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Background: WHO stated the environment is an important factor affecting the development of hospice care. The environment is the sum of factors affecting behavior besides the individual factors. Currently, a scale to comprehensively assess the hospice environment of nurse is still lacking. This study aimed to develop an instrument to investigate the environmental factors affecting hospice care of nurses. Methods: Literature review and a semi-structured interview were conducted to form the items pool of the Hospice Care Environment Scale. Two rounds of Delphi expert consultation were conducted by 16 experts to revise the scale dimensions and entries to form the Hospice Care Environment Scale. A psychometric evaluation was then performed among 530 oncology nurses in a large tertiary oncology hospital in Hubei Province. The 500 valid questionnaires were randomly divided into two groups in a 1:1 ratio, sample 1 (n1 = 250) for item screening and sample 2 (n2 = 250) for quality evaluation of the resulting scale. Item analysis, reliability analysis, validity analysis and acceptability analysis were performed. Result: The Hospice Care Environment Scale consists of two dimensions and 13 entries. The Cronbach's α coefficient of the Hospice Care Environment Scale was 0.970, and the Cronbach's α coefficient of the two dimensions were 0.952 and 0.969, respectively, with the Item-content validity index and average Scale- content validity index of the scale was both 1.000. The validation factor analysis showed the standardized path coefficients of each item were basically above 0.5, and the factor structure model was stable and suitable. The average completion time of the scale was about 3 min, which had good feasibility. Conclusion: The Hospice Care Environment Scale to assess the environment of hospice care services, has good content and construct validity and reliability. This scale can provide guidance to evaluate the hospice care environment. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is a serious threat to women's health with high morbidity and mortality. The development of more effective therapies for the treatment of breast cancer is strongly warranted. Growing evidence suggests that targeting glucose metabolism may be a promising cancer treatment strategy. We previously identified a new glyceraldehyde-3-phosphate dehydrogenase (GAPDH) inhibitor, DC-5163, which shows great potential in inhibiting tumor growth. Here, we evaluated the anticancer potential of DC-5163 in breast cancer cells. Methods: The effects of DC-5163 on breast cancer cells were investigated in vitro and in vivo. Seahorse, glucose uptake, lactate production, and cellular ATP content assays were performed to examine the impact of DC-5163 on cellular glycolysis. Cell viability, colony-forming ability, cell cycle, and apoptosis were assessed by CCK8 assay, colony formation assay, flow cytometry, and immunoblotting respectively. The anticancer activity of DC-5163 in vivo was evaluated in a mouse breast cancer xenograft model. Results: DC-5163 suppressed aerobic glycolysis and reduced energy supply of breast cancer cells, thereby inhibiting breast cancer cell growth, inducing cell cycle arrest in the G0/G1 phase, and increasing apoptosis. The therapeutic efficacy was assessed using a breast cancer xenograft mouse model. DC-5163 treatment markedly suppressed tumor growth in vivo without inducing evident systemic toxicity. Micro-PET/CT scans revealed a notable reduction in tumor 18F-FDG and 18F-FLT uptake in the DC-5163 treatment group compared to the DMSO control group. Conclusions: Our results suggest that DC-5163 is a promising GAPDH inhibitor for suppressing breast cancer growth without obvious side effects. 18F-FDG and 18F-FLT PET/CT can noninvasively assess the levels of glycolysis and proliferation in tumors following treatment with DC-5163. [ABSTRACT FROM AUTHOR]

Efficiently removing excess reactive oxygen species (ROS) generated by various factors on the ocular surface is a promising strategy for preventing the development of dry eye disease (DED). The currently available eye drops for DED treatment are palliative, short-lived and frequently administered due to the short precorneal residence time. Here, we developed nanozyme-based eye drops for DED by exploiting borate-mediated dynamic covalent complexation between n-FeZIF-8 nanozymes (n-Z(Fe)) and poly(vinyl alcohol) (PVA) to overcome these problems. The resultant formulation (PBnZ), which has dual-ROS scavenging abilities and prolonged corneal retention can effectively reduce oxidative stress, thereby providing an excellent preventive effect to alleviate DED. In vitro and in vivo experiments revealed that PBnZ could eliminate excess ROS through both its multienzyme-like activity and the ROS-scavenging activity of borate bonds. The positively charged nanozyme-based eye drops displayed a longer precorneal residence time due to physical adhesion and the dynamic borate bonds between phenyboronic acid and PVA or o-diol with mucin. The in vivo results showed that eye drops could effectively alleviate DED. These dual-function PBnZ nanozyme-based eye drops can provide insights into the development of novel treatment strategies for DED and other ROS-mediated inflammatory diseases and a rationale for the application of nanomaterials in clinical settings. Highlights: Modification of dynamic covalent bonds based on borate bonds can improve the solubility and dispersion of Fe-based nanozymes in solution. The nanozyme-based eye drops enable reactive groups to bind to the chemical groups present in the mucin layer to confer carrier adhesion, thereby increasing the retention time of the carrier on the ocular surface. Nanozyme-based eye drops have synergistic effects on Fe-based nanozymes, and borate bonds effectively neutralize excess ROS in the microenvironment of the ocular surface, thereby reducing oxidative stress and direct oxidative damage. Nanozyme-based eye drops could effectively alleviate DED and may be a promising nanotherapeutic strategy for DED treatment. [ABSTRACT FROM AUTHOR]

Background: Single-cell clustering has played an important role in exploring the molecular mechanisms about cell differentiation and human diseases. Due to highly-stochastic transcriptomics data, accurate detection of cell types is still challenged, especially for RNA-sequencing data from human beings. In this case, deep neural networks have been increasingly employed to mine cell type specific patterns and have outperformed statistic approaches in cell clustering. Results: Using cross-correlation to capture gene–gene interactions, this study proposes the scCompressSA method to integrate topological patterns from scRNA-seq data, with support of self-attention (SA) based coefficient compression (CC) block. This SA-based CC block is able to extract and employ static gene–gene interactions from scRNA-seq data. This proposed scCompressSA method has enhanced clustering accuracy in multiple benchmark scRNA-seq datasets by integrating topological and temporal features. Conclusion: Static gene–gene interactions have been extracted as temporal features to boost clustering performance in single-cell clustering For the scCompressSA method, dual-channel SA based CC block is able to integrate topological features and has exhibited extraordinary detection accuracy compared with previous clustering approaches that only employ temporal patterns. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to assess the microbial variations and biomarkers in the vaginal and oral environments of patients with human papillomavirus (HPV) and cervical cancer (CC) and to develop novel prediction models. Materials and methods: This study included 164 samples collected from both the vaginal tract and oral subgingival plaque of 82 women. The participants were divided into four distinct groups based on their vaginal and oral samples: the control group (Z/KZ, n = 22), abortion group (AB/KAB, n = 17), HPV-infected group (HP/KHP, n = 21), and cervical cancer group (CC/KCC, n = 22). Microbiota analysis was conducted using full-length 16S rDNA gene sequencing with the PacBio platform. Results: The vaginal bacterial community in the Z and AB groups exhibited a relatively simple structure predominantly dominated by Lactobacillus. However, CC group shows high abundances of anaerobic bacteria and alpha diversity. Biomarkers such as Bacteroides, Mycoplasma, Bacillus, Dialister, Porphyromonas, Anaerococcus, and Prevotella were identified as indicators of CC. Correlations were established between elevated blood C-reactive protein (CRP) levels and local/systemic inflammation, pregnancy, childbirth, and abortion, which contribute to unevenness in the vaginal microenvironment. The altered microbial diversity in the CC group was confirmed by amino acid metabolism. Oral microbial diversity exhibited an inverse pattern to that of the vaginal microbiome, indicating a unique relationship. The microbial diversity of the KCC group was significantly lower than that of the KZ group, indicating a link between oral health and cancer development. Several microbes, including Fusobacterium, Campylobacter, Capnocytophaga, Veillonella, Streptococcus, Lachnoanaerobaculum, Propionibacterium, Prevotella, Lactobacillus, and Neisseria, were identified as CC biomarkers. Moreover, periodontal pathogens were associated with blood CRP levels and oral hygiene conditions. Elevated oral microbial amino acid metabolism in the CC group was closely linked to the presence of pathogens. Positive correlations indicated a synergistic relationship between vaginal and oral bacteria. Conclusion: HPV infection and CC impact both the vaginal and oral microenvironments, affecting systemic metabolism and the synergy between bacteria. This suggests that the use of oral flora markers is a potential screening tool for the diagnosis of CC. [ABSTRACT FROM AUTHOR]

Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of hematological malignancies with poor survival, while treatment options for relapsed or refractory (R/R) disease remain quite limited, with a median progression-free survival of only 3–4 months. Notably, the emergence of innovative therapeutic agents and regimens holds promise for durable responses and improved survival for patients with R/R PTCL. We summarize recent advances in the treatment of R/R PTCL from the 2023 ASH Annual Meeting, highlighting novel agents targeting EZH1/2, JAK1, PI3K, KIR3DL2, CD38/CD3xCD28, or CDK9, as well as therapeutic regimens in combination with stem cell transplantation, immunomodulators, epigenetic modifying agents, or CD30/CD16A bispecific antibodies. [ABSTRACT FROM AUTHOR]

Background: A few patients with inflammatory myopathy showed anti-mitochondrial antibody (AMA) positivity. This study aimed to report the clinical and pathological findings with vacuoles in 3 cases of such patients. Methods: Three cases with myositis from the Myositis Clinical Database of Peking University First Hospital were identified with AMA positivity. Their clinical records were retrospectively reviewed and the data was extracted. All the 3 cases underwent muscle biopsy. Results: Three middle-aged patients presented with chronic-onset weakness of proximal limbs, marked elevation of creatine kinase, and AMA-positivity. Two of the 3 cases meet the criteria of primary biliary cholangitis. All the 3 cases presented with cardiac involvement and proteinuria. Two cases developed type 2 respiratory failure. MRI of the thigh muscle showed multiple patches of edema bilaterally in both cases, mostly in the adductor magnus. Pathological findings include degeneration of muscle fibers, diffused MHC-I positivity, and complement deposits on cell membranes. Vacuoles without rims of different sizes were discovered under the membrane of the muscle fibers. A few RBFs were discovered in case 1, while a diffused proliferation of endomysium and perimysium was shown in case 2. Conclusions: AMA-positive inflammatory myopathy is a disease that could affect multiple systems. Apart from inflammatory changes, the pathological findings of muscle can also present vacuoles. [ABSTRACT FROM AUTHOR]

