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In this paper, we investigate the blow-up rate and global existence of solutions to a parabolic system with absorption under the homogeneous Dirichlet boundary. By using the comparison principle and super-sub solution method, we obtain some sufficient conditions for the global existence and blow-up in finite time of solutions and establish some estimates of the upper and lower bounds of the blow-up rates. For the special case, if the domain is symmetric, for example, if it is a ball, the results of this paper also hold. [ABSTRACT FROM AUTHOR]

Background. Inflammation plays a key role in the pathophysiology and progression of acute kidney injury (AKI). Red cell distribution width (RDW) to platelet ratio (RPR) is a novel inflammatory index, and its prognostic effect on critically ill patients with AKI is rarely investigated. This work is aimed at investigating the association between RPR and in-hospital mortality in these patients. Methods. Data were extracted from the Medical Information Mart for Intensive Care III database. All-cause death during hospitalization was selected as the primary outcome. Receiver operating characteristic (ROC) curve was used to determine the optimal cut-off value, and the area under the curve (AUC) was applied to compare predictive ability among different indices. Cox proportional hazard models were utilized to assess the association between RPR and in-hospital mortality. Restricted cubic spline analysis for multivariate Cox model was performed to explore the shape of the relationship between RPR and mortality. Results. A total of 24,166 critically ill patients with AKI were included. The relationship of RPR and in-hospital mortality was nonlinear with a trend to rise rapidly and then gradually. For mortality prediction, RPR had the optimal cut-off value of 0.093, of which the AUC was 0.791 (95% confidence interval (CI): 0.773–0.810), which was higher than those of RDW, platelet, sequential organ failure assessment score, simplified acute physiology score II, neutrophil to lymphocyte ratio, and platelet to lymphocytes ratio. After adjustments for various confounders, high RPR showed a significant association with increased mortality with hazard ratios of 1.46 (95% CI: 1.40–1.55) for categorical variable and 1.88 (95% CI: 1.80–1.97) for continuous variables in the fully adjusted model. Conclusions. Elevated RPR on admission is substantially associated with high risk of in-hospital mortality in critically ill patients with AKI and thus may serve as a novel predictor of prognosis for these patients. [ABSTRACT FROM AUTHOR]

Objectives: Increasing life expectancy and decreasing mortality in patients with HIV infection are well documented. However, details of how many of the years of healthy life are damaged by HIV infection vs. good health have not been understood. We conducted this study to provide a comprehensive assessment of the levels and trends of the global burden, as measured by disability-adjusted life years (DALYs), of HIV infection.Methods: Data on HIV-related DALY were obtained from the Global Burden of Disease Study 2019. The absolute numbers and age-standardised rates of DALYs due to HIV were reported between 1990 and 2019. Estimated annual percentage changes in age-standardised rates by sex, region and nation were calculated to quantify the temporal trends in HIV burden.Results: Global HIV infection caused 47.63 million DALYs in 2019, presenting a 1.28-fold increase from 1990 to 2019. In 2019, years of life lost contributed to most of the total DALYs, but the increases in HIV-related years lived with disability have outpaced increases in years of life lost. The age-standardised rates of HIV-related DALYs in 2019 decreased as the sociodemographic indexes increased. The highest age-standardised rates were observed in sub-Saharan Africa, and the greatest increments over time were detected in Oceania.Conclusions: Globally, HIV continues to cause enormous healthy life loss. The first and foremost strategy for controlling the HIV burden is still the reduction of premature deaths, and much effort needs to be exerted to mitigate the harm of comorbidities. [ABSTRACT FROM AUTHOR]

MitoTEMPO, a mitochondrial antioxidant, has protective effects on liver-related diseases. However, the role of MitoTEMPO on nonalcoholic fatty liver disease (NAFLD) and its possible mechanisms are largely unknown. Here, we investigated the effects of MitoTEMPO on NAFLD using high fat diet- (HFD-) induced obese mice as animal models. MitoTEMPO was intraperitoneally injected into HFD mice. Liver morphological changes were observed by H&E and Oil Red O staining, and the frequency of MDSCs in peripheral blood was analyzed by flow cytometry. Moreover, real-time quantitative PCR, western blot, and immunohistochemistry were conducted to detect the mRNA and protein expressions in the liver tissues. The results showed that the hepatic steatosis in liver tissues of HFD mice injected with MitoTEMPO was significantly ameliorated. Additionally, MitoTEMPO reduced the frequency of CD11b+Gr-1+ MDSCs in peripheral circulation and decreased Gr-1+ cell accumulation in the livers. Further studies demonstrated that MitoTEMPO administration suppressed the mRNA and protein expressions of MDSC-associated proinflammatory mediators, such as monocyte chemoattractant protein-1 (MCP-1), S100 calcium-binding protein A8 (S100A8), and S100 calcium-binding protein A9 (S100A9). Our results suggest that MitoTEMPO appears to be a potential chemical compound affecting certain immune cells and further ameliorates inflammation in obese-associated NAFLD. [ABSTRACT FROM AUTHOR]

