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Obstructive sleep apnea (OSA) is caused by repeated blockage of the upper respiratory airways during sleep. The traditional evaluation methods for OSA severity are yet limited. This study aimed to screen gene signatures to effectively evaluate OSA severity. Expression profiles of peripheral blood mononuclear cells in the different severities of OSA patients were accessed from Gene Expression Omnibus (GEO) database. A total of 446 differentially expressed genes (DEGs) were screened among the varying severities of OSA samples by analysis of variance (ANOVA) test. A total of 1,152 DEGs were screened between the pre- and post-treatment OSA samples by using t test. Overlap of the two groups of DEGs was selected (88 DEGs) for Metascape enrichment analysis. Afterwards, Mfuzz package was used to perform soft clustering analysis on these 88 genes, by which 6 clusters were obtained. It was observed that the gene expression condition of the cluster 3 was positively associated with OSA severity degree; also, the gene expression condition in cluster 4 was negatively correlated with OSA severity. A total of 10 gene markers related to OSA progression were selected from cluster 3 and cluster 4. Their expression levels and correlation were analyzed. The marker genes in cluster 3 and cluster 4 were examined, finding that most genes were significantly correlated with apnea hypopnea index (AHI). An accurate and objective assessment of the severity of OSA is of great significance for formulating follow-up treatment strategies for patients with OSA. In this paper, a set of marker genes that can detect the severity of OSA were screened by bioinformatics methods, which could be jointly used with the traditional OSA diagnostic index to achieve a more reliable OSA severity evaluation.

The receptor Triggering Receptor Expressed on Myeloid cells 2 (TREM2) is associated with several neurodegenerative diseases including Alzheimer's Disease and TREM2 stimulation represents a novel therapeutic opportunity. TREM2 can be activated by antibodies targeting the stalk region, most likely through receptor dimerization. Endogenous ligands of TREM2 are suggested to be negatively charged apoptotic bodies, mimicked by phosphatidylserine incorporated in liposomes and other polyanionic molecules likely binding to TREM2 IgV fold. However, there has been much discrepancy in the literature on the nature of phospholipids (PLs) that can activate TREM2 and on the stability of the corresponding liposomes over time. We describe optimized liposomes as robust agonists selective for TREM2 over TREM1 in cellular system. The detailed structure/activity relationship studies of lipid polar heads indicate that negatively charged lipid heads are required for activity and we identified the shortest maximally active PL sidechain. Optimized liposomes are active on both TREM2 common variant and TREM2 R47H mutant. Activity and selectivity were further confirmed in different native TREM2 expressing cell types including on integrated cellular responses such as stimulation of phagocytic activity. Such tool agonists will be useful in further studies of TREM2 biology in cellular systems alongside antibodies, and in the design of small molecule synthetic TREM2 agonists.

We examined the apoptotic response of two glioblastoma cells, p53 wild type U87 and p53 mutated T98G, to doxorubicin, bortezomib, and vorinostat, which respectively target DNA, 26S proteasome and histone deacetylase, to clarify p53ʹs function in apoptosis. We demonstrated that doxorubicin induced apoptosis in U87 cells but not in T98G cells. The level of p53 was definitively correlated to the extent of DNA damage and apoptosis initiation. Dominant-negative p53 reduced p21 expression, but did not affect doxorubicin-induced apoptosis, so the transcriptional activity of p53 seemed not to participate in doxorubicin-induced apoptosis. However, p53 concentrated into the nucleus during heavy apoptosis. Bortezomib could induce apoptosis in U87 with high sensitivity and T98G cells with low sensitivity. In contrast, vorinostat promoted apoptosis in both U87 and T98G cells and reduced the basal level of p53 in U87 cells, indicating that p53 played no role in the vorinostat-induced apoptosis. To clearly define the role of p53 in bortezomib- and doxorubicin-induced apoptosis, we combined doxorubicin with bortezomib to treat U87 cells to assess this combination’s effect on apoptosis and p53 status. Interestingly, the combination of doxorubicin with bortezomib engendered compound stress, resulting in a synergistic outcome for apoptosis in U87 cells. However, the amounts of p53 in the total count and in the nucleus were much lower with the combination than with doxorubicin alone, suggesting that p53 played no role in either the compound stress, doxorubicin-only or bortezomib-induced apoptosis.

Tibial plafond fractures, especially the AO/OTA type C3 ones that take place in young patients with excessive facet fragmentation and cartilage loss that preclude anatomical reduction and effective internal fixation, are devastating situations that often subject to primary arthrodesis. The aim of the current study is to introduce a joint preserving technique by using osteochondral autograft to treat such difficult cases and to evaluate its short-term outcome.A total of 11 patients suffering AO-OTA type C3 tibial plafond fractures with irreparable area treated with osteochondral autograft and ORIF, with an average follow-up period of 34 months, were analyzed. Visual analogue scale (VAS), short-form 36 (SF-36), American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, and ankle range of motion (ROM) were assessed for functional outcome evaluation. The weight-bearing AP and lateral radiograph, as well as CT reconstructive images were examined to evaluate bony union and the occurrence of post-traumatic arthritis.At the final follow-up, the mean VAS scale was 2.2. The mean AOFAS and SF-36 scores were 86.3 and 84.5 respectively. Among all the included patients, 8 achieved both AOFAS and SF-36 scores above 80. The average ankle range of motion was 29.9°. No infection, compartment syndrome, post-traumatic arthrosis or donor site pain was noted in the current study. No patient received secondary ankle arthrodesis at the end of the follow-up.Although primary ankle arthrodesis is an effective method, routine ankle arthrodesis should be carried out with second thoughts in patients, especially patients with relatively young age, suffering AO-OTA type C3 tibial plafond fractures with irreducible area. On the other hand, osteochondral autograft transplantation may provide a chance to relieve pain without sacrificing the joint.

The mutation of ClZISO identified in EMS-induced watermelon leads to photosensitive flesh in watermelon. Watermelon (Citrullus lanatus) has a colorful flesh that attracts consumers and benefits human health. We developed an ethyl-methanesulfonate mutation library in red-fleshed line '302' to create new flesh color lines and found a yellow-fleshed mutant which accumulated ζ-carotene. The initial yellow color of this mutant can be photobleached within 10 min under intense sunlight. A long-term light-emitting diode (LED) light treatment turned flesh color from yellow to pink. We identified this unique variation as photosensitive flesh mutant ('psf'). Using bulked segregant analysis, we fine-mapped an EMS-induced G-A transversion in 'psf' which leads to a premature stop codon in 15-cis-ζ-carotene isomerase (ClZISO) gene. We detected that wild-type ClZISO is expressed in chromoplasts to catalyze the conversion of 9,15,9'-tri-cis-ζ-carotene to 9,9'-di-cis-ζ-carotene. The truncated ClZISO

Gallbladder cancer is a malignant tumor with a high mortality rate. Accumulating evidence supports that lncRNA MEG3 may halt the progression of gallbladder cancer, while the downstream mechanism is rarely studied. Thus, we aim to investigate the molecular basis of the tumor-suppressing role of lncRNA MEG3 in gallbladder cancer. The expression of lncRNA MEG3 and CXCL3 was measured in patient serum and cell lines of gallbladder cancer. The viability, apoptosis, migration, and invasion of gallbladder cancer cells were assessed following ectopic MEG3 expression, as detected by CCK-8, flow cytometry, and Transwell assays. The interaction among lncRNA MEG3, EZH2, and CXCL3 was explored through ChIP, RNA pull-down, and RIP assays. The effects of lncRNA MEG3 and CXCL3 on tumor growth were evaluated by a mouse xenograft model. lncRNA MEG3 was expressed at a low level in gallbladder cancer patient serum and cell lines, while CXCL3 was highly expressed. MEG3 overexpression repressed the malignant behaviors of gallbladder cancer cells and promoted their apoptosis. MEG3 was mainly localized in the nucleus. MEG3 bound to EZH2, and EZH2 catalyzed the H3K27 trimethylation of the CXCL3 promoter region. MEG3 downregulated CXCL3 by activating EZH2-mediated H3K27 trimethylation of CXCL3; MEG3 overexpression attenuated cancer cell malignant behaviors in vitro and suppressed tumor growth in vivo in gallbladder cancer by inhibiting CXCL3 expression. Altogether, our results indicate that lncRNA MEG3 impedes gallbladder cancer development via the EZH2-CXCL3 axis, offering potential biomarkers for gallbladder cancer management.