Background: A lack of health resources is a common problem after the outbreak of infectious diseases, and resource optimization is an important means to solve the lack of prevention and control capacity caused by resource constraints. This study systematically evaluated the similarities and differences in the application of coronavirus disease (COVID-19) resource allocation models and analyzed the effects of different optimal resource allocations on epidemic control. Methods: A systematic literature search was conducted of CNKI, WanFang, VIP, CBD, PubMed, Web of Science, Scopus and Embase for articles published from January 1, 2019, through November 23, 2023. Two reviewers independently evaluated the quality of the included studies, extracted and cross-checked the data. Moreover, publication bias and sensitivity analysis were evaluated. Results: A total of 22 articles were included for systematic review; in the application of optimal allocation models, 59.09% of the studies used propagation dynamics models to simulate the allocation of various resources, and some scholars also used mathematical optimization functions (36.36%) and machine learning algorithms (31.82%) to solve the problem of resource allocation; the results of the systematic review show that differential equation modeling was more considered when testing resources optimization, the optimization function or machine learning algorithm were mostly used to optimize the bed resources; the meta-analysis results showed that the epidemic trend was obviously effectively controlled through the optimal allocation of resources, and the average control efficiency was 0.38(95%CI 0.25–0.51); Subgroup analysis revealed that the average control efficiency from high to low was health specialists 0.48(95%CI 0.37–0.59), vaccines 0.47(95%CI 0.11–0.82), testing 0.38(95%CI 0.19–0.57), personal protective equipment (PPE) 0.38(95%CI 0.06–0.70), beds 0.34(95%CI 0.14–0.53), medicines and equipment for treatment 0.32(95%CI 0.12–0.51); Funnel plots and Egger's test showed no publication bias, and sensitivity analysis suggested robust results. Conclusion: When the data are insufficient and the simulation time is short, the researchers mostly use the constructor for research; When the data are relatively sufficient and the simulation time is long, researchers choose differential equations or machine learning algorithms for research. In addition, our study showed that control efficiency is an important indicator to evaluate the effectiveness of epidemic prevention and control. Through the optimization of medical staff and vaccine allocation, greater prevention and control effects can be achieved. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer is characterized by high invasiveness, heterogeneity, and late diagnosis, leading to high incidence and mortality rates. It is a significant public health concern globally. Early prevention is crucial in reducing the occurrence of gastric cancer, and dietary prevention, particularly focusing on carotenoids, has been considered a convenient and effective approach. However, the association between carotenoid intake and gastric cancer incidence remains controversial. Methods: A systematic search was conducted in PubMed, Ovid Embase, Web of Science, and Cochrane databases from inception to January 5, 2023. Two reviewers independently screened search results, extracted relevant data, and evaluated study quality. Statistical analysis was performed using the "metan" command in STATA 16 software. Random-effects or fixed-effects models were chosen based on the magnitude of heterogeneity among studies. Results: This study included a total of 35 publications, consisting of 23 case–control studies and 12 cohort studies. Meta-analysis of case–control studies showed that alpha-carotene (OR = 0.71, 95% CI: 0.55–0.92), beta-carotene (OR = 0.62, 95% CI: 0.53–0.72), and lutein (OR = 0.82, 95% CI: 0.69–0.97) significantly reduced the risk of gastric cancer, while beta-cryptoxanthin (OR = 0.88, 95% CI: 0.75–1.04) and lycopene (OR = 0.86, 95% CI: 0.73–1.00) showed no significant correlation. Meta-analysis of cohort studies indicated no significant associations between any of the five carotenoids and gastric cancer incidence (alpha-carotene: RR = 0.81, 95% CI: 0.54–1.23; beta-carotene: RR = 0.86, 95% CI: 0.64–1.16; beta-cryptoxanthin: RR = 0.86, 95% CI: 0.64–1.16; lutein: RR = 0.94, 95% CI: 0.69–1.29; lycopene: RR = 0.89, 95% CI: 0.69–1.14). Conclusions: The relationship between carotenoids and gastric cancer incidence may vary depending on the type of study conducted. Considering that evidence from cohort studies is generally considered stronger than evidence from case–control studies, and high-quality randomized controlled trials show no significant association between carotenoids and gastric cancer incidence, current evidence does not support the supplementation of carotenoids for gastric cancer prevention. Further targeted research is needed to explore the association between the two. [ABSTRACT FROM AUTHOR]

Premature ovarian failure (POF) is a leading cause of women's infertility without effective treatment. The purpose of this study was to investigate the protective effects of Luffa cylindrica fermentation liquid (LF) on cyclophosphamide (CTX) -induced POF in mice and to preliminarily investigate the underlying mechanisms. Thirty-two Balb/c mice were divided into four groups randomly. One group served as the control, while the other three received CTX injections to establish POF models. A 14-day gavage of either 5 or 10 μL/g LF was administered to two LF pretreatment groups. To analyze the effects of LF, the ovarian index, follicle number, the levels of serum sex hormones, superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), inflammatory factors, and apoptosis of the ovarian cells were measured. The effects of LF pretreatment on the expression of TLR4/NF-κB and apoptosis pathways were also evaluated. We found that LF pretreatment increased the ovarian index and the number of primordial and antral follicles while decreasing those of atretic follicles. LF pretreatment also increased the serum levels of estradiol (E2) and anti-Müllerian hormone (AMH), while decreasing those of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Furthermore, LF pretreatment increased the levels of SOD and GSH in the ovaries, while decreasing those of MDA, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). LF administration reduced the amount of TUNEL+ ovarian cells and the levels of TLR4 and NF-κB P65 protein expression. In conclusion, LF has antioxidant, anti-inflammatory as well as anti-apoptotic effects against CTX-induced POF, and the inhibition of TLR4/NF-κB and apoptosis pathways may be involved in its mechanisms. [ABSTRACT FROM AUTHOR]

Purpose: Hypoxia is one of the most frequent adverse events under deep sedation in the semiprone position. We hypothesized that supraglottic jet oxygenation and ventilation (SJOV) via Wei nasal jet tube (WNJ) can reduce the incidence of hypoxia in patients under deep sedation during endoscopic retrograde cholangiopancreatography (ERCP). Methods: A total of 171 patients were divided into three groups: N group, supplementary oxygen via a nasopharyngeal airway (4–6 L/min); W group, supplementary oxygen via WNJ (4–6 L/min); WS group, SJOV via WNJ. The primary outcome was the incidence of adverse events, including sedation-related adverse events [SRAEs, hypoxemia (SpO2 = 75–89% lasted less than 60 s); severe hypoxemia (SpO2 < 75% at any time or SpO2 < 90% lasted more than 60 s] and subclinical respiratory depression (SpO2 = 90–95%). Other intraoperative and post-operative adverse events were also recorded as secondary outcomes. Results: Compared with the N group, the incidence of hypoxemia and subclinical respiratory depression in the WS group was significantly lower (21% vs. 4%, P = 0.005; 27% vs. 6%, P = 0.002). Compared with Group W, the incidence of hypoxemia and subclinical respiratory depression in Group WS was also significantly less frequent (20% vs. 4%, P = 0.009; 21% vs. 6%, P = 0.014). No severe hypoxia occurred in the group WS, while four and one instances were observed in the group N and group W respectively. There were no significant differences in other adverse events among the three groups. Conclusion: SJOV can effectively improve oxygenation during ERCP in deeply sedated semiprone patients. [ABSTRACT FROM AUTHOR]

Background: Many studies have explored the relationship between C-reactive protein (CRP) levels and survival outcomes in patients with ovarian cancer (OC); however, consistent results have not been reported. As such, this meta-analysis was performed to accurately assess the prognostic and clinicopathological roles of CRP in OC. Methods: The PubMed, Web of Science, Embase, and Cochrane Library databases were systematically searched for relevant studies published from inception to April 7, 2023. The effect of CRP level(s) and OC prognostic outcomes was analyzed by computing the combined hazard ratio (HR) and corresponding 95% confidence interval (CI). Thereafter, the association between CRP level(s) and clinicopathological factors was evaluated using a combined odds ratio (OR) and corresponding 95% CI. Results: The present meta-analysis included 15 studies comprising 3202 subjects. According to the combined data, higher CRP levels were markedly associated with unfavorable overall survival (OS) (HR 1.23 [95% CI 1.11–1.37]; p < 0.001) and progression-free survival (PFS) (HR 1.55 [95% CI 1.30–1.84]; p < 0.001) in patients with OC. Furthermore, the results indicated that high CRP levels were significantly correlated with International Federation of Gynecology and Obstetrics (FIGO) stages III–IV (p < 0.001), residual tumor size ≥ 1 cm (p < 0.001), histological grade 3 (p = 0.040), and ascites volume ≥ 500 mL (p < 0.001). Conclusion: The results of this meta-analysis demonstrated that higher serum CRP levels were strongly associated with dismal OS and PFS in subjects with OC. High CRP levels were also significantly associated with clinical factors implicated in tumor aggressiveness and the development of OC. [ABSTRACT FROM AUTHOR]

As a kind of environmental noise, infrasonic noise has negative effects on various human organs. To date, research has shown that infrasound impairs cognitive function, especially the ability for learning and memory. Previously, we demonstrated that impaired learning and memory induced by infrasound was closely related with glia activation; however, the underlying mechanisms remain unclear. Connexin 43 hemichannels (Cx43 HCs), which are mainly expressed in hippocampal astrocytes, are activated under pathological conditions, lending support to the hypothesis that Cx43 HCs might function in the impaired learning and memory induced by infrasound. This study revealed that that blocking hippocampal Cx43 HCs or downregulating hippocampal Cx43 expression significantly alleviated impaired learning and memory induced by infrasound. We also observed that infrasound exposure led to the abundant release of glutamate and ATP through Cx43 HCs. In addition, the abundant release of glutamate and ATP depended on proinflammatory cytokines. Our finds suggested that the enhanced release of ATP and glutamate by astroglial Cx43 HCs may be involved in the learning and memory deficits caused by infrasound exposure. [ABSTRACT FROM AUTHOR]

As a kind of environmental noise, infrasonic noise has negative effects on various human organs. To date, research has shown that infrasound impairs cognitive function, especially the ability for learning and memory. Previously, we demonstrated that impaired learning and memory induced by infrasound was closely related with glia activation; however, the underlying mechanisms remain unclear. Connexin 43 hemichannels (Cx43 HCs), which are mainly expressed in hippocampal astrocytes, are activated under pathological conditions, lending support to the hypothesis that Cx43 HCs might function in the impaired learning and memory induced by infrasound. This study revealed that that blocking hippocampal Cx43 HCs or downregulating hippocampal Cx43 expression significantly alleviated impaired learning and memory induced by infrasound. We also observed that infrasound exposure led to the abundant release of glutamate and ATP through Cx43 HCs. In addition, the abundant release of glutamate and ATP depended on proinflammatory cytokines. Our finds suggested that the enhanced release of ATP and glutamate by astroglial Cx43 HCs may be involved in the learning and memory deficits caused by infrasound exposure. [ABSTRACT FROM AUTHOR]