Background and Aim. Aspartate aminotransferase-to-platelet ratio index (APRI) is widely used in the assessment of fibrosis and cirrhosis, especially in patients with chronic hepatitis. However, the prognostic value of APRI in patients with chronic hepatitis with regard to the prediction of hepatocellular carcinoma (HCC) occurrence remains controversial. The objective of this meta-analysis is to investigate the association between APRI and HCC risk on the basis of cohort studies. Methods. We systematically reviewed PubMed, EMBASE, Web of Science, and Chinese National Knowledge Infrastructure databases for relevant cohort studies up to May 1, 2019. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for total and subgroup analyses were calculated with Stata 12.0 software for the assessment of the relationship between APRI and HCC risk. Results. A total of 13 studies, involving 8897 patients, were included in the meta-analysis, of which 11 explored the association between pretreatment APRI and HCC risk and four reported the relationship between posttreatment APRI and HCC risk. Pooled results showed that an elevated level of pretreatment APRI was associated with increased HCC risk (HR=2.56, 95% CI: 1.78–3.68). When stratified by hepatitis type, high pretreatment APRI predicted HCC development in patients with chronic hepatitis B (CHB) and C (CHC) but not in alcoholic liver cirrhosis (ALC). In the subgroup analyses of study region, cut-off value, sample size, and analysis method, the relationship between high pretreatment APRI and increased HCC risk was significant. Meanwhile, patients with a high level of posttreatment APRI suffered from high HCC risk (HR=3.69, 95% CI: 2.52–5.42). Conclusion: Results revealed a significant association between elevated APRI and HCC development in patients with chronic hepatitis, suggesting that APRI might serve as a valuable predictor for HCC risk in patients with chronic hepatitis. [ABSTRACT FROM AUTHOR]

Background: The pretreatment aspartate aminotransferase-to-alanine aminotransferase (De Ritis) ratio is reportedly valuable in prognosis prediction of various malignancies. However, its value in the prognosis of nasopharyngeal carcinoma (NPC) has not yet been reported. This study aimed to evaluate the effect of the De Ritis ratio on the survival outcomes of patients with nonmetastatic NPC. Methods: We retrospectively reviewed the medical data of 1023 patients with nonmetastatic NPC admitted between 2009 and 2013 at a single center. The Fine and Gray competing risk regression model was used to analyze the associations between the De Ritis ratio and the survival outcomes of cancer-specific survival (CSS) and progression-free survival (PFS) by using the subdistribution hazard ratio (SHR) and 95% confidence interval (CI) as size effects. The Cox proportional hazard model was used to evaluate the correlation between the De Ritis ratio and overall survival (OS) by using hazard ratio (HR) and 95% CI as size effects. Results: Patients were divided into two groups in accordance with the pretreatment De Ritis ratio by using an optimal cutoff value of 1.65. Compared with the patients with low De Ritis ratio (< 1.65), those with elevated De Ritis ratio (≥ 1.65) had poorer prognosis with regard to CSS, PFS, and OS. Notably, multivariate analyses showed that high De Ritis ratio was independently associated with poor CSS (SHR = 1.64, 95% CI: 1.25–2.16), PFS (SHR = 1.69, 95% CI: 1.30–2.19), and OS (HR = 1.81, 95% CI: 1.39–2.40). Conclusion: Pretreatment De Ritis ratio can be an independent prognostic predictor for patients with nonmetastatic NPC. [ABSTRACT FROM AUTHOR]

Background: Numerous studies have reported the association between pretreatment serum aspartate transaminase to alanine transaminase (AST/ALT) ratio and prognosis in multiple cancers. However, the results remain controversial and no consensus has been reached. Thus, we conducted this meta-analysis to quantitatively assess the prognostic value of pretreatment AST/ALT ratio in solid tumors. Methods: A systematic literature search was conducted by using PubMed, EMBASE, Web of Science, Cochrane Library, and Wanfang databases, as well as several trial registry platforms, including ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, and Chinese Clinical Trial Registry, up to April 5, 2019. HR and 95% CI for overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) were calculated to estimate the effect size. Results: A total of 18 studies with 9,400 patients were included. Overall, a high level of pretreatment AST/ALT ratio was significantly associated with worse OS (pooled HR=1.70, 95% CI=1.38–2.09). The statistical significance was observed in all cancer types, including renal cell carcinoma (pooled HR=1.64, 95% CI=1.30–2.05), liver cancer (pooled HR=1.16, 95% CI=1.04–1.29), urinary tract urothelial carcinoma (pooled HR=1.96, 95% CI=1.53–2.51), bladder cancer (pooled HR =2.66, 95% CI=1.69–4.20), and other cancers (pooled HR=1.44, 95% CI=1.18–1.76). Moreover, an increased level of serum AST/ALT ratio predicted unfavorable CSS (pooled HR=2.07, 95% CI=1.74–2.46) and RFS (pooled HR=1.51, 95% CI=1.15–1.99). Conclusion: Elevated level of serum AST/ALT ratio before treatment is significantly associated with poor clinical outcomes of OS, CSS, and RFS in patients with solid tumors. Pretreatment AST/ALT ratio can serve as a useful prognostic predictor for malignant patients. [ABSTRACT FROM AUTHOR]

The incidence of synchronous multiple primary lung cancer (SMPLC) has been increased in recent years. Because of a variance in clinical management and outcome, it is important to distinguish SMPLC from a primary tumor with intrapulmonary metastases. Here, we reported a diagnosis and treatment procedure regarding a case of a 58‐year‐old woman who presented with synchronous multiple tumor lesions in separate lungs. Using a next generation sequencing technology, a discordant EGFR gene profile from the separate lungs was revealed for this patient. After standard treatment procedures, the therapeutic effects were evaluated by response evaluation criteria in solid tumors (RECIST). This case shows an essential role in the combination of molecular features, together with pathological analysis, during the management of SMPLC, but challenges still required considering during dealing the cases of SMPLC. [ABSTRACT FROM AUTHOR]

