tissue culture plantlets transplanting robot to cut and transplant strip tissue culture seedlings accurately while guaranteeing the real-time requirements, a fast search method based on traditional template-matching algorithm is proposed for node recognition. Lossless compression of binary image was utilized to optimize the memory storage. A fast search method is proposed to shorten the running time of the algorithm effectively while not depressing the accuracy of recognition. An experimental prototype of image processing subsystem is developed to verify the proposed method.

Background: Acute coronary syndrome (ACS) is closely related to unstable plaques and secondary thrombosis. The inflammatory cells in plaques and their inflammatory products may be the cause for plaque instability and ruptures. The study aimed to disclose the changes of inflammatory factors including serum intracellular adhesion molecule-1 (ICAM-1), chitinase-3-like protein 1 (YKL-40), and lipoprotein-associated phospholipase A2 (Lp-PLA2) in patients with ACS and its clinical significance. Methods: A total of 120 patients with coronary heart disease (CHD) were categorized into 2 groups: 69 with ACS and 51 with stable angina pectoris (SAP); 20 patients with chest pain and normal angiography served as a control group. The 120 patients with CHD were categorized into single-vessel disease group, double-vessel disease group, and three-vessel disease group based on the number of coronary artery stenosis. The severity of coronary artery stenosis was quantified based on coronary angiography using Gensini score. They were further divided into mild CHD group with its Gensini score 54 (n = 36). Serum levels of ICAM-1, YKL-40, and Lp-PLA2 of different groups were determined by enzyme-linked immunosorbent assay. Correlation between ICAM-1, YKL-40, Lp-PLA2, and Gensini score was analyzed. Results: The levels of serum inflammatory factors ICAM-1, YKL-40, and Lp-PLA2 were significantly higher in the ACS group than those in control group and SAP group (all P < 0.05); and compared with control group, no significant difference was observed in terms of the serum ICAM-1, YKL-40, and Lp-PLA2 levels in the SAP group (P > 0.05).The levels of serum ICAM-1, YKL-40, and Lp-PLA2 were not significantly different among control group, single-vessel disease group, double-vessel disease group, and three-vessel disease group (all P > 0.05). The levels of serum ICAM-1, YKL-40, and Lp-PLA2 were not significantly different among control group, mild CHD group (Gensini score 54) (all P > 0.05). Nonparametric Spearman correlation analysis showed that the levels of serum ICAM-1, YKL-40, and Lp-PLA2 were not correlated with the Gensini score in CHD patients (r = 0.093, r = –0.149, and r = –0.085, all P > 0.05; respectively). Conclusions: The serum levels of ICAM-1, YKL-40, and Lp-PLA2 were correlated with different clinical types of CHD, but not well correlated the severity and extent of artery stenosis, suggesting that ICAM-1, YKL-40, and Lp-PLA2 might be involved in occurrence of instability of atherosclerotic plaque, and might reflect the severity of CHD mostly through reflecting the plaque stability.

Objective. To systematically review the effect of invigorating Pi and detoxification (Jianpi Jiedu, (JPJD)) herbs in advanced colorectal cancer (CRC) patients receiving chemotherapy. Methods. Three English and four Chinese databases were searched. Literature was screened by EndNote X7 and data were analyzed by RevMan 5.2. Results. This review comprised 12 randomized clinical studies of 701 patients. The results showed that JPJD herbs improved the therapeutic effect on Chinese medicine symptoms [risk ratio (RR) = 1.59; 95% confidence interval (CI): 1.35~1.88] and Karnofsky performance score [RR = 2.07; 95% CI: 1.52~2.82] for advanced CRC patients receiving chemotherapy, lowered the Chinese medicine symptoms’ score [weighted mean difference = −2.44; 95% CI: −3.23~−1.64], reduced the incidence of nausea and vomiting [RR = 0.23; 95% CI: 0.11~0.49], improved platelet at toxicity grades III-IV [odds ratio = 0.29; 95% CI: 0.12~0.74] and I–IV [RR = 0.65; 95% CI: 0.51~0.82], and improved white blood cell at toxicity grades III-IV [RR = 0.37; 95% CI: 0.23~0.58] and I–IV [RR = 0.69; 95% CI: 0.60~0.79]. However, the results showed no significant effect on tumor response. Conclusion. JPJD herbs can improve quality of life, relieve symptoms, and reduce adverse events of advanced CRC patients receiving chemotherapy.

