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Background: The Bispectral Index (BIS) and the Patient State Index (PSI) are commonly used measures to assess intraoperative sedation depth. However, model differences lead to different results, which in turn interferes with clinicians' judgment on the depth of anesthesia. Remimazolam tosilate (RT) for injection is a new benzodiazepine used in sedation. In its clinical application, there are few effective indicators for sedation depth monitoring. To close this gap, this study aims to compare BIS and PSI in measuring the sensitivity and specificity of intraoperative RT and to explore the safety of RT for intraspinal anesthesia in elderly patients. Methods: This study included 40 patients undergoing elective electro-prostatectomy with intraspinal anesthesia, who were monitored by BIS and PSI simultaneously during operation. Remimazolam tosylate 0.1 mg/kg was intravenously administered after the intraspinal anesthesia when patients were in a completely painless status. Then BIS, PSI, the Modified Observer's Assessment of Alertness and Sedation (MOAA/S) scores and vital signs were observed and recorded per minute for 10 min. Pearson's correlation analysis and linear regression model were used to compare BIS and PSI sedation scores, and to test their associations with the MOAA/S score, respectively. ROC curves were drawn to compare the sensitivity and specificity of BIS and PSI. Changes of vital signs were presented as mean ± standard deviation. Perioperative liver and kidney function indicators were analyzed using a paired t-test to evaluate the safety of RT for intraspinal anesthesia in the elderly patients. Results: According to Pearson's correlation analysis, a significant (P < 0.01) correlation between BIS and PSI was found when used to monitor intraoperative sedation of RT (r = 0.796). Significant associations between BIS and MOAA/S (r = 0.568, P < 0.01), and between PSI and MOAA/S (r = 0.390, P < 0.01) were also found. The areas under the ROC curves of BIS and PSI were 0.801 ± 0.022 and 0.734 ± 0.026, respectively, suggesting that both measures may predict patients' state of consciousness and BIS was more accurate than PSI. Vital signs remained stable throughout the study. No abnormal changes of clinical significance were found based on laboratory test results of liver and kidney function. Conclusion: BIS and PSI are strongly associated for monitoring the sedation of RT intraoperatively. Both methods can accurately reflect sedation depth. According to correlation analyses with MOAA/S scale and ROC curves, BIS is more accurate than PSI during such intraoperative monitoring. In addition, RT can be safely used in elderly patients under intraspinal anesthesia for supportive sedation, with stable vital signs and sound kidney and liver safety profiles. Trial registration: http://www.chictr.org.cn (ChiCTR2100051912). [ABSTRACT FROM AUTHOR]

Verticillium wilt (VW) of cotton poses a serious threat to the quality and yield of cotton. Verticillium dahliae is the primary causal agent of cotton VW. Moreover, V. dahliae can infect more than 200 species of dicotyledonous plants. The fungal cell wall plays a crucial role in its growth, development and pathogenicity. However, the mechanism of cell wall synthesis in V. dahliae and its role in pathogenesis remains unclear. In this study, we identified two chitin synthase (CHS) genes VdChs5 and VdChs7 containing myosin motor-like domain (MMD) and characterized their role in virulence of V. dahliae. The results showed that the functions of VdChs5 and VdChs7 were largely redundant, and target deletion of both VdChs5 and VdChs7 in V. dahliae did not affect vegetative growth, but reduced conidial production. ΔVdChs5Chs7 deletion mutant failed to colonize and proliferate in cotton vascular tissue, and exhibited significantly reduced virulence on cotton, suggesting that VdChs5 and VdChs7 are necessary for pathogenesis. In addition, the thickness of the cell wall in ΔVdChs5Chs7 showed significantly decreased, and ΔVdChs5Chs7 mutant exhibited hypersensitivity to cell wall perturbing agents and reactive oxygen species (ROS), indicating that VdChs5 and VdChs7 play key roles in cell wall integrity. Further, host-induced gene silencing (HIGS) silenced transcripts of VdChs5 and VdChs7 in susceptible cotton (Gossypium hirsutum L. acc. TM-1) enhanced resistance to cotton VW. Taken together, our data demonstrated that VdChs5 and VdChs7 play pivotal roles in proliferation, cell wall integrity, and pathogenicity, and provided a novel strategy to improve Verticillium wilt resistance in cotton and other susceptible host plants. [ABSTRACT FROM AUTHOR]

Background: To explore the expression pattern and role of the novel long non-coding RNA LATS2 antisense transcript 1 (LATS2-AS1-001) in gastric cancer (GC). Methods: qRT-PCR was applied to evaluate LATS2-AS1-001 expression and correlation with LATS2 in GC. In vitro experiments were performed to investigate the role of LATS2-AS1-001 in GC cells. RNA immunoprecipitation (RIP) was performed to assess the interaction between EZH2 and LATS2-AS1-001. LATS2/YAP1 signaling pathway proteins were detected by immunoblot. Oncomine and KMPLOT data analysis was conducted to assess the prognostic value of YAP1 in GC. Results: Decreased expression levels of LATS2-AS1-001 and LATS2 were confirmed in 357 GC tissues compared with the normal mucosa. A strong positive correlation between LATS2-AS1-001 and LATS mRNA expression was found in Pearson Correlation analysis (r = 0.719, P < 0.001). Furthermore, ROC curve analysis revealed areas under the curves for LATS2-AS1-001 and LATS2 of 0.7274 and 0.6865, respectively (P < 0.001), which indicated that LATS2-AS1-001 and LATS could be used as diagnostic indicators in GC. Moreover, ectopic expression of LATS2-AS1-001 decreased cell viability, induced G0/G1 phase arrest, and inhibited cell migration and invasion in GC cells. Mechanistically, overexpressing LATS2-AS1-001 upregulated LATS2 and induced YAP1 phosphorylation via binding to EZH2. Oncomine and KMPLOT database analysis demonstrated YAP1 was highly expressed in human GC samples, and high YAP1 expression predicted poor patient prognosis in GC. Conclusion: This study revealed that lncRNA LATS2-AS1-001 might serve as a potential diagnostic index in GC and act as a suppressor of GC progression. [ABSTRACT FROM AUTHOR]