Background/Aims: Serum apolipoprotein A1 (apoA1) has been reported to be abnormally expressed in several malignancies. However, the prognostic role of apoA1 in solid tumors is still controversial. We conducted this meta-analysis to obtain a more accurate evaluation of prognostic significance of apoA1 in Chinese patients with solid tumors.Methods: A comprehensive literature search of electronic databases was carried out up to August 2018. We included studies investigating the association between pretreatment serum apoA1 level and clinicopathological features, including survival outcomes, in solid tumors. Hazard ratios (HRs) and odds ratio (ORs) with 95% confidence intervals (CIs) were applied as effect size estimates. Results: A total of 13 studies and 8052 patients were included in our meta-analysis. Elevated level of pretreatment serum apoA1 was markedly associated with an improved OS (pooled HR = 0.608, 95% CI = 0.557 – 0.665, P < 0.001). The statistical significances were observed in all cancer types, including digestive system malignancies (pooled HR = 0.633; 95% CI = 0.550–0.727; P < 0.001), urinary system cancers (pooled HR = 0.471; 95% CI = 0.352–0.630; P < 0.001), nasopharyngeal cancer (pooled HR = 0.642; 95% CI = 0.538–0.766; P < 0.001) and non-small cell lung cancer (pooled HR = 0.526; 95% CI = 0.329–0.841; P = 0.007), but not in breast cancer (pooled HR = 0.573; 95% CI = 0.266–1.246; P = 0.155). Meanwhile, cancer patients with a low level of serum apoA1 suffered an unfavorable DFS (pooled HR = 0.714, 95% CI = 0.603 – 0.845, P < 0.001). Moreover, abnormal serum apoA1 was significantly correlated to tumor size (pooled OR = 0.640, 95% CI = 0.475 – 0.863, P = 0.003), tumor differentiation (pooled HR = 0.724, 95% CI = 0.565 – 0.929, P = 0.011), and tumor stage (pooled HR = 0.493, 95% CI = 0.384 – 0.633, P < 0.001). Conclusion: Elevated level of pretreatment serum apoA1 was significantly associated with longer survival in patients with solid tumors. Pretreatment serum apoA1 could serve as a novel positive factor for malignant patient prognosis in Chinese population. [ABSTRACT FROM AUTHOR]

Polysaccharide of Tetrastigma hemsleyanum (THP) exert antioxidant, antibacterial, lipid-lowering, and anti-inflammatory properties, especially some evidences have highlighted the efficiency of it as an anti-tumor agent. However, as a biological macromolecule with bidirectional immune regulation, the immunological enhancement effects of THP on macrophages and its underlying mechanisms are still largely unknown. In the present study, THP was prepared and characterized, and then the effect of THP on Raw264.7 cell activation was investigated. Structural characteristics of THP showed that the average molecular weight was 370.26 kDa, and the main monosaccharide composition was galactose, glucuronic acid, mannose, and glucose at a ratio of 31.56: 25.15: 19.44: 12.60, with high viscosity causing by relative high uronic acid. For immunomodulatory activity investigation, THP promoted the production of NO, IL-6 and TNF-α, as well as the expression of IL-1β, MCP-1, iNOS and COX-2, which were almost completely inhibited by TLR4 antagonist. Further study showed that THP could activate NF-κB and MAPK signaling pathways, and thus enhanced the phagocytic activity of Raw264.7 macrophages. In conclusion, the present study provided evidences that THP could be served as a new immunomodulator in both functional foods and the pharmaceutical field. [Display omitted] • THP induced the production of pro-inflammatory factors in Raw264.7 macrophages. • THP promoted the phagocytic activity of Raw264.7 cells. • THP exerted immunoregulatory effect via TLR4-mediated NF-κB and MAPK signaling pathways. [ABSTRACT FROM AUTHOR]

Objective: It’s difficult to differentiate sepsis from non-sepsis, especially non-infectious SIRS, because no good standard exists for proof of infection. Soluble CD14 subtype (sCD14-ST), recently re-named presepsin, was identified as a new marker for the diagnosis of sepsis in several reports. However, the findings were based on the results of individual clinical trials, rather than a comprehensive and overall estimation. Thus, we conducted this systematic review and meta-analysis to estimate the pooled accuracy of presepsin in patients with sepsis suspect. Methods: A comprehensive electronic search was performed via internet retrieval system up to 15 December 2014. Methodological quality assessment was applied by using the QUADAS2 tool. The diagnostic value of presepsin in sepsis was evaluated by using the pooled estimate of sensitivity, specificity, likelihood ratio, and diagnostic odds ratio, as well as summary receiver operating characteristics curve. Results: Nine studies with 10 trials and 2159 cases were included in the study. Only two trials had low concerns regarding applicability, whereas all trials were deemed to be at high risk of bias. Heterogeneity existed in the non-threshold effect, but not in the threshold effect. The pooled sensitivity of presepsin for sepsis was 0.78 (0.76–0.80), pooled specificity was 0.83 (0.80–0.85), pooled positive likelihood ratio was 4.63 (3.27–6.55), pooled negative likelihood ratio was 0.22 (0.16–0.30), and pooled diagnostic odds ratio was 21.73 (12.81–36.86). The area under curve of summary receiver operating characteristics curve was 0.89 (95%CI: 0.84 to 0.94) and Q* index was 0.82 (95%CI: 0.77 to 0.87). Conclusion: This meta-analysis demonstrates that presepsin had some superiority in the management of patients, and may be a helpful and valuable biomarker in early diagnosis of sepsis. However, presepsin showed a moderate diagnostic accuracy in differentiating sepsis from non-sepsis which prevented it from being recommended as a definitive test for diagnosing sepsis in isolation, but the results should be interpreted cautiously. [ABSTRACT FROM AUTHOR]