Background: Spinal subdural hematoma (SSH) is a rare cause of compression of the neutral elements of the spinal cord. However, little is known about the presentation of acute SSH after lumbar spine surgery. The reason for this may be that symptomatic SSH occurs rarely and is not given enough attention by spine surgeons. Currently, the decision to perform MRI postoperatively is more dependent on surgeon preference; therefore, no high-quality studies have been published. Our team reports our experience in the diagnosis and management of SSH after lumbar decompression and fusion surgery. Methods: We retrospectively studied 215 patients who underwent routine MRI following minimal invasive transforaminal lumbar interbody fusion (MI-TLIF) between 2020-01-01 and 2022-06-30. The patients were divided into SSH group (17 cases) and non-SSH group (198 cases) according to the occurrence of SSH. Univariate analysis and multivariate logistic regression analysis were performed to identify relevant risk factors that increase the risk of SSH postoperatively. Results: None of the patients presented with serious neurologic symptoms, such as lower extremity paralysis or cauda equina syndrome that required emergency hematoma debridement. SSH was found in 17 (7.9%) patients and non-SSH in 198 (92.1%). Factors affecting SSH were presence of hypertension, presence of diabetes and postoperative anticoagulant therapy. The significantly independent risk factor of postoperative SSH were diabetes (P = 0.008, OR: 6.988) and postoperative anticoagulant therapy (P = 0.003, OR: 8.808). Conclusions: SSH after MI-TLIF is not a rare condition, with generally no requirement of emergency evacuation. Comprehensive anti-symptomatic treatment could achieve satisfactory results. Diabetes mellitus and postoperative anticoagulant therapy are independent risk factors for SSH. Spine surgeons should hold applicability of the use of anticoagulants after lumbar surgery. [ABSTRACT FROM AUTHOR]

Background: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Unhealthy dietary habit is one of major risk factors of NAFLD. However, the associations between specific types of fish and meat consumption and NAFLD remain inconclusive. We explored the associations of fish and meat consumption with NAFLD risk in middle-aged and older Chinese. Methods: We collected information on 1,862 participants aged 50 years or older from Guangzhou Biobank Cohort Study in 2009 to 2010. Fish and meat consumption was assessed using a validated food-frequency questionnaire. NAFLD was diagnosed by ultrasound. Multivariable logistic regression was used to examine the associations of fish and meat consumption with the presence of NAFLD. Results: The average age was 61.0 (standard deviation = 6.5) years for the participants, 50.2% were women, and 37.2% were diagnosed with NAFLD. After adjusting for age, sex, education, family income, occupation, smoking status, drinking status, physical activity and several metabolic traits, compared with 0 serving/week (one serving = 50 g), fatty fish consumption of ≥ 3 servings/week showed higher odds of NAFLD (odds ratio (OR) and 95% confidence interval (CI): 1.64 (1.12, 2.39)). The highest (≥ 11 servings/week of red meat and poultry; ≥ 3 servings/week of processed meat) versus the lowest (0–3 servings/week of red meat and poultry; 0 serving/week of processed meat) consumption of all other types of meats, including red meat, poultry and processed meat, showed no association with NAFLD (1.17 (0.75, 1.81), 1.02 (0.42, 2.50) and 0.85 (0.50, 1.45), respectively). Aquatic and sea food, and red meat had negative indirect effects on NAFLD via systolic blood pressure and/or high-density lipoprotein cholesterol. Processed meat had positive indirect effects on NAFLD via body mass index, waist circumference, fasting plasma glucose and triglycerides. Conclusion: High consumption of fatty fish was associated with higher NAFLD risk. Our results, if causal, provide evidence that limiting consumption of fatty fish can be considered as part of NAFLD lifestyle prevention and treatment. [ABSTRACT FROM AUTHOR]

Background: To compare the triage performance of HPV viral loads reflected by cycle threshold values (CtV) from two different HPV testing assays: the PCR based Cobas4800 and the isothermal amplification based AmpFire assay. Methods: We used the data from a sub-study of The Chinese Multi-Center Screening Trial and analyzed the data of the cases positive in both Cobas4800 and AmpFire assays with recorded CtV. Spearman's correlation was applied to analyze the association between CtV from AmpFire and Cobas4800 assays, as well as the correlation between CtV and the histological lesion grades. The 50th percentile of CtV was used as the cutoff to construct triage algorithms for HPV-positive cases. McNemar's test was used to analyze the differences in sensitivity and specificity for detecting CIN2 + and CIN3 + in different triage algorithms. Results: Four hundred forty-six HPV positive women who had consistent HPV results from Cobas4800 and AmpFire in terms of the HPV genotype and reported Ct values were included in the analysis. The mean CtV of hrHPV tested by Cobas4800 and AmpFire were linear correlated. Direct association were showed between the severity of cervical lesions and the HPV viral loads reflected by CtV of hrHPV, HPV16, non-16/18 hrHPV and A9 group from both assays. HPV16/18 genotyping combined with low-CtV for non-16/18 hrHPV, especially A9 group, were demonstrated to be satisfactory in the sensitivity and specificity for detecting CIN2 + or CIN3 +. Conclusion: Ct value represented a good triage marker in both PCR-based and isothermal amplification HPV detection. [ABSTRACT FROM AUTHOR]

Background: As a member of the Janus kinase (JAK) family, which includes JAK1, JAK2 and JAK3, tyrosine kinase 2 (TYK2) plays an important role in signal transduction and immune system regulation. Moreover, it is also involved in the development of many types of inflammatory and autoimmune diseases, such as psoriasis and systemic lupus erythematosus (SLE). TYK2 is an attractive therapeutic target, and selective inhibition of TYK2 over other JAK family members is critical for the development of TYK2 small molecule inhibitors. However, targeting the catalytic region of the TYK2 ATP-binding site is a major challenge due to the high structural homology between the catalytic regions of the JAK family proteins. Results: In this study, we developed a novel small molecule inhibitor (QL-1200186) by targeting the pseudokinase regulatory domain (Janus homology 2, JH2) of the TYK2 protein. The binding sites of QL-1200186 were predicted and screened by molecular docking. The inhibitory effects on IFNα, IL-12 and IL-23 signaling were tested in cell lines, human peripheral blood cells and human whole blood. The pharmacokinetic (PK) and pharmacodynamic properties of QL-1200186 were verified in mice. QL-1200186 showed high affinity for TYK2 JH2 and had no apparent selectivity for the TYK2 and JAK homologous kinase domains; these effects were demonstrated using biochemical binding, signaling pathway transduction (JAK1/2/3) and off-target effect assays. More importantly, we revealed that QL-1200186 was functionally comparable and selectivity superior to two clinical-stage TYK2 inhibitors (BMS-986165 and NDI-034858) in vitro. In the PK studies, QL-1200186 exhibited excellent exposure, high bioavailability and low clearance rates in mice. Oral administration of QL-1200186 dose-dependently inhibited interferon-γ (IFNγ) production after interleukin-12 (IL-12) challenge and significantly ameliorated skin lesions in psoriatic mice. Conclusion: These findings suggest that QL-1200186 is a highly selective and potent inhibitor of TYK2. QL-1200186 could be an appealing clinical drug candidate for the treatment of psoriasis and other autoimmune diseases. -PuiM22MyQoZC1Ksigy-wD Video Abstract [ABSTRACT FROM AUTHOR]

Background: The cytochrome P450 (CYP) superfamily is the largest enzyme metabolism family in plants identified to date, and it is involved in many biological processes, including secondary metabolite biosynthesis, hormone metabolism and stress resistance. However, the P450 gene superfamily has not been well studied in pear (Pyrus spp.). Results: Here, the comprehensive identification and a comparative analysis of P450 superfamily members were conducted in cultivated and wild pear genomes. In total, 338, 299 and 419 P450 genes were identified in Chinese white pear, European pear and the wild pear, respectively. Based on the phylogenetic analyses, pear P450 genes were divided into ten clans, comprising 48 families. The motif and gene structure analyses further supported this classification. The expansion of the pear P450 gene family was attributed to whole-genome and single-gene duplication events. Several P450 gene clusters were detected, which have resulted from tandem and proximal duplications. Purifying selection was the major force imposed on the long-term evolution of P450 genes. Gene dosage balance, subfunctionalization and neofunctionalization jointly drove the retention and functional diversification of P450 gene pairs. Based on the association analysis between transcriptome expression profiles and flavonoid content during fruit development, three candidate genes were identified as being closely associated with the flavonoid biosynthesis, and the expression of one gene was further verified using qRT-PCR and its function was validated through transient transformation in pear fruit. Conclusions: The study results provide insights into the evolution and biological functions of P450 genes in pear. [ABSTRACT FROM AUTHOR]

Background: Cervical stiffness, coronal imbalance and limited hip movement all play crucial roles in designing the corrective surgery for ankylosing spondylitis-related thoracolumbar kyphosis (AS-TLK). However, a comprehensive classification and tailored strategies for directing clinical work are lacking. This study aims to investigate the types and surgical strategies for AS-TLK that consider cervical stiffness, coronal imbalance and hip involvement as the key factors. Methods: 25 consecutive AS-TLK patients were divided into three types according to their accompanying features: Type I: with a flexible cervical spine; Type IIA: with a stiff cervical spine; Type IIB: with coronal imbalance; Type IIC: with limited hip movement. Type III is the mixed type with at least two conditions of Type II. Individual strategies were given correspondingly. Spinal-pelvic-femoral parameters were measured, Scoliosis Research Society outcome instrument-22 (SRS-22) was used and complications were recorded and analysed. Results: All patients (Type I 10, Type II 8 and Type III 7) underwent surgery successfully. 13 cases with 16 complications were recorded and cured. The patients were followed up for 24–65 months with an average of 33.0 ± 9.6 months. Both the sagittal and coronal parameters were corrected and decreased significantly (all, p < 0.05). SRS-22 scores showed a satisfactory outcome. Conclusion: Thoracolumbar kyphosis secondary to ankylosing spondylitis are complex and variable. Considering the factors of cervical stiffness, coronal imbalance and hip involvement assists in making decisions individually and achieving a desired surgical result. [ABSTRACT FROM AUTHOR]