Background: When the coupling interval is matched, ventricular parasystole can form a stable fusion QRS complex with sinus rhythm. Ablation of a fusion QRS complex has been rarely reported and is unexpectedly difficult.Case Presentation: We describe a case of ventricular parasystole from muscle sleeves of the right ventricular outflow tract. The patient was a 54-year-old woman who was admitted to the hospital because of frequent palpitations for 3 months. Anti-arrhythmic drugs had been ineffective, and she had no history of cardiovascular disease. Because the fusion QRS complex interfered with the conventional mapping technique, we could not eliminate the ventricular parasystole successfully.Results and Conclusions: Finally, we used the reversed U curve method and found that the source of ventricular arrhythmia was in the right cusp according to the special local potential. A fusion QRS complex formed by ventricular parasystole and nodal ventricular activation make mapping and ablation difficult. The special local potential was the only evidence available to confirm the target of ablation satisfactorily. [ABSTRACT FROM AUTHOR]

Background: Evidence on the role of physical activity (PA) on healthcare utilization and expenditure is limited in China. We aimed to examine the association between the total physical activity (TPA) per week, healthcare service use and expenditure. Methods: We extracted the data from China Health and Retirement Longitudinal Study (CHARLS) 2011, 2013, and 2015. Participants more than 50 years old who completed the follow-up for the three waves were enrolled. We converted the volume of vigorous physical activity (VPA) into an equivalent volume of moderate physical activity (MPA) and calculated the TPA per week for each participant. 12,927 of the 17,708 participants in CHARLS were included in our analysis. More than one-third of participants over 50 years old never participate in any moderate or intensity activity, and the median of self-reported moderate or intensity PA was about 525 (IQR 0–1680) MET-minutes per week in 2015. Results: Compared to inactive subjects, the highest level of TPA was significantly related to the decreased risk number of inpatient visits (IRR: 0.58; 95% CI:0.50–0.67, p < 0.001), inpatient hospital days (IRR: 0.60; 95% CI: 0.42–0.84, p < 0.01), healthcare expenditure (IRR: 0.71; 95% CI: 0.65–0.79, p < 0.001) and catastrophic health expenditures (OR: 0.57; 95% CI: 0.45–0.72, p < 0.001) after adjusting for covariates. Conclusions: Engaging in moderate-to-vigorous PA may drive a potential decrease in healthcare utilization, healthcare expenditure and household financial risk with a dose–response relationship in China, and some possible policy implications in public health may be considered to promote exercise in the middle-aged and elderly to reduce the medical burden on individuals and healthcare systems. [ABSTRACT FROM AUTHOR]

Background: Phthalate esters (PAEs) are known to have hormone-like properties, and there is a growing trend of children expressing a gender identity different from assigned sex. However, there has been limited research in the potential links between PAEs exposure and gender identity. Methods: A total of 571 children (278 boys) completed the follow-up from Oct 2017 to Oct 2020 in Childhood Blood Pressure and Environmental Factors (CBPEF) cohort in Xiamen, China. Urinary PAE metabolites were measured at three time of visits using ultraperformance liquid chromatography-tandem mass spectrometry. The Children's Sex Role Inventory scale was used to assess gender identity (masculinity, femininity, androgyny and undifferentiated), and Tanner definition was used to define puberty timing. Generalized linear models and log-binomial regression were used to assess the relationships between PAEs exposure, gender trait scores and gender identity. Results: Overall, the concentration of most PAEs in more than 90% of participants was above the limit of detection values. In visit 1, there were 10.1% boys with femininity and 11.3% girls with masculinity; while these figures increased to 10.8% and 12.3% during follow-up, respectively. Early puberty onset accounted for 24.8% and 25.6% among boys and girls. Long-term exposure to mono-2-ethylhexyl phthalate (MEHP) (β = 1.20, 95%CI = 0.13, 2.28), mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP) (β = 1.25, 95%CI = 0.22, 2.28) and mono-2-ethyl-5-oxohexyl phthalate (MEOHP) (β = 1.40, 95%CI = 0.24, 2.56) was associated with the increased differences of femininity trait scores in boys who enter puberty earlier, prolonged exposure to di(2-ethylhexyl) phthalate (DEHP) might also have such a positive impact (β = 1.38, 95%CI = 0.36, 2.41). For gender identity, persistent exposure to low molecular weight phthalates (LMWP) was negatively associated with undifferentiated type among boys entering puberty earlier (RR = 0.18, 95%CI = 0.05, 0.75, P < 0.05), and most of the PAE metabolites exposures showed risk ratios > 1 for their femininity. Conclusion: Long-term exposure to PAEs increase the femininity trait scores in boys with early onset of puberty. Although the mechanisms remain to be determined, environmental pollution might have subtle, yet measurable effects on childhood gender identity. Reducing these chemicals exposure has important public implications on gender development. [ABSTRACT FROM AUTHOR]

Background: Rapeseed cake is an important agricultural waste. After enzymatic fermentation, rapeseed cake not only has specific microbial diversity but also contains a lot of fatty acids, organic acids, amino acids and their derivatives, which has potential value as a high-quality organic fertilizer. However, the effects of fermented rapeseed cake on tea rhizosphere microorganisms and soil metabolites have not been reported. In this study, we aimed to elucidate the effect of enzymatic rapeseed cake fertilizer on the soil of tea tree, and to reveal the correlation between rhizosphere soil microorganisms and nutrients/metabolites. Results: The results showed that: (1) The application of enzymatic rapeseed cake increased the contents of soil organic matter (OM), total nitrogen (TN), total phosphorus (TP), available nitrogen (AN), and available phosphorus (AP); increased the activities of soil urease (S-UE), soil catalase (S-CAT), soil acid phosphatase (S-ACP) and soil sucrase (S-SC); (2) The application of enzymatic rapeseed cake increased the relative abundance of beneficial rhizosphere microorganisms such as Chaetomium, Inocybe, Pseudoxanthomonas, Pseudomonas, Sphingomonas, and Stenotrophomonas; (3) The application of enzymatic rapeseed cake increased the contents of sugar, organic acid, and fatty acid in soil, and the key metabolic pathways were concentrated in sugar and fatty acid metabolisms; (4) The application of enzymatic rapeseed cake promoted the metabolism of sugar, organic acid, and fatty acid in soil by key rhizosphere microorganisms; enzymes and microorganisms jointly regulated the metabolic pathways of sugar and fatty acids in soil. Conclusions: Enzymatic rapeseed cake fertilizer improved the nutrient status and microbial structure of tea rhizosphere soil, which was beneficial for enhancing soil productivity in tea plantations. These findings provide new insights into the use of enzymatic rapeseed cake as an efficient organic fertilizer and expand its potential for application in tea plantations. [ABSTRACT FROM AUTHOR]