Radiofrequency ablation (RFA) comparative efficacy of treatments using video-assisted thoracoscopic sympathectomy (VATS) in the long term remains uncertain in patients with palmar hyperhidrosis (PHH). This study aimed to compare the efficacy and safety of RFA and VATS in patients with PHH. We recruited patients aged ≥ 14 years with diagnosed PHH from 14 centres in China. The treatment options of RFA or VATS were assigned to two cohort in patients with PHH. The primary outcome was the efficacy at 1-year. A total of 807 patients were enrolled. After propensity score matching, the rate of complete remission was lower in RFA group than VATS group (95% CI 0.21–0.57; p < 0.001). However, the rates of palmar dryness (95% CI 0.38–0.92; p = 0.020), postoperative pain (95% CI 0.13–0.33; p < 0.001), and surgery-related complications (95% CI 0.19–0.85; p = 0.020) were lower in RFA group than in VATS group, but skin temperature rise was more common in RFA group (95% CI 1.84–3.58; p < 0.001). RFA had a lower success rate than VATS for the complete remission of PHH. However, the symptom burden and cost are lower in patients undergoing RFA compared to those undergoing VATS. Trial Registration: ChiCTR2000039576, URL: http://www.chictr.org.cn/index.aspx. [ABSTRACT FROM AUTHOR]

Simple Summary: The effect of optimized mating methods for long-term selection has not been studied in cattle breeding. In this study, the linear programming and optimal contribution selection methods on the genetic gain and inbreeding level of beef cattle were explored and evaluated using a simulation strategy. Our results showed that the linear programming method can effectively improve the genetic gain in the population during long-term selection in the breeding process, and the optimal contribution selection method can maintain a balance between improving genetic gain and controlling inbreeding level. Our findings can provide theoretical guidance for the long-term and sustainable genetic gain in breeding populations in farm animals. The optimized selection method can maximize the genetic gain in offspring under the premise of controlling the inbreeding level of the population. At present, genetic gain has been largely improved by using genomic selection in multiple farm animals. However, the design of the optimal selection method and assessment of its effects during long-term selection in beef cattle breeding are yet to be fully explored. In this study, a simulated beef cattle population was constructed, and 15 generations of simulated breeding were carried out using the linear programming breeding strategy (LP) and optimal contribution selection strategy (OCS), respectively. The truncation selection strategy (TS−I and TS−II) was used as the control. During the breeding process, genetic parameters including genetic gain, average kinship coefficient, QTL effect variance, and average observed heterozygosity were calculated and compared across generations. Our results showed that the LP method can significantly improve the genetic gain in the population, especially the genetic performance of the traits with high heritability and the traits with high weight in the breeding process, but the inbreeding level of the population is higher under LP strategy. Although the genetic gain in the population under the OCS strategy is lower than the TS−II strategy, this method can effectively control the inbreeding level of the population. Our findings also suggest that the LP and OCS method can be used as an effective means to improve genetic gain, while the OCS method is a more ideal method to obtain sustainable genetic gain during long-term selection. [ABSTRACT FROM AUTHOR]

Background: Larynx cancer is one of the most common cancers in head and neck, and imposes heavy burden on individual and societies. A comprehensive understanding of the burden of larynx cancer is necessary to improve prevention and control strategies. However, the secular trend of larynx cancer incidence and mortality in China remains unclear. Methods: The incidence and deaths rates of larynx cancer from 1990 to 2019 were collected from the Global Burden of Disease Study 2019 database. The temporal trend of larynx cancer was analyzed using a joinpoint regression model. The age–period–cohort model was used to explore the age, period, and cohort effects on larynx cancer and predict future trends up to 2044. Results: From 1990 to 2019, the age‐standardized incidence rate of larynx cancer in China increased by 1.3% (95% CI 1.1 to 1.5) in males, but decreased by 0.5% (95% CI −0.1 to 0) in females. The age‐standardized mortality rate of larynx cancer in China decreased by 0.9% (95% CI −1.1 to −0.6) and 2.2% (95% CI −2.8 to −1.7) in males and females, respectively. Among the four risk factors, smoking and alcohol use contributed to a heavier burden compared to occupational exposure to asbestos and sulfuric acid with respect to mortality. Age effects showed that the incidence and deaths of larynx cancer were concentrated in people older than 50 years old. Period effects exerted the most significant effect on larynx cancer incidence for males. In terms of cohort effects, people born in the earlier cohorts presented a higher risk of larynx cancer compared with the later cohorts. From 2020 to 2044, the age‐standardized incidence rates of larynx cancer continued to increase in males, whereas the age‐standardized mortality rates continued to decrease in both males and females. Conclusion: The burden of larynx cancer in China has a significant gender difference. The age‐standardized incidence rates will continue to increase in males up to 2044. The disease pattern and risk factors of larynx cancer should be comprehensively studied to promote the development of timely intervention measures and relieve the burden effectively. [ABSTRACT FROM AUTHOR]