Background: Gut microbiota plays a significant role in host survival, health, and diseases; however, compared to other livestock, research on the gut microbiome of donkeys is limited. Results: In this study, a total of 30 donkey samples of rectal contents from six regions, including Shigatse, Changdu, Yunnan, Xinjiang, Qinghai, and Dezhou, were collected for metagenomic sequencing. The results of the species annotation revealed that the dominant phyla were Firmicutes and Bacteroidetes, and the dominant genera were Bacteroides, unclassified_o_Clostridiales (short for Clostridiales) and unclassified_f_Lachnospiraceae (short for Lachnospiraceae). The dominant phyla, genera and key discriminators were Bacteroidetes, Clostridiales and Bacteroidetes in Tibet donkeys (Shigatse); Firmicutes, Clostridiales and Clostridiales in Tibet donkeys (Changdu); Firmicutes, Fibrobacter and Tenericutes in Qinghai donkeys; Firmicutes, Clostridiales and Negativicutes in Yunnan donkeys; Firmicutes, Fibrobacter and Fibrobacteres in Xinjiang donkeys; Firmicutes, Clostridiales and Firmicutes in Dezhou donkeys. In the functional annotation, it was mainly enriched in the glycolysis and gluconeogenesis of carbohydrate metabolism, and the abundance was the highest in Dezhou donkeys. These results combined with altitude correlation analysis demonstrated that donkeys in the Dezhou region exhibited strong glucose-conversion ability, those in the Shigatse region exhibited strong glucose metabolism and utilization ability, those in the Changdu region exhibited a strong microbial metabolic function, and those in the Xinjiang region exhibited the strongest ability to decompose cellulose and hemicellulose. Conclusion: According to published literature, this is the first study to construct a dataset with multi-regional donkey breeds. Our study revealed the differences in the composition and function of gut microbes in donkeys from different geographic regions and environmental settings and is valuable for donkey gut microbiome research. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide, and is characterized by insidious onset, rapid progression, and poor prognosis. Immunotherapy is a first-line treatment for advanced HCC. The identification of immune-related prognostic markers may be an effective strategy to predict and improve clinical response rate of immunotherapy. Methods: The DESeq2, edgeR, and limma R packages were used to compare the transcriptomes of HCC with different prognoses. Cancer-related databases such as UALCAN, TNMplot, GEPIA, muttarget and Human Protein Atlas (HPA), and the Kaplan–Meier Plotter platform were used to analyze the relationship between CLDN18 and the clinical characteristics, as well as prognosis of HCC. The co-expressed genes of CLDN18 were obtained from LinkedOmics platform, and GO functional enrichment and KEGG pathway analysis were performed. The CIBERSORT, TIMER, Timer 2.0 and TISIDB algorithms were used to analyze immune infiltration. Results: CLDN18 was differentially expressed in HCC patients with different prognoses, and its expression level in PBMC was positively correlated with the stage of BCLC. In addition, CLDN18 was significantly overexpressed in HCC tumor tissues compared to adjacent non-tumor tissues, which was consistent with PBMC sequencing results and immunohistochemical data from human protein profiles. CLDN18 was also positively correlated with HCC staging and grading, and high expression levels of CLDN18 predicted shorter overall survival. Functional annotation of CLDN18 in HCC revealed enrichment of the cellular senescence and protein activation cascade, along with biological processes such as cell cycle, inflammatory response, and cellular ketone metabolism. In addition, CLDN18 was also associated with tumor infiltrating immune cells, suppressive immune cell markers, T lymphocyte depletion and activation of HCC, and low expression of CLDN18 was associated with higher CD8 + T cell infiltration and better survival rates. Conclusions: CLDN18 is a potential prognostic marker and immunotherapeutic target for HCC. [ABSTRACT FROM AUTHOR]

Objective: Non-suicidal self-injury (NSSI) behaviors are prevalent in adolescents and have adverse effects on physical and mental health. However, little is known about the relationship between NSSI and alexithymia, or the underlying mechanisms that could explain this relationship. This study aimed to elucidate the current status of NSSI in adolescent depression, and analyze the relationship between alexithymia, loneliness, resilience, and adolescent depression with NSSI, so as to provide a theoretical basis for psychotherapeutic interventions. Method: The study sample involved inpatients and outpatients from 12 hospitals across China and adolescents with depression who met the DSM-5 diagnostic criteria for depression episode. The following scales were used: The Functional Assessment of Self-Mutilation, Toronto Alexithymia Scale, UCLA Loneliness Scale, and Connor Davidson Resilience Scale. Results: The detection rate of NSSI in adolescents with depression from 2021.01.01-2022.01.01 was 76.06% (1782/2343). Spearman's correlation analysis revealed a significant correlation between alexithymia, loneliness, resilience and NSSI in depressed adolescents, and the results of the non-parametric test showed that the differences between the two groups for each factor were statistically significant. Binary logistic regression results showed that alexithymia (B = 0.023, p = 0.003, OR = 1.023, 95% CI: 1.008–1.038) and depression (B = 0.045, p < 0.001, OR = 1.046, 95% CI: 1.026–1.066) are risk factors for NSSI, resilience (B = − 0.052, p < 0.001, OR = 0.949, 95% CI: 0.935 − 0.964) is a protective factor for NSSI. Alexithymia directly predicted NSSI and also indirectly influenced NSSI through the mediated effect of resilience. Loneliness moderates the first half of the path of this mediated model. Conclusion: The present study confirms a moderated mediation effect: Alexithymia can have an impact on NSSI behaviors in depressed adolescents through the mediating role of resilience. Loneliness, as a moderating variable, moderated the first half of the pathway of the mediating model. We discuss perspectives for future research and interventions based on the findings of the study. [ABSTRACT FROM AUTHOR]

Background: Although observational studies have established some socioeconomic traits to be independent risk factors for pelvic organ prolapse (POP), they can not infer causality since they are easily biased by confounding factors and reverse causality. Moreover, it remains ambiguous which one or several of socioeconomic traits play predominant roles in the associations with POP risk. Mendelian randomization (MR) overcomes these biases and can even determine one or several socioeconomic traits predominantly accounting for the associations. Objective: We conducted a multivariable Mendelian randomization (MVMR) analysis to disentangle whether one or more of five categories of socioeconomic traits, "age at which full-time education completed (abbreviated as "EA")", "job involving heavy manual or physical work ("heavy work")", "average total household income before tax (income)", "Townsend deprivation index at recruitment (TDI)", and "leisure/social activities" exerted independent and predominant effects on POP risk. Methods: We first screened single-nucleotide polymorphisms (SNPs) as proxies for five individual socioeconomic traits and female genital prolapse (FGP, approximate surrogate for POP due to no GWASs for POP) to conduct Univariable Mendelian randomization (UVMR) analyses to estimate causal associations of five socioeconomic traits with FGP risk using IVW method as major analysis. Additionally, we conducted heterogeneity, pleiotropy, and sensitivity analysis to assess the robustness of our results. Then, we harvested a combination of SNPs as an integrated proxy for the five socioeconomic traits to perform a MVMR analysis based on IVW MVMR model. Results: UVMR analyses based on IVW method identified causal effect of EA (OR 0.759, 95%CI 0.629–0.916, p = 0.004), but denied that of the other five traits on FGP risk (all p > 0.05). Heterogeneity analyses, pleiotropy analyses, "leave-one-out" sensitivity analyses and MR-PRESSO adjustments did not detect heterogeneity, pleiotropic effects, or result fluctuation by outlying SNPs in the effect estimates of six socioeconomic traits on FGP risk (all p > 0.05). Further, MVMR analyses determined a predominant role of EA playing in the associations of socioeconomic traits with FGP risk based on both MVMR Model 1 (OR 0.842, 95%CI 0.744–0.953, p = 0.006) and Model 2 (OR 0.857, 95%CI 0.759–0.967, p = 0.012). Conclusion: Our UVMR and MVMR analyses provided genetic evidence that one socioeconomic trait, lower educational attainment, is associated with risk of female genital prolapse, and even independently and predominantly accounts for the associations of socioeconomic traits with risk of female genital prolapse. [ABSTRACT FROM AUTHOR]

Background: This study aimed to observe the potential impact of known cuproptosis-related genes (CRGs) on triple negative breast cancer (TNBC) development, as well as their associated molecular mechanisms, immune infiltration mechanisms and potential therapeutic agents. Results: Based on the Cox Proportional Hazard Model, 11 CRGs may be especially important in TNBC development and progression (considered as the Key-TNBC-CRGs). The expression of several Key-TNBC-CRGs (e.g., ATP7A, PIK3CA, LIAS, and LIPT) are associated with common mutations. The SCNA variation of 11 Key-TNBC-CRGs are related to differences immune infiltration profiles. In particular, depletion of ATP7A, ATP7B, CLS, LIAS, and SCL31A1 and while high amplification of NLRP3 and LIPT2 are correlated with decreased immune infiltration. In our Cox proportional hazards regression model, there is a significant difference in the overall survival between high-risk and low-risk groups. The HR in the high-risk group is 3.891 versus the low-risk group. And this model has a satisfactory performance in Prediction of 5–15-year survival, in particular in the 10-year survival (AUC = 0.836). Finally, we discovered some potential drugs for TNBC treatment based on the strategy of targeting 11 Key-TNBC-CRGs, such as Dasatinib combined with ABT-737, Erastin or Methotrexate, and Docetaxel/Ispinesib combination. Conclusion: In conclusion, CRGs may play important roles in TNBC development, and they can impact tumor immune microenvironment and patient survival. The Key-TNBC-CRGs interact mutually and can be influenced by common BC-related mutations. Additionally, we established a 11-gene risk model with a robust performance in prediction of 5–15-year survival. As well, some new drugs are proposed potentially effective in TNBC based on the CRG strategy. [ABSTRACT FROM AUTHOR]

Background: Neurosurgical patients represent a high-risk population for postoperative pulmonary complications (PPCs). A lower intraoperative driving pressure (DP) is related to a reduction in postoperative pulmonary complications. We hypothesized that driving pressure-guided ventilation during supratentorial craniotomy might lead to a more homogeneous gas distribution in the lung postoperatively. Methods: This was a randomized trial conducted between June 2020 and July 2021 at Beijing Tiantan Hospital. Fifty-three patients undergoing supratentorial craniotomy were randomly divided into the titration group or control group at a ratio of 1 to 1. The control group received 5 cmH2O PEEP, and the titration group received individualized PEEP targeting the lowest DP. The primary outcome was the global inhomogeneity index (GI) immediately after extubation obtained by electrical impedance tomography (EIT). The secondary outcomes were lung ultrasonography scores (LUSs), respiratory system compliance, the ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO2/FiO2) and PPCs within 3 days postoperatively. Results: Fifty-one patients were included in the analysis. The median (IQR [range]) DP in the titration group versus the control group was 10 (9–12 [7–13]) cmH2O vs. 11 (10–12 [7–13]) cmH2O, respectively (P = 0.040). The GI tract did not differ between groups immediately after extubation (P = 0.080). The LUSS was significantly lower in the titration group than in the control group immediately after tracheal extubation (1 [0–3] vs. 3 [1–6], P = 0.045). The compliance in the titration group was higher than that in the control group at 1 h after intubation (48 [42–54] vs. 41 [37–46] ml·cmH2O-1, P = 0.011) and at the end of surgery (46 [42–51] vs. 41 [37–44] ml·cmH2O-1, P = 0.029). The PaO2/FiO2 ratio was not significantly different between groups in terms of the ventilation protocol (P = 0.117). At the 3-day follow-up, no postoperative pulmonary complications occurred in either group. Conclusions: Driving pressure-guided ventilation during supratentorial craniotomy did not contribute to postoperative homogeneous aeration, but it may lead to improved respiratory compliance and lower lung ultrasonography scores. Clinical trial registration: ClinicalTrials.gov NCT04421976. [ABSTRACT FROM AUTHOR]