Objective: To improve prediction, the AJCC staging system was revised to be consistent with upfront surgery (UFS) and neoadjuvant therapy (NAT) for PDAC. Background: The AJCC staging system was designed for patients who have had UFS for PDAC, and it has limited predictive power for patients receiving NAT. Methods: We examined 146 PDAC patients who had resection after NAT and 1771 who had UFS at Changhai Hospital between 2012 and 2021. The clinicopathological factors were identified using Cox proportional regression analysis, and the Neoadjuvant Therapy Compatible Prognostic (NATCP) staging was developed based on these variables. Validation was carried out in the prospective NAT cohort and the SEER database. The staging approach was compared to the AJCC staging system regarding predictive accuracy. Results: The NAT cohort's multivariate analysis showed that tumor differentiation and the number of positive lymph nodes independently predicted OS. The NATCP staging simplified the AJCC stages, added tumor differentiation, and restaged the disease based on the Kaplan-Meier curve survival differences. The median OS for NATCP stages IA, IB, II, and III was 31.7 months, 25.0 months, and 15.8 months in the NAT cohort and 30.1 months, 22.8 months, 18.3 months, and 14.1 months in the UFS cohort. Compared to the AJCC staging method, the NATCP staging system performed better and was verified in the validation cohort. Conclusions: Regardless of the use of NAT, NATCP staging demonstrated greater predictive abilities than the existing AJCC staging approach for resected PDAC and may facilitate clinical decision-making based on accurate prediction of patients' OS. [ABSTRACT FROM AUTHOR]

Background: Renal cell carcinoma (RCC) is characterized by a high rate of distant metastasis, which leads to poor prognosis in patients with advanced RCC. PUS10 has been recognized as a member of the pseudouridine synthase family, and recently other functions beyond the synthesis of the RNA modification have been uncovered. However, little is known about its role in diseases such as cancer. Methods: RT-qPCR, western blot and immunohistochemistry were used to measure the expression of PUS10 in RCC tissues. Transwell assay, wound healing assay, and in vivo metastasis model were conducted to determine the function of PUS10 in RCC progression. MicroRNA sequencing and GEO database were used to screen for the downstream microRNAs of PUS10. RNA immunoprecipitation, dual luciferase reporter assay, immunostaining, and rescue experiments were employed to establish the PUS10/miR-194-5p/nuclear distribution protein C(NUDC)/Cofilin1 axis in RCC migration. Chromatin immunoprecipitation and dual luciferase reporter assay were used to verify its upstream transcriptional regulator. Results: The expression of PUS10 was significantly decreased in RCC tissues, and low expression predicted poor prognosis. In vitro and in vivo experiments showed that PUS10 suppressed RCC migration, which, however, was independent of its classical pseudouridine catalytic function. Mechanically, PUS10 promoted the maturation of miR-194-5p, which sequentially inhibited RCC migration via disrupting NUDC-dependent cytoskeleton. Furthermore, hypoxia and HIF-1 A were found involved in the downregulation of PUS10. Conclusion: We unraveled PUS10 restrained RCC migration via the PUS10/miR-194-5p/NUDC/Cofilin1 pathway, which independent of its classical catalytic function. Furthermore, a linkage between the critical tumor microenvironment hallmark with malfunction of the forementioned metastasis inhibition mechanism was presented, as demonstrated by repressed expression of PUS10 due to hypoxia and HIF-1A. [ABSTRACT FROM AUTHOR]

Background: Mac-2 Binding Protein Glycosylation isomer (M2BPGi) is a novel serological glyco-biomarker for staging liver fibrosis. Here, we aimed to evaluate the efficiency of serum M2BPGi in identifying liver fibrosis stages in Chinese patients with chronic hepatitis C infection.Methods: Serum M2BPGi levels were evaluated in 680 patients with chronic hepatitis C and 164 healthy controls who underwent the Fibro Scan® test of liver fibrosis. The diagnostic accuracy of serum M2BPGi values was compared to that of other fibrosis markers, including Fibro Scan®, the aspartate transaminase to platelet ratio index (APRI), the fibrosis index based on four factors (FIB4), and the gamma-glutamyltranspeptidase to platelet ratio (GPR).Results: Among the chronic hepatitis C patients, the median serum M2BPGi level increased with increasing fibrosis score as follows: 0.88 (≤F2), 1.70 (F2/F3), and 5.68 (cirrhosis). M2BPGi concentrations could also distinguish between healthy controls (0.38 ± 0.24) and hepatitis C patients (1.57 ± 2.28). After adjusting for potential confounders, M2BPGi was the most significant factor associated with the liver stiffness measurement (effect size = 0.275, P < 0.001). The optimum cutoff values of serum M2BPGi for patients with F2 and F4 were 0.945 and 1.355, respectively. The area under the curve of serum M2BPGi for prediction of significant fibrosis (F ≥ 4) using was comparable to that of APRI (0.892 vs. 0.873), while it was superior to that of other alternative markers, including FIB4 (0.818) and GPR (0.851). Compared with other non-invasive markers, M2BPGi had the greatest specificity for diagnosing cirrhosis and cirrhosis in hepatitis C patients.Conclusions: Our results suggest that the level of serum M2BPGi would be a simple and reliable diagnostic tool for identifying liver fibrosis stage in Chinese patients with chronic hepatitis. [ABSTRACT FROM AUTHOR]