Background: Signal peptide-CUB-EGF domain-containing protein 3 (SCUBE3), a secreted multifunctional glycoprotein whose transcript expression is restricted to the tooth germ epithelium during the development of embryonic mouse teeth, has been demonstrated to play a crucial role in the regulation of tooth development. Based on this, we hypothesized that epithelium-derived SCUBE3 contributes to bio-function in dental mesenchymal cells (Mes) via epithelium–mesenchyme interactions. Methods: Immunohistochemical staining and a co-culture system were used to reveal the temporospatial expression of the SCUBE3 protein during mouse tooth germ development. In addition, human dental pulp stem cells (hDPSCs) were used as a Mes model to study the proliferation, migration, odontoblastic differentiation capacity, and mechanism of rhSCUBE3. Novel pulp–dentin-like organoid models were constructed to further confirm the odontoblast induction function of SCUBE3. Finally, semi-orthotopic animal experiments were performed to explore the clinical application of rhSCUBE3. Data were analysed using one-way analysis of variance and t-tests. Results: The epithelium-derived SCUBE3 translocated to the mesenchyme via a paracrine pathway during mouse embryonic development, and the differentiating odontoblasts in postnatal tooth germ subsequently secreted the SCUBE3 protein via an autocrine mechanism. In hDPSCs, exogenous SCUBE3 promoted cell proliferation and migration via TGF-β signalling and accelerated odontoblastic differentiation via BMP2 signalling. In the semi-orthotopic animal experiments, we found that SCUBE3 pre-treatment-induced polarized odontoblast-like cells attached to the dental walls and had better angiogenesis performance. Conclusion: SCUBE3 protein expression is transferred from the epithelium to mesenchyme during embryonic development. The function of epithelium-derived SCUBE3 in Mes, including proliferation, migration, and polarized odontoblastic differentiation, and their mechanisms are elaborated for the first time. These findings shed light on exogenous SCUBE3 application in clinic dental pulp regeneration. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is one of the most common complications for critically ill patients with cirrhosis, but it has remained unclear whether urine output fluctuations are associated with the risk of AKI in such patients. Thus, we explored the influence of 24-h urine-output trajectory on AKI in patients with cirrhosis through latent category trajectory modeling. This retrospective cohort study examined patients with cirrhosis using the MIMIC-IV database. Changes in the trajectories of urine output within 24 h after admission to the intensive care unit (ICU) were categorized using latent category trajectory modeling. The outcome examined was the occurrence of AKI during ICU hospitalization. The risk of AKI in patients with different trajectory classes was explored using the cumulative incidence function (CIF) and the Fine-Gray model with the sub-distribution hazard ratio (SHR) and the 95% confidence interval (CI) as size effects. The study included 3,562 critically ill patients with cirrhosis, of which 2,467 (69.26%) developed AKI during ICU hospitalization. The 24-h urine-output trajectories were split into five classes (Classes 1–5). The CIF curves demonstrated that patients with continuously low urine output (Class 2), a rapid decline in urine output after initially high levels (Class 3), and urine output that decreased slowly and then stabilized at a lower level (Class 4) were at higher risk for AKI than those with consistently moderate urine output (Class 1). After fully adjusting for various confounders, Classes 2, 3, and 4 were associated with a higher risk of AKI compared with Class 1, and the respective SHRs (95% CIs) were 2.56 (1.87–3.51), 1.86 (1.34–2.59), and 1.83 1.29–2.59). The 24-h urine-output trajectory is significantly associated with the risk of AKI in critically ill patients with cirrhosis. More attention should be paid to the dynamic nature of urine-output changes over time, which may help guide early intervention and improve patients' prognoses. [ABSTRACT FROM AUTHOR]

Objective: To investigate the clinical effect of posterior surgery in the treatment of craniovertebral junction (CVJ) deformities with torticollis and methods for preventing and treating complications in order to obtain a reasonable treatment strategy. Methods: From January 2007 to December 2017, 78 patients who suffered from CVJ deformities with torticollis treated by posterior surgery were analyzed. The surgical techniques were all posterior correction and fusion to restore the anatomical alignment of the craniovertebral junction. The visual analog score (VAS) and Short Form‐36 (SF‐36) health survey questionnaire were utilized to evaluate preoperative and postoperative neck pain, and changes in the torticollis angle and atlas‐dens interval (ADI) were evaluated through anteroposterior X‐ray and computed tomography. Intra‐ and postoperative complications were all recorded. One‐way ANOVA, LSD‐t test, and χ2 test were performed to evaluate the difference between the preoperative and postoperative data. Results: The mean follow‐up time was 37.4 ± 15.7 months, the average operation time was 115.6 ± 12.8 min, and the average blood loss was 170.8 ± 26.3 mL. According to the deformity site, the range of posterior correction and fusion was as follows: 38 cases of C1–C2, 33 cases of C0–C2, and seven cases of C0–C3. The preoperative SF‐36, VAS, torticollis angle, and ADI were 42.6 ± 8.8, 4.8 ± 1.1, 37.2 ± 11.2°, and 4.9 ± 2.3 mm, respectively. The difference was significant at 3 months post operation (p < 0.05), and there was no significant difference at the final follow‐up compared with 3 months post operation (p > 0.05). Conclusion: It can objectively achieve favorable correction and satisfactory clinical effects under posterior correction and fixation for CVJ deformities with torticollis. Intra‐ and postoperative complications can be settled by proper management. [ABSTRACT FROM AUTHOR]