Background: Although observational studies have established some socioeconomic traits to be independent risk factors for pelvic organ prolapse (POP), they can not infer causality since they are easily biased by confounding factors and reverse causality. Moreover, it remains ambiguous which one or several of socioeconomic traits play predominant roles in the associations with POP risk. Mendelian randomization (MR) overcomes these biases and can even determine one or several socioeconomic traits predominantly accounting for the associations. Objective: We conducted a multivariable Mendelian randomization (MVMR) analysis to disentangle whether one or more of five categories of socioeconomic traits, "age at which full-time education completed (abbreviated as "EA")", "job involving heavy manual or physical work ("heavy work")", "average total household income before tax (income)", "Townsend deprivation index at recruitment (TDI)", and "leisure/social activities" exerted independent and predominant effects on POP risk. Methods: We first screened single-nucleotide polymorphisms (SNPs) as proxies for five individual socioeconomic traits and female genital prolapse (FGP, approximate surrogate for POP due to no GWASs for POP) to conduct Univariable Mendelian randomization (UVMR) analyses to estimate causal associations of five socioeconomic traits with FGP risk using IVW method as major analysis. Additionally, we conducted heterogeneity, pleiotropy, and sensitivity analysis to assess the robustness of our results. Then, we harvested a combination of SNPs as an integrated proxy for the five socioeconomic traits to perform a MVMR analysis based on IVW MVMR model. Results: UVMR analyses based on IVW method identified causal effect of EA (OR 0.759, 95%CI 0.629–0.916, p = 0.004), but denied that of the other five traits on FGP risk (all p > 0.05). Heterogeneity analyses, pleiotropy analyses, "leave-one-out" sensitivity analyses and MR-PRESSO adjustments did not detect heterogeneity, pleiotropic effects, or result fluctuation by outlying SNPs in the effect estimates of six socioeconomic traits on FGP risk (all p > 0.05). Further, MVMR analyses determined a predominant role of EA playing in the associations of socioeconomic traits with FGP risk based on both MVMR Model 1 (OR 0.842, 95%CI 0.744–0.953, p = 0.006) and Model 2 (OR 0.857, 95%CI 0.759–0.967, p = 0.012). Conclusion: Our UVMR and MVMR analyses provided genetic evidence that one socioeconomic trait, lower educational attainment, is associated with risk of female genital prolapse, and even independently and predominantly accounts for the associations of socioeconomic traits with risk of female genital prolapse. [ABSTRACT FROM AUTHOR]

Background: Neurosurgical patients represent a high-risk population for postoperative pulmonary complications (PPCs). A lower intraoperative driving pressure (DP) is related to a reduction in postoperative pulmonary complications. We hypothesized that driving pressure-guided ventilation during supratentorial craniotomy might lead to a more homogeneous gas distribution in the lung postoperatively. Methods: This was a randomized trial conducted between June 2020 and July 2021 at Beijing Tiantan Hospital. Fifty-three patients undergoing supratentorial craniotomy were randomly divided into the titration group or control group at a ratio of 1 to 1. The control group received 5 cmH2O PEEP, and the titration group received individualized PEEP targeting the lowest DP. The primary outcome was the global inhomogeneity index (GI) immediately after extubation obtained by electrical impedance tomography (EIT). The secondary outcomes were lung ultrasonography scores (LUSs), respiratory system compliance, the ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO2/FiO2) and PPCs within 3 days postoperatively. Results: Fifty-one patients were included in the analysis. The median (IQR [range]) DP in the titration group versus the control group was 10 (9–12 [7–13]) cmH2O vs. 11 (10–12 [7–13]) cmH2O, respectively (P = 0.040). The GI tract did not differ between groups immediately after extubation (P = 0.080). The LUSS was significantly lower in the titration group than in the control group immediately after tracheal extubation (1 [0–3] vs. 3 [1–6], P = 0.045). The compliance in the titration group was higher than that in the control group at 1 h after intubation (48 [42–54] vs. 41 [37–46] ml·cmH2O-1, P = 0.011) and at the end of surgery (46 [42–51] vs. 41 [37–44] ml·cmH2O-1, P = 0.029). The PaO2/FiO2 ratio was not significantly different between groups in terms of the ventilation protocol (P = 0.117). At the 3-day follow-up, no postoperative pulmonary complications occurred in either group. Conclusions: Driving pressure-guided ventilation during supratentorial craniotomy did not contribute to postoperative homogeneous aeration, but it may lead to improved respiratory compliance and lower lung ultrasonography scores. Clinical trial registration: ClinicalTrials.gov NCT04421976. [ABSTRACT FROM AUTHOR]

Background: Growing evidence has demonstrated that DNA methylation (DNAm) plays an important role in Alzheimer's disease (AD) and that DNAm differences can be detected in the blood of AD subjects. Most studies have correlated blood DNAm with the clinical diagnosis of AD in living individuals. However, as the pathophysiological process of AD can begin many years before the onset of clinical symptoms, there is often disagreement between neuropathology in the brain and clinical phenotypes. Therefore, blood DNAm associated with AD neuropathology, rather than with clinical data, would provide more relevant information on AD pathogenesis. Methods: We performed a comprehensive analysis to identify blood DNAm associated with cerebrospinal fluid (CSF) pathological biomarkers for AD. Our study included matched samples of whole blood DNA methylation, CSF Aβ42, phosphorylated tau181 (pTau181), and total tau (tTau) biomarkers data, measured on the same subjects and at the same clinical visits from a total of 202 subjects (123 CN or cognitively normal, 79 AD) in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. To validate our findings, we also examined the association between premortem blood DNAm and postmortem brain neuropathology measured on a group of 69 subjects in the London dataset. Results: We identified a number of novel associations between blood DNAm and CSF biomarkers, demonstrating that changes in pathological processes in the CSF are reflected in the blood epigenome. Overall, the CSF biomarker-associated DNAm is relatively distinct in CN and AD subjects, highlighting the importance of analyzing omics data measured on cognitively normal subjects (which includes preclinical AD subjects) to identify diagnostic biomarkers, and considering disease stages in the development and testing of AD treatment strategies. Moreover, our analysis revealed biological processes associated with early brain impairment relevant to AD are marked by DNAm in the blood, and blood DNAm at several CpGs in the DMR on HOXA5 gene are associated with pTau181 in the CSF, as well as tau-pathology and DNAm in the brain, nominating DNAm at this locus as a promising candidate AD biomarker. Conclusions: Our study provides a valuable resource for future mechanistic and biomarker studies of DNAm in AD. [ABSTRACT FROM AUTHOR]

Cardiac malignancies in children are extremely rare and they with hypereosinophilia are rather relatively uncommon. The majority of individuals may survive over the long term even with heart tumors provided they don't have any significant symptoms and their hemodynamics are unaffected. But we should nevertheless be aware of them, especially when they are coupled with persistent hypereosinophilia and the development of a hemodynamic anomaly. The case of a malignant heart tumor with hypereosinophilia in a 13-year-old girl is presented in this paper. She exhibited an echocardiographic deficit and a heart murmur. Additionally, it was difficult to treat her hypereosinophilia. Nevertheless, it was resolved the day after the operation. We presume that there is a certain relationship between them. This study gives clinicians a wide range of options for analyzing the connections between malignancy and hypereosinophilia. [ABSTRACT FROM AUTHOR]

Purpose: Causative factors of breast cancer include infections, such as Epstein–Barr virus (EBV) infection. The aim of this study was to analyze the clinicopathological features of EBV-positive (IBC) and determine if EBV affects programmed cell death receptor 1 (PD-1)/PD ligand 1 (PD-L1) expression in IBC, similar to other EBV-infected tumors with PD-L1/PD-1 expression. Methods: We collected 140 samples of IBC tissues and 25 samples of adjacent tissues. All patients were followed-up by telephone from the day of surgery to December 2020. Chromogenic in-situ hybridization was performed to evaluate EBV-encoded RNA (EBER). Immunohistochemistry was performed to evaluate PD-L1 and PD-1 expressions. The correlation between PD1/PDL1 expression and clinicopathological features was also analyzed. Results: EBER was detected in 57 of 140 (40.7%) IBC tissues and not detected in any adjacent tissue (P < 0.05). Clinicopathologic features of patients were consistent with EBV-associated IBC. EBV infection was correlated with the mass size, menopausal status, axillary lymph node metastasis, vascular invasion, Ki-67 index, clinical stage, and estrogen receptor and progesterone receptor expressions (all P < 0.05), but not with the histological type, invasive ductal carcinoma histological grade, or human epidermal growth factor receptor 2 (HER2) expression (all P > 0.05). The positive rate of PD-1/PD-L1 expression was higher in the EBV-positive group than in the EBV-negative group (P < 0.05). The Kaplan–Meier univariate survival analysis showed that EBV was associated with poor disease-free survival and overall survival in patients with IBC. PD-L1/PD-1 expression could predict a poor prognosis. Conclusions: In this study, clinicopathologic characteristics of patients were consistent with EBV-infected IBC. Patients with EBV-positive breast cancer were more likely to have elevated PD-1/PDL-1 expression compared to those with EBV-negative breast cancer. This finding could serve as a basis to explore therapeutic targets, particularly immunotherapy, for patients with IBC. [ABSTRACT FROM AUTHOR]

Purpose: Proximal humerus fractures (PHFs) are common. With the development of locking plates, open reduction and internal fixation (ORIF) of the proximal humerus can provide excellent clinical outcomes. The quality of fracture reduction is crucial in the locking plate fixation of proximal humeral fractures. The purpose of this study was to determine the impact of 3-dimensional (3D) printing technology and computer virtual technology assisted preoperative simulation on the reduction quality and clinical outcomes of 3-part and 4-part proximal humeral fractures. Method: A retrospective comparative analysis of 3-part and 4-part PHFs undergoing open reduction internal fixation was performed. Patients were divided into 2 groups according to whether computer virtual technology and 3D printed technology were used for preoperative simulation: the simulation group and the conventional group. Operative time, intraoperative bleeding, hospital stay, quality of fracture reduction, Constant scores, American Society for Shoulder and Elbow Surgery (ASES) scores, shoulder range of motion, complications, and revision surgeries were assessed. Results: This study included 67 patients (58.3%) in the conventional group and 48 patients (41.7%) in the simulation group. The patient demographics and fracture characteristics were comparable in these groups. Compared with the conventional group, the simulation group had shorter operation time and less intraoperative bleeding (P < 0.001, both). Immediate postoperative assessment of fracture reduction showed a higher incidence of greater tuberosity cranialization of < 5 mm, neck-shaft angle of 120° to 150°, and head shaft displacement of < 5 mm in the simulation group. The incidence of good reduction was 2.6 times higher in the simulation group than in the conventional group (95% CI, 1.2–5.8). At the final follow-up, the chance of forward flexion > 120° (OR 5.8, 95% CI 1.8–18.0) and mean constant score of > 65 (OR 3.4, 95% CI 1.5–7.4) was higher in the simulation group than the conventional group, as well as a lower incidence of complications in the simulation group was obtained (OR 0.2, 95% CI 0.1–0.6). Conclusions: This study identified that preoperative simulation assisted by computer virtual technology and 3D printed technology can improve reduction quality and clinical outcomes in treatment of 3-part and 4-part PHFs. [ABSTRACT FROM AUTHOR]