BACKGROUND Despite substantial attention paid to the epidemic of nonalcoholic fatty liver disease (NAFLD) in adults, data on the burden and sexual dimorphism of NAFLD in Asian children have not yet been synthesized. METHODS We conducted a literature search of 735 references up to April 2021. Pooled analyses, stratified analyses and meta-regression were all performed. RESULTS Thirty-three study populations were finally included. Nine of them comprising 20 595 children showed an overall NAFLD prevalence of 5.53% (95% CI 3.46%-8.72%), in which, 36.64% (95% CI, 27.99%-46.26%) NAFLD subjects had elevated levels of ALT. The prevalence rate of NAFLD increased about 1.6-fold from 2004 to 2010 to the last decade. Male predominant trends were observed in paediatric NAFLD (boys: 8.18%, 95% CI 4.93%-13.26%; girls: 3.60%, 95% CI 1.60%-7.87%). Moreover, meta-analysis showed that after 10 years of age, boys were more prone to have NAFLD than girls (OR = 1.75; P = .0012). In addition, the pooled prevalence of NAFLD increased sequentially in normal-weight (1.49%, 95% CI 0.88%-2.51%, n = 2610), overweight (16.72%, 95% CI 7.07%-34.65%, n = 1265) and obese children (50.13%, 95% CI 41.99%-58.27%, n = 6434 individuals). After full covariate adjustment, the multivariate meta-regression also showed that boy percentage (P = .0396) and body mass index (P

Objective To assess the feasibility and results of tibial cortex transverse distraction (TCTD) followed by open correction with internal fixation (OCIF) for foot and ankle deformity with concurrent ulcers. Methods A retrospective analysis was conducted. Between 2010 and 2019, a two‐stage management of TCTD followed by OCIF was performed in 13 patients (13 feet). There were five males and eight females with a mean age of 33.8 ± 14.6 years. Ten patients had a right‐side lesion, and three patients had a left‐side lesion. The etiology of deformity included seven cases of congenital neurological disease, one case of Charcot–Marie–Tooth disease, one case of trauma sequelae, and three cases of myelomeningocele. Duration of disease, size of ulcers, surgical procedures, healing time, external fixation time, and complications of these patients were recorded. The Texas wound classification and National Pressure Ulcer Advisory Panel (NPUAP) classification were used for assessing the ulcers. The modified Dimeglio score of deformity and American Orthopeadic Foot and Ankle Society (AOFAS) ankle‐hindfoot score were applied to evaluate the status before treatment and the results at final follow‐up. Results The TCTD and wound debridement were performed in all patients, and an additional Ilizarov correction technique was added in two patients. All ulcers were healed in 3 months after first‐stage treatment. The median patient self‐report time of ulcer healing was 2.0 weeks (IQR, 1.8–3.3). The median external fixation time was 138.0 days (IQR, 134.5–141.5) days. After second‐stage operative correction, the patients were followed‐up for an average of 28.0 ± 2.9 months. At the final follow‐up, the modified Dimeglio score of deformity was decreased from 6.7 ± 2.1 to 1 (IQR, 0.0–1.0), and the mean AOFAS score was improved from 42.9 ± 19.1 to 82.6 ± 7.7. Before the treatment, there were eight patients with severe deformity, four patients with moderate deformity, and one patient with mild deformity. Postoperatively, seven patients were classified as mild deformity and six patients had a postural foot. The results of AOFAS ankle‐hindfoot score were defined as excellent in three patients, as good in five, and as fair in five. Complications include one case of mild displacement of the osteotomized cortex and one case of pin‐tract infection. No delayed union, nonunion, relapse of ulcers, or deformity were observed. Conclusions The two‐stage management of TCTD followed by OCIF could be considered as an alternative treatment for foot and ankle deformities combined with chronic ulcers., We applied a two‐stage management of tibial cortex transverse distraction (TCTD) followed by open correction with internal fixation (OCIF) for foot and ankle deformities combined with chronic ulcers. This strategy could be considered as an alternative treatment for recalcitrant ulcers with deformity in foot and ankle, as complete healing of ulcers and excellent correction of deformity were achieved in this case series.

Background Extensive cervicofacial reconstruction is challenging for plastic surgeons. Because of the location of the adjacent scalp flap nourished by the superficial temporal artery (STA), it can be a candidate for cervicofacial reconstruction. Objectives This article aims to report a combined treatment of an expanded island STA flap and an 810-nm diode laser hair removal technique for extensive cervicofacial defects. Methods Between January 2015 and December 2018, 10 patients with lower face and neck scar contraction were reconstructed with a bilateral or unilateral expanded STA island flap and an 810-nm diode laser for hair removal in this retrospective study. Hair removal via the 810-nm laser was started when the injected volume reached the volume of the expander, with a fluence of 35 to 40 J/cm2 and a 1 to 2 Hz repetition rate. Before second-stage surgery, the hair reduction rate was assessed. Twelve months after surgery, the degree of epilation efficacy according to the satisfaction scale and Global Aesthetic Improvement Scale was evaluated. Results This study included 2 single-pedicle flaps and 8 double-pedicle flaps. The average size of the implanted expanders was 600 mL. The average injected volume was 1405 mL. Before second surgery, there was a 67.4% hair reduction rate. Twelve months after surgery, the results of Global Aesthetic Improvement Scale were very good (3), good (6), average (1), and poor (0). Conclusions The expanded island STA flap and 810-nm diode laser technique may be a novel treatment option for severe face and neck aesthetic reconstruction.

Quaternary climate oscillations and geographical heterogeneity play important roles in determining species and genetic diversity distribution patterns, but how these factors affect the migration and differentiation of East Asian plants species at the population level remains poorly understood. The Aquilegia ecalcarata complex, a group that originated in the Late Tertiary and is widely distributed throughout East Asia, displays high genetic variation that is suitable for studying elaborate phylogeographic patterns and demographic history related to the impact of Quaternary climate and geography. We used plastid genome data from 322 individuals in 60 populations of the A. ecalcarata complex to thoroughly explore the impact of Quaternary climate oscillations and geography on the phylogeographic patterns and demographic history of the A. ecalcarata complex through a series of phylogenetic, divergence time estimation, and demographic history analyses. The dry, cold climate and frequent climate oscillations that occurred during the early Pleistocene and the Mid-Pleistocene transition led to the differentiation of the A. ecalcarata complex, which was isolated in various areas. Geographically, the A. ecalcarata complex can be divided into Eastern and Western Clades and five subclades, which conform to the divergence of the East Asian flora. Our results clearly show the impact of Quaternary climate and geography on evolutionary history at the population level. These findings promote the understanding of the relationship between plant genetic differentiation and climate and geographical factors of East Asia at the population level.

Traditional wood-based panels are usually made from large-diameter trees and rely on adhesives for compactness, which negatively impacts the environment and human health. However, the widely distributed small-diameter shrubs are good raw materials for wood-based panels with abundant fibers, but are often under-exploited. This research reports the preparation of self-bonding biocomposites from

Recent advances have highlighted the relationships between gut dysbiosis and Parkinson's disease (PD). Microbiota transplantation from PD patients to mice can induce increased alpha-synuclein-mediated motor deficits. Human studies have identified differences in the gut microbiota of PD patients compared to healthy controls. We undertook a systematic review to evaluate the available evidence for the involvement of gut bacteria in the etiology of PD.The PubMed databank, the China National Knowledge Infrastructure databank, and Wanfang Data were searched from inception until June 2021 to identify human case-control studies that investigated relationships between PD and microbiota quantified from feces. We evaluated the resulting studies focusing on bacterial taxa that were different between PD patients and healthy controls.Twenty-six studies were found in which 53 microbial families and 98 genera exhibited differences between patients with PD and healthy controls. The genera identified by more than two studies as increased in PD were Bifidobacterium, Alistipes, Christensenella, Enterococcus, Oscillospira, Bilophila, Desulfovibrio, Escherichia/Shigella, and Akkermansia, while Prevotella, Blautia, Faecalibacterium, Fusicatenibacter, and Haemophilus had three or more reports of being lower in PD patients. More than one report demonstrated that Bacteroides, Odoribacter, Parabacteroides, Butyricicoccus, Butyrivibrio, Clostridium, Coprococcus, Lachnospira, Lactobacillus, Megasphaera, Phascolarctobacterium, Roseburia, Ruminococcus, Streptococcus, and Klebsiella were altered in both directions.Our review shows that the involvement of the gut microbiome in the etiology of PD may involve alterations of short-chain fatty acids (SCFAs)-producing bacteria and an increase in putative gut pathobionts. SCFAs-producing bacteria may vary above or below an "optimal range," causing imbalances. Considering that Bifidobacterium, Lactobacillus, and Akkermansia are beneficial for human health, increased Bifidobacterium and Lactobacillus in the PD gut microbiome may be associated with PD medications, especially COMT inhibitors, while a high level of Akkermansia may be associated with aging.