Background. As a novel inflammatory index, the ratio of red cell distribution width (RDW) to platelet count (RPR) may have prognostic value in some critical illnesses. However, studies on the prognostic influence of RPR in patients with sepsis are few. This study is aimed at investigating the association between RPR levels and 28-day mortality in patients with sepsis. Methods. Data of patients with sepsis were obtained from the Medical Information Mart for Intensive Care III database. The best cut-off value was calculated by establishing the receiver operating characteristic curve (ROC), and the predictive ability of different indicators was compared through the area under the curve (AUC). The association between RPR levels and 28-day mortality was assessed using the Cox proportional hazards model. Restrictive cubic spline analysis was applied to the multivariable Cox model to investigate the nonlinear relationship between RPR and 28-day mortality. Results. A total of 3367 patients with sepsis were included in the study. A nonlinear relationship was observed between RPR and 28-day mortality, showing a trend of a first rapid increase and a gradual increase. For the prediction of mortality, the best cut-off value for RPR was 0.109, with an AUC of 0.728 (95% confidence interval [CI]: 0.709–0.747). The predictive capability of RPR was superior to those of RDW, platelet, SOFA score, and SAPS II score. After adjusting for various confounding factors, high RPR was significantly associated with increased mortality with adjusted hazard ratios of 1.210 (95% CI: 1.045–1.400) for categorical variables and 2.826 (95% CI: 2.025–3.944) for continuous variables. Conclusion. Elevated RPR level is significantly correlated with a high risk of 28-day mortality in patients with sepsis and can be a new predictor of patient prognosis. [ABSTRACT FROM AUTHOR]

Background: Human dental pulp stem cells (hDPSCs) have received widespread attention in the fields of tissue engineering and regenerative medicine. Although amphiregulin (AREG) has been shown to play a vital function in the biological processes of various cell types, its effects on DPSCs remain largely unknown. The aim of this study was to explore the specific role of AREG as a biologically active factor in the regeneration of dental pulp tissue. Methods: The growth of hDPSCs, together with their proliferation and apoptosis, in response to AREG was examined by CCK-8 assay and flow cytometry. We explored the effects of AREG on osteo/odontogenic differentiation in vitro and investigated the regeneration and mineralization of hDPSCs in response to AREG in vivo. The effects of AREG gain- and loss-of-function on DPSC differentiation were investigated following transfection using overexpression plasmids and shRNA, respectively. The involvement of the mitogen-activated protein kinase (MAPK) or phosphatidylinositol 3-kinase (PI3K)/Akt pathways in the mineralization process and the expression of odontoblastic marker proteins after AREG induction were investigated by using Alizarin Red S staining and Western blotting, respectively. Results: AREG (0.01–0.1 µg/mL) treatment of hDPSCs from 1 to 7 days increased hDPSCs growth and affected apoptosis minimally compared with negative controls. AREG exposure significantly promoted hDPSC differentiation, shown by increased mineralized nodule formation and the expression of odontoblastic marker protein expression. In vivo micro-CT imaging and quantitative analysis showed significantly greater formation of highly mineralized tissue in the 0.1 μg/mL AREG exposure group in DPSC/NF-gelatin-scaffold composites. AREG also promoted extracellular matrix production, with collagen fiber, mineralized matrix, and calcium salt deposition on the composites, as shown by H&E, Masson, and Von Kossa staining. Furthermore, AREG overexpression boosted hDPSC differentiation while AREG silencing inhibited it. During the differentiation of hDPSCs, AREG treatment led to phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and PI3K/Akt. Notably, a specific inhibitor of ERK, JNK, and PI3K/Akt signaling markedly reduced AREG-induced differentiation, as well as levels of phosphorylated ERK and JNK in hDPSCs. Conclusions: The data indicated that AREG promoted odontoblastic differentiation and facilitated regeneration and mineralization processes in hDPSCs. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is the most common and serious complication of sepsis, accompanied by high mortality and disease burden. The early prediction of AKI is critical for timely intervention and ultimately improves prognosis. This study aims to establish and validate predictive models based on novel machine learning (ML) algorithms for AKI in critically ill patients with sepsis.Methods: Data of patients with sepsis were extracted from the Medical Information Mart for Intensive Care III (MIMIC- III) database. Feature selection was performed using a Boruta algorithm. ML algorithms such as logistic regression (LR), k-nearest neighbors (KNN), support vector machine (SVM), decision tree, random forest, Extreme Gradient Boosting (XGBoost), and artificial neural network (ANN) were applied for model construction by utilizing tenfold cross-validation. The performances of these models were assessed in terms of discrimination, calibration, and clinical application. Moreover, the discrimination of ML-based models was compared with those of Sequential Organ Failure Assessment (SOFA) and the customized Simplified Acute Physiology Score (SAPS) II model.Results: A total of 3176 critically ill patients with sepsis were included for analysis, of which 2397 cases (75.5%) developed AKI during hospitalization. A total of 36 variables were selected for model construction. The models of LR, KNN, SVM, decision tree, random forest, ANN, XGBoost, SOFA and SAPS II score were established and obtained area under the receiver operating characteristic curves of 0.7365, 0.6637, 0.7353, 0.7492, 0.7787, 0.7547, 0.821, 0.6457 and 0.7015, respectively. The XGBoost model had the best predictive performance in terms of discrimination, calibration, and clinical application among all models.Conclusion: The ML models can be reliable tools for predicting AKI in septic patients. The XGBoost model has the best predictive performance, which can be used to assist clinicians in identifying high-risk patients and implementing early interventions to reduce mortality. [ABSTRACT FROM AUTHOR]