Study design: Retrospective cohort study. Objective: The purpose of this study was to evaluate the reliability of modified classification system of migrated nucleus pulposus and its clinical application value. Methods: We retrieved 1000 lumbar MRI of different patients in Hangzhou Hospital of Traditional Chinese Medicine from January 2016 to December 2019 for interpretation, and screened 105 migrated lumbar MRI for inclusion in the study. Three spinal surgeons made classification according to the modified classification method. Two weeks later, the sorting data of the patients were shuffled and the classification was judged by three doctors again. The consistency and repeatability of the improved classification were evaluated by Kappa coefficient. The general data of the included patients were collected. The patients were followed up for 2 years, and the risk factors of surgical treatment of patients with migrated lumbar disc herniation were analyzed. The treatment plan, surgical approach, operation time, VAS score, ODI score and other relevant data of the included patients were collected to evaluate the guiding effect of the classification system on clinical practice. Results: In this study, the incidence of migrated lumbar disc herniation was about 10.5%, and most of the patients were male. Patients with higher BMI are more likely to develop this disease. Our study confirmed that the modified classification has moderate to high confidence. During the 2-year follow-up period, 66 patients (62.9%) were treated conservatively, and the patients with conservative treatment were mainly A2 and B2 type (59.1%). Thirty-nine patients (37.1%) underwent surgical treatment. The patients recovered well after operation, and the low back pain and ODI index were significantly improved at 1 year after operation (P < 0.05). We suggest that type A1 and B1 migrated nucleus pulposus can be removed by posterior approach. For type A2, B2, C1, C2, the lateral approach is recommended to remove the nucleus pulposus directly. Logistic regression and ROC analysis showed that disease duration (≥ 1 year) and BMI (≥ 24) maybe were risk factors for surgical treatment of patients with migrated lumbar disc herniation. Conclusion: The modified classification has good reliability. In the current study, the experience level of spine surgeons does not affect the reliability of the classification system. Our study confirmed that this classification has a good reference value for guiding the treatment plan and the choice of surgical approach. [ABSTRACT FROM AUTHOR]

Lymph node metastasis (LNM) is an important factor affecting the prognosis of patients with gastric adenocarcinoma (STAD), which is the most common malignancy of the human digestive system. Current detection techniques have limited sensitivity and specificity, and there is a lack of effective biomarkers to screen for LNM. Therefore, it is critical to screen for biomarkers that predict LNM in STAD. Gene expression differential analysis (false discovery rate < 0.05, |log2Fold change| ≥1.5) was performed on 102 LNM samples, 224 non-LNM samples, and 29 normal gastric tissue samples from The Cancer Genome Atlas (TCGA) STAD dataset, and 269 LNM-specific genes (DEGs) were obtained. Enrichment analysis showed that LNM-specific genes functioned mainly in cytokine-cytokine receptor interactions, calcium signaling, and other pathways. Ten DEGs significantly associated with overall survival in STAD patients were screened by multivariate Cox regression, and an LNM-based 10-mRNA prognostic signature was established (Logrank P < 0.0001). This 10-mRNA signature was well predicted in both the TCGA training set and the Gene Expression Omnibus validation dataset (GSE84437) and was associated with survival in patients with LNM or advanced-stage STAD. Using Kaplan-Meier survival, receiver operating characteristic curve, C-index analysis, and decision curve analysis, the 10-mRNA signature was found to be a more effective predictor of prognosis in STAD patients than the other two reported models (P < 0.0005). Protein-protein interaction network and gene set enrichment analysis of the 10-mRNA signature revealed that the signature may affect the expression of multiple biological pathways and related genes. Finally, the expression levels of prognostic genes in STAD tissues and cell lines were verified using qRT-PCR, Western blot, and the Human Protein Atlas database. Taken together, the prognostic signature constructed in this study may become an indicator for clinical prognostic assessment of LNM-STAD and provide a new strategy for future targeted therapy. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the clinical efficacy of unilateral wiltse transforaminal lumbar interbody fusion (TLIF) combined with unilateral nail bar system fixation for single-level lumbar degenerative diseases with the assistance of a new automatic retraction device in a retrospective comparative study. Methods: A total of 46 patients with single-level lumbar degenerative diseases from September 2019 to December 2021 were retrospectively analyzed. Bilateral nail bar fixation with bullet-type fusion cage (ctrl group, 24 patients) and unilateral nail bar fixation on the affected side with kidney-like fusion cage (study group, 22 patients) were performed in TLIF via wiltse intermuscular approach assisted by a new automatic retraction device. The differences in intraoperative blood loss, operative time, intraoperative fluoroscopy time, postoperative drainage, bed rest, VAS score, ODI score, JOA score, serological creatine kinase (CK), the proportion of multifidus atrophy, modified Pfirrmann classification and intervertebral space height of the upper intervertebral disc were compared between the two groups based on clinical and imaging data. Results: Intraoperative bleeding, operative time, and postoperative drainage were significantly lower in study group than ctrl group, and there were no significant differences in bed rest time and intraoperative fluoroscopy time between them. In addition, there was no statistical difference in CK between the study group and the ctrl group at 24 and 48 h postoperatively. Moreover, no statistically significant difference was found in VAS score of low back pain, VAS score of lower limb pain, ODI index, modified Pfirrmann classification of the upper intervertebral disc and intervertebral space height of the upper intervertebral disc between two groups. The atrophy ratio of multifidus muscle was significantly lower in the study group. Conclusion: The new automatic retraction device assisted unilateral TLIF surgery with wiltse approach combined with unilateral nail bar fixation is a simple, effective and easy to master surgical method for single-level lumbar degenerative diseases. [ABSTRACT FROM AUTHOR]

Background: Tumor micronecrosis is a histopathological feature predicting poor prognosis in patients with hepatocellular carcinoma (HCC) who underwent liver resection. However, the role of tumor micronecrosis in liver transplantation remains unclear. Methods: We retrospectively reviewed patients with HCC who underwent liver transplantation between January 2015 and December 2021 at our center. We then classified them into micronecrosis(−) and micronecrosis(+) groups and compared their recurrence-free survival (RFS) and overall survival (OS). We identified independent prognostic factors using Cox regression analysis and calculated the area under the receiver operating characteristic curve (AUC) to evaluate the predictive value of RFS for patients with HCC after liver transplantation. Results: A total of 370 cases with evaluable histological sections were included. Patients of the micronecrosis(+) group had a significantly shorter RFS than those of the micronecrosis(−) group (P = 0.037). Shorter RFS and OS were observed in micronecrosis(+) patients without bridging treatments before liver transplantation (P = 0.002 and P = 0.007), while no differences were detected in those with preoperative antitumor therapies that could cause iatrogenic tumor necrosis. Tumor micronecrosis improved the AUC of Milan criteria (0.77–0.79), the model for end-stage liver disease score (0.70–0.76), and serum alpha-fetoprotein (0.63–0.71) for the prediction of prognosis after liver transplantation. Conclusion: Patients with HCC with tumor micronecrosis suffer from a worse prognosis than those without this feature. Tumor micronecrosis can help predict RFS after liver transplantation. Therefore, patients with HCC with tumor micronecrosis should be treated with adjuvant therapy and closely followed after liver transplantation. Clinical trials registration: Not Applicable. [ABSTRACT FROM AUTHOR]

Background: Certain types of human papillomavirus (HPV) induce long-lasting infections that cause cervical cancer. This study evaluated the prevalence of HPV infections and the distribution of their genotypes among clinic patients and healthy women in Beijing, China. Methods: Cervical specimens were collected from 12,100 patients and 1176 subjects who underwent physical examinations at Dongzhimen Hospital, Beijing University of Chinese Medicine, between March 2016 and September 2020. HPV genotyping was performed using commercial kits designed to detect 15 high-risk and 2 low-risk HPV genotypes. Results: There was a higher overall prevalence of HPV among the clinic patients (21.0%) than among the healthy women (11.9%). The most common HPV genotypes among the patients were: HPV-52 (5.4%), HPV-16 (3.4%), HPV-58 (3.2%), HPV-51 (2.6%), HPV-39 (2.0%), HPV-56 (2.0%), and HPV-66 (2.0%). Among the healthy women: HPV-52 (3.0%), HPV-51 (1.8%), HPV-58 (1.6%), HPV-66 (1.5%), HPV-16 (1.2%), HPV-56 (1.2%), and HPV-18 (1.1%). Multiple HPVs were detected in 29.1% of the gynecological outpatients and in 23.6% of the women receiving physical examinations. The most common pairs of HPV types detected were HPV-52 and HPV-16 in the clinic patients, and HPV-52 and HPV-56 in the healthy women. Age-specific HPV positivity and peak prevalence were observed among the individuals in both groups for women aged less than 25 years and those between 61 and 65 years of age. Conclusions: Our results provide current estimates of HPV prevalence and genotypes in the Beijing region. The epidemiological characteristics observed also provide a reference for the development of cervical cancer screening strategies and selection of HPV vaccine antigen targets for this region. A comparison of these HPV prevalence data with those from other regions suggests that regional vaccines may be an important direction for future research. [ABSTRACT FROM AUTHOR]

