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This study aimed to investigate the effect of dexamethasone (DEX) on chemotaxis and phagocytic activity of neutrophils for spermatozoa and semen quality of preserved boar semen. The different concentrations of dexamethasone were added to boar semen dilutions to detect its effects on the chemotaxis of neutrophils and phagocytosis of neutrophils and sperm motility sperm malformation rate, plasma membrane integrity, mitochondrial activity, and spermatozoa motility parameters. The study results showed that the experimental groups of DEX significantly inhibited the phagocytosis and chemotaxis of PMNs for spermatozoa. With the increased concentration of DEX, there was an inhibition effect on PMNs activity. In addition, under 17 °C storage conditions, the addition of DEX 1 × 10

Routine assessment of sperm DNA integrity involves the time-consuming and complex process of staining sperm chromatin. Here, we report a Raman spectroscopy method combined with extended multiplicative signal correction (EMSC) for the extraction of characteristic fingerprints of DNA-intact and DNA-damaged sperm cells directly on glass slides. Raman results of sperm cell DNA integrity on glass substrates were validated one-to-one with clinical sperm cell staining. Although the overall Raman spectral pattern showed considerable similarity between DNA-damaged and DNA-intact sperm cells, differences in specific Raman spectral responses were observed. We then employed and compared multivariate statistical analysis based on principal component analysis-linear discriminant analysis (PCA-LDA) and partial least-squares-discriminant analysis (PLS-DA), and the classifications were validated by leave-one-out-cross-validation (LOOCV) and k-fold cross-validation methods. In comparison, the PLS-DA model showed relatively better results in terms of diagnostic sensitivity, specificity, and the classification rate between the sperm DNA damaged group and the DNA intact group. Our results demonstrate the potential of Raman based label-free DNA assessment of sperm cell on glass substrates as a simple method toward clinical applications.

Background Carotid plaque and triglyceride-glucose (TyG) index are associated with insulin resistance. However, a highly debated question is whether there is an association between the TyG index and carotid plaque incidence. Thus we performed an in-depth longitudinal study to investigate the relationship between carotid plaque occurrence and the TyG index among Chinese individuals. Methods Two thousand and three hundred seventy subjects (1381 males and 989 females) were enrolled and followed up for three years. The subjects were stratified into four groups based on the quartile of the TyG index at baseline. Univariate and multivariate Cox proportional hazard models were conducted to examine the role of TyG played in the carotid plaque. The strength of association was expressed as hazard ratio (HR) and 95% confidence interval (CI). Results After three years of follow-up, 444 subjects were detected with newly formed carotid plaque. The overall 3-year cumulative carotid plaque incidence was 18.7%, and the risk of carotid plaque increased with elevated TyG index (p Conclusions The TyG index can be used as a dose-responsive indicator of carotid plaque in the Chinese population. Elderly males with dyslipidemia, diabetes, or hypertension should be more vigilant about their TyG index since they are susceptible to developing carotid plaque. Physicians are encouraged to monitor the TyG index to help identify and treat patients with carotid plaque at an early stage.

To evaluate the efficacy of oblique lumbar interbody fusion combined with unilateral pedicle screw fixation via Wiltse approach in the treatment of lumbar spinal stenosis.From July 2017 to January 2019, 90 patients with lumbar spinal stenosis, including 38 males and 52 females, aged from 43 to 75 years old with an average of(59.9±8.8) years old, and were treated with oblique lumbar interbody fusion(OLIF) combined with Wiltse unilateral pedicle screw fixation. Surgical decompression and fixation was performed in 50 cases of single segment, 32 cases of double segments and 8 cases of three segments. The distribution of responsible segments included 8 cases of LAll patients were followed up from 12 to 33 months, with an average of (20.2±6.6) months. Mean operation time was (103.3±35.9) min, and mean intraoperative blood loss was (70.4±17.8) ml. VAS of low back pain leg pain, and ODI decreased from 6.2±1.1, 6.1±0.9 and (59.9±4.2)% to 2.7±0.5, 2.5±0.5 and (31.3±8.8)%. SF-36 scale significantly increased from (37.2±3.1) to (54.9±6.1) at the six months postoperation(OLIF combined with unilateral pedicle screw fixation via Wiltse approach is effective in treating lumbar spinal stenosis with minimally invasive advantages such as less trauma and less complications. Under the premise of strictly grasping the indications, this method could also achieve satisfactory clinical results in multi-segments oprations.

IntroductionLung cancer ranks the leading cause of cancer-related death worldwide. This retrospective cohort study was designed to determine time-dependent death hazards of diverse causes and conditional survival of lung cancer.MethodsWe collected 816,436 lung cancer cases during 2000-2015 in the SEER database, after exclusion, 612,100 cases were enrolled for data analyses. Cancer-specific survival, overall survival and dynamic death hazard were assessed in this study. Additionally, based on the FDA approval time of Nivolumab in 2015, we evaluated the effect of immunotherapy on metastatic patients’ survival by comparing cases in 2016-2018 (immunotherapy era, n=7135) and those in 2013-2016 (non-immunotherapy era, n=42061).ResultsOf the 612,100 patients, 285,705 were women, the mean (SD) age was 68.3 (11.0) years old. 252,558 patients were characterized as lung adenocarcinoma, 133,302 cases were lung squamous cell carcinoma, and only 78,700 cases were small cell lung carcinomas. TNM stage was I in 140,518 cases, II in 38,225 cases, III in 159,095 cases, and IV in 274,262 patients. 164,394 cases underwent surgical intervention. The 5-y overall survival and cancer-specific survival were 54.2% and 73.8%, respectively. The 5-y conditional survival rate of cancer-specific survival is improved in a time-dependent pattern, while conditional overall survival tends to be steady after 5-y follow-up. Except from age, hazard disparities of other risk factors (such as stage and surgery) diminished over time according to the conditional survival curves. After 8 years since diagnosis, mortality hazard from other causes became higher than that from lung cancer. This critical time point was earlier in elder patients while was postponed in patients with advanced stages. Moreover, both cancer-specific survival and overall survival of metastatic patients in immunotherapy era were significantly better than those in non-immunotherapy era (PConclusionsOur findings expand on previous studies by demonstrating that non-lung-cancer related death risk becomes more and more predominant over the course of follow-up, and we establish a personalized web-based calculator to determine this critical time point for long-term survivors. We also confirmed the survival benefit of advanced lung cancer patients in immunotherapy era.

PURPOSE: Although the cost and complexity of managing diabetes is increasing around the world, placing greater burden on patients and their families, the cost of drug regimens prescribed to Chinese patients has not been evaluated. This study was conducted to evaluate the temporal changes in the costs and drugs used for people with diabetes. METHODS: Patients enrolled in Beijing Medical Insurance with outpatient medical records from 2016 through 2018 were included in this study. The outcomes of interest were: (1) the number of outpatient medications, (2) the number of comorbidities diagnosed, (3) the estimated annual cost of the outpatient drug regimen, (4) the drug therapy strategies used for diabetic patients, and (5) the most commonly prescribed classes of drugs. RESULTS: Over the 3-year period, there was a significant decrease (9.0%, P

Long noncoding RNAs (lncRNAs) are known to regulate DNA damage response (DDR) and genome stability in proliferative cells. However, it remains unknown whether lncRNAs are involved in these vital biological processes in post-mitotic neurons. Here, we report and characterize a lncRNA, termed Brain Specific DNA-damage Related lncRNA1 (BS-DRL1), in the central nervous system. BS-DRL1 is a brain-specific lncRNA and depletion of BS-DRL1 in neurons leads to impaired DDR upon etoposide treatment in vitro. Mechanistically, BS-DRL1 interacts with HMGB1, a chromatin protein that is important for genome stability, and is essential for the assembly of HMGB1 on chromatin. BS-DRL1 mediated DDR exhibits cell-type specificity in the cortex and cerebellum in gamma-irradiated mice and BS-DRL1 knockout mice show impaired motor function and concomitant purkinje cell degeneration. Our study extends the understanding of lncRNAs in DDR and genome stability and implies a protective role of lncRNA against neurodegeneration., Long noncoding RNAs (lncRNAs) are known to regulate the DNA damage response (DDR), however their role in the brain is less well studied. Here, the authors demonstrate a neuron-specific role for Brain Specific DNA-damage Related lncRNA1 (BS-DRL1) and show BS-DRL1 modulates DDR by interacting with HMGB1 in a cell-type specific manner.