Background: Chemotherapy-induced nausea and vomiting (CINV) is one of the most common and distressing side effects in patients with cancer. The introduction and development of antiemetic drugs have significantly improved the ability of clinicians to control CINV, but it is not easy to translate to practical application, owing to financial issues, provider-related barriers, and patient factors. Nondrug therapies are needed to alleviate the symptoms of CINV. Acupuncture is an appropriate adjunctive treatment for CINV, but additional evidence is needed.Methods/design: This study is a multicenter, randomized, sham-controlled prospective clinical trial. A total of 136 participants will be randomly allocated into the intervention group (verum acupuncture) or the control group (sham acupuncture) in a 1:1 ratio. All treatment will be given for 5 days. Participants in both groups will receive acupuncture sessions twice on the first day of chemotherapy and once consecutively on the following 4 days. Each session takes approximately 30 minutes. The primary outcome measure will be the Common Terminology Criteria for Adverse Events to assess CINV. The secondary outcome measures will be the Eastern Cooperative Oncology Group score, Simplified Nutritional Appetite Questionnaire, and Hospital Anxiety and Depression scale. Safety will be assessed at each visit.Discussion: The results of this trial will provide clinical evidence for the effect and safety of acupuncture for CINV.Trial Registrations: ISRCTN Registry identifier: ISRCTN13287728 ). Registered on 28 February 2015. ClinicalTrials.gov identifier: NCT02369107 . Registered on 17 February 2015. [ABSTRACT FROM AUTHOR]

Background: Owing to the Crabtree effect, Saccharomyces cerevisiae produces a large amount of ethanol in the presence of oxygen and excess glucose, leading to a loss of carbon for the biosynthesis of non-ethanol chemicals. In the present study, the potential of a newly constructed Crabtree negative S. cerevisiae, as a chassis cell, was explored for the biosynthesis of various non-ethanol compounds. Results: To understand the metabolic characteristics of Crabtree negative S. cerevisiae sZJD-28, its transcriptional profile was compared with that of Crabtree positive S. cerevisiae CEN.PK113-11C. The reporter GO term analysis showed that, in sZJD-28, genes associated with translational processes were down-regulated, while those related to carbon metabolism were significantly up-regulated. To verify a potential increase in carbon metabolism for the Crabtree negative strain, the production of non-ethanol chemicals, derived from different metabolic nodes, was then undertaken for both sZJD-28 and CEN.PK113-11C. At the pyruvate node, production of 2,3-butanediol and lactate in sZJD-28-based strains was remarkably higher than that of CEN.PK113-11C-based ones, representing 16.8- and 1.65-fold increase in titer, as well as 4.5-fold and 0.65-fold increase in specific titer (mg/L/OD), respectively. Similarly, for shikimate derived p-coumaric acid, the titer of sZJD-28-based strain was 0.68-fold higher than for CEN.PK113-11C-based one, with a 0.98-fold increase in specific titer. While farnesene and lycopene, two acetoacetyl-CoA derivatives, showed 0.21- and 1.88-fold increases in titer, respectively. From malonyl-CoA, the titer of 3-hydroxypropionate and fatty acids in sZJD-28-based strains were 0.19- and 0.76-fold higher than that of CEN.PK113-11C-based ones, respectively. In fact, yields of products also improved by the same fold due to the absence of residual glucose. Fed-batch fermentation further showed that the titer of free fatty acids in sZJD-28-based strain 28-FFA-E reached 6295.6 mg/L with a highest reported specific titer of 247.7 mg/L/OD in S. cerevisiae. Conclusions: Compared with CEN.PK113-11C, the Crabtree negative sZJD-28 strain displayed a significantly different transcriptional profile and obvious advantages in the biosynthesis of non-ethanol chemicals due to redirected carbon and energy sources towards metabolite biosynthesis. The findings, therefore, suggest that a Crabtree negative S. cerevisiae strain could be a promising chassis cell for the biosynthesis of various chemicals. [ABSTRACT FROM AUTHOR]

Background: Bone marrow stromal cells (BMSCs) are multipotent cells that support angiogenesis, wound healing, and immunomodulation. In the hematopoietic niche, they nurture hematopoietic cells, leukemia, tumors and metastasis. BMSCs secrete of a wide range of cytokines, growth factors and matrix proteins which contribute to the pro-tumorigenic marrow microenvironment. The inflammatory cytokines IFN-γ and TNF-α change the BMSC secretome and we hypothesized that factors produced by tumors or leukemia would also affect the BMSC secretome and investigated the interaction of leukemia cells with BMSCs.Methods: BMSCs from healthy subjects were co-cultured with three myeloid leukemia cell lines (TF-1, TF-1α and K562) using a trans-well system. Following co-culture, the BMSCs and leukemia cells were analyzed by global gene expression analysis and culture supernatants were analyzed for protein expression. As a control, CD34+ cells were also cocultured with BMSCs.Results: Co-culture induced leukemia cell gene expression changes in stem cell pluripotency, TGF-β signaling and carcinoma signaling pathways. BMSCs co-cultured with leukemia cells up-regulated a number of proinflammatory genes including IL-17 signaling-related genes and IL-8 and CCL2 levels were increased in co-culture supernatants. In contrast, purine metabolism, mTOR signaling and EIF2 signaling pathways genes were up-regulated in BMSCs co-cultured with CD34+ cells.Conclusions: BMSCs react to the presence of leukemia cells undergoing changes in the cytokine and chemokine secretion profiles. Thus, BMSCs and leukemia cells both contribute to the creation of a competitive niche more favorable for leukemia stem cells. [ABSTRACT FROM AUTHOR]

