The histone variant H2A.W defines heterochromatin and promotes chromatin condensation in Arabidopsis.

Histone variants play crucial roles in gene expression, genome integrity, and chromosome segregation. We report that the four H2A variants in Arabidopsis define different genomic features, contributing to overall genomic organization. The histone variant H2A.W marks heterochromatin specifically and acts in synergy with heterochromatic marks H3K9me2 and DNA methylation to maintain transposon silencing. In vitro, H2A.W enhances chromatin condensation by promoting fiber-to-fiber interactions via its conserved C-terminal motif. In vivo, H2A.W is required for heterochromatin condensation, demonstrating that H2A.W plays critical roles in heterochromatin organization. Similarities in conserved motifs between H2A.W and another H2A variant in metazoans suggest that plants and animals share common mechanisms for heterochromatin condensation.

Impact of Metastatic Lymph Nodes on Survival of Patients with pN1-Category Esophageal Squamous Cell Carcinoma: A Long-Term Survival Analysis.

BACKGROUND: The morbidity and mortality rates of esophageal squamous cell carcinoma (ESCC) are high in China. The overall survival (OS) of patients with ESCC is related to lymph node (LN) metastasis (LNM). This study aimed to discuss the impact of metastasis in LN stations on the OS of patients with pathologic N1 (pN1) ESCC. METHODS: Data were obtained from the Esophageal Cancer Case Management database of Sichuan Cancer Hospital and Institute (SCCH-ECCM). Additionally, data of patients with pN1-category ESCC collected between January 2010 and December 2017 were retrospectively analyzed. RESULTS: Data from 807 patients were analyzed. The median OS of the patients with one metastatic LN (group 1) was 49.8 months (95 % confidence interval [CI], 30.8-68.9 months), whereas the OS of those with two metastatic LNs (group 2) was only 33.3 months (P = 0.0001). Moreover, group 1 did not show a significantly longer OS than group 2.1 (patients with 2 metastatic LNs in 1 LNM station; P = 0.5736), but did show a significantly longer OS than group 2.2 (patients with 2 metastatic LNs in 2 LNM stations; P < 0.0001). After propensity score-matching, the 5-year survival rate for group 1 was 28 %, whereas that for group 2 was 14 % (P = 0.0027). CONCLUSIONS: The OS for the patients with one metastatic LN in one LNM was not significantly longer than for the patients with two metastatic LNs in one LNM station. Patients with one LNM station had a significantly longer OS than those with two LNM stations. Thus, the number of LNM stations is a significant determinant of OS in pN1 ESCC.

USP5 facilitates bladder cancer progression by stabilizing the c-Jun protein.

BACKGROUND: Bladder cancer is the second most common genitourinary malignancy worldwide. The death rate of bladder cancer has increased every year. However, the molecular mechanism of bladder cancer is not sufficiently studied. Deubiquitinating enzymes (DUBs) play an important role in carcinogenesis. Several studies have demonstrated that USP5 associated with malignancy and pathological progression in hepatocellular carcinoma, colorectal and non-small cell lung cancer. However, the role of USP5 in bladder cancer need to be explored. METHODS: The USP5 expression was analysed using the web server GEPIA. To explore USP5 function in bladder cancer, we constructed USP5-knockout cell lines in T24 cells. A FLAG-USP5 (WT USP5) plasmid and a plasmid FLAG-USP5 C335A (catalytic-inactive mutant) used to overexpress USP5 in EJ cells. CCK8, colony formation, transwell and scratch assays were used to assess cell viability, proliferation and migration. RNA sequencing (RNA-seq) and dual-luciferase reporter assays were performed to screen the pathway. Coimmunoprecipitation and immunofluorescence were used to explore the interaction between USP5 and c-Jun. Cycloheximide (CHX) chase assays were performed to establish the effect of USP5 on c-Jun stability. Xenograft mouse model was used to study the role of USP5 in bladder cancer. RESULTS: USP5 expression is increased in bladder cancer patients. Genetic ablation of USP5 markedly inhibited bladder cancer cell proliferation, viability, and migration both in vitro and in vivo. RNA-seq and luciferase pathway screening showed that USP5 activated JNK signalling, and we identified the interaction between USP5 and c-Jun. USP5 was found to activate c-Jun by inhibiting its ubiquitination. CONCLUSIONS: Our results show that high USP5 expression promotes bladder cancer progression by stabilizing c-Jun and that USP5 is a potential therapeutic target in bladder cancer.

ST14 interacts with TMEFF1 and is a predictor of poor prognosis in ovarian cancer.