Background Next-generation sequencing (NGS) based on liquid biopsy has been an emerging technology to identify tumor-specific genetic aberrations in adult lymphoma. However, there were few studies on the genomic profiling of plasma circulating tumor-derived DNA (ctDNA) in pediatric mature B-NHL. Methods Paraffin-embedded tissue (FFPE) and plasma samples from the newly diagnosed patients were collected and sequenced by 475 genes panel before, during and post of treatment. Clinical stage system, risk stratification and treatment of pediatric mature B-NHL followed a the modified BFM-95 protocol. Results A total of 53 pediatric mature B-NHLs were enrolled，including 35 Burkitt lymphoma, 18 diffused large B cell lymphoma/high-grade B cell lymphoma (DLBCL/HGBCL). We collected 38 tissue and 124 plasma samples for somatic mutation testing. The number of somatic mutations and the TOP 5 genes detected in the 38 tissues and 31 baseline plasma samples, were 416 vs 496, and MYC(71%), DDX3X(45%)，ID3 (42%), TP53(40%), SMARCA4(29%) (Fig1. A)vs MYC(52%), DDX3X(45%)，ID3(42%), TP53(36%), GNA13(23%) (Fig1. B), respectively. The median allele frequency of mutations in plasma was 3%(ranged from 0.2% to 96.6%) and MYC, DDX3X, ID3, TP53, SMARCA4,ARID1A shows higher max somatic allele frequency (MSAF), indicated that was the early events in tumor genesis. The sensitivity of plasma ctDNA to detecting tissue mutations was 63.4% in the 19 matched samples (11 samples from BL and 8 samples from DLBCL/HGBCL) and the sensitivity in BL and DLBCL/HGBCL were 64.1% and 62%, respectively. All genomic alteration types, including single nucleotide variants (SNVs), indels, and gene fusions were detected in similar proportions in each sample type and the gene mutation rate of every gene detected in paired tissue and ctDNA samples. Among the 37 mature B-NHL patients, 6 patients were collected plasma samples after resection of tumor, of which 4 patients was not detected the somatic gene mutations in plasma (Fig. 2). The abundance of ctDNA in patients with stage IV (N=10) was significantly higher than that of stage I-II (N=6) (P=0.0002) and stage III patients(N=15)(P With a median follow-up of 182 Days, 33 patients have completed anti-tumor treatment, 27 patients completed post-treatment PET-CT, and 20 patients have done ctDNA testing synchronously. PET-CT showed tumor residue in 4 patients, of which 2 patients showed no tumor residue in pathology and ctDNA, 1 patient showed tumor residue in pathology but not in ctDNA and with tumor progression 6 months after treatment, 1 patient unable to take biopsy showed no tumor residue in ctDNA and was no tumor reccourence with regular follow-up. At the last follow-up, 1 patient was disease progression, and all of the 53 patients survived. Conclusion Plasma ctDNA testing by NGS was practicable in pediatric mature B-NHL. The abundance of ctDNA is significantly related to tumor burden. CtDNA testing may be more sensitive than PET-CT for residual disease assessment. Nevertheless, sample size expansion is required to verify such conclusions. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Severe acute lung injury (ALI) cause significant morbidity and mortality worldwide. MicroRNAs (miRNAs) are possible biomarkers and therapeutic targets for ALI. We aimed to explore the role of miR-762, a known oncogenic factor, in the pathogenesis of ALI. Levels of miR-762 in lung tissues of LPS-treated ALI mice and blood cells of patients with lung injury were measured. Injury of human lung epithelial cell line A549 was induced by LPS stimulation. A downstream target of miR-762, NFIX, was predicted using online tools. Their interactions were validated by luciferase reporter assay. Effects of targeted regulation of the miR-762/NFIX axis on cell proliferation, apoptosis, and inflammatory responses were tested in vitro in A549 cells in vivo with an ALI mouse model. We found that upregulation of miR-762 expression and downregulation of NFIX expression were associated with lung injury. Either miR-762 inhibition or NFIX overexpression in A549 lung cells significantly attenuated LPS-mediated impairment of cell proliferation and viability. Notably, increasing expressions of miR-762 inhibitor or NFIX in vivo via airway lentivirus infection alleviated the LPS-induced ALI in mice. Further, targeted downregulation of miR-762 expression or upregulation of NFIX expression in A549 cells markedly down-regulates NF-κB/IRF3 activation, and substantially reduces the production of inflammatory factors, including TNF-α, IL-6, and IL-8. This study reveals a novel role for the miR-762/NFIX pathway in ALI pathogenesis and sheds new light on targeting this pathway for diagnosis, prevention, and therapy.

In this paper, LIPSS (laser-induced periodic surface structures) are generated on the K9 glass surface by using an ultrashort pulsed laser with pulse width of 8 ps, wavelength of 532 nm and repetition frequency of 1 KHz. Two kinds of LIPSS are generated on the surface of K9 glass, in the laser fluence range from 1.52 J/cm2 to 9.38 J/cm2 and pulse number from 1 to 50, namely low space frequency LIPSS (LSFL) and supra-wavelength periodic surface structures (SWPSS). When the laser fluence is increased, LSFL (F = 1.9 J/cm2 ~ 9.38 J/cm2) can be generated on the surface of K9 glass. LSFL with a period in the range of 480 nm to 510 nm are found with 1 to 20 pulses when the laser fluences higher than 1.9 J/cm2. For low pulse numbers, the depth of the LSFL structures grows with increasing pulse number. It is noticed that when the laser fluence reaches the threshold of the LIPSS (LSFL), the formation of the LIPSS happened together with the removal of the material surface. In other words, the ablation craters are formed gradually at higher pulse numbers with the laser fluence above the LIPSS formation threshold. Furthermore, the depth of the ablation crater is increased with higher pulse numbers, and SWPSS appear at the bottom of the crater. The period of SWPSS is 1.2 μm to 1.5 μm. The LSFL found in this paper can be used to reduce the reflection coefficient of the K9 material from 4% to less than 2.2 % at wavelengths above 1.2 μm.