Aims Although current guidelines recommend reduction of salt intake in patients with diabetes, the benefits of reducing salt intake in people with type 2 diabetes mellitus (T2DM) lack clear evidence. Therefore, we performed a meta-analysis of available randomized controlled trials (RCTs) of sodium restriction and blood pressure (BP) in patients with T2DM. Data synthesis We performed a systematic search of the online databases that evaluated the effect of dietary sodium restriction on BP in patients with T2DM. Sodium intake was expressed by 24 h urinary sodium excretion (UNaV). Q statistics and I2 were used to explore between-study heterogeneity. A random-effects model was used in the presence of significant heterogeneity; otherwise, a fixed-effects model was applied. Eight RCTs with 10 trials (7 cross-over and 3 parallel designs) were included in the meta-analysis. Compared with ordinary sodium intake, dietary sodium restriction significantly decreased UNaV (weighted mean difference, WMD: −38.430 mmol/24 h; 95% CI: −41.665 mmol/24 h to −35.194 mmol/24 h). Sodium restriction significantly lowered systolic BP (WMD: −5.574 mm Hg; 95% CI: −8.314 to −2.834 mm Hg; I2 = 0.0%) and diastolic BP (WMD: −1.675 mm Hg; 95% CI: −3.199 to −0.150 mm Hg; I2 = 0.0%) with low heterogeneity among the studies. No publication bias was found from Begg's and Egger's tests. Conclusions Sodium restriction significantly reduces SBP and DBP in patients with T2DM.

Breast cancer (BC) ranks first in morbidity and mortality among female malignant tumors worldwide. This study is aimed at clarifying clinical value of contrast-enhanced ultrasound (CEUS) in the diagnosis and differentiation of BC. A total of 108 BC patients admitted to our hospital from January 2019 to December 2021 were enrolled. All patients underwent conventional color Doppler ultrasound and CEUS imaging examination. All ultrasound images were analyzed by a senior (5+ years) sonographer. The lesion location, echo, size, and color Doppler flow imaging (CDFI) blood flow distribution of benign and malignant BC were assessed. The transverse and longitudinal diameters of malignant BC presented significant elevation compared with the control group ( P < 0.05 ). CEUS is more reliable than conventional ultrasound in the differentiation of benign and malignant breast lesions, and CEUS has the best reliability. The comparison of CEUS observation indicators between benign and malignant groups demonstrated that CEUS enhancement patterns (time and intensity) and morphological features (lesion boundary, shape, range, homogeneity, and filling defect) presented statistical significance ( P < 0.01 ). Irregular shape and range expansion were high-specificity indicators (all >90.00%); fast-forward, high enhancement, clear boundary, and range expansion were high-sensitivity (all >90.00%); and fast-forward, high enhancement, and clear boundary were low-specificity indicators (all 80.00%). The area under curve of CEUS ( 0.735 ± 0.053 ) presented elevation relative to conventional ultrasound ( 0.901 ± 0.024 ), with statistical significance ( Z 1 = 2.462 , P < 0.05 ). Relative to conventional ultrasound, the specificity and positive predictive value of CEUS presented elevation ( P < 0.05 ). In conclusion, in the differentiation of benign and malignant breast lesions, CEUS has better diagnostic accuracy and reliability than conventional ultrasound. The diagnostic advantages of CEUS are to elevate the diagnostic specificity and positive predictive value and reduce the misdiagnosis rate.

On August 25, 2021, the FDA approved ivosidenib for the treatment of adult patients with unresectable locally advanced or metastatic hepatocellular isocitrate dehydrogenase 1 (IDH1) mutated cholangiocarcinoma (CCA) as detected by an FDA-approved test with disease progression after 1 to 2 prior lines of systemic therapy for advanced disease. The approval was based on data from Study AG120-C-005 (ClarIDHy), a double-blind placebo-controlled trial that randomly allocated (2:1) patients to receive either ivosidenib or placebo. Independently assessed progression-free survival (PFS) was the primary endpoint. With a median follow-up of 6.9 months, the HR for PFS was 0.37 [95% confidence interval (CI), 0.25–0.54; P < 0.0001). Overall survival (OS) was the key secondary endpoint. At the final analysis of OS, with 70.5% of patients in the placebo arm receiving ivosidenib post disease progression, a non–statistically significant improvement in the ivosidenib arm with an HR = 0.79 (95% CI, 0.56–1.12) and median OS of 10.3 months (95% CI, 7.8–12.4) and 7.5 months (95% CI, 4.8–11.1) in the ivosidenib and placebo arms, respectively, were reported. Adverse reactions occurring in >20% of patients receiving ivosidenib were fatigue/asthenia, nausea, diarrhea, abdominal pain, ascites, vomiting, cough, and decreased appetite. Adverse reactions occurring in >20% of patients receiving placebo were fatigue/asthenia, nausea, abdominal pain, and vomiting. This is the first approval for the subset of patients with CCA harboring an IDH1 mutation.

Multiple sensor technologies including electronic nose (E-nose), electronic tongue (E-tongue), colorimeter and texture analyzer combined with chemometrics and dada fusion strategies were applied to characterize the flavor quality of traditional Chinese fermented soybean paste. Principal components analysis (PCA) was performed to divide the selected soybean pastes into three clusters which was not completely consistent with geographical regions of selected samples. Support vector machine regression (SVR) outperformed partial least squares regression (PLSR) in quantitatively predicting sensory attributes. Additionally, prediction of overall flavor of soybean paste based on data fusion of multiple sensor information, with a correlation coefficient of prediction (Rp) of 0.9636 based on SVR, was better than prediction of E-nose and E-tongue data fusion (Rp = 0.9267). This study suggested multiple sensor technologies coupled with chemometrics can be a promising tool for flavor assessment and characterization of fermented soybean paste or other food matrixes.

Stressors can have negative effects on well-being, but little is known about how an individual's inability to precisely forecast upcoming stress could be a risk factor for well-being. Antecedents and outcomes of two stress forecasting variables, anticipated stress level and underestimation errors in stress forecasting (operationalized by the residual change scores obtained by regressing the evening experienced stress on the morning anticipated stress), were investigated. In a daily diary study of 110 undergraduate students over a workweek, poor sleep quality and negative affect reported in the morning predicted a higher anticipated stress of the upcoming day. Poor sleep quality was found to be related to less underestimation errors (i.e., more overestimation). Mispredicting the daily stress level was found to predict greater health complaints and negative affect by the end of the day. Those high on trait resilience were found to make fewer underestimation errors on average. Worse emotional outcomes were associated with underestimation errors during stress forecasting than with overestimation errors. This study demonstrates that examining an individual's experience in forecasting upcoming stressors is an important area for future research in determining points of intervention to promote adaptive management of daily demands.