Objective To be able to treat irreducible unilateral vertically displaced pelvic ring disruption (UVDPRD) using closed reduction, we introduced a technique named Unlocking Closed Reduction Technique (UCRT) and evaluated its effectiveness with improved pelvic closed reduction system (PCRS). Methods A retrospective study was performed in our department. Between January 2014 and December 2017, 43 patients whose UVDPRD were not successfully reduced using transcondylar traction. Subsequently, they were treated with UCRT using improved PCRS. The study included 19 male and 24 female patients, with a mean age at the time of the operation of 46.2 years. During surgery, operation time and blood loss were recorded. Post‐surgical reduction quality was evaluated using Matta scoring criteria and patient lower‐extremity functional outcome was evaluated using Majeed functional scoring criteria. Results When used with improved PCRS, UCRT achieved pelvic reduction in all 43 cases of irreducible UVDPRD with postoperative pelvic reduction quality rated excellent and good for 42/43 (97.6%) patients according to the Matta scoring criteria (Matta Score, Unlocking Closed Reduction Technique (UCRT) first unlocks the dislocated iliosacral joint or overlapping edges of the sacral fracture through a force generated by framed‐based unlocking reduction device (FBURD) that pulls the posterior ilium laterally and then corrects the cranial and posterior displacement of posterior ring through transcondylar traction force.

Esophageal squamous cell carcinoma (ESCC) causes aggressive and lethal malignancies with extremely poor prognoses, and accounts for about 90% of cases of esophageal cancer. Neuropilin and tolloid-like 2 (NETO2) protein coding genes have been associated with various human cancers. Nevertheless, little information is reported about the phenotypic expression and its clinical significance in ESCC progression. Here, our study found that NETO2 expression in ESCC patients was associated with tumor clinical stage and lymph node metastasis status. Gain-of-function and loss-of-function analyses showed that NETO2 stimulated ESCC cell proliferation while suppressing apoptosis in vitro and enhanced tumor growth in vivo. Moreover, knockdown of NETO2 significantly inhibited migration and invasion in combination with regulation of epithelial-mesenchymal transition (EMT) related markers. Mechanistically, overexpression of NETO2 increased the phosphorylation of ERK, PI3k/AKT, and Nuclear factor erythroid-2-related factor 2(Nrf2), whereas silencing NETO2 decreased the phosphorylation of these targets. Our data suggest that Nrf2 was a critical downstream event responsible for triggering the PI3K/AKT and ERK signaling pathways and plays a crucial role in NETO2-mediated tumorigenesis. Taken together, NETO2 acts as an oncogene and might serve as a novel therapeutic target or prognostic biomarker in ESCC patients.

Objectives Violence affected daily life in prehistoric societies, especially at conflict zones where different peoples fought over resources and for other reasons. In this study, cranial trauma was analyzed to discuss the pattern of violence experienced by three Bronze to early Iron Age populations (1,000-100 BCE) that belonged to the Subeixi culture. These populations lived in the Turpan Basin, a conflict zone in the middle of the Eurasian Steppe. Methods The injuries on 129 complete crania unearthed from the Subeixi cemeteries were examined for crude prevalence rate (CPR), trauma type, time of occurrence, possible weapon, and direction of the blow. Thirty-three injuries identified from poorly preserved crania were also included in the analyses except for the CPR. Data was also compared between the samples and with four other populations that had violence-related backgrounds. Results Overall, 16.3% (21/129) of the individuals showed violence-induced traumatic lesions. Results also indicated that most of the injuries were perimortem (81.6%), and that women and children were more involved in conflict than the other comparative populations. Wounds from weapons accounted for 42.1% of the identified cranial injuries. Distribution analysis suggested no dominant handedness of the attackers, and that blows came from all directions including the top (17.1%). Wounds caused by arrowheads and a special type of battle-ax popular in middle and eastern Eurasian Steppe were also recognized. Discussion A comprehensive analysis of the skeletal evidence, historical records, and archeological background would suggest that the raiding to be the most possible conflict pattern reflected by the samples. The attackers were likely to have been nomadic invaders from the steppe (such as the Xiongnu from historical records), who attacked the residents in the basin more likely for their resources rather than territory or labor force.

Background Dyslipidemia contributes to an increased risk of carotid atherosclerosis. However, the association between the ratio of low-density lipoprotein cholesterol (LDL-C) to high-density lipoprotein cholesterol (HDL-C) and carotid plaque formation has not been well documented. This study aims to assess the role of LDL-C/HDL-C in the risk of carotid plaque formation in a Chinese population. Methods We followed 2,191 participants who attended the annual routine health examination. Cox proportional hazards regression, restricted cubic spline (RCS), and subgroup analysis were applied to evaluate the association between the LDL-C/HDL-C ratio and carotid plaques. The hazard ratio (HR) and 95% confidence interval (CI) were used to estimate the strength of the association. Results Among 2,191 participants, 388 had incident carotid plaques detected, with a median follow-up time of 1.05 years. Compared with subjects younger than 45 years, those aged 45 to 59 years (HR: 2.00, 95% CI: 1.55–2.58) and over 60 years (HR: 3.36, 95% CI: 2.47–4.58) had an increased risk of carotid plaque formation. Males (HR: 1.26, 95% CI: 1.01–1.56), diabetes (HR: 1.46, 95% CI: 1.06–2.01) and a high LDL-C/HDL-C ratio (HR: 1.22, 95% CI: 1.07–1.38) were significantly linked with the occurrence of carotid plaques. After adjusting for potential confounding factors, we observed that a high LDL-C/HDL-C ratio promoted carotid plaque events (HR: 1.30, 95% CI: 1.12–1.50). The RCS analysis revealed a significant nonlinear association. The association was stronger among females (P-interaction Conclusion A high LDL-C/HDL-C ratio could accelerate the occurrence of carotid plaques. Older men with diabetes and dyslipidemia are the critical target population. Women may be more likely to benefit from lipid-lowering interventions and thus avoid carotid plaque formation.

The surgery for esophageal cancer arising after prior gastrectomy is technically difficult with high morbidity and mortality. Endoscopic submucosal dissection (ESD) is a minimally invasive endoscopic treatment for superficial SCC with high curative resection rate. But few studies are concerned about ESD under these circumstances. The aim of this study was to elucidate the short- and long-term outcomes of ESD for superficial esophageal squamous cell cancer (SCC) in patients with prior gastrectomy. From January 2009 to January 2019, 37 patients with prior gastrectomy who underwent ESD for superficial esophageal SCC were retrospectively enrolled at the Zhongshan Hospital, Fudan University in Shanghai, China. Rates of en bloc resection, complete resection, curative resection, incidence of postoperative bleeding, perforation and postoperative stricture were evaluated as short-term outcomes. Overall survival, and local recurrence-free survival were evaluated as long-term outcomes. The rate of en bloc resection, complete resection and curative resection were 94.6%, 86.5% and 78.4%, respectively. No perforation was observed. 1 (2.7%) patient experienced postoperative bleeding. During the median observation of 43 months, 3 (8.6%) patients experienced esophageal stricture, successfully managed by balloon dilation. 3(8.6%) patients had local recurrence after ESD with 5-year local recurrence-free survival rate of 91.4%. During the observation period, 4 patients died of other reasons. The 1, 3, 5-year overall survival rates were 97.1%, 97.1% and 91.4%. The short-term outcomes indicate ESD is technically difficult with lower resection completeness in patients after gastrectomy, while the long-term outcomes are rather favorable.

Directed forgetting (DF) or intentional forgetting can impair the recall of items cued to be forgotten (so-called cost) but can also improve the recall of items cued to be remembered (so-called benefit), following the cost-benefit principle. However, whether the forget cue is the cause of intentional forgetting is doubtful. Several studies suggest that intentional forgetting is extremely hard by introducing a noncue condition, but it is not enough to explain how the cost-benefit principle works without forgetting. Here, two series of experiments are designed to test the voluntary control ability of attentional resource allocation from memory benefits to costs. In the Experiment 1 series, we changed the position and content of cues, replicating the DF effect and the analogous effect without a forget cue. The results showed that precueing can mildly upregulate memory attentional resources to improve performance while incurring memory costs for other items. Since forced remembering can also induce memory costs and benefits, the cost-benefit principle may not be attributed to DF. In the Experiment 2 series, we further demonstrated that memory costs and benefits exist when implicit cues are employed. Overall, when the results of all memory costs in the above experiments are compared with a noncue condition as the baseline in Experiment 2c, there exist no significant differences. The current results indicate that we can voluntarily upregulate our memory performance for certain items but cannot voluntarily downregulate memory encoding, generalizing the selective attentional resource control account to the cost-benefit principle beyond the directed-forgetting effect.