Background: Local tissue damage caused by electrical burns is often deep and severe. High-voltage electrical burns are common in the head, neck and torso areas. These are mostly caused by direct contact with the power supply and are often accompanied by deep injuries of the nerve, blood vessel, muscle, tendon, and bone. We must pay great attention to the clinical treatment of these parts injured by electrical burn. Case presentation: The first case involved a migrant worker who touched a 6-kV high-tension wire when welding steel; this electric shock caused burns in many places. Deep electrical burn wounds were mainly located on the left shoulder and back, characterized by widespread skin and soft tissue defect and bone necrosis. We utilized a lower trapezius myocutaneous flap to repair these wounds in the neck and back caused by deep electrical burns. The flap survived completely and the wound was effectively repaired. The function and shape of the shoulder and back after the restoration were satisfactory. The second case involved a 29-year-old who accidentally touched a high-voltage wire while working and was burned by a 30,000-V electric shock. His wounds were mainly located on the left head, neck, back and left upper limbs. We designed a 30 cm × 12 cm right trapezius myocutaneous flap which completely covered the wound surface; the electrical burn wounds on the neck and back were effectively repaired. After the electrical burn wound was repaired, the neck function returned to normal with a satisfactory shape. Conclusion: The authors report two cases of patients who were burned by high voltage. We used lower trapezius myocutaneous flaps to repair their wounds, which achieved satisfactory clinical results. This study has provided a reliable surgical method for the clinical treatment of deep electrical burn wounds in the neck, shoulders and back. [ABSTRACT FROM AUTHOR]

Backgroud: Endoscopic surgery can be used as the main treatment for advanced recurrent nasopharyngeal carcinoma (rNPC). However, there is a huge clinical controversy about the need for consolidated immunotherapy after surgery. Methods: We performed a retrospective propensity score-matched analysis (1:2) of patients with locally advanced rNPC who underwent endoscopic nasopharyngectomy (ENPG) combined with anti-programmed cell death protein-1 (PD-1) monotherapy or ENPG alone. The survival rate was analyzed by Kaplan–Meier method. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS), objective response rate (ORR) and disease control rate (DCR). Potential surgical-related complications and immune-related adverse events (AEs) were also assessed. Results: We recruited 10 patients receiving ENPG plus anti-PD-1 monotherapy and 20 receiving ENPG alone. During the mean follow-up of 23.8 months, a significant improvement in the 2-year PFS was detected in the consolidation immunotherapy group compared to the ENPG alone group (80.0% vs. 40.0%; HR = 0.258; 95% CI: 0.09–0.72; p = 0.04), while the 2-year OS in the consolidation immunotherapy group was not significantly longer than that in the ENPG alone group (90.0% vs. 75.0%; HR = 0.482; 95% CI: 0.08–3.00; p = 0.50). The incidence of surgical-related complications in the consolidation immunotherapy group and ENPG alone group was 70.0 and 60.0%, respectively. Immune-related AEs were similar between the toripalimab arm (75.0%) and the camrelizumab arm (66.7%). Surgical-related complications depend on symptomatic treatments. Immune-related AEs were mild and tolerable. Conclusions: Consolidation immunotherapy regimen for patients with advanced rNPC after ENPG compared to ENPG alone provides a superior PFS rate with a manageable safety profile. [ABSTRACT FROM AUTHOR]

Atherosclerosis, which is a vascular pathology characterized by inflammation and plaque build-up within arterial vessel walls, acts as the important cause of most cardiovascular diseases. Except for a lipid-depository and chronic inflammatory, increasing evidences propose that epigenetic modifications are increasingly associated with atherosclerosis and are of interest from both therapeutic and biomarker perspectives. The chronic progressive nature of atherosclerosis has highlighted atherosclerosis heterogeneity and the fact that specific cell types in the complex milieu of the plaque are, by far, not the only initiators and drivers of atherosclerosis. Instead, the ubiquitous effects of cell type are tightly controlled and directed by the epigenetic signature, which, in turn, is affected by many proatherogenic stimuli, including low-density lipoprotein, proinflammatory, and physical forces of blood circulation. In this review, we summarize the role of DNA methylation and histone post-translational modifications in atherosclerosis. The future research directions and potential therapy for the management of atherosclerosis are also discussed. 3_oGVuwH1TkeHfgUq_GtC4 Video Abstract [ABSTRACT FROM AUTHOR]

Background: Fangcang shelter hospitals have played an important role in the battle against the COVID-19 epidemic in China. Patients' verbal and physical attacks on medical workforce are prone to occur in such hospitals. This study explored the impacts of patient mistreatment on healthcare workers' role behaviors (service performance and patient-oriented organizational citizenship behavior). Methods: We examined the influence of patient mistreatment on service performance and patient-oriented organizational citizenship behavior, as well as the mediating effect of emotional exhaustion and the moderating effect of displaced aggression by patients, using hierarchical linear regression and conditional process analysis. Results: Patient mistreatment was positively associated with emotional exhaustion among healthcare workers, while emotional exhaustion was negatively associated with service performance and patient-oriented organizational citizenship behavior. Mediation analysis revealed that emotional exhaustion mediated the association between patient mistreatment and both types of role behaviors. Moderated mediation analysis found that the mediation effect was weaker when the displaced aggression by patients was high. Conclusions: The findings clarified the relationship among patient mistreatment, emotional exhaustion, service performance, and patient-oriented organizational citizenship behavior. Additional assistance should be provided to healthcare workers dealing with patient mistreatment. Displaced aggression by patients attenuates the positive effects of patient mistreatment on the emotional exhaustion of healthcare workers. Our findings reveal the mechanism and boundary conditions of patient mistreatment affecting healthcare workers' service performance and patient-oriented organizational citizenship behavior. [ABSTRACT FROM AUTHOR]