TMEFF1 is a new protein involved in the physiological functions of the central nervous system, and we previously reported TMEFF1 can promote ovarian cancer. ST14 was determined to be involved in the processes of epidermal differentiation, epithelial cell integrity, and vascular endothelial cell migration, etc. The relationship between ST14 and TMEFF1 in the ovary remains unknown. In this study, we detected the expression of ST14 and TMEFF1 in 130 different ovarian cancer tissues through immunohistochemistry. We determined ST14 and TMEFF1 were highly expressed in ovarian cancer, indicating a higher degree of tumor malignancy and a worse prognosis. Tissues significantly expressing ST14 also highly expressed TMEFF1, and the expression of the two proteins was positively correlated. Consistently, immunofluorescence double staining demonstrated the co-localization of ST14 and TMEFF1 in the same region, and immunoprecipitation confirmed the interaction between ST14 and TMEFF1. TMEFF1 expression was also reduced after knocking down ST14 through Western blot. MTT, wound healing and Transwell assays results determined that knockdown of ST14 inhibited proliferation, migration and invasion of ovarian cancer cells in vitro, but the inhibitory effect was restored after adding TMEFF1 exogenous protein. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways analysis showed that ST14 and its related genes were enriched in the processes of epithelial formation, intercellular adhesion, protein localization, and mitosis regulation. We also clarified the kinase, microRNA, and transcription factor target networks and the impact of genetic mutations on prognosis. Overall, high expression of ST14 and TMEFF1 in ovarian cancer predicts higher tumor malignancy and a worse prognosis. ST14 and TMEFF1 co-localize and interact with each other in ovarian cancer. ST14 can regulate TMEFF1 expression to promote proliferation, migration and invasion of ovarian cancer cells. We speculate that the relationship between ST14 and TMEFF1 in ovarian cancer could become a potential target for anti-cancer therapy.

Consolidation chemotherapy after definitive concurrent chemoradiotherapy in patients with inoperable esophageal squamous cell carcinoma: a multicenter non-inferiority phase III randomized clinical trial.

BACKGROUND: Definitive concurrent chemoradiotherapy (dCCRT) is the gold standard for the treatment of locally advanced esophageal squamous cell carcinoma (ESCC). However, the potential benefits of consolidation chemotherapy after dCCRT in patients with esophageal cancer remain debatable. Prospective randomized controlled trials comparing the outcomes of dCCRT with or without consolidation chemotherapy in patients with ESCC are lacking. In this study, we aim to generate evidence regarding consolidation chemotherapy efficacy in patients with locally advanced, inoperable ESCC. METHODS: This is a multicenter, prospective, open-label, phase-III randomized controlled trial comparing non-inferiority of dCCRT alone to consolidation chemotherapy following dCCRT. In total, 600 patients will be enrolled and randomly assigned in a 1:1 ratio to receive either consolidation chemotherapy after dCCRT (Arm A) or dCCRT alone (Arm B). Overall survival will be the primary endpoint, whereas progression-free survival, locoregional progression-free survival, distant metastasis-free survival, and treatment-related toxicity will be the secondary endpoints. DISCUSSION: This study aid in further understanding the effects of consolidation chemotherapy after dCCRT in patients with locally advanced, inoperable ESCC. TRIAL REGISTRATION: ChiCTR1800017646.

EQ-5D-5L Population Norms for China Derived From a National Health Survey.

OBJECTIVES: To develop the EQ-5D-5L (5L) population norms for China and to assess the relationship between various factors and 5L data. METHODS: This study used data derived from the Psychology and Behavior Investigation of Chinese Residents, a national sample survey of 21 909 representative participants aged 12 years and above. Participants' health-related quality of life (HRQoL) was measured by the 5L. Their socioeconomic characteristics, behavioral factors, and health conditions were also obtained from the survey. Norm scores were generated and compared for different socioeconomic variables. Multiple linear and logistic regressions were used to assess the relationships of the 3 kinds of variables with the 5L utility, visual analog scale (VAS) scores and 5L health problems. RESULTS: The mean (SD) age of participants was 39.4 (18.9) years, and 50.0% of them were female. The mean (SD) utility and VAS scores were 0.940 (0.138) and 73.4 (21.6), respectively. Participants reported considerably more problems in anxiety/depression (26.2%) and pain/discomfort (22.2%) dimensions. The gender difference in HRQoL is attenuated. The participants older than 75 years suffered from a sharp decline in HRQoL; the participants in Shanghai and Tibet provinces reported lower utility and VAS scores and more health problems. Those who were younger, with better socioeconomic status and healthier lifestyles, and without diseases tended to report higher utility and VAS scores and fewer health problems. CONCLUSIONS: This study derived the 5L population norms for China based on a representative population sample.