Background Periprosthetic fracture is a leading reason for readmission following total hip arthroplasty. Most of these fractures occur during the early postoperative period before bone ingrowth. Before ingrowth occurs, the femoral component can rotate relative to the femoral canal, causing a spiral fracture pattern. We sought to evaluate, in a paired cadaver model, whether the torsional load to fracture was higher in collared stems. The hypothesis was that collared stems have greater load to fracture under axial and torsional loads compared with collarless stems. Methods Twenty-two cadaveric femora (11 matched pairs) with a mean age of 77 ± 10.2 years (range, 54 to 90 years) were harvested. Following dissection, the femora were evaluated with use of a dual x-ray absorptiometry scanner and T scores were recorded. We utilized a common stem that is available with the same intraosseous geometry with and without a collar. For each pair, 1 femur was implanted with a collared stem and the contralateral femur was implanted with a collarless stem with use of a standard broaching technique. A compressive 68-kg load was applied to simulate body weight during ambulation. A rotational displacement was then applied until fracture occurred. Peak torque prior to fracture was measured with use of a torque meter load cell and data acquisition software. Results The median torque to fracture was 65.4 Nm for collared stems and 43.1 Nm for uncollared stems (p = 0.0014, Wilcoxon signed-rank test). The median T score was -1.95 (range, -4.1 to -0.15). The median difference in torque to fracture was 29.18 Nm. As expected in each case, the mode of failure was a spiral fracture around the implant. Conclusions Collared stems seemed to offer a protective effect in torsional loading in this biomechanical model comparing matched femora. Clinical relevance These results may translate into a protective effect against early periprosthetic Vancouver B2 femoral fractures that occur before osseous integration has occurred.

To assess the neural and non-neural contributions to spasticity in the impaired ankle of children with cerebral palsy (CP).Instrumented tapping of the Achilles tendon was done isometrically to minimize non-neural contributions and elicit neural contributions. Robot-controlled ankle stretching was done at various velocities, including slow stretching, with minimized neural contributions. Spasticity was assessed as having neural (phasic and tonic stretch reflex torque, tendon reflex gain, contraction rate, and half relaxation rate) and non-neural origin (elastic stiffness and viscous damping) in 17 children with CP (six females and 11 males; mean age [SD] 10y 8mo [3y 11mo], range 4y-18y) and 17 typically developing children (six females and 11 males; mean age [SD] 12y 7mo [2y 9mo], range 7y-18y). All torques were normalized to weight×height.Children with CP showed increased phasic and tonic stretch reflex torque (p=0.004 and p=0.001 respectively), tendon reflex gain (p=0.02), contraction rate (p=0.038), half relaxation rate (p=0.02), elastic stiffness (p=0.01), and viscous damping (p=0.01) compared to typically developing children.Controlled stretching and instrumented tendon tapping allow the systematic quantification of various neural and non-neural changes in CP, which can be used to guide impairment-specific treatment.Ankle spasticity is associated with increased phasic and tonic stretch reflexes, tendon reflex gain, and contraction and half relaxation rates. Ankle spasticity is also associated with increased elastic stiffness and viscous damping.Contribuciones neuronales y no neuronales a la espasticidad del tobillo en niños con parálisis cerebral OBJETIVO: Evaluar las contribuciones neurales y no neurales a la espasticidad en el tobillo comprometido de niños con parálisis cerebral (PC). MÉTODO: La percusión instrumentada en el tendón de Aquiles se realizó de forma isométrica para minimizar las contribuciones no neurales y un tirón del tendón exagerado, para obtener contribuciones neurales. El estiramiento del tobillo controlado por robot se realizó a varias velocidades, incluido el estiramiento lento, con contribuciones neurales minimizadas. Se evaluó la espasticidad como neural (torque reflejo de estiramiento fásico y tónico, ganancia del reflejo tendinoso, tasa de contracción y media tasa de relajación) y origen no neural (rigidez elástica y amortiguación viscosa) en 17 niños con PC (seis mujeres y 11 varones; edad media [DE] 10a 8m [3a 11m], rango 4a-18a) y 17 niños con desarrollo típico (seis mujeres y 11 hombres; edad media [SD] 12a 7m [2a 9m], rango 7a-18a). Todos los pares de torsion se normalizaron al peso × altura. RESULTADOS: Los niños con PC mostraron un aumento del torque reflejo de estiramiento fásico y tónico (p = 0,004 y p = 0,001 respectivamente), ganancia refleja del tendón (p = 0,02), tasa de contracción (p = 0,038), tasa de relajación media (p = 0,02), rigidez elastica (p = 0,01) y amortiguación viscosa (p = 0,01) en comparación con los niños con desarrollo normal. INTERPRETACIÓN: El estiramiento controlado y la percusión instrumentada del tendón, permiten la cuantificación sistemática de varios cambios neuronales y no neuronales en la PC, que pueden usarse para guiar el tratamiento específico de la discapacidad.Contribuições neurais e não neurais para a espasticidade do tornozelo em crianças com paralisia cerebral OBJETIVO: Avaliar as contribuições neurais e não-neurais para a espasticidade no tornozelo comprometido de crianças com paralisia cerebral (PC). MÉTODO: O golpeamento instrumentalizado do tendão de Aquiles foi realizado isometricamente para minimizar as contribuições não-neurais e um desvio exagerado do tendão, e assim eliciar as contribuições neurais. O alongamento do tornozelo controlado por um robô foi realizado em várias velocidades, incluindo alongamento lento, com contribuições neurais limitadas. A espasticidade foi avaliada como tendo origem neural (torque do reflexo fásico e tônico, ganho do reflexo tendinoso, taxa de contração, e taxa de meio relaxamento) e não-neural (rigidez elástica e amortecimento viscoso) em 17 crianças com PC (seis do sexo feminino e 11 do sexo masculino; média de idade [DP] 10a 8m [3 11m], variação 4a-18a) e 17 crianças com desenvolvimento típico (seis do sexo feminino e 11 do sexo masculino; média de idade [DP] 12a 7m [2a 9m], variação 7a-18a). Todos os torques foram normalizados para peso x altura. RESULTADOS: Crianças com PC mostraram aumento do torque do reflexo tônico e fásico e (p=0,004 e p=0,001 respectivamente), ganho do reflexo tendinoso (p=0,02), taxa de contração (p=0,038), taxa de meio relaxamento (p=0,02), rigidez elástica (p=0,01), e amortecimento viscoso (p=0,01) em comparação com as crianças com desenvolvimento típico. INTERPRETAÇÃO: O alongamento controlado e o golpeamento instrumentalizado do tendão permitem quantificação sistemática de várias mudanças neurais e não-neurais em PC, as quais podem ser usadas para guiar tratamento específico para a deficiência observada.

Microvascular disturbance, excessive inflammation and gliosis are key pathophysiologic changes in relation to functional status following the traumatic spinal cord injury (SCI). Continuous release of vascular endothelial growth factor (VEGF) to the lesion site was proved be able to promote the vascular remodelling, whereas the effects on reduction of inflammation and gliosis remain unclear. Currently, aiming at exploring the synergistic roles of VEGF and neurotrophin-3 (NT-3) on angiogenesis, anti-inflammation and neural repair, we developed a technique to co-deliver VEGF

To compare the cervical sagittal balance and surgical outcomes between anterior cervical discectomy and fusion (ACDF) and hybrid decompression and fusion (HDF; 1-level corpectomy combined with 1-level discectomy) for consecutive 3-level cervical spondylotic myelopathy (CSM).From January 2013 to June 2016, 82 patients with 3-level CSM who underwent ACDF (n = 40) and HDF (n = 42) were retrospectively reviewed. Perioperative parameters, clinical outcomes, and radiologic sagittal alignment were analyzed and compared.Patients were followed up for 35.5 ± 6.5 months (range, 25-53 months). All patients had achieved significant improvement in Neck Disability Index and Japanese Orthopedic Association scores after operation, with similar clinical outcomes between both groups (P0.05). In the ACDF group, 2 patients were found with axial symptoms, and 1 with hoarseness. In the HDF group, 5 patients were found with axial symptoms, 1 with hoarseness, 1 with dysphagia, and 1 with pseudarthrosis. The ACDF group had less operation time and bleeding compared with the HDF group (P0.05). The restoration of segmental and C2-7 lordosis were significantly greater in the ACDF group than the HDF group (P0.05). The C2-7 sagittal vertical axis and T1 slope minus C2-7 lordosis decreased in the ACDF group at final follow-up (P0.05); however, there was no obvious change in those of the HDF group (P0.05).Both ACDF and HDF were safe and effective for the treatment of 3-level CSM. ACDF showed superiority to HDF in terms of less blood loss, shorter operation time, and better postoperative sagittal balance.