The liver kinase B1 (LKB1) is an important tumor suppressor and its loss-of-function mutations are observed in around 16% of non-small cell lung cancer (NSCLC) cases. One of the main functions of LKB1 is to activate AMP-activated protein kinase (AMPK) via direct phosphorylation. Under metabolic or energy stress conditions, the LKB1-AMPK axis inhibits the anabolic pathways and activates the catabolic pathways to maintain metabolic homeostasis for cell survival. In this study, we found that LKB1-mutant NSCLC cells are particularly susceptible to cell death induced by glucose starvation, but not by other forms of starvation such as amino acid starvation or serum starvation. Reconstitution of LKB1 in LKB1-mutant cells or LKB1 knockout in LKB1-wild type cells highlighted the importance of the LKB1-AMPK axis for cell survival under glucose starvation. Mechanistically, in LKB1-mutant cells, glucose starvation elicits oxidative stress, which causes AMPK protein oxidation and inactivation, and eventually cell death. Importantly, this process could be effectively reversed and rescued by 2DG (a glucose analog capable of producing NADPH, a key antioxidant), A769662 (an allosteric AMPK activator), and N-acetyl cysteine (NAC) (a ROS scavenger), indicating the presence of a vicious circle between AMPK inactivation and ROS in LKB1-mutant NSCLC cells under glucose starvation. Our study thus elucidates the critical role of redox balance in determining the susceptibility to cell death under glucose starvation in LKB1-mutant NSCLC cells. The findings from this study reveal important clues in search of novel therapeutic strategies for LKB1-mutant NSCLC by targeting glucose metabolism and redox balance.

INTRODUCTION: We compared characteristics and outcomes by treatment sequence among patients with metaplastic breast cancer (MBC), an aggressive subtype. METHODS: Women ≥18 years old with newly diagnosed Stage I-III MBC from 2003 to 2018 who received any treatment in our health system were identified. Unadjusted overall survival (OS) was estimated with the Kaplan-Meier method; the log-rank test was used to compare survival differences between recipients of neoadjuvant (NACT) and adjuvant chemotherapy (ACT). RESULTS: Of the 91 MBC patients identified, 60 received chemotherapy. NACT recipients (n = 20, median age 46.5 y) were younger than ACT recipients (n = 40, median age 60.5 y, p < 0.001) but similar with regards to race and radiation receipt. There was no significant OS difference between NACT and ACT recipients (log-rank p = 0.15), which remained true when patients were stratified by age (≥50 y vs < 50 y). CONCLUSIONS: Among MBC patients, NACT recipients were younger than ACT recipients, but there was no survival difference by treatment sequence.

Supraclavicular nerve injury is one of the common complications after clavicle open reduction internal fixation (ORIF) affecting up to 55% of patients. There is debate about whether sparing supraclavicular nerves improves functional outcomes and patient satisfaction. The purpose of this study was to compare numbness, patient-reported outcomes and surgical time in patients undergoing clavicle ORIF using supraclavicular nerve sparing and supraclavicular nerve sacrificing techniques.We conducted a retrospective cohort study with prospective survey of 108 patients with clavicular fractures treated with ORIF at a level 1 trauma centre. Patients were divided into two groups: 1) ORIF with supraclavicular nerve sparing techniques and 2) ORIF with supraclavicular nerve sacrificing techniques. Questionnaires were conducted and subjective numbness around supraclavicular nerve distribution was our primary outcome measure. Secondary outcome measures included the Quick Disability of the Arm, Shoulder and Hand (QuickDASH) score, a numeric rating scale for pain and satisfaction with treatment and surgical time.An overall response rate of 92% was achieved with an average follow-up of 16 months. There were 20 patients in the supraclavicular nerve sparing group and 79 patients in the supraclavicular nerve sacrificing group. 76% of all patients experienced numbness post-operatively and 91% of these patients experienced persistent numbness at final follow-up. There was no significant difference between the groups for age, gender, time to follow-up and mechanism of injury. Patients in the supraclavicular nerve sparing group had significantly less numbness at final follow-up (35% vs 86%, P0.001; OR=0.21 95%CI 0.11-0.40). There was no significant difference in the QuickDASH score nor the NRS for pain and function. Sparing supraclavicular nerves did not result in a significantly longer operation.Our study demonstrates that identification and protection of the supraclavicular nerves result in significantly less numbness following clavicle ORIF but does not affect patient reported functional outcomes.

Pancreatic cancer is a common gastrointestinal tumor with increasing morbidity and mortality, and it is difficult to differentiate it from chronic mass pancreatitis. F-18-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT) can be used for diagnosis of pancreatic cancer, staging, radiotherapy planning, evaluation of efficacy and recurrence, and differentiation from posttreatment fibrosis but the sensitivity and specificity of diagnosis of chronic pancreatitis are poor. Magnetic resonance imaging (MRI) not only shows the morphology, location, and size of organs and lesions but also has the advantages of low radiation, high soft tissue contrast, and multiparameter imaging, which can help determine the nature of occupying pancreatic lesions. In this study, the watershed algorithm (WA) was used to segment the abdominal images to extract images of pancreatic cancer cells and to compare the value of F-FDG PET/CT combined with MRI in the diagnosis of pancreatic occupying lesions.

Background The safety and effectiveness of lung segmentectomy in patients with early non-small cell lung cancer (NSCLC) remains controversial. We have therefore reviewed the clinicopathologic characteristics and survival outcomes of patients treated with lobectomy or segmentectomy for early T (> 2 and ≤ 3 cm) N0M0 NSCLC. Methods We obtained data from the Surveillance, Epidemiology, and End Results database for patients who underwent lobectomy or segmentectomy between 2004 and 2015. To reduce bias and imbalances between the treatment groups, propensity score matching analysis was performed. We used Kaplan–Meier curves to estimate overall survival (OS) and lung cancer-specific survival (LCSS). We conducted univariate and multivariate Cox proportional hazards regression analyses to identify independent prognostic factors for OS and cancer-specific survival, and applied the Cox proportional hazards model to create forest plots. Results Before matching, both univariate and multivariate Cox regression analyses revealed that patients who underwent lobectomy exhibited better OS (P P = 0.001) than patients who underwent segmentectomy. However, after matching, survival differences between the groups were not significant; OS (P = 0.434) and LCSS (P = 0.593). Regression analyses revealed that age and tumor grade were independent predictors of OS and LCSS (P Conclusions Patients with stage T (> 2 and ≤ 3 cm) N0M0 NSCLC undergoing segmentectomy can obtain OS and LCSS similar to those obtained with lobectomy. Further studies are required considering the solid component effects and pathologic tumor types regarding segmentectomies. Additional long-term survival and outcome analyses should be conducted with larger cohorts.

BACKGROUND: Women of color with breast cancer are less likely to undergo post-mastectomy reconstruction compared with White women, but it is unclear whether their perioperative outcomes are worse. The goal of this study was to investigate differences in preoperative comorbidities and postoperative complications by race/ethnicity among women with breast cancer undergoing postmastectomy reconstruction. STUDY DESIGN: Data were collected from the National Inpatient Sample database of the Healthcare Cost and Utilization Project from 2012 to 2016. Patient demographics, types of reconstruction, comorbid conditions, Charlson-Deyo Combined Comorbidity (CDCC) scores, length of stay (LOS), and perioperative complications were abstracted. Multivariate linear and logistic regression were performed to model LOS and likelihood of postoperative complications, respectively. RESULTS: Compared with White women (n = 19,730), Black women (n = 3,201) underwent autologous reconstruction more frequently (40.7% vs 28.3%), had more perioperative comorbidities (eg diabetes: 12.9% vs 5.8%), higher CDCC scores (% CDCC ≥ 4: 5.5% vs 2.7%), and longer LOS (median 3 vs 2 days, all p < 0.001). Being Black (vs white: +0.13 adjusted days, 95% CI 0.06 to 0.19) was also associated with longer LOS and an increased likelihood of surgical complications (vs White: odds ratio 1.24, 95% CI 1.09 to 1.42, both p < 0.01), but this association did not persist when outcomes were limited to microsurgical complications. CONCLUSION: Disparities in postmastectomy breast reconstruction between Black and White women extend beyond access to care and include perioperative factors and outcomes. These findings suggest an important opportunity to mitigate inequities in reconstruction through perioperative health optimization and improved access to and co-management with primary care.