Background: Female mosquitoes need a blood meal after mating for their eggs to develop, and this behavior leads to the spread of pathogens. Therefore, understanding the molecular regulation of reproduction in female mosquitoes is essential to control mosquito vector populations. In this study, we reported that microRNA-989 (miR-989), which targets 5-HTR1 (encoding secreted 5-hydroxytryptamine receptor1), is essential for mosquito reproduction. Methods: The spatiotemporal expression profile of miR-989 was detected using quantitative real-time reverse transcription PCR (RT-qPCR). miR-989 antagomirs and antagomir-negative control (NC) were designed and synthesized to knock down the expression of endogenous miR-989 in female mosquitoes. RNA sequencing was used to analyze the ovarian response to miR-989 deletion. The targets of miR-989 were predicted and confirmed using RNAhybrid and dual-luciferase assays. Results: miR-989 is exclusively expressed in female mosquito ovaries and responds to blood feeding. Injection of the miR-989 antagomir resulted in smaller ovaries and reduced egg production. 5-HTR1 was demonstrated as a target of miR-989. The deletion of miR-989 contributed to the upregulation of 5-HTR1 expression. Knockdown of 5-HTR1 rescued the adverse egg production caused by miR-989 silencing. Thus, miR-989 might play an essential role in female reproduction by targeting 5-HTR1. Conclusions: We found that miR-989 targets 5-HTR1 and participates in the regulation of reproduction in female mosquitoes. These findings expand our understanding of reproduction-related miRNAs and promote new control strategies for mosquitoes. [ABSTRACT FROM AUTHOR]

Background: Chronic obstructive pulmonary disease (COPD) represents a prevalent ailment, progressively surging within the ranks of coal mine laborers. The current study endeavors to elucidate the effects of dust exposure and smoking on COPD incidence amongst coal mine workers, while concurrently devising preventive strategies for this affliction. Method: A nested case–control study was conducted encompassing 1,416 participants aged ≥ 18 years, spanning the duration from (2017–2018) until 2020. A meticulous matching process yielded a cohort of 708 COPD patients, each paired with a control subject, forming a harmonious 1:1 ratio. Multiple logistic regression analysis was employed to scrutinize the associations between smoking, dust exposure with COPD among coal workers. Results: The COPD prevalence within the cohort of coal workers under investigation amounted to 22.66%, with an accompanying incidence density of 0.09/person-year. Following meticulous adjustment for confounding variables, it was discerned that cumulative dust exposure within the range of 47.19 ~ (OR: 1.90, 95% CI: 1.05, 3.44), 101.27 ~ (OR: 1.99, 95% CI: 1.17, 3.39), as well as smoking indices of 72 ~ (OR: 1.85, 95% CI: 1.19, 2.88), 145 ~ (OR: 1.74, 95% CI: 1.17, 2.61), 310 ~ (OR: 1.85, 95% CI: 1.23, 2.77) engender an escalated vulnerability to COPD among coal workers. Furthermore, interaction analysis discerned an absence of both multiplicative and additive interactions between dust exposure, smoking, and COPD occurrence amidst coal workers. Conclusion: Dust exposure and smoking were unequivocally identified as precipitating risk factors for COPD incidence within the population of coal workers, albeit devoid of any discernible interaction between these two causal agents. [ABSTRACT FROM AUTHOR]

Background: Osteoporosis is a systemic bone disease which can increase the risk of osteoporotic fractures. Dual-energy X-ray absorptiometry (DXA) is considered as the clinical standard for diagnosing osteoporosis by detecting the bone mineral density (BMD) in patients, but it has flaws in distinguishing between calcification and other degenerative diseases, thus leading to inaccurate BMD levels in subjects. Mindways quantitative computed tomography (Mindways QCT) is a classical QCT system. Similar to DXA, Mindways QCT can directly present the density of trabecular bone, vascular or tissue calcification; therefore, it is more accurate and sensitive than DXA and has been widely applied in clinic to evaluate osteoporosis. iCare QCT osteodensitometry was a new phantom-based QCT system, recently developed by iCare Inc. (China). It has been gradually applied in clinic by its superiority of taking 3-dimensional BMD of bone and converting BMD values to T value automatically. This study aimed at evaluating the osteoporosis detection rate of iCare QCT, compared with synchronous Mindways QCT (USA). Methods: In this study, 131 patients who underwent hip phantom-based CT scan were included. Bone mineral density (BMD) of the unified region of interests (ROI) defined at the European spine phantom (ESP, German QRM) including L1 (low), L2 (medium), and L3 (high) vertebral bodies was detected for QCT quality control and horizontal calibration. Every ESP scan were taken for 10 times, and the mean BMD values measured by iCare QCT and Mindways QCT were compared. Hip CT scan was conducted with ESP as calibration individually. T-scores gained from iCare QCT and Mindways QCT were analyzed with Pearson correlation test. The detection rates of osteoporosis were compared between iCare QCT and Mindways QCT. The unified region of interests (ROI) was delineated in the QCT software. Results: The results showed that there was no significant difference between iCare QCT and Mindways QCT in the evaluation of L1, L2, and L3 vertebrae bodies in ESP. A strong correlation between iCare QCT and Mindways QCT in the assessment of hip T-score was found. It was illustrated that iCare QCT had a higher detection rate of osteoporosis with the assessment of hip T-score than Mindways QCT did. In patients < 50 years subgroup, the detection rate of osteoporosis with iCare QCT and Mindways QCT was equal. In patients ≥ 50 years subgroup, the detection rate of osteoporosis with iCare QCT (35/92, 38.0%) was higher than that with Mindways QCT. In female subgroup, the detection rate of osteoporosis with iCare QCT was significantly higher than Mindways QCT. In male subgroup, the detection rate of osteoporosis with iCare QCT was also markedly higher than Mindways QCT. The detection rate of osteoporosis by iCare QCT was higher than Mindways QCT with hip bone assessment. Of course, the results of the present study remain to be further verified by multicenter studies in the future. [ABSTRACT FROM AUTHOR]