Background Although high serum cholesterol is widely recognized as a major risk factor for heart disease, the health effects of low cholesterol are less clear. Several studies have found a correlation between low cholesterol and depression, but the results are inconsistent. Methods Data from the National Health and Nutrition Examination Survey (NHANES) 2005-2018 were utilized in this cross-sectional study. The analysis of the relationship between cholesterol and depression was performed at three levels: low total cholesterol, low high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol. The inclusion criteria were as follows: (1) people with low ( Results After controlling for potential confounding factors in the multivariate logistic regression, no association was observed between depression and low total cholesterol (OR=1.0, 95% CI: 0.9-1.2), low LDL cholesterol (OR=1.0, 95% CI: 0.8-1.4), or low HDL cholesterol (OR=0.9, 95% CI: 0.8-1.1). The results stratified by sex also showed no association between low total cholesterol, low LDL cholesterol, low HDL cholesterol and depression in either men or women. Conclusion This population-based study did not support the assumption that low cholesterol was related to a higher risk of depression. This information may contribute to the debate on how to manage people with low cholesterol in clinical practice.

High alcohol-producing Klebsiella pneumoniae (HiAlc Kpn) in the gut microbiota had been demonstrated to be the causative agent of fatty liver disease (FLD). However, the catabolic pathways for alcohol production in vivo remain unclear. Here, we characterized the genome of HiAlc and medium alcohol-producing (MedAlc) Kpn and constructed an adh (an essential gene encoding alcohol dehydrogenase) knock-out HiAlc Kpn W14 strain (W14Δadh) using CRISPR-Cas9 system. Subsequently, we established the mouse model via gavage administration of HiAlc Kpn W14 and W14 Δadh strains, respectively. Proteome and metabolome analysis showed that 10 proteins and six major metabolites involved in the 2,3-butanediol fermentation pathway exhibited at least a three-fold change or greater during intestinal growth. Compared with HiAlc Kpn W14-fed mice, W14Δadh-fed mice with weak alcohol-producing ability did not show apparent pathological changes at 4 weeks, although some steatotic hepatocytes were observed at 12 weeks. Our data demonstrated that carbohydrate substances are catabolized to produce alcohol and 2,3-butanediol via the 2,3-butanediol fermentation pathway in HiAlc Kpn, which could be a promising clinical diagnostic marker. The production of high amounts of endogenous alcohol is responsible for the observed steatosis effects in hepatocytes in vivo.

Background Previous studies found the dysbiosis of intestinal microbiota in diabetic kidney disease (DKD), especially the decreased SCFA‐producing bacteria. We aimed to investigate the concentration of the stool and serum short‐chain fatty acids (SCFAs), gut microbiota‐derived metabolites, in individuals with DKD and reveal the correlations between SCFAs and renal function. Methods A total of 30 participants with DKD, 30 participants with type 2 diabetes mellitus (DM), and 30 normal controls (NC) in HwaMei Hospital were recruited from 1/1/2018 to 12/31/2019. Participants with DKD were divided into low estimated glomerular filtration rate (eGFR)(eGFR, In this study,we measured the concentrations of fecal and serum SCFAs in the participants with DKD and it showed that serum and fecal SCFAs levels (fecal level in particular) were lowered, and there was a negative correlation between SCFAs and renal function.

The spectrum of endoscopic resection methods, including full thickness techniques, has enabled removal of most smaller gastric submucosal tumours (SMTs). We developed an extended transmural endoscopic dissection technique for lesions with predominately extraluminal growth arising from the muscularis propria. It consists of transmural intraperitoneal access with the endoscope besides the lesion followed by subserosal dissection from the outside. The technique was successful in two patients with smaller (2–3 cm) gastric stromal tumours; lesions were resected completely and short-term follow-up was normal. Further studies are warranted to confirm the safety and feasibility of this this new approach. With the popularisation of endoscopy and the development of endoscopic ultrasonography (EUS), the detection rate of gastrointestinal (GI) SMT has increased significantly.1 Complete surgical resection is still recognised as the primary and the most important way to treat gastric SMT and to get clear pathological diagnosis.2 Minimally invasive endoscopic therapy received increasing recognition due to its advantages of less invasiveness, fewer complications, quicker recovery and lower costs compared with open surgery or laparoscopic surgery. Gastric SMTs derived from mucosal and submucosal layers could be resected by endoscopic mucosal resection and endoscopic submucosal dissection, while those originated from deep layers of the gastric wall can be resected using endoscopic full-thickness resection (EFTR), which intentionally perforates the gastric wall to achieve complete resection.3 With an increasing emphasis on protecting the intact of mucosa, endoscopic mucosa-sparing lateral dissection was developed to reduce the postoperative complications.4 Inspired by the submucosal tunnelling endoscopic resection (STER)5 technique, in which maintenance of mucosal integrity and the longitudinal submucosal tunnel lead to rapid healing and decreased risk of pleural infection, STER for extraluminal tumours was reported for resection of SMTs with a predominant extraluminal growth pattern or extra-GI tumours.6 However, for most SMTs with a predominately extraluminal …

The prevalence of non-alcoholic fatty liver disease (NAFLD) in China as assessed using vibration-controlled transient elastography (VCTE) and its consistency with ultrasound is still unknown. We aimed to conduct a head-to-head comparison of consecutive measurements of NAFLD with ultrasound or VCTE to evaluate the discrepancy in the prevalence and distribution of NAFLD screened by two non-invasive techniques.We collected VCTE and ultrasound examination data from 4,388 participants who underwent health check-ups at the Health Promotion Center of Jiangsu Province Hospital between January 2017 and December 2019. The major outcome was the presence of hepatic steatosis, which was defined as a median controlled attenuation parameter (CAP) ≥ 248 dB/m by VCTE or the definition of steatosis by ultrasound.Among the 4,388 participants, 2,214 were diagnosed with NAFLD by VCTE (CAP ≥ 248 dB/m, 50.46%). Participants with severe steatosis (CAP ≥ 280 dB/m) were commonly male (77.94% vs. 50.38%, P 0.001), were obese (45.09% vs. 1.79%, P 0.001), had a worse metabolic profile, had elevated liver enzyme levels, and had advanced fibrosis. The prevalence of ultrasound-diagnosed NAFLD was 56.42%. After consistency analysis, VCTE and ultrasound showed moderate agreement regarding the diagnosis of NAFLD (κ = 0.475). We then compared the characteristics and clinical features of the four groups classified by the diagnosis results of the two techniques. NAFLD participants diagnosed by VCTE only were older, more obese, and had worse metabolic and biochemical profiles than NAFLD participants diagnosed by ultrasound only; in particular, the former had a higher proportion of abnormal alanine aminotransferase and aspartate aminotransferase levels and a higher proportion of advanced fibrosis than the latter.More than half of Chinese adults were affected by NAFLD according to VCTE. Screening based on VCTE is more likely to identify NAFLD patients with severe clinical features than ultrasound. Therefore, VCTE is a more practical non-invasive tool for the screening and follow-up of NAFLD in China.