Mounting evidence supports that angiotensin-converting enzyme 2 (ACE2) may exert a vital function in multiple complications induced by diabetes. The aim of this research was to verify the function of ACE2 in diabetic angiopathy (DA). In our study, it was revealed that high glucose (HG) treatment impeded cell proliferation and induced cell apoptosis. Moreover, ACE2 level was reduced in HG-stimulated HMEC-1 cells. Functional assays demonstrated that ACE2 addition promoted cell viability, suppressed apoptosis, oxidative stress, ROS generation, and inflammation in HG-stimulated HMEC-1 cells. Furthermore, the activation of the JAK2/STAT3 pathway induced by HG was impeded by overexpression of ACE2. Besides, JAK2/STAT3 pathway inhibitor AG490 reversed the changes of cell viability, apoptosis, oxidative stress, and inflammation caused by ACE2 deletion in HG-treated HMEC-1 cells. In sum, our findings highlighted that ACE2 promoted the viability and restrained the oxidative stress, inflammation, and apoptosis in HG-induced microvascular endothelial cells (VECs) injury via regulating the JAK2/STAT3 pathway, suggesting ACE2 might be a potential therapeutic target for DA treatment.

The current pandemic of COVID-19 is fueled by more infectious emergent Omicron variants. Ongoing concerns of emergent variants include possible recombinants, as genome recombination is an important evolutionary mechanism for the emergence and re-emergence of human viral pathogens. In this study, we identified diverse recombination events between two Omicron major subvariants (BA.1 and BA.2) and other variants of concern (VOCs) and variants of interest (VOIs), suggesting that co-infection and subsequent genome recombination play important roles in the ongoing evolution of SARS-CoV-2. Through scanning high-quality completed Omicron spike gene sequences, 18 core mutations of BA.1 (frequency >99%) and 27 core mutations of BA.2 (nine more than BA.1) were identified, of which 15 are specific to Omicron. BA.1 subvariants share nine common amino acid mutations (three more than BA.2) in the spike protein with most VOCs, suggesting a possible recombination origin of Omicron from these VOCs. There are three more Alpha-related mutations in BA.1 than BA.2, and BA.1 is phylogenetically closer to Alpha than other variants. Revertant mutations are found in some dominant mutations (frequency >95%) in the BA.1. Most notably, multiple characteristic amino acid mutations in the Delta spike protein have been also identified in the “Deltacron”-like Omicron Variants isolated since November 11, 2021 in South Africa, which implies the recombination events occurring between the Omicron and Delta variants. Monitoring the evolving SARS-CoV-2 genomes especially for recombination is critically important for recognition of abrupt changes to viral attributes including its epitopes which may call for vaccine modifications.

Paraquat (PQ) poisoning often leads to severe lung injuries, in which the mitochondria damage plays a critical role. Mitoquinone (MitoQ), a newly designed mitochondria-targeted antioxidant, has been proved for its benefit in mitochondria protection. However, the role of MitoQ in PQ-induced lung injury remains unclear. Thus, this study was performed to investigate the effect of MitoQ on PQ-induced lung injury and its underlying mechanisms. Our work showed that PQ caused the inhibition of A549 lung epithelial cell viability in a dose-dependent manner, while MitoQ remarkably mitigated the PQ-induced cell viability suppression. Besides this, PQ-mediated apoptosis of A549 cells was significantly attenuated by MitoQ, as indicated by the TUNEL assay and mitochondria membrane potential assay. Moreover, the intracellular reactive oxygen species (ROS) production was also dramatically suppressed when cotreated MitoQ with PQ. This could be ascribed to enhanced mitochondrial fusion mediated by Mitofusin 1 (MFN1)/Mitofusin 2 (MFN2), because MitoQ preserved mitochondrial network integrity, as reflected by MitoTracker staining, and MitoQ also increased the expression of MFN1/MFN2 in A549 cells after PQ treatment. Our data suggested MitoQ mitigated PQ-induced lung epithelial cell injury by promoting MFN1/MFN2-mediated mitochondrial fusion, and MitoQ might be a potential candidate drug for the treatment of PQ-induced lung injury.

Aberrant self-renewal of leukemia initiation cells (LICs) drives aggressive acute myeloid leukemia (AML). Here, we report that UHRF1, an epigenetic regulator that recruits DNMT1 to methylate DNA, is highly expressed in AML and predicts poor prognosis. UHRF1 is required for myeloid leukemogenesis by maintaining self-renewal of LICs. Mechanistically, UHRF1 directly interacts with Sin3A-associated protein 30 (SAP30) through two critical amino acids, G572 and F573 in its SRA domain, to repress gene expression. Depletion of UHRF1 or SAP30 derepresses an important target gene, MXD4, which encodes a MYC antagonist, and leads to suppression of leukemogenesis. Further knockdown of MXD4 can rescue the leukemogenesis by activating the MYC pathway. Lastly, we identified a UHRF1 inhibitor, UF146, and demonstrated its significant therapeutic efficacy in the myeloid leukemia PDX model. Taken together, our study reveals the mechanisms for altered epigenetic programs in AML and provides a promising targeted therapeutic strategy against AML.

Gadolinium (Gd)-contrast MRI for reliable detection of blood–brain barrier (BBB) breakdown is widely used in neuromyelitis optica spectrum disorder (NMOSD) attack. Nonetheless, little is known about the predictive role of gadolinium-enhancing lesion in prognosis of NMOSD attack. The aim of this work is to investigate the predictive value of persistently Gd-enhanced lesions to medium-term outcome after attack. Data for this analysis came from an ongoing prospective cohort study (CLUE). NMOSD patients with acute attack were enrolled from January 2019 to March 2020. All patients underwent Gd-contrast MRI at baseline and 1 month, and disability was assessed by Expanded Disability Status Scale (EDSS). Primary outcome was EDSS improvement from baseline to month 6. Multiple logistic regression identified predictors for poor recovery of NMOSD attack. Forty-one participants were analyzed, of which 21 patients had persistently Gd-enhancing lesions. Patients in no enhancement (NE) group showed a significant shift in 6-month EDSS distributions compared with those in persistent enhancement (PE) group (p = 0.005). Poor recovery rate of the PE group was higher than that of the NE group at 6 months (p = 0.033). In patients with aquaporin-4-positive, first-attack, transverse myelitis or in a high-dose steroid treatment subgroup, the improvement of EDSS scores in the PE group was still less compared with that in the NE group (p

Family socio-economic status (SES) is significantly related to disparities in children's executive function. Children from economically disadvantaged backgrounds perform worse on executive function tasks than their peers from high-SES families. The protective factors in the relationship between SES and executive function have not been sufficiently investigated, especially from the perspective of parents' and children's perceptions and expectations regarding SES. Therefore, this study aimed to examine whether parental subjective SES and children's subjective social mobility separately moderated the relationship between family SES and children's executive function among 885 participants aged 9-13 years. The results showed that family SES was positively related to the three components of executive function (cognitive flexibility, inhibitory control, and working memory). Moreover, the relationship between SES and cognitive flexibility was weak among the children with a high level of subjective social mobility or those whose parents had high levels of subjective SES. Among children from families with economic hardship, subjective social mobility is a potential protective factor mitigating the negative effects of low family SES on their cognitive flexibility.

Background/Aims Nonalcoholic fatty liver disease (NAFLD) is closely related to gut-microbiome. There is a paucity of research on which strains of gut microbiota affect the progression of NAFLD. This study explored the NAFLD-associated microbiome in humans and the role of Lactobacillus in the progression of NAFLD in mice. Methods The gut microbiome was analyzed via next-generation sequencing in healthy people (n=37) and NAFLD patients with elevated liver enzymes (n=57). Six-week-old male C57BL/6J mice were separated into six groups (n=10 per group; normal, Western, and four Western diet + strains [109 colony-forming units/g for 8 weeks; L. acidophilus, L. fermentum, L. paracasei, and L. plantarum]). Liver/body weight ratio, liver pathology, serum analysis, and metagenomics in the mice were examined. Results Compared to healthy subjects (1.6±4.3), NAFLD patients showed an elevated Firmicutes/Bacteroidetes ratio (25.0±29.0) and a reduced composition of Akkermansia and L. murinus (P