Background: The global incidence of nonalcoholic fatty liver disease (NAFLD) is rapidly escalating, positioning it as a principal public health challenge with significant implications for population well-being. Given its status as a cornerstone of China's economic structure, the steel industry employs a substantial workforce, consequently bringing associated health issues under increasing scrutiny. Establishing a risk assessment model for NAFLD within steelworkers aids in disease risk stratification among this demographic, thereby facilitating early intervention measures to protect the health of this significant populace. Methods: Use of cross-sectional studies. A total of 3328 steelworkers who underwent occupational health evaluations between January and September 2017 were included in this study. Hepatic steatosis was uniformly diagnosed via abdominal ultrasound. Influential factors were pinpointed using chi-square (χ2) tests and unconditional logistic regression analysis, with model inclusion variables identified by pertinent literature. Assessment models encompassing logistic regression, random forest, and XGBoost were constructed, and their effectiveness was juxtaposed in terms of accuracy, area under the curve (AUC), and F1 score. Subsequently, a scoring system for NAFLD risk was established, premised on the optimal model. Results: The findings indicated that sex, overweight, obesity, hyperuricemia, dyslipidemia, occupational dust exposure, and ALT serve as risk factors for NAFLD in steelworkers, with corresponding odds ratios (OR, 95% confidence interval (CI)) of 0.672 (0.487–0.928), 4.971 (3.981–6.207), 16.887 (12.99–21.953), 2.124 (1.77–2.548), 2.315 (1.63–3.288), 1.254 (1.014–1.551), and 3.629 (2.705–4.869), respectively. The sensitivity of the three models was reported as 0.607, 0.680 and 0.564, respectively, while the precision was 0.708, 0.643, and 0.701, respectively. The AUC measurements were 0.839, 0.839, and 0.832, and the Brier scores were 0.150, 0.153, and 0.155, respectively. The F1 score results were 0.654, 0.661, and 0.625, with log loss measures at 0.460, 0.661, and 0.564, respectively. R2 values were reported as 0.789, 0.771, and 0.778, respectively. Performance was comparable across all three models, with no significant differences observed. The NAFLD risk score system exhibited exceptional risk detection capabilities with an established cutoff value of 86. Conclusions: The study identified sex, BMI, dyslipidemia, hyperuricemia, occupational dust exposure, and ALT as significant risk factors for NAFLD among steelworkers. The traditional logistic regression model proved equally effective as the random forest and XGBoost models in assessing NAFLD risk. The optimal cutoff value for risk assessment was determined to be 86. This study provides clinicians with a visually accessible risk stratification approach to gauge the propensity for NAFLD in steelworkers, thereby aiding early identification and intervention among those at risk. [ABSTRACT FROM AUTHOR]

Background: During the transition period, the insufficient dry matter intake and a sharply increased in energy consumption to produce large quantities of milk, high yielding cows would enter a negative energy balance (NEB) that causes an increase in ketone bodies (KBs) and decrease in reproduction efficiency. The excess concentrations of circulating KBs, represented by β-hydroxybutyric acid (BHBA), could lead to oxidative damage, which potentially cause injury to follicular granulosa cells (fGCs) and delayed follicular development. Sirtuin 3 (Sirt3) regulates mitochondria reactive oxygen species (mitoROS) homeostasis in a beneficial manner; however, the molecular mechanisms underlying its involvement in the BHBA-induced injury of fGCs is poorly understood. The aim of this study was to explore the protection effects and underlying mechanisms of Sirt3 against BHBA overload-induced damage of fGCs. Results: Our findings demonstrated that 2.4 mmol/L of BHBA stress increased the levels of mitoROS in bovine fGCs. Further investigations identified the subsequent mitochondrial dysfunction, including an increased abnormal rate of mitochondrial architecture, mitochondrial permeability transition pore (MPTP) opening, reductions in mitochondrial membrane potential (MMP) and Ca2+ release; these dysfunctions then triggered the caspase cascade reaction of apoptosis in fGCs. Notably, the overexpression of Sirt3 prior to treatment enhanced mitochondrial autophagy by increasing the expression levels of Beclin-1, thus preventing BHBA-induced mitochondrial oxidative stress and mitochondrial dysfunction in fGCs. Furthermore, our data suggested that the AMPK-mTOR-Beclin-1 pathway may be involved in the protective mechanism of Sirt3 against cellular injury triggered by BHBA stimulation. Conclusions: These findings indicate that Sirt3 protects fGCs from BHBA-triggered injury by enhancing autophagy, attenuating oxidative stress and mitochondrial damage. This study provides new strategies to mitigate the fGCs injury caused by excessive BHBA stress in dairy cows with ketosis. [ABSTRACT FROM AUTHOR]

Background: The wide spread of carbapenem-resistance clones of Acinetobacter baumannii has made it a global public problem. Some studies have shown that the prevalence of Acinetobacter baumannii clones can change over time. However, few studies with respect to the change of epidemiological clones in Acinetobacter baumannii during Corona Virus Disease 2019 (COVID-19) were reported. This study aims to investigate the molecular epidemiology and resistance mechanisms of Acinetobacter baumannii during COVID-19., Results: A total of 95 non-replicated Acinetobacter baumannii isolates were enrolled in this study, of which 60.0% (n = 57) were identified as carbapenem-resistant Acinetobacter baumannii (CRAB). The positive rate of the bla OXA-23 gene in CRAB isolates was 100%. A total of 28 Oxford sequence types (STs) were identified, of which the most prevalent STs were ST540 (n = 13, 13.7%), ST469 (n = 13, 13.7%), ST373 (n = 8, 8.4%), ST938 (n = 7, 7.4%) and ST208 (n = 6, 6.3%). Differently, the most widespread clone of Acinetobacter baumannii in China during COVID-19 was ST208 (22.1%). Further study of multidrug-resistant ST540 showed that all of them were carrying bla OXA-23 , bla OXA-66 , bla ADC-25 and bla TEM-1D , simultaneously, and first detected Tn2009 in ST540. The bla OXA-23 gene was located on transposons Tn2006 or Tn2009. In addition, the ST540 strain also contains a drug-resistant plasmid with msr(E), armA, sul1 and mph(E) genes., Conclusion: The prevalent clones of Acinetobacter baumannii in our organization have changed during COVID-19, which was different from that of China. ST540 strains which carried multiple drug-resistant mobile elements was spreading, indicating that it is essential to strengthen the molecular epidemiology of Acinetobacter baumannii., (© 2024. The Author(s).)