Background Research on acetylation modification and its modification sites will be of great significance for revealing the mechanism of disease and developing new targeted medicines. In this study, we aim to construct a complete atlas of acetylome in the DSS-induced ulcerative colitis mice model (UC model) Methods A high-resolution mass spectrometry-based quantitative approach was employed to identify lysine-acetylated proteins and acetylation sites. Bioinformatics analysis and in vitro experiments verified anti-inflammatory effects of HSP90B1-K142ac. Results 2597 acetylation events and 1914 sites were quantified, highlighting 140 acetylation site changes in the colitis colon tissue. 91 acetylation sites in 75 proteins were up-regulated, and 49 acetylation sites in 39 proteins were down-regulated in the UC models. The differentially acetylated proteins mainly consisted of non-histone proteins located in the cytoplasm and mitochondria. KEGG and protein-protein interaction networks analysis showed that the differentially acetylated proteins were enriched in the TCA cycle, fatty acid metabolism, and protein processing in the endoplasmic reticulum. 68% of the differentially metabolized enzymes have a down-regulated trend in acetylation levels. The acetylation level of lysine 142 in HSP90B1 was found to be obvious in the UC colon, and point mutation of HSP90B1-K142ac would result in the decreasing secretion of TNF-α and IL-2 in LPS-stimulated cultured cells. Conclusion Our work built a complete atlas of acetylome and revealed the potential role of metabolic enzymes and heat shock proteins in DSS-induced colitis.

HCV patients are usually under substantial oxidative stress because of viral infection. A total of 177 patients with HCV infection and 198 age- and sex-matched healthy controls were enrolled in this study. We evaluated the urinary levels of 8-oxo-7, 8-dihydro-2'deoxyguanosine (8-oxodGuo) and 8-oxo-7, 8-dihydroguanosine (8-oxoGuo) in patients with HCV infection and explored the factors affecting the urinary 8-oxodGuo or 8-oxoGuo levels. Biomarkers of liver function, cancer, and inflammation were determined. Nonparametric correlations were used to evaluate the correlation between 8-oxoGuo or 8-oxodGuo and various laboratory biochemical indicators. Results showed that the levels of urinary 8-oxoGuo both in male and female patients with HCV infection were significantly higher than those in healthy controls (both p < 0.0001), while the urinary 8-oxodGuo levels only in male patients with HCV infection were significantly higher than those in healthy controls (p < 0.01). Urinary 8-oxoGuo was significantly associated with the white blood cell count, C-reactive protein level, and 8-oxodGuo level (p = 0.016, p = 0.003, and p = 0.000, respectively). Urinary 8-oxodGuo was significantly associated with the white blood cell count and 8-oxoGuo level (p = 0.018 and p = 0.000, respectively). A regression equation of urinary 8-oxoGuo or 8-oxodGuo was also established using the biomarkers in plasma. The results suggested that patients with a high C-reactive protein level are likely to have high urinary 8-oxoGuo levels as well, which may be useful for assessing the level of inflammation and oxidative stress in HCV patients.Supplemental data for this article is available online at https://doi.org/10.1080/15257770.2021.1961272 .

The base frame provides a stable support for the helix, antihelix, and tragus–antitragus complex in microtia reconstruction, and this support is vital to attain a highly defined outline for a reconstructed auricle. The success of base frame sculpting depends on appropriate treatment of the cartilage, mainly the sixth and seventh costal cartilages, which may have different characteristics. The aim of this study was to demonstrate the relevant details for base frame fabrication under various scenarios. Between 2016 and 2019, a total of 352 patients with microtia underwent autologous auricular reconstruction. Concerning the different sizes and characteristics of the costal cartilage used for the base frame reconstruction, we describe the related methods for fabrication and introduce corresponding strategies for proper management. We found that 90% of the patients responded at follow-up, and 76% of them were satisfied with the cosmetically refined auricle with harmonious integrity. The elaborate design and appropriate utilization of costal cartilage for base frame sculpting is one of the most significant and fundamental processes in microtia reconstruction. It contributes to achieving a clearly defined outline of the auricle with harmonious integrity, which is as important as the other projected subunits.

ObjectiveThe association between non-alcoholic fatty liver disease (NAFLD) and thyroid hormones in euthyroid subjects is unclear. We investigated the relationship between thyroid function and the severity of hepatic steatosis and liver fibrosis in a large cohort of euthyroid Chinese adults.MethodsA total of 3496 participants were enrolled. Liver ultrasonography was used to define the presence of NAFLD (n=2172) or the absence of NAFLD (n=1324). Anthropometric and biochemical measurements were made and thyroid function parameters including free triiodothyronine (FT3), free thyroxine (FT4), thyroid‐stimulating hormone (TSH) were measured. The severity of hepatic steatosis and liver stiffness was assessed by transient elastography.ResultsLevels of FT3 were significantly higher in the severe NAFLD group and moderate NAFLD group than in the mild NAFLD group (5.18 ± 0.58 vs 5.11 ± 0.57 vs 4.98 ± 0.60 pmol/L, Pvs 5.29 ± 0.48 vs 5.20 ± 0.50 pmol/L, Pvs 63.1% vs 73.3%, Pvs 18.6% vs 20.8%, PConclusionsThere are positive associations of FT3 levels with the severity of hepatic steatosis and the presence of liver fibrosis in NAFLD with euthyroidism.

Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematopoietic neoplasms. The progression of malignancy is closely associated with immune regulation. Macrophages are indispensable tissue components and have been proposed to play a role in the pathophysiology of hematopoietic malignancies. However, the specific role of macrophages in the development of MDS remains unclear. Here, we investigated the characteristics and phenotypic evolution of macrophages from patients with MDS. Macrophages from patients with MDS expressed CD68, CD86 and CD163. Furthermore, MDS macrophages exhibited more M2-related characteristics. Moreover, a number of phenotype-associated genes in MDS macrophages exhibited diverse responses to iron overload or iron chelation upon stimulation by ferric chloride or deferoxamine (DFO, an iron chelator). Ferric chloride polarized MDS macrophages to exhibit more M1-related characteristics, a phenomenon that could be partially reversed by DFO. Therefore, this study reveals the characteristics and phenotypic evolution of MDS macrophages and broadens the knowledge of macrophage plasticity in hematopoietic malignancies.

Background For certain human cancers, sperm associated antigen 5 (SPAG5) exerts important functions for their development and progression. However, whether RNA interference (RNAi) targeting SPAG5 has antitumor effects has not been determined clinically. Results The results indicated that Fe-doped chrysotile nanotubes (FeSiNTs) with a relatively uniform outer diameter (15–25 nm) and inner diameter (7–8 nm), and a length of several hundred nanometers, which delivered an siRNA against the SPAG5 oncogene (siSPAG5) efficiently. The nanomaterials were designed to prolong the half-life of siSPAG5 in blood, increase tumor cell-specific uptake, and maximize the efficiency of SPAG5 silencing. In vitro, FeSiNTs carrying siSPAG5 inhibited the growth, migration, and invasion of bladder cancer cells. In vivo, the FeSiNTs inhibited growth and metastasis in three models of bladder tumors (a tail vein injection lung metastatic model, an in-situ bladder cancer model, and a subcutaneous model) with no obvious toxicities. Mechanistically, we showed that FeSiNTs/siSPAG5 repressed PI3K/AKT/mTOR signaling, which suppressed the growth and progression of tumor cells. Conclusions The results highlight that FeSiNTs/siSPAG5 caused no activation of the innate immune response nor any systemic toxicity, indicating the possible therapeutic utility of FeSiNTs/siSPAG5 to deliver siSPAG5 to treat bladder cancer. Graphic abstract

Long noncoding RNAs (lncRNAs) have been shown to play important roles in various tumors including colorectal cancer (CRC). Here, we obtained data from RNA-sequencing analysis using 3 paired of CRC tissues and corresponding normal tissues. Through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, the biological functions of these dysregulated genes were identified. Moreover, we analyzed the expression levels of lncRNA PGM5-AS1 and B3GALT5-AS1 by quantitative real-time PCR (qRT-PCR) assay. To evaluate the accuracy of the lncRNA-mRNA co-expression network we built, we also detected PGM5 expression and analyzed the relationship between PGM5-AS1 and PGM5 in CRC. In addition, we explored the potential function of PGM5-AS1 in vitro and in vivo. In conclusion, we identified dysregulated lncRNAs and constructed the lncRNA-mRNA co-expression network in CRC. Then, we showed that the expression levels of PGM5-AS1, B3GALT5-AS1 and PGM5 were significantly downregulated in CRC tissues compared with corresponding normal tissues. Besides, PGM5-AS1 expression was positively associated with PGM5 expression. These findings were consistent with our RNA-sequencing data. Functionally, overexpression of PGM5-AS1 could induce cell apoptosis and cell cycle arrest in CRC. Animal study indicated that PGM5-AS1 overexpression inhibited CRC growth in vivo. This work provides dysregulated lncRNAs as candidates for further study in CRC. The lncRNA-mRNA co-expression network brings novel insights into further function research. More importantly, PGM5-AS1 is a critical tumor suppressor in CRC.