Background Matrix metalloproteinases (MMPs) polymorphisms have been implicated in the pathogenesis of glaucoma risk. However, the results were controversial. We performed a meta-analysis to evaluate the precise associations between MMPs polymorphisms and glaucoma risk. Methods Related studies were reviewed by searching electronic databases within four databases. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the association between the most common polymorphisms of MMPs and glaucoma risk. Heterogeneity, publication bias and sensitivity analysis were conducted to guarantee the statistical power. Results Overall, 11 selected articles involving 2,388 cases and 2,319 controls were included in this meta-analysis. Significant associations were only found between MMP-9 rs17576 G > A polymorphism (GA vs. GG: OR = 0.80, 95%CI = 0.67-0.97, P = 0.02, I2 = 0%), MMP-9 rs3918249 C > T polymorphism (TT vs. CC + CT: OR = 0.71, 95%CI = 0.51-0.98, P = 0.04, I2 = 0%) and glaucoma risk in the general population. Subgroup analysis also suggested that MMP-9 rs17576 G > A was related to glaucoma in the Caucasian population (GA vs. GG: OR = 0.67, 95%CI = 0.45-1.00, P = 0.05; GA + AA vs. GG: OR = 0.66, 95%CI = 0.45-0.97, P = 0.03, I2 = 0%). Conclusions Our meta-analysis demonstrates that MMP-9 rs17576 G > A polymorphism might be a protective factor against the development of glaucoma in Caucasian population.

Background & Aims The discovery of effective and reliable biomarkers to detect hepatitis B virus (HBV)-positive hepatocellular carcinoma (HCC) at an early stage may improve the survival of HCC. The aim of this study was to establish serum microRNA (miRNA) profiles as diagnostic biomarkers for HBV-positive HCC. Methods We used deep sequencing to screen serum miRNAs in a discovery cohort (n=100). Quantitative polymerase chain reaction (qPCR) assays were then applied to evaluate the expression of selected miRNAs. A diagnostic 2-miRNA panel was established by a logistic regression model using a training cohort (n=182). The predicted probability of being detected as HCC was used to construct the receiver operating characteristic (ROC) curve. Area under the ROC curve (AUC) was used to assess the diagnostic performance of the selected miRNA panel. Results The predicted probability of being detected as HCC by the 2-miRNA panel was calculated by: logit P=−2.988 + 1.299 × miR-27b-3p + 1.245 × miR-192-5p. These results were further confirmed in a validation cohort (n=246).The miRNA panel provided a high diagnostic accuracy of HCC (AUC=0.842, P

// Xin-Ya Du 1, * , Yuan-Yuan Hu 2, * , Chun Xie 1, * , Chun-Yan Deng 3 , Cai-Yun Liu 2 , Zhi-Guo Luo 5 , Yu-Ming Niu 2, 4 , Ming Shen 6, 7 1 Department of Stomatology, People’s Hospital of New District Longhua Shenzhen, Shenzhen 518109, China 2 Department of Stomatology, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, China 3 Intensive Care Unit, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, China 4 Center for Evidence-Based Medicine and Clinical Research, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, China 5 Department of Clinical Oncology, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, China 6 Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, China 7 Department of Dental Implant, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing 210029, China * These authors contributed equally to this work Correspondence to: Yu-Ming Niu, email: niuyuming@yeah.net Ming Shen, email: mingshen85@yahoo.com Keywords: let-7, KRAS, polymorphism, cancer Received: August 23, 2016 Accepted: January 06, 2017 Published: January 16, 2017 ABSTRACT Association between let-7-KRAS rs712 polymorphism and cancer risk was inconsistent. We therefore conducted this meta-analysis to clarify the association between let-7-KRAS rs712 polymorphism and cancer risk with STATA 14.0 software. A systemic literature search in online databases (PubMed, Embase, CNKI and Wanfang database) was preformed to obtain relevant articles. A total of 13 case-control studies involving 3,453 patients and 4,470 controls were identified up to May 16, 2015. The pooled results indicated that significantly increased risk were observed in Chinese population in T vs. G (OR = 1.21, 95% CI = 1.03–1.42) and TT vs. GG + GT genetic models (OR = 1.69, 95% CI = 1.17–2.42). Sensitivity analysis was conducted and the result without heterogeneity showed significant associations in all five genetic models. Subgroup analyses of cancer type indicated a similar result in digestive cancer (for T vs. G: OR = 1.41, 95% CI = 1.26–1.57; GT vs. GG: OR = 1.24, 95% CI = 1.07–1.43; TT vs. GG: OR = 2.53, 95% CI = 1.86–3.44; GT + TT vs. GG: OR = 1.36, 95% CI = 1.19–1.56; TT vs. GG + GT: OR = 2.35, 95% CI = 1.73–3.19). In summary, these evidences demonstrate that let-7-KRAS rs712 G > T polymorphism might be associated with digestive system cancer risk in the Chinese population.