Background: Using nanotechnology to improve the efficiency of tumor treatment represents a major research interest in recent years. However, there are paradoxes and obstacles in using a single nanoparticle to fulfill all the requirements of complex tumor treatment. Results: In this paper, a programmed-triggered nanoplatform (APP NPs), which is sequentially responsive to light and hypoxia, is rationally integrated for photoacoustic (PA) imaging-guided synergistic cancer photo-chemotherapy. The nanoplatform is constructed by in situ hybridization of dopamine monomer in the skeleton of PCN-224 and loading prodrug banoxantrone (AQ4N). Upon first-stage irradiation with a 660 nm laser, cellular internalization was effectively promoted by a photosensitizer-mediated photochemical effect. Furthermore, under second-stage irradiation, APP NPs exhibit a notably high photothermal conversion efficiency and sufficient reactive oxygen species (ROS) production for photothermal therapy (PTT) and photodynamic therapy (PDT), respectively, which not only triggers rapid intercellular drug release but also consequently aggravates tumor hypoxia levels, and aggravated hypoxia can further active the cytotoxicity of AQ4N for chemotherapy. Both in vitro and in vivo studies confirm that the dual-stage light guided photo-chemotherapy strategy exhibits a greatly enhanced anticancer effects and superior therapeutic safety. Conclusion: This work represents a versatile strategy to construct a dual-stage light induced PDT/PTT and hypoxia-activated chemotherapy nanoplatform and will be promising for the development of multistimuli-responsive nanosystems with programmable functions for precise cancer therapy. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD) is a neurodegenerative disease and is clinically characterized by a series of motor symptoms (MS) and nonmotor symptoms (NMS). NMS often appear before MS, while cognitive impairment mostly occurs within a few years after the diagnosis of PD. Therefore, we aimed to predict the risk factors for cognitive impairment (CI) in PD patients based on transcranial sonography, clinical symptoms, and demographic characteristics. Methods: Based on the occurrence time of CI, a total of 172 PD patients were divided into non-CI (N-CI, n = 48), CI at the first treatment (F-CI, n = 58), and CI at the last treatment (L-CI, n = 66) groups. Clinical data (including MS and NMS) and ultrasonic data of all patients at the first treatment and the last treatment were collected retrospectively. Independent samples t tests were used to compare continuous data, and chi-square tests were used to compare categorical data. The risk factors for CI and Parkinson's disease dementia were identified by logistic regression analysis, and an ROC curve was established to explore the diagnostic efficacy. Results: 1) The age of onset, first treatment and smoking history of CI patients were significantly different from those of N-CI patients. When age of first treatment ≥61 years was considered the boundary value to diagnose CI, the sensitivity and specificity were 77.40 and 66.70%, respectively. 2) The severity of depression was significantly different between F-CI and N-CI patients at the first treatment, while the cumulative and new or aggravated memory deficit was significantly different between the L-CI and N-CI patients at the last treatment. 3) There was a significant difference in TCS grading between the first and last treatment in L-CI patients. 4) Depression, sexual dysfunction, and olfactory dysfunction in NMS were independent risk factors for CI during the last treatment. 5) The sensitivity and specificity of predicting CI in PD patients were 81.80 and 64.60%, respectively. Conclusions: PD patients with CI were older, and most of them had a history of smoking. Furthermore, there was good diagnostic efficiency for predicting CI in PD via TCS combined with clinical characteristics (especially NMS). [ABSTRACT FROM AUTHOR]

Background: Several treatments induce liver hypertrophy for patients with liver malignancies but insufficient future liver remnant (FLR). Herein, the aim of this study is to compare the efficacy and safety of existing surgical techniques using network meta-analysis (NMA). Methods: We searched PubMed, Web of Science, and Cochrane Library from databases for abstracts and full-text articles published from database inception through Feb 2022. The primary outcome was the efficacy of different procedures, including standardized FLR (sFLR) increase, time to hepatectomy, resection rate, and R0 resection margin. The secondary outcome was the safety of different treatments, including the rate of Clavien-Dindo≥3a and 90-day mortality. Results: Twenty-seven studies, including three randomized controlled trials (RCTs), three prospective trials (PTs), and twenty-one retrospective trials (RTs), and a total number of 2075 patients were recruited in this study. NMA demonstrated that the Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) had much higher sFLR increase when compared to portal vein embolization (PVE) (55.25%, 95% CI 45.27–65.24%), or liver venous deprivation(LVD) (43.26%, 95% CI 22.05–64.47%), or two-stage hepatectomy (TSH) (30.53%, 95% CI 16.84–44.21%), or portal vein ligation (PVL) (58.42%, 95% CI 37.62–79.23%). ALPPS showed significantly shorter time to hepatectomy when compared to PVE (−32.79d, 95% CI −42.92–22.66), or LVD (−34.02d, 95% CI −47.85–20.20), or TSH (−22.85d, 95% CI −30.97–14.72), or PVL (−43.37d, 95% CI −64.11–22.62); ALPPS was considered as the highest resection rate when compared to TSH (OR=6.09; 95% CI 2.76–13.41), or PVL (OR =3.52; 95% CI 1.16–10.72), or PVE (OR =4.12; 95% CI 2.19–7.77). ALPPS had comparable resection rate with LVD (OR =2.20; 95% CI 0.83–5.86). There was no significant difference between them when considering the R0 marge rate. ALPPS had a higher Clavien-Dindo≥3a complication rate and 90-day mortality compared to other treatments, although there were no significant differences between different procedures. Conclusions: ALPPS demonstrated a higher regeneration rate, shorter time to hepatectomy, and higher resection rate than PVL, PVE, or TSH. There was no significant difference between them when considering the R0 marge rate. However, ALPPS developed the trend of higher Clavien-Dindo≥3a complication rate and 90-day mortality compared to other treatments. [ABSTRACT FROM AUTHOR]

Background: Post-craniotomy pain is a common occurrence which is associated with poor outcomes. Pre-emptive scalp infiltration with dexamethasone and ropivacaine has been proven effective in previous studies but with limited clinical significance. Dexamethasone palmitate emulsion (D-PAL) is a pro-drug incorporating dexamethasone into lipid microspheres with greater anti-inflammatory activity and fewer side effects than free dexamethasone. However, its effects in post-craniotomy pain management remain unknown. This study hypothesizes that pre-emptive scalp infiltration with ropivacaine plus D-PAL emulsion can achieve superior analgesic effects to ropivacaine alone in adult patients undergoing craniotomy. Methods/design: This is a single center, randomized controlled trial enrolling 130 patients scheduled for supratentorial craniotomy, which is expected to last longer than 4 h. We compare the efficacy and safety for postoperative pain relief of ropivacaine plus D-PAL group and ropivacaine alone group following pre-emptive scalp infiltration. Primary outcome will be pain Numerical Rating Scale at 24 h postoperatively. Secondary outcomes will include further analgesia evaluations and drug-related complications within a follow-up period of 3 months. Discussion: This is the first randomized controlled trial aiming to assess the possible benefits or disadvantages of D-PAL emulsion for incisional pain in craniotomy. It may provide an alternative to optimize pain outcome for neurosurgical patients. Trial registration: ClinicalTrials.gov (NCT04488315). Registered on 19 July 2020. [ABSTRACT FROM AUTHOR]

Background: Clear cell renal cell cancer (ccRCC) is accompanied by T-cell infiltration. In this study, we sought to determine the difference in T-cell infiltration and the T-cell receptor (TCR) immune repertoire between ccRCC and peritumour tissue.Methods: T-cell infiltration was examined using immunohistochemistry (IHC) and haematoxylin and eosin (HE) staining. The chi-squared test and Pearson correlation analysis were applied to evaluate the relationship between clinical traits and CD3, CD4, and CD8 expression. Immune repertoire sequencing (IR-Seq) was used to describe the profile of the TCR repertoire.Results: The adjacent tissue showed increased expression of CD3, CD4 and CD8 compared with ccRCC tissue (PCD3 = 0.033; PCD4 = 0.014; PCD8 = 0.004). Indicated CD3+ T-cell density in ccRCC tissue was positively correlated with that in peritumour tissue (P = 0.010, r = 0.514), which implied the T cells in peritumour tissue directly infect the number of cells infiltrating in ccRCC tissue. Moreover, there was a positive correlation between Vimentin expression and indicated positive T-cell marker in ccRCC tissue (PCD3 = 0.035; PCD4 = 0.020; PCD8 = 0.027). Advanced stage revealed less CD4+ T-cell infiltration in ccRCC tissue (PCD4 = 0.023). The results from IR-Seq revealed an obvious increase in VJ and VDJ segment usage, as well as higher complementarity-determining region 3 (CDR3) amino acid (aa) clonotypes in ccRCC. The matched antigen recognized by the TCR of ccRCC may be potential targets.Conclusions: The current study collectively demonstrates diminished T-cell infiltration and increased CDR3 aa diversity in ccRCC, which may be associated with immunotherapeutic targets for ccRCC patients. [ABSTRACT FROM AUTHOR]

Background: Hip-preserving revision in patients with failed treatment of femoral trochanteric fracture is still a major challenge. Whether the medial support reconstruction could benefit the patients and improve the success rate of hip-preserving revision is still controversial. Hence, the purpose of this study was to evaluate the clinical significance and prognosis of medial support reconstruction during the hip-preserving revision of failed femoral trochanteric fracture treatment.Methods: Patients with failed femoral trochanteric fractures treatments addressed by hip-preserving revision at our hospital from January 2014 to December 2020 were analyzed retrospectively. 31 patients were included and divided into a medial support group (n = 16) and a non-medial support group (n = 15). The fracture healing rate was the primary measurement. In addition, the differences in Oxford Hip Score (OHS), quality of life, surgical trauma, and complications were also evaluated.Results: The fracture healing rate (100%, 16/16 vs. 66.67%, 10/15), the OHS (42.06 ± 4.12 vs. 30.93 ± 11.56, M ± SD), and the mental component score of the 12-item Short-Form Survey (SF-12) (54.48 ± 5.38 vs. 47.90 ± 3.47, M ± SD), were significantly better and the incidence of complications [0(0/16) vs. 40%(6/15)] was significantly lower in the medial support group than the non-medial support group (p < 0.05). No significant differences in the physical component score of the SF-12, surgical trauma and reduction in collodiaphyseal angle of affected femur were observed between groups.Conclusions: The reconstruction of medial support seems important for revision following failed treatment of femoral trochanteric fractures. Due to the medial augmentation and improvement of the mechanical stability for proximal femur, the patients might benefit from fracture healing prognosis and functional. [ABSTRACT FROM AUTHOR]

Background: In recent years, mitochondrial dysfunction has been extensively studied and published, but research on the effects of mitochondrial dysfunction on bone metabolism and related diseases is only just beginning. Furthermore, no studies have been carried out to systematically illustrate this area from a scientometric point of view. The goal of this research is to review existing knowledge and identify new trends and possible hotspots in this area.Methods: All publications related to the relationship between mitochondrial dysfunction and bone metabolism and related diseases from 2003 to 2022 were searched at the Web of Science Core Collection (WoSCC) on May 7, 2022. Four different analytical tools: VOSviewer 1.6.18, CiteSpace V 6.1, HistorCite (12.03.07), and Excel 2021 were used for the scientometric research.Results: The final analysis included 555 valid records in total. Journal of Biological Chemistry (Co-citations = 916) is the most famous journal in this field. China (Percentage = 37%), the United States (Percentage = 24%), and Korea (Percentage = 12%) are the most productive countries. Blanco FJ and Choi EM are the main researchers with significant academic influence. Current research hotspots are basic research on mitochondrial dysfunction and the prevention or treatment of bone metabolism-related diseases.Conclusion: The study of the consequences of mitochondrial dysfunction on bone metabolism and associated diseases is advancing rapidly. Several prominent researchers have published extensive literature and are widely cited. Future research in this area will focus on oxidative stress, aging, gene expression, and the pathogenesis of bone metabolism-related diseases. [ABSTRACT FROM AUTHOR]