The creation of a high-defining tragus and antitragus complex remains a demanding challenge during staged lobule-type microtia reconstruction. The success of the complex carving relies greatly on proper operation of the cartilage, which is commonly residual cartilage of various sizes. The authors discuss the relevant details for sculpting the tragus and antitragus complex based on cartilage remnants in various conditions.A series of 562 lobule-type microtia patients underwent autogenous costal cartilage auricular reconstruction between 2007 and 2016. Because of the various sizes and shapes of the remnant cartilage used for the tragus and antitragus complex reconstruction, the authors have described possible scenarios for fabrication and introduced relevant tactics for appropriate treatment.Corresponding methods for various scenarios in tragus and antitragus complex fabrication have been shown to demonstrate a satisfactory appearance. The results demonstrate the achievement of a harmonious tragus and antitragus complex for the integrity of a constructed ear.Proper use of the residual cartilage for tragus and antitragus complex sculpture plays a vital role in acquiring a favorable contour of the auricle in microtia reconstruction. The introduced approach enhances the aesthetics and functionality of the complex for modern life.Therapeutic, IV.

In the past decade, substantial evidence established that long noncoding RNAs are serious about mediating the evolution of malignancies. In previous studies, LINC00365, which has not been reported in colorectal cancer (CRC), was selected using the bioinformatics analysis in GSE109454 and GSE41655 data sets. However, the function and mechanism of LINC00365 are still obscure. In our study, LINC00365 was found upregulated in CRC specimens and intimately connected with the prognosis of patients with CRC. In addition, LINC00365 overexpression enhances the cell abilities of proliferation, migration, and invasion in vitro. Meanwhile, mechanistic studies showed that LINC00365 might involve in CRC cell progression by mediating the Wnt/β-catenin pathway. Furthermore, LINC00365 upregulation increased CDK1 protein expression. In conclusion, this study suggests that LINC00365 acts as a vital part in facilitating CRC progression and might play as a therapeutic target for patients with CRC.

Stable cartilage regeneration has always been a challenge in both tissue engineering research and clinical practice. This study explored the feasibility of using a chondrocyte sheet technique stimulated by microRNAs to regenerate cartilage. We tested the involvement of hsa-miR-193b-3p in the microtia patient remnant auricular chondrocyte extracellular matrix (ECM). We observed in vitro chondrocyte proliferation, ECM synthesis, as well as the increase in the expression of type II collagen (COL2A1) and decrease in the expression of matrix metalloproteinase 16 (MMP16) of the chondrocyte sheets. COL2A1 deposition and MMP16 degradation of regenerative cartilage tissue were examined in vivo. A dual-luciferase reporter showed that the MMP16 gene was the direct target of miR-193b-3p. These results suggested that miR-193b-3p promotes chondrocyte sheet ECM synthesis by inhibiting MMP16. Since the evidence suggests that MMP16 is a critical regulator of chondrocyte ECM, this finding points the way towards a method that both strengthens the ECM and inhibits MMPs.

Recent studies indicate that evolution of the craniofacial skeleton is influenced by dietary behavior, which in turn alters masticatory efficacy and temporomandibular joint (TMJ) stability. In this study the mechanical properties of the masticatory system and the integrity of the TMJ in human populations from Northern China, dated to between 3800 BCE and 100 CE, were assessed. The results demonstrate that the mechanical efficiency is comparable to other modern human populations, though variations are present across different populations. While the ratio of overall weighted muscle efficiency for incisor loading vs. molar loading in pastoral and some recent agricultural groups is similar to early Homo sapiens, the ratio in more ancient agricultural groups is similar to the ratio in populations with heavy anterior paramasticatory activities, such as Neandertals, Inuits, and Native Americans. The TMJ vulnerability negatively correlates with the maxillary dental arch size, and positively with the condylar size. These findings suggest that there are multi-directional strategies in adaptation to heavy anterior teeth loading, such as increasing anterior teeth loading efficiency, increasing facial height, increasing facial breath and facial orthognathy, or decreasing anterior facial length. Furthermore, populations or individuals with a smaller dental arch and high biting efficiency could more easily injure the TMJ during unilateral loadings, which may explain the higher prevalence of TMJ disorders in modern humans, especially in women. These findings further reflect the impact of diachronic changes of the masticatory apparatus and lifestyle and their impact on oral health during recent human history.

Heart failure (HF) has become a global public health problem due to its unclear pathogenesis. Our previous studies have found that RNA oxidation is associated with the occurrence and development of a variety of chronic diseases in the elderly, but whether RNA oxidation is related to the pathogenesis of HF remains unclear. Male Dahl salt-sensitive rats (DSSR) were divided into 8% NaCl groups and 0.3% NaCl groups. The blood pressure of DSSR, HE staining of cardiac tissue, cardiac function index of colour Doppler echocardiography and plasma N-terminal probrain Natriuretic Peptide (NT-ProBNP) were used to evaluate the model making. The levels of 8-hydroxyguanosine (8-oxoGsn) and 8-hydroxydeoxyguanosine (8-oxodGsn) in myocardium and urine of DSSR were determined by high-performance liquid chromatography-mass spectrometry (LC-MS/MS). The expression of ERK-MAPK pathway and MTH1 was detected by Western blot (WB). Rats in the 8% NaCl group developed heart failure symptoms such as increased blood pressure, myocardial hypertrophy, decreased diastolic function, and increased plasma NT-ProBNP. The content of 8-oxoGsn in urine and heart tissue also increased, which was positively correlated with the related indicators of heart failure. This process is also accompanied by the sequential activation of ERK-MAPK pathway molecules and the increase of MTH1. The mechanism of RNA oxidation and inhibition is related to the occurrence and development of HF, which may be involved through ERK-MAPK pathway.

Myocardial ischaemia/reperfusion (I/R) injury attenuates the beneficial effects of reperfusion therapy. Poly(ADP‐ribose) polymerase (PARP) is overactivated during myocardial I/R injury. Mitophagy plays a critical role in the development of myocardial I/R injury. However, the effect of PARP activation on mitophagy in cardiomyocytes is unknown. In this study, we found that I/R induced PARP activation and mitophagy in mouse hearts. Poly(ADP‐ribose) polymerase inhibition reduced the infarct size and suppressed mitophagy after myocardial I/R injury. In vitro, hypoxia/reoxygenation (H/R) activated PARP, promoted mitophagy and induced cell apoptosis in cardiomyocytes. Poly(ADP‐ribose) polymerase inhibition suppressed H/R‐induced mitophagy and cell apoptosis. Parkin knockdown with lentivirus vectors inhibited mitophagy and prevented cell apoptosis in H/R‐treated cells. Poly(ADP‐ribose) polymerase inhibition prevented the loss of the mitochondrial membrane potential (ΔΨm). Cyclosporin A maintained ΔΨm and suppressed mitophagy but FCCP reduced the effect of PARP inhibition on ΔΨm and promoted mitophagy, indicating the critical role of ΔΨm in H/R‐induced mitophagy. Furthermore, reactive oxygen species (ROS) and poly(ADP‐ribosylation) of CypD and TSPO might contribute to the regulation of ΔΨm by PARP. Our findings thus suggest that PARP inhibition protects against I/R‐induced cell apoptosis by suppressing excessive mitophagy via the ΔΨm/Parkin pathway.

Objectives Intentional cranial modification (ICM) was a long-established tradition used to reshape the head. Unfortunately, motivation of the act is unclear. It has been found in recent and contemporary human populations throughout the Old and New Worlds, yet the drawback of the quest into the origin, diffusion, and meanings of ICM is the lack of early materials for scientific examination. This study reports the discovery of ICM from the Neolithic Houtaomuga Site in Northeast China and the importance in deepening our knowledge of this intriguing tradition. Materials and methods Twenty-five skeletons unearthed from the Neolithic cultural Phases 1-4 in the Houtaomuga Site were visually screened for ICM features. Cranial measurements were conducted to quantify the degree of variation in the modified skulls and typical ones were computer tomography (CT) scanned to obtain a diploe structure and 3D model. Results Eleven skulls carrying signs of ICM from both sexes varying in age from juveniles to full adults were identified ranging from 12,000 BP to 5,000 BP. Three types of modification patterns were observed and most of them were of typical fronto-occipital modification pattern. In particular, there were remarkable variations in the curvature of the crania along the sagittal direction. Discussion Overall, the antiquity as well as the cultural and genetic continuity of the population in Houtaomuga Site demonstrated the earliest confirmed ICM cases from the easternmost Old World, and the longest in situ duration of ICM practice at one single Neolithic site. This circumstance largely contributes to our understanding of the origins and distribution of ICM in Eurasia and the American continent.