Background and Aims Butyric acid is an intestinal microbiota-produced short-chain fatty acid, which exerts salutary effects on alleviating nonalcoholic fatty liver disease (NAFLD). However, the underlying mechanism of butyrate on regulating hepatic lipid metabolism is largely unexplored. Methods A mouse model of NAFLD was induced with high-fat diet feeding, and sodium butyrate (NaB) intervention was initiated at the eighth week and lasted for 8 weeks. Hepatic steatosis was evaluated and metabolic pathways concerning lipid homeostasis were analyzed. Results Here, we report that administration of NaB by gavage once daily for 8 weeks causes an augmentation of insulin-induced gene (Insig) activity and inhibition of lipogenic gene in mice fed with high-fat diet. Mechanistically, NaB is sufficient to enhance the interaction between Insig and its upstream kinase AMP-activated protein kinase (AMPK). The stimulatory effects of NaB on Insig-1 activity are abolished in AMPKα1/α2 double knockout (AMPK−/−) mouse primary hepatocytes. Moreover, AMPK activation by NaB is mediated by LKB1, as evidenced by the observations showing NaB-mediated induction of phosphorylation of AMPK, and its downstream target acetyl-CoA carboxylase is diminished in LKB1–/– mouse embryonic fibroblasts. Conclusions These studies indicate that NaB serves as a negative regulator of hepatic lipogenesis in NAFLD and that NaB attenuates hepatic steatosis and improves lipid profile and liver function largely through the activation of LKB1-AMPK-Insig signaling pathway. Therefore, NaB has therapeutic potential for treating NAFLD and related metabolic diseases., Graphical abstract

As an essential biochemical indicator in the fields of pregnancy and oncology, human chorionic gonadotropin (HCG) can be evaluated using colloidal gold immunochromatographic paper and quantified using a biochemical analyzer based on the principle of the antibody sandwich method. In view of the inaccuracy of the former and the complication of the latter, this study constructed an accurate, sensitive and simple unlabeled biosensor based on peptide aptamer CGGGPPLRINRHILTR for HCG detection. Molecular Operating Environment (MOE) was used to simulate the aptamer and protein docking, and western blot (WB) was used to verify the binding effect and ratio. The peptide aptamer was characterized and was then reduced with tris-(2-carboxyethyl)-phosphine hydrochloride (TCEP). After electrochemical deposition of chloroauric acid on the screen-printed electrode (SPE), the aptamer was self-assembled on the electrode surface under optimal conditions. The active site of the electrode surface was blocked with 6-mercapto-1-hexanol (MCH) and BSA. The electrochemical impedance spectrum (EIS) was used to quantify HCG in the matrix. Showing a good linear relationship in the range of 5-1500 mIU mL-1, with a detection limit of 1 mIU mL-1, the biosensor remained stable at room temperature for 14 days. Because of its small size, stability, sensitivity and accuracy, this biosensor has great potential to become a portable diagnostic device for HCG.

Background Stress-related gastric mucosal damage or ulcer remains an unsolved issue for critically ill patients. Stress ulcer prophylaxis has been part of routine intensive care, but uncertainty and controversy still exist. Co-secreted with mucins, intestinal trefoil factor (ITF) is reported to promote restitution and regeneration of intestinal mucosal epithelium, although the mechanism remains unknown. Aim To elucidate the protective effects of ITF on gastric mucosa and explore the possible mechanisms. Methods We used a rat model of gastric mucosal damage induced by water immersion restraint stress and lipopolysaccharide-treated human gastric epithelial cell line to investigate the potential effects of ITF on damaged gastric mucosa both in vivo and in vitro. Results ITF promoted the proliferation and migration and inhibited necrosis of gastric mucosal epithelia in vitro. It also preserved the integrity of gastric mucosa by upregulating expressions of occludin and zonula occludens-1. In the rat model, pretreatment with ITF ameliorated the gastric mucosal epithelial damage and facilitated mucosal repair. The protective effects of ITF were confirmed to be exerted via activation of Akt signaling, and the specific inhibitor of Akt signaling LY249002 reversed the protective effects. Conclusion ITF might be a promising candidate for prevention and treatment of stress-induced gastric mucosal damage, and further studies should be undertaken to verify its clinical feasibility.

Background The latest guidance on chronic fatigue syndrome (CFS) recommends exercise therapy. Tai Chi, an exercise method in traditional Chinese medicine, is reportedly helpful for CFS. However, the mechanism remains unclear. The present longitudinal study aimed to detect the influence of Tai Chi on functional brain connectivity in CFS. Methods The study recruited 20 CFS patients and 20 healthy controls to receive eight sessions of Tai Chi exercise over a period of one month. Before the Tai Chi exercise, an abnormal functional brain connectivity for recognizing CFS was generated by a linear support vector model. The prediction ability of the structure was validated with a random forest classification under a permutation test. Then, the functional connections (FCs) of the structure were analyzed in the large-scale brain network after Tai Chi exercise while taking the changes in the Fatigue Scale-14, Pittsburgh Sleep Quality Index (PSQI), and the 36-item short-form health survey (SF-36) as clinical effectiveness evaluation. The registration number is ChiCTR2000032577 in the Chinese Clinical Trial Registry. Results 1) The score of the Fatigue Scale-14 decreased significantly in the CFS patients, and the scores of the PSQI and SF-36 changed significantly both in CFS patients and healthy controls. 2) Sixty FCs were considered significant to discriminate CFS (P = 0.000, best accuracy 90%), with 80.5% ± 9% average accuracy. 3) The FCs that were majorly related to the left frontoparietal network (FPN) and default mode network (DMN) significantly increased (P = 0.0032 and P = 0.001) in CFS patients after Tai Chi exercise. 4) The change of FCs in the left FPN and DMN were positively correlated (r = 0.40, P = 0.012). Conclusion These results demonstrated that the 60 FCs we found using machine learning could be neural biomarkers to discriminate between CFS patients and healthy controls. Tai Chi exercise may improve CFS patients’ fatigue syndrome, sleep quality, and body health statement by strengthening the functional connectivity of the left FPN and DMN under these FCs. The findings promote our understanding of Tai Chi exercise’s value in treating CFS.

Although circular RNAs (circRNAs) are known to play key roles in non-alcoholic fatty liver disease, much about their targets and mechanisms remains unknown. We therefore investigated the actions and mechanisms of hsa_circ_0048179 in an in vitro model of NAFLD. HepG2 cells were exposed to oleate/palmitate (2:1 ratio) for 24 h to induce intracellular lipid accumulation. Using CCK-8 assays, flow cytometry, fluorescence microscopy, western blotting, RT-qPCR, and Oil red O staining, we found that oleate/palmitate treatment reduced cell viability while increasing apoptosis and lipid accumulation in HepG2 cells. Levels of the antioxidant enzyme GPX4 were decreased in oleate/palmitate-treated HepG2 cells, and there were corresponding increases in reactive oxygen species and damage to mitochondrial cristae. Levels of hsa_circ_0048179 expression were also suppressed by oleate/palmitate treatment, and GPX4 levels were markedly increased in HepG2 cells following transfection with hsa_circ_0048179. Analysis of its mechanism revealed that hsa_circ_0048179 upregulated GPX4 levels by acting as a competitive “sponge” of miR-188-3p and that hsa_circ_0048179 attenuated oleate/palmitate-induced lipid accumulation in HepG2 cells by sponging miR-188-3p. Collectively, our findings suggest that hsa_circ_0048179 may play a key role in the pathogenesis of steatosis and may thus be a useful target for drug development.

BACKGROUND: We examined whether the National Comprehensive Cancer Network distress thermometer (DT), a patient-reported outcome measure, could be used to identify levels and causes of distress associated with racial/ethnic disparities in time to care among patients with breast cancer. METHODS: We identified women aged ≥18 years with stage O-IV breast cancer who were diagnosed in a single health system between January 2014 and July 2016. The baseline visit was defined as the first postdiagnosis, pretreatment clinical evaluation. Zero-inflated negative binomial (ZINB) regression (modeling non-zero DT scores and DT scores = 0) and logistic regression (modeling DT score ≥ 4, threshold for social services referral) were used to examine associations between baseline score (0 = none to 10 = extreme) and types of stressors (emotional, familial, practical, physical, spiritual) after adjustment for race/ethnicity and other characteristics. Linear regression with log transformation was used to identify predictors of time to evaluation and time to treatment. RESULTS: A total of 1029 women were included (median baseline DT score = 4). Emotional, physical, and practical stressors were associated with distress in both the ZINB and logistic models (all P < .05). Black patients (n = 258) were more likely to report no distress than Whites (n = 675; ZINB zero model odds ratio, 2.72; 95% CI, 1.68-4.40; P < .001) despite reporting a similar number of stressors (P = .07). Higher DT scores were associated with shorter time to evaluation and time to treatment while being Black and having physical or practical stressors were associated with delays in both (all P < .05). CONCLUSIONS: Patient-reported stressors predicted delays in time to care, but patient-reported levels of distress did not, with Black patients having delayed time to care despite reporting low levels of distress. We describe anticipatory, culturally responsive strategies for using patient-reported outcomes to address observed disparities.