Background: An elevated systemic immune-inflammation index (SII) is associated with higher mortality in patients with coronary artery disease and other diseases. However, the potential of SII for predicting mortality in the general population has been underexplored. Therefore, this study aimed to analyze the relationship between the SII and all-cause, cardiovascular disease, and cardiocerebrovascular disease mortality in the general population., Methods: This study involved 26,855 participants (≥ 18 years) from the National Health and Nutrition Examination Survey 1999-2014 who were grouped according to the SII tertiles. Survival differences between the groups were analyzed using log-rank tests and Kaplan-Meier plots. Furthermore, multivariate Cox regression and restricted cubic spline analyses were used to examine the relationship between the SII and all-cause, cardiovascular, and cardio-cerebrovascular mortality., Results: Overall, 1947 (7.425%) participants died following an average follow-up of 87.99 ± 54.04 months. Among these, 325 (1.210%) deaths were related to cardiovascular diseases and 392 (1.459%) to cardio-cerebrovascular mortality. Kaplan-Meier analysis revealed statistically significant differences in all-cause, cardiovascular, and cerebrovascular mortality between the SII tertiles (log-rank test: all P < 0.001). Multi-adjusted models showed that participants in the highest tertile of SII had a higher risk of death from all-cause (hazard ratio [HR] = 1.48, 95% confidence interval [CI] 1.48-1.48) and cardiovascular mortality (HR = 1.60, 95% CI 1.60-1.61) compared with those in the lowest tertile. In addition, the restricted cubic spline curve indicated a nonlinear association between SII and all-cause mortality (P < 0.001), with threshold value of SII at 18.284. There was a 15% decrease in the risk of all-cause mortality for each twofold change in SII on the left flank (HR = 0.85, 95% CI 0.69-1.05) and a 42% increase (HR = 1.42, 95% CI 1.23-1.64) on the right flank of the inflection point. In addition, the risk of cardiovascular mortality increased nonlinearly by 39% per twofold change in SII (HR = 1.39, 95% CI 1.07-1.81). There was also a nonlinear increase in the risk of cardio-cerebrovascular mortality per twofold change in SII (HR = 1.29, 95% CI 1.00-1.66)., Conclusions: In the general population, the SII was significantly associated with all-cause, cardiovascular, and cardio-cerebrovascular mortality, regardless of the established risk factors., (© 2023. The Author(s).)

Background: Ovarian cancer (OC) causes the highest rates of mortality among women's genital tract malignancies. Micro-ribonucleic acid (miRNA), the most abundant long noncoding RNAs transmitted by exosomes, has been revealed to be a potential marker for OC since 2008. In this study, we aimed to determine the possible roles of miRNAs derived from exosomes in the early diagnosis of OC through miRNA microarray, besides, exploring the underlying mechanisms of miRNAs in the OC progression., Methods: We isolated exosomes from high invasive OC cell line HO8910PM and its parent cell line HO8910 using transmission electron microscopy and western blot, and performed miRNA microarray to identify the exosome-transmitted miRNA from the two cell lines, respectively. The expression profile was obtained by quantitative analysis, and then the differentially expressed individuals were screened. miRNA-30a-5p, a stable miRNA in both cells of our sequencing data was set for further study. MiR-30a-5p mimics, inhibitor and their corresponding negative controls were applied in OC cells. Then the cell proliferation, migration, and invasion of different groups were analyzed via cell counting-kit 8 (CCK8), wound healing, and Transwell analyses. Besides, ZBE2 and LDH2 expressions were detected by qRT-PCR., Results: Combined with the data report of miRNA microarray technology, we set miR-30a-5p as our target miRNA to analyze its molecular function in regulating proliferation, migration, and invasion in OC cells. Our results showed that the miR-30a-5p overexpression could significantly enhance the capability of proliferation, migration, and invasion of HO8910 and HO8910PM cells, whereas the miR-30a-5p inhibition showed the opposite tendency (all P < 0.05). Besides, miR-30a-5p may be involved in these oncogenic processes through the upregulation of ZEB2 and LDH2., Conclusion: Our results demonstrate that exosome-transmitted miRNA-30a-5p promotes the malignant behavior of OC cells, which may be served as a promising diagnostic and prognostic marker for patients with OC., (© 2023. The Author(s).)

Background: Antiepileptic drugs (AEDs) harm bone health and are significantly associated with osteoporosis development. In this study, we aimed to explore the mechanisms involved in carbamazepine (CBZ) and microRNA (miR)-20a-5p/ubiquitin-specific peptidase 10 (USP10)/S-phase kinase-associated protein 2 (SKP2) axis in osteoporosis., Methods: Human bone marrow mesenchymal stem cells (BMSCs) were treated with different concentrations of CBZ. Knocking down or overexpressing miR-20a-5p, USP10, and SKP2 cell lines were constructed. The expressions of miR-20a-5p, USP10, SKP2, runt-related transcription factor 2 (Runx2), Alkaline phosphatase (ALP), Osterix (Osx), osteocalcin (OCN) and Collagen I were detected with western blot (WB) and reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR). Alizarin Red S (ARS) staining was performed to measure calcium deposition. Dual-luciferase assay and RNA immunoprecipitation (RIP) were applied to verify the binding relationship between miR-20a-5p and USP10. USP10 and SKP2 combination was verified by Co-Immunopurification (Co-IP). The stability of the SKP2 protein was verified by Cycloheximide chase assay., Results: CBZ could reduce cell activity. ALP activity and ARS staining were enhanced in the osteogenic induction (OM) group. The expressions of Runx2, ALP, Osx, OCN and Collagen I were increased. CBZ reduced miR-20a-5p expressions. Verification experiments showed miR-20a-5p could target USP10. USP10 increased SKP2 stability and promoted SKP2 expression. CBZ regulated miR-20a-5p/USP10/SPK2 and inhibited BMSCs osteogenic differentiation., Conclusions: CBZ regulated USP10 through miR-20a-5p to affect the deubiquitination of SKP2 and inhibit osteogenic differentiation, which provided a new idea for osteoporosis treatment., (© 2023. The Author(s).)