BACKGROUND Methotrexate (MTX) is an efficacious treatment for psoriasis; however, its widespread application is limited by its unpredictable efficacy. OBJECTIVES To investigate the association of clinical factors and variants of psoriasis susceptibility genes with clinical responses to MTX in a prospective cohort. METHODS A total of 221 patients with psoriasis were recruited. Patients who achieved Psoriasis Area and Severity Index (PASI) improvement ≥ 75% at week 12 were defined as responders, whereas those with PASI improvement < 50% were defined as nonresponders. In 90 screening patients, genetic variants for 18 single-nucleotide polymorphisms in 14 susceptibility genes, and HLA-Cw6 status were initially compared for responders and nonresponders. Statistically significant associations in genetic variants were verified in all 221 patients. RESULTS Overall, 49% and 45% of patients achieved PASI 75 improvement during screening and verification stages, respectively. Concomitant arthritis with psoriasis and high body mass index (BMI) negatively affect the efficacy of MTX. TT genotype of rs10036748 in TNIP1 was significantly associated with PASI 75 response at week 12 (54% and 37%, P < 0·05). A significantly higher PASI 90 response was observed in patients with TT genotype of rs10036748 (27% vs. 12%, P < 0·01) and TC/TT genotype of rs4112788 in LCE3D (25% vs. 13%, P < 0·05) at week 12 compared with those who had other genotypes. After adjustment for all confounding factors, only BMI (P < 0·05), arthritis (P < 0·05) and genotype of rs10036748 (P < 0·05) were significantly associated with clinical responses to MTX. CONCLUSIONS Patients with psoriasis with TT genotype of rs10036748 in TNIP1, with lower BMI, without arthritis will achieve a better response to MTX.

Objectives The Hui people are the adherents of Muslim faith and distributing throughout China. There are two contrasting hypotheses about the origin and diversification of the Hui people, namely, the demic diffusion involving the mass movement of people or simple cultural diffusion. Materials and methods We collected 621 unrelated male individuals from 23 Hui populations all over China. We comprehensively genotyped more than 100 informative Y-chromosomal single nucleotide polymorphisms and 17 Y-chromosomal short tandem repeats (STRs) on those samples. Results Co-analyzed with published worldwide populations, our results suggest the origin of Hui people has involved massive assimilation of indigenous East Asians with about 70% in total of the paternal ancestry could be traced back to East Asia and the left 30% to various regions in West Eurasia. Discussion The genetic structure of the extant Hui populations was primarily shaped by the indigenous East Asian populations as they contribute the majority part of the paternal lineages of Hui people. The West Eurasian admixture was probably a sex-biased male-driven process since we have not found such a high proportion of West Eurasian gene flow on autosomal STRs and maternal mtDNA.

Human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-EXOs) play an important role in the regulation of the immune system and inflammatory responses; however, their role in acute liver failure (ALF) and related pathological conditions is unclear. In this study, we found that hUCMSC-EXOs can reduce the expression of the NLRP3 inflammasome and downstream inflammatory factors in acute liver failure. Western blot and ELISA results showed that hUCMSC-EXOs decreased the expression of NLRP3, caspase-1, IL-1β and IL-6 in LPS-stimulated RAW 264.7 macrophages. In vivo, the hUCMSC-EXOs repaired damaged liver tissue and decreased the expression of the NLRP3 inflammasome and the levels of ALT and AST in a mouse ALF model. The results of this study provide a new strategy for the application of human umbilical cord mesenchymal stem cell-derived exosomes in the treatment of ALF.

Colorectal cancer (CRC) is one of the most frequently diagnosed digestive system cancer. The aim of the present study was to investigate the interactions among messenger RNAs (mRNAs), microRNAs (miRNAs), and long noncoding RNAs (lncRNAs) in CRC to reveal the mechanisms of CRC. Differentially expressed genes (DEGs) were identified from public gene expression data sets. One thousand eighty-one common dysregulated mRNAs in two data sets were identified. Gene function analysis and protein-protein interaction network analysis indicated that these DEGs might play important roles in CRC. LINC00365 was selected through coding- noncoding network analysis and its expression was validated upregulated in 22 paired clinical samples and four CRC cell lines. A competing endogenous RNA network composed of 70 miRNAs, nine mRNAs, and LINC00365 was constructed. Eight of nine mRNAs were validated upregulated in The Cancer Genome Atlas data set. Our results suggested that LINC00365 was an oncogene in CRC and it could regulate the expression of several mRNAs through sponging miRNAs.

The impact of portal hypertension (PH) on postoperative short-term outcomes and long-term survival in hepatocellular carcinoma (HCC) patients has lately been discussed controversially. This study aimed to explore the influence of PH on postoperative outcomes in HCC patients undergoing surgical resection.Patients undergoing hepatectomy for HCC from 2010 to 2014 were enrolled. The impact of PH on postoperative complications, posthepatectomy liver failure (PHLF) and overall survival (OS) was evaluated.A total of 355 HCC patients were enrolled; 129 (36.3%) experienced postoperative complications and 21 (5.9%) developed PHLF. PH was identified as an independent predictor of PHLF. Patients with PH experienced a higher incidence of complications and PHLF than patients without PH. On the Cox proportional hazards regression model, PH was verified as a risk factor of OS for BCLC stage 0/A and B patients. Patients without PH had significantly better long-term survival compared to patients with PH both in the total cohort and in cirrhosis subgroup.Liver resection in HCC patients with PH showed a significantly increased postoperative complications and PHLF, and revealed a decreasing long-term survival than non-PH patients. Besides, tumor burden also played an important role in determining the OS. However, due to the improvement in surgical technique and perioperative management, surgery was feasible in carefully selected HCC patients with PH.

Background Acute decompensation (AD) has been shown to be associated with a high mortality rate for cirrhosis patients. This study aimed to develop a prognostic nomogram to evaluating the individual prognosis for AD of cirrhosis in chronic hepatitis B (CHB). Methods The nomogram was developed using data from a retrospective study on 509 patients hospitalized for AD of CHB cirrhosis from October 2008 to February 2014 at the Beijing Ditan Hospital, Capital Medical University. The predictive accuracy, discriminative ability, and clinical net benefit were evaluated by concordance index (C-index), calibration curves, and decision curve analysis (DCA). The results were validated on 620 patients consecutively enrolled from January 2005 to December 2010 at the Renji Hospital, Shanghai Jiao Tong University,. Results On multivariate analysis of the derivation cohort, independent factors included in the nomogram were age, previous decompensation, bacterial infection, hepatic encephalopathy, and total bilirubin. The calibration curve for the probability of survival showed good agreement between the nomogram and actual observation. The nomogram had a C-index of 0.897, which was statistically higher than the C-index values of CTP (0.793), MELD (0.821), SOFA (0.868), or the Chronic Liver Failure Consortium AD (CLIF-C AD) (0.716) scores (p

To explore clinical effects of minimally invasive osteotomy and manual reduction in treating hallux valgus.From January 2018 to May 2019, 31 patients (42 feet) with hallux valgus were treated with minimally invasive osteotomy and manual reduction, including 3 males and 28 females aged from 18 to 76 years old with an average of (50.1± 4.9) years old. Preoperative and postoperative hallux valgus (HVA), intermetatarsal angles(IMA), length difference between 1 and 2 metatarsals were recorded and compared, and American Orthopedic Foot and Ankle Society (AOFAS)score were observed and measured.Thirty-one patients (42 feet) were followed up from 14 to 18 months with an average of (15.1± 1.2) months. HVA, IM before operation were (38.5±5.4)°, (13.0± 1.1)°, and improved to (14.3±4.7)°and (9.1±1.5)°after operation respectively(Minimally invasive osteotomy and manual reduction in treating hallux valgus have advantages of shorter operation time, less length of incision, and could correct hallux valgus deformity, improve front feet and receive good clinical effect in further.