Background: Central venous catheter (CVC) insertion complications are a prevalent and important problem in the intensive care unit (ICU), and source control by immediate catheter removal is considered urgent in patients with septic shock suspected to be caused by catheter-related bloodstream infection (CRBSI). We sought to determine the impact of immediate reinsertion of a new catheter (IRINC) on mortality among patients after CVC removal for suspected CRBSI. Methods: A propensity score-matched cohort of patients with suspected CRBSI who underwent IRINC or no IRINC in a 32-bed ICU in a university hospital in China from January 2009 through April 2021. Catheter tip culture and clinical symptoms were used to identify patients with suspected CRBSI. The Kaplan–Meier method was used to analyse 30-day mortality before and after propensity score matching, and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality in the matched cohort were estimated with Cox proportional hazards models. Results: In total, 1,238 patients who had a CVC removed due to suspected CRBSI were identified. Among these patients, 877 (70.8%) underwent IRINC, and 361 (29.2%) did not. Among 682 propensity score-matched patients, IRINC was associated with an increased risk of 30-day mortality (HR, 1.481; 95% CI, 1.028 to 2.134) after multivariable, multilevel adjustment. Kaplan–Meier analysis found that IRINC was associated with the risk of mortality both before matching (P = 0.00096) and after matching (P = 0.018). A competing risk analysis confirmed the results of the propensity score-matched analysis. The attributable risk associated with bloodstream infection was not significantly different (HR, 1.081; 95% CI 0.964 to 1.213) among patients with suspected CRBSI in terms of 30-day mortality compared with that associated with other infections. Conclusions: In this cohort study, IRINC was associated with higher 30-day mortality compared to delayed CVC or no CVC among patients with suspected CRBSI. A large-sample randomized controlled trial is needed to define the best management for CVC in cases of suspected CRBSI because IRINC may also be associated with noninfectious complications. Trial registration This study was registered with the China Clinical Trials Registry (URL: http://www.chictr.org.cn/index.aspx) under the following registration number: ChiCTR1900022175. [ABSTRACT FROM AUTHOR]

Background. Acute kidney injury (AKI) is an important complication in critically ill patients, especially in sepsis and septic shock patients. Early prediction of AKI in septic shock can provide clinicians with sufficient information for timely intervention so that improve the patients' survival rate and quality of life. The aim of this study was to establish a nomogram that predicts the risk of AKI in patients with septic shock in the intensive care unit (ICU). Methods. The data were collected from the Medical Information Mart for Intensive Care III (MIMIC-III) database between 2001 and 2012. The primary outcome was AKI in the 48 h following ICU admission. Univariate and multivariate logistic regression analyses were used to screen the independent risk factors of AKI. The performance of the nomogram was evaluated according to the calibration curve, receiver operating characteristic (ROC) curve, decision curve analysis, and clinical impact curve. Results. A total of 2415 patients with septic shock were included in this study. In the training and validation cohort, 1091 (64.48%) of 1690 patients and 475 (65.52%) of 725 patients developed AKI, respectively. The predictive factors for nomogram construction were gender, ethnicity, congestive heart failure, diabetes, obesity, Simplified Acute Physiology Score II (SAPS II), angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARBs), bilirubin, creatinine, blood urea nitrogen (BUN), and mechanical ventilation. The model had a good discrimination with the area under the ROC curve of 0.756 and 0.760 in the training and validation cohorts, respectively. The calibration curve for probability of AKI in septic shock showed optimal agreement between prediction by nomogram and actual observation. Decision curve and clinical impact curve analysis indicated that the nomogram conferred high clinical net benefit. Conclusion. The proposed nomogram can quickly and effectively predict the risk of AKI at an early stage in patients with septic shock in ICU, which can provide information for timely and efficient intervention in patients with septic shock in the ICU setting. [ABSTRACT FROM AUTHOR]

Introduction: Mucosal-associated invariant T (MAIT) cells are a group of unconventional T cells, which strongly express CD161 and are involved in defending against infectious pathogens and inflammatory diseases. They are activated by inflammatory cytokines, secrete various cytokines and cytotoxic molecules, and express chemokine receptors and integrins. However, the underlying mechanisms of MAIT cells in colon cancer are still not fully understood. Methods: The phenotype and frequency of circulating MAIT cells were investigated by flow cytometry in colon cancer patients and healthy donors. CD161 was examined in cancerous and paracancerous nontumor tissues of colon cancer patients by immunohistochemistry. The serum levels of IFN-γ and IL-17A were analyzed by ELISA. Finally, MAIT cells were also detected in peripheral blood and tumor tissues in a CT26 tumor-bearing mice model. Results: The percentages of CD4+CD8− MAIT cells, CD4−CD8+ MAIT cells, and CD4−CD8− MAIT cells increased in the peripheral blood of colon cancer patients compared with healthy donors. The expression of CD161 protein in colon cancer cancerous tissues was higher than that in the paracancerous nontumor tissues. The killer cell lectin-like receptor B1 (KLRB1), a coding gene for CD161, was positively associated with the gene expressions of immune inhibitory receptors, such as CTLA4, HAVCR2, PDCD1, and CD274 in colon cancer. Furthermore, the serum levels of IFN-γ and CEA were positively correlated with CD8+ MAIT cells in the peripheral blood of colon cancer patients. Conclusion: Taken together, our data suggest that the circulating MAIT cells and the expression of CD161 protein in the tumor tissues increased in colon cancer patients, and MAIT cells may participate immune activities in colon cancer. [ABSTRACT FROM AUTHOR]