BACKGROUND: Elderly women with clinically node-positive (cN+) breast cancer (BC) often have comorbidities that limit life expectancy and complicate treatment. We sought to determine whether the number of lymph nodes (LNs) retrieved among older women with node-positive breast cancer was associated with overall survival (OS). METHODS: Using the National Cancer Database (2010–2015), women 70–90y with cN+ BC and ≥1 LN removed were categorized by treatment sequence: upfront surgery or neoadjuvant chemotherapy (NAC). Multivariable Cox proportional hazards models with restricted cubic splines characterized the functional association of LN retrieval with OS; threshold values of LN retrieval were estimated. Cox proportional hazards models were used to estimate the association of LN retrieval groups with OS. RESULTS: In the upfront surgery cohort, a non-linear association was identified between LNs retrieved and OS. In the NAC cohort, no association was identified. For the upfront surgery cohort, the optimal threshold value of LN retrieval was 21 LN (90% CI 18–23). Based on this estimate, LN retrieval groups were created: 23 LNs. After adjustment, retrieval of

Allogeneic hematopoietic stem cell transplantation (HCT) is a potentially curative treatment for both malignant and nonmalignant hematologic diseases; however, reported rates of treatment-related mortality approach 30%. Outcomes are worse in patients who begin HCT with functional impairments. To detect such impairments, a geriatric assessment (GA) is recommended in adults age ≥65 years. Younger HCT candidates also may be impaired because of chemotherapy regimens pre-HCT. Therefore, we hypothesized that GA can be beneficial for adult patients of all ages and subsequently created a clinical pretransplantation optimization program to assess all HCT candidates using a modified GA. One-hundred fifty-seven patients were evaluated in 4 functional domains- physical, cognitive, nutritional, and psychological-at 2 time points prior to HCT-new patient evaluation (NPE) and sign-off (SO)-between October 2017 and January 2020. At NPE, 80.9% of the patients had at least 1 domain with a functional impairment, and physical (P = .006), cognitive (P = .04), and psychological (P = .04) impairments were associated with an increased likelihood of not proceeding to HCT. In addition, patients age 18 to 39 years were more likely than older patients to have a physical function impairment (P = .001). Between NPE and SO, 51.9% of the patients had resolution of 1 or more impairments, and nutritional impairment at SO was predictive of worse overall survival (P = .01). Our study shows that GA can identify functional impairments in patients of all ages. Early identification of impairments could facilitate referrals to supportive care and resolution of impairments prior to HCT, suggesting that GA could be recommended for HCT candidates of all ages.

Malignant phyllodes (MP) and primary breast sarcomas (PBS) are rare neoplasms with overlapping histopathologic features. We compared overall survival (OS) and estimated the association of surgery and therapies with OS.We utilized the National Cancer Database (2004-2016). Patients without surgery, unknown surgery, or margins, or Stage IV disease were excluded. Kaplan-Meier curves and Cox proportional hazards models were used to estimate unadjusted and adjusted OS, respectively.A total of 3209 (59.5%) MP, and 2185 (40.5%) PBS were identified. Despite a larger median tumor size in MP (46 vs. 40 mm PBS, p 0.001), lumpectomy rate was higher for MP (52.9% vs. 27.0% PBS, p 0.001). Compared to MP, PBS patients more frequently received radiation (28.9% vs. 24%), and chemotherapy (28.1% vs. 4%), both p 0.001. Unadjusted OS was lower for PBS (57% vs. 85% MP, log-rank p 0.001). PBS (vs. MP) had persistently worse survival (hazard ratio [HR]: 1.98, 95% confidence interval [CI]: 1.69-2.31) after adjustment. Receipt of adjuvant therapies was not associated with OS (either neoplasm); however, lumpectomy was associated with improved OS (vs. mastectomy) for both PBS (HR: 0.59, 95% CI: 0.50-0.75) and MP (HR: 0.65, 95% CI: 0.53-0.81). Positive margins had no association with OS for MP (HR: 1.09, 95% CI: 0.75-1.60), but was associated with worse survival for PBS (HR: 2.35, 95% CI: 1.82-3.02).We found significant survival differences between MP and PBS, with PBS having a consistently worse OS. Our findings support surgery as the mainstay of treatment for both tumor types and suggest that lumpectomy may be a reasonable option for select patients without compromising outcomes.

Background Identification of potential novel targets for reversing resistance to Epidermal Growth Factor Receptor (EGFR)-tyrosine kinase inhibitors (EGFR-TKIs) holds great promise for the treatment of relapsed lung adenocarcinoma (LUAD). In the present study, we aim to investigate the role of methyltransferase-like 7B (METTL7B) in inducing EGFR-TKIs resistance in LUAD and whether it could be a therapeutic target for reversing the resistance. Methods METTL7B-overexpressed LUAD cell lines, gefitinib and osimertinib-resistant Cell-Derived tumor Xenograft (CDX) and Patient-Derived tumor Xenograft (PDX) mouse models were employed to evaluate the role of METTL7B in TKIs resistance. Ultraperformance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS) was used to identify the metabolites regulated by METTL7B. Methylated RNA immunoprecipitation (MeRIP)-qPCR analysis was performed to measure the N6-methyladenosine (m6A) status of mRNA of METTL7B targeted genes. Gold nanocluster-assisted delivery of siRNA targeting METTL7B (GNC-siMETTL7B) was applied to evaluate the effect of METTL7B in TKIs resistance. Results Increased expression of METTL7B was found in TKIs-resistant LUAD cells and overexpression of METTL7B in LUAD cells induced TKIs resistance both in vitro and in vivo. Activated ROS-metabolism was identified in METTL7B-overexpressed LUAD cells, accompanied with upregulated protein level of GPX4, HMOX1 and SOD1 and their enzymatic activities. Globally elevated m6A levels were found in METTL7B-overexpressed LUAD cells, which was reduced by knock-down of METTL7B. METTL7B induced m6A modification of GPX4, HMOX1 and SOD1 mRNA. Knock-down of METTL7B by siRNA re-sensitized LUAD cells to gefitinib and osimertinib both in vitro and in vivo. Conclusions This study uncovered a new critical link in METTL7B, glutathione metabolism and drug resistance. Our findings demonstrated that METTL7B inhibitors could be used for reversing TKIs resistance in LUAD patients.

Patients undergoing allogeneic (allo) and autologous (auto) hematopoietic cell transplantation (HCT) require extensive hospitalizations or daily clinic visits for the duration of their transplantation. Home HCT, wherein patients live at home and providers make daily trips to the patient's residence to perform assessments and deliver any necessary interventions, may enhance patient quality of life and improve outcomes. We conducted the first study of home HCT in the United States to evaluate this model in the US healthcare setting and to determine the effect on clinical outcomes and quality of life. This case-control study evaluated patients who received home HCT at Duke University in Durham, North Carolina, from November 2012 to March 2018. Each home HCT patient was matched with 2 controls from the same institution who had received standard treatment based on age, disease, and type of transplant for outcomes comparison. Clinical outcomes were abstracted from electronic health records, and quality of life was assessed via Functional Assessment of Cancer Therapy-Bone Marrow Transplant. Clinical outcomes were compared with Student's t-test or Fisher's exact test (continuous variables) or chi-square test (categorical variables). Quality of life scores were compared using the Student t-test. All analyses used a significance threshold of 0.05. Twenty-five patients received home HCT, including 8 allos and 17 autos. Clinical outcomes were not significantly different between the home HCT patients and their matched controls; home HCT patients had decreased incidence of relapse within 1 year of transplantation. Pre-HCT quality of life was well preserved for autologous home HCT patients. This Phase I study demonstrated that home HCT can be successfully implemented in the United States. There was no evidence that home HCT outcomes were inferior to standard-of-care treatment, and patients undergoing autologous home HCT were able to maintain their quality of life. A Phase II randomized trial of home versus standard HCT is currently underway to better compare outcomes and costs.