Background: Spontaneous rupture is a life-threatening complication of hepatocellular carcinoma (HCC). Recent trends in surgical treatments avoid emergency hepatectomy (EH) and favor emergency transarterial embolization (TAE) followed by delayed hepatectomy (DH). Still, there is debate on which is the better treatment option and whether delaying hepatectomy increases peritoneal metastasis. Aim: To provide evidence-based references for the optimal management of patients with spontaneously ruptured HCC by comparing the outcomes of EH and DH. Methods: Literature on postoperative outcomes of EH and DH in patients with spontaneously ruptured HCC published between the date of the database establishment and May 2022, was identified in the PubMed, EMBASE, and Cochrane Library databases. Revman 5.3 software was used for statistical analyses. Results: Nine publications were identified, including a total of 681 patients. Of those, 304 underwent EH, and 377 underwent TAE followed by DH. The meta-analysis results indicated that the in-hospital mortality rate in the EH patient group was significantly higher than that in the DH patient group (relative risk (RR) = 2.17, 95% confidence interval (CI) 1.03–4.57, p =0.04). There was no significant differences in the rates of postoperative complications (RR = 1.21, 95% CI 0.77–1.90, p = 0.40), postoperative hospital stay (WMD = − 0.64, 95% CI − 5.61–4.34, p = 0.80), recurrence (RR = 1.09, 95% CI 0.94–1.25, p = 0.27), peritoneal metastasis (RR = 1.06, 95% CI 0.66–1.71, p = 0.80), 1-year survival (RR = 0.91, 95% CI 0.80–1.02, p = 0.11), or 3-year survival (RR = 0.81, 95% CI 0.61–1.09, p = 0.17) in survivors between the two patient groups. Conclusion: The postoperative outcomes of the spontaneously ruptured HCC survivors who received EH were similar to those who received emergency TAE followed by DH. However, the in-hospital mortality rate was higher in EH patients. Based on the findings, DH with TAE first strategy might be considered over EH as the first line treatment modality. However, these findings await further validation by future high-quality studies. [ABSTRACT FROM AUTHOR]

Background: Previous studies on associations of alcohol use with memory decline showed inconclusive results. We examined these associations using longitudinal data from the Guangzhou Biobank Cohort Study (GBCS) and explored whether these associations varied by sex and age group. Methods: Memory function was assessed by delayed 10-word recall test (DWRT) and immediate 10-word recall test (IWRT) at both baseline (2003–2008) and follow-up (2008–2012) examinations, expressed as the mean annual change and mean annual rate of change in scores. Memory cognitive impairment was defined by DWRT scores of less than 4. Multivariable linear regression models and restricted cubic spline were used for data analysis. Results: Of 14,827 participants without memory cognitive impairment at baseline, 90.2% were never or occasional drinkers, 5% moderate drinkers, 1.5% excessive drinkers, and 3.3% former drinkers. The mean (standard deviation) age was 60.6 (6.6) years old. During an average of 4.1 years follow-up, 1000 (6.7%) participants developed memory cognitive impairment. After adjusting for confounders, compared with never or occasional drinkers, moderate and excessive drinkers had significant decline in DWRT scores (β, 95% confidence interval (CI) = -0.04 (-0.08 to -0.01), and − 0.07 (-0.14 to 0.01), respectively), and IWRT scores (β, 95% CI = -0.10 (-0.19 to -0.01), and − 0.15 (-0.30 to 0.01), respectively) annually. With respect to the mean annual rate of change, moderate and excessive drinkers also showed greater decline in DWRT scores (β, 95% CI = -1.02% (-1.87% to -0.16%), and − 1.64% (-3.14% to -0.14%), respectively). The associations did not vary by sex and age group (all P values for interaction ≥ 0.10). Conclusion: Compared to never or occasional alcohol use, moderate and excessive alcohol users had greater memory decline and the associations did not vary by sex and age group. [ABSTRACT FROM AUTHOR]

Background: Lung cancer is the most common malignant tumor, and it has a high mortality rate. However, the study of miRNA-mRNA regulatory networks in the plasma of patients with non-small cell lung cancer (NSCLC) is insufficient. Therefore, this study explored the differential expression of mRNA and miRNA in the plasma of NSCLC patients. Methods: The Gene Expression Omnibus (GEO) database was used to download microarray datasets, and the differentially expressed miRNAs (DEMs) were analyzed. We predicted transcription factors and target genes of the DEMs by using FunRich software and the TargetScanHuman database, respectively. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) was used for GO annotation and KEGG enrichment analysis of downstream target genes. We constructed protein-protein interaction (PPI) and DEM-hub gene networks using the STRING database and Cytoscape software. The GSE20189 dataset was used to screen out the key hub gene. Using The Cancer Genome Atlas (TCGA) and UALCAN databases to analyze the expression and prognosis of the key hub gene and DEMs. Then, GSE17681 and GSE137140 datasets were used to validate DEMs expression. Finally, the receiver operating characteristic (ROC) curve was used to verify the ability of the DEMs to distinguish lung cancer patients from healthy patients. Results: Four upregulated candidate DEMs (hsa-miR199a-5p, hsa-miR-186-5p, hsa-miR-328-3p, and hsa-let-7d-3p) were screened from 3 databases, and 6 upstream transcription factors and 2253 downstream target genes were predicted. These genes were mainly enriched in cancer pathways and PI3k-Akt pathways. Among the top 30 hub genes, the expression of KLHL3 was consistent with the GSE20189 dataset. Except for let-7d-3p, the expression of other DEMs and KLHL3 in tissues were consistent with those in plasma. LUSC patients with high let-7d-3p expression had poor overall survival rates (OS). External validation demonstrated that the expression of hsa-miR-199a-5p and hsa-miR-186-5p in peripheral blood of NSCLC patients was higher than the healthy controls. The ROC curve confirmed that the DEMs could better distinguish lung cancer patients from healthy people. Conclusion: The results showed that miR-199a-5p and miR-186-5p may be noninvasive diagnostic biomarkers for NSCLC patients. MiR-199a-5p-KLHL3 may be involved in the occurrence and development of NSCLC. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal cancers worldwide with high mortality, which is mainly due to the lack of reliable biomarkers for PDAC diagnosis/prognosis in the early stages and effective therapeutic strategies for the treatment. Cancer-derived small extracellular vesicles (sEVs), which carry various messages and signal biomolecules (e.g. RNAs, DNAs, proteins, lipids, and glycans) to constitute the key features (e.g. genetic and phenotypic status) of cancer cells, are regarded as highly competitive non-invasive biomarkers for PDAC diagnosis/prognosis. Additionally, new insights on the biogenesis and molecular functions of cancer-derived sEVs pave the way for novel therapeutic strategies based on cancer-derived sEVs for PDAC treatment such as inhibition of the formation or secretion of cancer-derived sEVs, using cancer-derived sEVs as drug carriers and for immunotherapy. This review provides a comprehensive overview of the most recent scientific and clinical research on the discovery and involvement of key molecules in cancer-derived sEVs for PDAC diagnosis/prognosis and strategies using cancer-derived sEVs for PDAC treatment. The current limitations and emerging trends toward clinical application of cancer-derived sEVs in PDAC diagnosis/prognosis and treatment have also been discussed. [ABSTRACT FROM AUTHOR]

Background: According to the Global Cancer Statistics in 2020, the incidence and mortality of colorectal cancer (CRC) rank third and second among all tumors. The disturbance of ubiquitination plays an important role in the initiation and development of CRC, but the ubiquitinome of CRC cells and the survival-relevant ubiquitination are poorly understood.Methods: The ubiquitinome of CRC patients (n = 6) was characterized using our own data sets of proteomic and ubiquitin-proteomic examinations. Then, the probable survival-relevant ubiquitination was searched based on the analyses of data sets from public databases.Results: For the ubiquitinomic examination, we identified 1690 quantifiable sites and 870 quantifiable proteins. We found that the highly-ubiquitinated proteins (n ≥ 10) were specifically involved in the biological processes such as G-protein coupling, glycoprotein coupling, and antigen presentation. Also, we depicted five motif sequences frequently recognized by ubiquitin. Subsequently, we revealed that the ubiquitination content of 1172 proteins were up-regulated and 1700 proteins were down-regulated in CRC cells versus normal adjacent cells. We demonstrated that the differentially ubiquitinated proteins were relevant to the pathways including metabolism, immune regulation, and telomere maintenance. Then, integrated with the proteomic datasets from the Clinical Proteomic Tumor Analysis Consortium (CPTAC) (n = 98), we revealed that the increased ubiquitination of FOCAD at Lys583 and Lys587 was potentially associated with patient survival. Finally, we depicted the mutation map of FOCAD and elucidated its potential functions on RNA localization and translation in CRC.Conclusions: The findings of this study described the ubiquitinome of CRC cells and identified abnormal ubiquitination(s) potentially affecting the patient survival, thereby offering new probable opportunities for clinical treatment. [ABSTRACT FROM AUTHOR]

Background: The relationship between the type of anesthesia and the survival outcomes of gastric cancer patients is uncertain. This study compared the overall outcome of gastric cancer patients after surgery with total intravenous anesthesia (TIVA) or inhalation anesthesia (IHA).Methods: Clinicopathological variables of gastric cancer patients were retrieved from the database of the Surgical Gastric Cancer Patient Registry in West China Hospital, Sichuan University. Patients were grouped according to whether they received TIVA or IHA during the operation. Propensity score (PS) matching was used to balance the baseline variables, and survival outcomes were compared between these two groups. In addition, studies comparing survival outcomes between TIVA and IHA used for gastric cancer surgery and published before April 20th, 2020, were identified, and their data were pooled.Results: A total of 2827 patients who underwent surgical treatment from Jan 2009 to Dec 2016 were included. There were 323 patients in the TIVA group and 645 patients in the IHA group, with 1:2 PS matching. There was no significant difference in overall survival outcomes between the TIVA and IHA groups before matching the cohort (p = 0.566) or after matching the cohort (p = 0.679) by log-rank tests. In the Cox hazard regression model, there was no significant difference between the TIVA and IHA groups before (HR: 1.054, 95% CI: 0.881-1.262, p = 0.566) or after (HR: 0.957, 95% CI: 0.779-1.177, p = 0.679) PS matching. The meta-analysis of survival outcomes between the TIVA and IHA groups found critical statistical value in the before PS matching cohort (HR 0.74, 95% CI: 0.57-0.96 p < 0.01) and after PS matching cohort (HR: 0.65, 95% CI: 0.46-0.94, p < 0.01).Conclusions: Combined with the results of previous studies, total intravenous anesthesia has been shown to be superior to inhalation anesthesia in terms of overall survival for gastric cancer patients undergoing surgical treatment. The selection of intravenous or inhalation anesthesia for gastric cancer surgery should take into account the long-term prognosis of the patient. [ABSTRACT FROM AUTHOR]