Background and aims: Currently, there are no definitive therapies for coronavirus disease 2019 (COVID-19). Gut microbial dysbiosis has been proved to be associated with COVID-19 severity and probiotics is an adjunctive therapy for COIVD-19. However, the potential benefit of probiotics in COVID-19 has not been studied. We aimed to assess the relationship of probiotics use with clinical outcomes in patients with COVID-19. Methods: We conducted a propensity-score matched retrospective cohort study of adult patients with COVID-19. Eligible patients received either probiotics plus standard care (probiotics group) or standard care alone (non-probiotics group). The primary outcome was the clinical improvement rate, which was compared among propensity-score matched groups and in the unmatched cohort. Secondary outcomes included the duration of viral shedding, fever, and hospital stay. Results: Among the propensity-score matched groups, probiotics use was related to clinical improvement rates (log-rank p = 0.028). This relationship was driven primarily by a shorter (days) time to clinical improvement [difference, −3 (−4 to −1), p = 0.022], reduction in duration of fever [−1.0 (−2.0 to 0.0), p = 0.025], viral shedding [−3 (−6 to −1), p < 0.001], and hospital stay [−3 (−5 to −1), p = 0.009]. Using the Cox model with time-varying exposure, use of probiotics remained independently related to better clinical improvement rate in the unmatched cohort. Conclusion: Our study suggested that probiotics use was related to improved clinical outcomes in patients with COVID-19. Further studies are required to validate the effect of probiotics in combating the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Background and aims: Currently, there are no definitive therapies for coronavirus disease 2019 (COVID-19). Gut microbial dysbiosis has been proved to be associated with COVID-19 severity and probiotics is an adjunctive therapy for COIVD-19. However, the potential benefit of probiotics in COVID-19 has not been studied. We aimed to assess the relationship of probiotics use with clinical outcomes in patients with COVID-19. Methods: We conducted a propensity-score matched retrospective cohort study of adult patients with COVID-19. Eligible patients received either probiotics plus standard care (probiotics group) or standard care alone (non-probiotics group). The primary outcome was the clinical improvement rate, which was compared among propensity-score matched groups and in the unmatched cohort. Secondary outcomes included the duration of viral shedding, fever, and hospital stay. Results: Among the propensity-score matched groups, probiotics use was related to clinical improvement rates (log-rank p = 0.028). This relationship was driven primarily by a shorter (days) time to clinical improvement [difference, −3 (−4 to −1), p = 0.022], reduction in duration of fever [−1.0 (−2.0 to 0.0), p = 0.025], viral shedding [−3 (−6 to −1), p < 0.001], and hospital stay [−3 (−5 to −1), p = 0.009]. Using the Cox model with time-varying exposure, use of probiotics remained independently related to better clinical improvement rate in the unmatched cohort. Conclusion: Our study suggested that probiotics use was related to improved clinical outcomes in patients with COVID-19. Further studies are required to validate the effect of probiotics in combating the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Objective: As a result of the pandemic of COVID‐19, the public have been experiencing psychological distress. However, the prevalence of psychological distress during the COVID‐19 pandemic remains unknown. Our objective was to evaluate the prevalence of psychological distress during COVID‐19 outbreak and their risk factors, especially their internal paths and causality. Methods: A nationwide cross‐sectional survey of the prevalence of mental disorders was conducted. We used Hospital Anxiety and Depression Scale (HADS) to estimate the prevalence of anxiety and depression. The internal paths and the causality of the psychological health were analyzed using a structural equation modeling (SEM) approach. Results: A total of 24,789 respondents completed the survey. We found that the overall prevalence of anxiety, depression, combination of anxiety, and depression were 51.6% (95% CI: 51.0–52.2), 47.5% (95% CI: 46.9–48.1), and 24.5% (95% CI: 24.0–25.0), respectively. The risk of psychological disorders in men was higher than that in women. The status of psychological health was different across different age groups, education levels, occupations, and income levels. The SEM analysis revealed that inadequate material supplies, low income, low education, lack of knowledge or confidence of the epidemic, and lack of exercise are major risk factors for psychological distress. Conclusions: The evidence from this survey poses serious challenges related to the high prevalence of psychological distress, but also offers strategies to deal with the mental health problems caused by the COVID‐19 pandemic. [ABSTRACT FROM AUTHOR]

• Kisspeptin/GPR54 was expressed in Leydig, Sertoli and germ cells of goat testes. • Kisspeptin plays a direct regulation role on testosterone secretion in Leydig cells. • Kisspeptin can directly stimulate Kiss1 / GPR54 mRNA expression in Leydig cells. • Kisspeptins play an autocrine role in goat Leydig cells. Kisspeptin, encoded by the Kiss1 gene, and its receptor GPR54 have a central regulatory role in the male reproduction. However, their functions in peripheral tissues, such as testes, remain unclear. This study investigated the local expressions and function of Kiss1 / GPR54 in goats' testes. The mRNA expression of Kiss1 / GPR54 in pubertal goat Leydig cells was detected through reverse transcriptase PCR (RT-PCR), and its protein expression in Leydig cells or the testis was examined by immunohistochemistry and Western blot analysis. Isolated and cultured Leydig cells were treated with different concentration of kisspeptin (0, 1, 10 and 100 μM) and kisspeptin antagonist for 4, 24 or 72 h. The direct effect of kisspeptin on testosterone secretion and Kiss1 / GPR54 mRNA expression was evaluated by ELISA and RT-PCR. Kiss1 / GPR54 mRNA and protein were expressed in Leydig cells and spermatids, and GPR54 were expressed in Sertoli cells. Kisspeptin treatment significantly stimulated testosterone secretion in Leydig cells, with the highest levels found under 24 h of treatment with 10 μM kisspeptin. Treatment with kisspeptin + kisspeptin antagonist significantly reduced the kisspeptin-stimulated testosterone secretion in Leydig cells. Kisspeptin treatment significantly enhanced the expression of Kiss1 / GPR54 mRNA in Leydig cells. These data suggest the local expressions of Kiss1 / GPR54 in goats' testes and its autocrine role in Leydig cells, which is helpful in understanding the regulation role of kisspeptin/GPR54 system in other peripheral tissues. [ABSTRACT FROM AUTHOR]