Dermatomyositis is an autoimmune disease characterized by damage to the skin and muscles. CD4GSE46239, GSE142807, GSE1551, and GSE193276 datasets were downloaded. The WGCNA and CIBERSORT algorithms were performed to identify the most correlated gene module with CD4In the brown module, 5 key genes (chromosome 1 open reading frame 106 (The

Non-alcoholic fatty liver disease (NAFLD) is a metabolic disorder defined as the presence of intrahepatic lipid deposition and steatosis as well as chronic inflammation without excessive alcohol consumption. Our previous studies found that inulin could dramatically improve lipid metabolism disorders in NAFLD murine models. In recent years, mounting evidence has approved that there are disproportionately increased bile acids (BAs) in patients with NAFLD while the hepatic bile acids signaling is suppressed. Meanwhile the primary function of bile acids is to promote the excretion of cholesterol and therefore keep the cholesterol metabolism balance. Hence, we investigate whether inulin exerts beneficial effects on lipid metabolism disorders by modulating bile acids signaling in our present study. And we found that inulin treatment significantly reversed the abnormal accumulation of bile acids in high-fat-induced NAFLD mice. Furthermore, our data confirmed that inulin supplementation attenuates NAFLD via restoring the activity of FXR accompanied by increasing hepatic bile acids de novo synthesis and further enhancing bile acids excretion in mice.

Introduction In order to study the role of the microbiome in hematopoietic stem cell transplantation (HCT), researchers collect stool samples from patients at various time points throughout HCT. However, stool collection requires active subject participation and may be limited by patient reluctance to handling stool. Methods We performed a prospective study on the impact of financial incentives on stool collection rates. The intervention group consisted of allogeneic HCT patients from 05/2017-05/2018 who were compensated with a $10 gas gift card for each stool sample. The intervention group was compared to a historical control group of allogeneic HCT patients from 11/2016-05/2017 who provided stool samples before the incentive was implemented. To control for possible changes in collections over time, we also compared a contemporaneous control group of autologous HCT patients from 05/2017-05/2018 with a historical control group of autologous HCT patients from 11/2016-05/2017; neither autologous HCT group was compensated. The collection rate was defined as the number of samples provided divided by the number of time points we attempted to obtain stool. Results There were 35 allogeneic HCT patients in the intervention group, 19 allogeneic HCT patients in the historical control group, 142 autologous HCT patients in the contemporaneous control group (that did not receive a financial incentive), and 75 autologous HCT patients in the historical control group. Allogeneic HCT patients in the intervention group had significantly higher average overall collection rates when compared to the historical control group allogeneic HCT patients (80% vs 37%, p Conclusion Our results demonstrate that a modest incentive can significantly increase collection rates. These results may help to inform the design of future studies involving stool collection.

Although hematopoietic stem cell transplantation (HCT) is the only curative treatment for acute myeloid leukemia (AML), it is associated with significant treatment related morbidity and mortality. There is great need for predictive biomarkers associated with overall survival (OS) and clinical outcomes. We hypothesized that circulating metabolic, inflammatory, and immune molecules have potential as predictive biomarkers for AML patients who receive HCT treatment. This retrospective study was designed with an exploratory approach to comprehensively characterize immune, inflammatory, and metabolomic biomarkers. We identified patients with AML who underwent HCT and had existing baseline plasma samples. Using those samples (n = 34), we studied 65 blood based metabolomic and 61 immune/inflammatory related biomarkers, comparing patients with either long-term OS (≥ 3 years) or short-term OS (OS ≤ 1 years). We also compared the immune/inflammatory response and metabolomic biomarkers in younger vs. older AML patients (≤30 years vs. ≥ 55 years old). In addition, the biomarker profiles were analyzed for their association with clinical outcomes, namely OS, chronic graft versus host disease (cGVHD), acute graft versus host disease (aGVHD), infection and relapse. Several baseline biomarkers were elevated in older versus younger patients, and baseline levels were lower for three markers (IL13, SAA, CRP) in patients with OS ≥ 3 years. We also identified immune/inflammatory response markers associated with aGVHD (IL-9, Eotaxin-3), cGVHD (Flt-1), infection (D-dimer), or relapse (IL-17D, bFGF, Eotaxin-3). Evaluation of metabolic markers demonstrated higher baseline levels of medium- and long-chain acylcarnitines (AC) in older patients, association with aGVHD (lactate, long-chain AC), and cGVHD (medium-chain AC). These differentially expressed profiles merit further evaluation as predictive biomarkers.

The belief in upward social mobility promotes the mental health and social adaptation of disadvantaged adolescents. However, efforts for upward mobility may facilitate psychosocial adaptation while undermining physical health for minority youth from disadvantaged backgrounds. Therefore, we aimed to examine how social mobility belief is associated with mental and physical health among Chinese rural-to-urban migrant adolescents and explore whether positive affect acts as a protective factor moderating these relationships.A total of 158 rural-to-urban migrant adolescents aged 10-14 completed a self-report questionnaire and underwent medical examination.Social mobility belief and positive affect were positively related to mental health (general self-efficacy). Positive affect interacted with social mobility belief in predicting physical health (self-rated health and allostatic load). For migrant adolescents with low levels of positive affect, strong belief in social mobility was associated with poor self-rated health and high allostatic load. For migrant adolescents with high levels of positive affect, their physical health was better and not associated with social mobility belief.Social mobility belief showed a double-edged sword effect; it was positively associated with mental adaptation while negatively associated with physical health among Chinese rural-to-urban migrant adolescents. Positive affect acted as a protective factor for decreasing the negative association between social mobility belief and physical health.

Virtual reality exposure therapy (VRET) has been commonly utilised as an extension of cognitive behavioural therapy (CBT). However, most studies examined its effectiveness among adults, with no study focusing on children with selective mutism (SM). We aimed to examine its feasibility and acceptability among children with SM. Twenty children aged 6–12 with SM diagnosis were recruited and completed six therapist-guided VRET sessions. Parents and clinicians completed measures at pre-VRET, post-VRET, 1-month and 3-month follow-up visits. At post-VRET, parent and child participants completed the acceptability questionnaires. Findings suggested the feasibility of VRET as all participants completed the programme with no attrition. Parents and child participants also reported VRET to be an acceptable and effective treatment for SM. Significant improvement in overall functioning were found at post-treatment and follow-up measures, but there were no significant changes in parent-rated speech frequency and anxiety measures. These support the acceptability of VRET as an adjunct modality (and not substitute) of CBT in SM treatment. Future studies, with more robust experimental designs and larger sample sizes, can be conducted to confirm its efficacy. As technology becomes more sophisticated, tools such as virtual environments can be explored to enhance evidence-based care for children and their families.

Background. Stroke can lead to disruption of the whole-brain network in patients. Acupuncture can modulate the functional network on a large-scale level in healthy individuals. However, whether and how acupuncture can make a potential impact on the disrupted whole-brain network after ischemic stroke remains elusive. Methods. 26 stroke patients with a right hemispheric subcortical infarct were recruited. We gathered the functional magnetic resonance imaging (fMRI) from patients with stroke and healthy controls in the resting state and after acupuncture intervention, to investigate the instant alterations of the large-scale functional networks. The graph theory analysis was applied using the GRETNA and SPM12 software to construct the whole-brain network and yield the small-world parameters and network efficiency. Results. Compared with the healthy subjects, the stroke patients had a decreased normalized small-worldness (σ), global efficiency (Eg), and the mean local efficiency (Eloc) of the whole-brain network in the resting state. There was a correlation between the duration after stroke onset and Eloc. Acupuncture improved the patients’ clustering coefficient (Cp) and Eloc but did not make a significant impact on the σ and Eg. The postacupuncture variables of the whole-brain network had no association with the time of onset. Conclusion. The poststroke whole-brain network tended to a random network with reduced network efficiency. Acupuncture was able to modulate the disrupted patterns of the whole-brain network following the subcortical ischemic stroke. Our findings shed light on the potential mechanisms of the functional reorganization on poststroke brain networks involving acupuncture intervention from a large-scale perspective.