Background The purpose of this study was to investigate the application value of serum 25(OH)D3, uric acid, triglyceride (TG), and homeostasis model assessment of insulin resistance (HOMA-IR) in male patients with hyperuricemia combined with hypogonadism. Methods From August 2018 to August 2020, a total of 198 male patients with primary hyperuricemia were prospectively enrolled in our hospital for inpatient treatment in the department of Metabolism and Endocrinology. They are divided into normal gonadal function group (normal group, n = 117) and hypogonadal function group (hypogonadism group, n = 81), according to free testosterone (FT) level, International Index of Erectile Function (IIEF-5), and androgen deficiency in the aging male (ADAM) questionnaires. Laboratory indexes were compared between two groups. Multivariate logistic regression was applied to analyze the influencing factors of hypogonadism. Results Among the 198 hyperuricemia patients, 40.91 % were hypogonadism. Compared with the normal group, the BMI, waist circumference (WC), and the prevalence of non-alcoholic fatty liver disease (NAFLD), hyperlipidemia (HLP), and obesity (OB) in the hypogonadism group were higher, and the difference was statistically significant (P P r = 0.556, 0.139, 0.473, 0.143, 0.134, 0.462, 0.419, 0.572, 0.601, P = 0.012, 0.027, 0.018, 0.019, 0.028, 0.029, 0.030, 0.009, 0.003, respectively). Taking the above indicators as independent variables and hypogonadism as the dependent variable, logistic regression analysis found that the risk factors for hypogonadism were SUA, WC, BMI, HOMA-IR, TG, TT, FT, E2, and 25(OH) D3. Conclusions Serum 25(OH)D3, SUA, HOMA-IR, TG levels were positively correlated with male hyperuricemia patients with hypogonadism. They have important application value in the diagnosis of male hyperuricemia patients with hypogonadism.

The prominent vessel sign (PVS) on susceptibility-weighted imaging (SWI) is not displayed in all cases of acute ischemia. We aimed to investigate the factors associated with the presence of PVS in stroke patients. Consecutive ischemic stroke patients admitted within 24 h from symptom onset underwent emergency multimodal MRI at admission. Associated factors for the presence of PVS were analyzed using univariate analyses and multivariable logistic regression analyses. A total of 218 patients were enrolled. The occurrence rate of PVS was 55.5%. Univariate analyses showed significant differences between PVS-positive group and PVS-negative group in age, history of coronary heart disease, baseline NIHSS scores, total cholesterol, hemoglobin, anterior circulation infarct, large vessel occlusion, and cardioembolism. Multivariable logistic regression analyses revealed that the independent factors associated with PVS were anterior circulation infarct (odds ratio [OR] 13.7; 95% confidence interval [CI] 3.5–53.3), large vessel occlusion (OR 123.3; 95% CI 33.7–451.5), and cardioembolism (OR 5.6; 95% CI 2.1–15.3). Anterior circulation infarct, large vessel occlusion, and cardioembolism are independently associated with the presence of PVS on SWI.

More and more evidence support the concept that RNA oxidation plays a substantial role in the progress of multiple diseases; however, only a few studies have reported RNA oxidation caused by microbial pathogens. Urinary 8-oxo-7,8-dihydroguanosine (8-oxo-Gsn) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dGsn), which are broadly used as indicators of oxidative damage of RNA and DNA, were analyzed in this study to determine which can be used as a biomarker of infection in challenged with

Background Whipple’s disease is a chronic infectious disease caused by the Gram-positive bacterium Tropheryma whipplei (TW), which not only affects the gastrointestinal tract and causes malabsorption of nutrients, but several other systems, such as the cardiovascular system, central nervous system, the joints, and the vascular system, can also be simultaneously involved. The aim of this report was to be able to alert the clinician to severe pneumonia caused by TW combined with Candida sp. Case presentation The case study was conducted on patients in September and November 2019. After routine examination and treatment, the results were not satisfactory. A bronchoalveolar lavage (BAL) using metagenomics next-generation sequencing was conducted on two adults who presented with fever, cough, and progressive dyspnea and who had no history of gastrointestinal symptoms, immunodeficiency diseases, or use of immunosuppressive agents. TW and Candida sp. were detected in in BAL. Conclusions This is a report of life-threatening pneumonia caused by TW combined with Candida sp. in a Chinese population.

Background Mental health is affected by both genetic and environmental factors. However, previous studies have showed conflict findings about the role of lifestyle and little is known about the situation of the Chinese population. The purpose of this study was to explore the relationship between the frequency of food consumption, physical exercise condition and mental health, as well as factors related to mental stress in Chinese. Methods We recruited 8160 residents who had health examinations in a public hospital during June 2016 to May 2018. Demographic characteristics, the frequency of food consumption, physical exercise condition and mental health status was collected by a questionnaire. We estimated the association using the odds ratio (OR) and 95% confidence interval (CI) based on Binary or ordinal logistic regression models. A classification and regression tree (CART) demonstrated the prediction of the value of a target variable based on other values. Results The logistic regression model and classification tree model both found that the frequency of fresh vegetables or fruit and fried foods consumption and the current state of drinking alcohol were related to mental stress. The degree of mental stress reduced significantly with increasing consumption of fish (OR = 0.80, 95% CI: 0.71–0.90) and regular exercise (OR = 0.55, 95% CI:0.48–0.64) in females and increased consumption of fish (OR = 0.55, 95% CI: 0.48–0.64) and cereal crop (OR = 0.77, 95% CI: 0.68–0.89), fish (OR = 0.87, 95%CI:0.77–0.96) and regular exercise (OR = 0.61, 95%CI:0.53–0.70) in males. On the contrary, the frequency of consumption of desserts (OR = 1.43, 95% CI: 1.26–1.62) and the current of drinking alcohol (OR = 1.47, 95%CI:1.21–1.79) in females and meat (OR = 1.47, 95%CI: 1.31–1.65), pickled and smoked food (OR = 1.18, 95%CI:1.05–1.32) and the current state of drinking alcohol (OR = 1.25, 95%CI:1.12–1.40) in males were related to an increased risk of mental health. Conclusions Our study showed that both the frequency of some food consumption and physical exercise condition were associated with mental health and affected the degree of stress, which provided novel insights into interventions.

Hemorrhagic shock (HS) is a medical emergency during trauma. Significant loss of tissue perfusion may result in cellular hypoxia, organ damage and death. The primary treatment of HS is control of the source of bleeding as soon as possible and fluid replacement (crystalloid solutions and blood transfusion). Metabolomics can identify novel biomarkers for various functional and organic diseases. Therefore, systematic exploration of the biological mechanisms of HS and blood transfusion enables the optimization of treatments for HS to reduce the occurrence of organ damage. In this study, a global metabolic profiling strategy is applied to evaluate metabolic changes in the HS rat model. A serum metabolic network with 58 significant metabolites was constructed for HS and resuscitation. Our investigation will offer insights into the pathogenesis.

Background The Mnk2 kinase, encoded by MKNK2 gene, plays critical roles in MAPK signaling and was involved in oncogenesis. Human MKNK2 pre-mRNA can be alternatively spliced into two splicing isoforms, the MKNK2a and MKNK2b, thus yielding Mnk2a and Mnk2b proteins with different domains. The involvement of Mnk2 alternative splicing in colon cancer has been implicated based on RNA-sequencing data from TCGA database. This study aimed at investigating the upstream modulators and clinical relevance of Mnk2 alternative splicing in colon adenocarcinoma (CAC). Methods PCR, western blotting and immunohistochemistry (IHC) were performed to assess the expression of Mnk2 and upstream proteins in CAC. The function of Mnk2 and its regulators were demonstrated in different CAC cell lines as well as in xenograft models. Two independent cohorts of CAC patients were used to reveal the clinical significance of MKNK2 alternative splicing. Results Comparing with adjacent nontumorous tissue, CAC specimen showed a decreased MKNK2a level and an increased MKNK2b level, which were correlated with KRAS mutation and tumor size. The SRSF1 (serine/arginine-rich splicing factor 1) was further confirmed to be the major splicing factor targeting MKNK2 in CAC cells. Higher expression of SRPK1/2 or decreased activity of PP1α were responsible for enhancing SRSF1 phosphorylation and nucleus translocation, subsequently resulted in a switch of MKNK2 alternative splicing. Conclusions Our data showed that phosphorylation and subcellular localization of SRSF1 were balanced by SRPK1/2 and PP1α in CAC cells. High nucleus SRSF1 promoted MKNK2 splicing into MKNK2b instead of MNK2a, consequently enhanced tumor proliferation.