Longitudinal patient-reported outcomes after minimally invasive McKeown esophagectomy for patients with esophageal squamous cell carcinoma.

PURPOSE: Surgery for esophageal squamous cell carcinoma (ESCC) is characterized by a poor prognosis and high complication rate, resulting in a heavy symptom burden and poor health-related quality of life (QOL). We evaluated longitudinal patient-reported outcomes (PROs) to analyze the correlations between symptoms and QOL and their changing characteristics during postoperative rehabilitation. METHODS: We investigated patients with ESCC who underwent minimally invasive McKeown esophagectomy at Sichuan Cancer Hospital between April 2019 and December 2019. Longitudinal data of the clinical characteristics and PROs were collected. The MD Anderson Symptom Inventory and European Organization for Research and Treatment of Cancer (EORTC) QOL questionnaires were used to assess symptoms and QOL and compare the trajectories of PROs during the investigation. RESULTS: A total of 244 patients with ESCC were enrolled in this study. Regarding QOL, role and emotional functions returned to baseline at 1 month after surgery, and cognitive and social functions returned to baseline at 3 months after surgery. However, physical function and global QOL did not return to baseline at 1 year after surgery. At 7 days and 1, 3, 6, and 12 months after surgery, the main symptoms of the patients were negatively correlated with physical, role, emotional, cognitive, and social functions and the overall health status (P < 0.05). CONCLUSION: Patients with ESCC experience reduced health-related QOL and persisting symptoms after minimally invasive McKeown esophagectomy, but a recovery trend was observed within 1 month. The long-term QOL after esophagectomy is acceptable.

Multimorbidity patterns and health-related quality of life among community-dwelling older adults: evidence from a rural town in Suzhou, China.

PURPOSE: The high prevalence of multimorbidity in aging societies has posed tremendous challenges to the healthcare system. The aim of our study was to comprehensively assess the association of multimorbidity patterns and health-related quality of life (HRQOL) among rural Chinese older adults. METHODS: This was a cross-sectional study. Data from 4,579 community-dwelling older adults aged 60 years and above was collected by the clinical examination and questionnaire survey. Information on 10 chronic conditions was collected and the 3-Level EQ-5D (EQ-5D-3L) was adopted to measure the HRQOL of older adults. An exploratory factor analysis was performed to determine multimorbidity patterns. Regression models were fitted to explore the associations of multimorbidity patterns with specific health dimensions and overall HRQOL. RESULTS: A total of 2,503 (54.7%) participants suffered from multimorbidity, and they reported lower HRQOL compared to those without multimorbidity. Three kinds of multimorbidity patterns were identified including cardiovascular-metabolic diseases, psycho-cognitive diseases and organic diseases. The associations between psycho-cognitive diseases/organic diseases and overall HRQOL assessed by EQ-5D-3L index score were found to be significant (ß = - 0.097, 95% CI - 0.110, - 0.084; ß = - 0.030, 95% CI - 0.038, - 0.021, respectively), and psycho-cognitive diseases affected more health dimensions. The impact of cardiovascular-metabolic diseases on HRQOL was largely non-significant. CONCLUSION: Multimorbidity was negatively associated with HRQOL among older adults from rural China. The presence of the psycho-cognitive diseases pattern or the organic diseases pattern contributed to worse HRQOL. The remarkable negative impact of psycho-cognitive diseases on HRQOL necessiates more attention and relevant medical assistance to older rural adults.

A pH-triggered N-oxide polyzwitterionic nano-drug loaded system for the anti-tumor immunity activation research.

Triple negative breast cancer (TNBC) has the characteristics of low immune cell infiltration, high expression of tumor programmed death ligand 1 (PD-L1), and abundant cancer stem cells. Systemic toxicity of traditional chemotherapy drugs due to poor drug selectivity, and chemotherapy failure due to tumor drug resistance and other problems, so it is particularly important to find new cancer treatment strategies for TNBC with limited treatment options. Both the anti-tumor natural drugs curcumin and ginsenoside Rg3 can exert anti-tumor effects by inducing immunogenic cell death (ICD) of tumor cells, reducing PD-L1 expression, and reducing cancer stem cells. However, they have the disadvantages of poor water solubility, low bioavailability, and weak anti-tumor effect of single agents. We used vinyl ether bonds to link curcumin (Cur) with N-O type zwitterionic polymers and at the same time encapsulated ginsenoside Rg3 to obtain hyperbranched zwitterionic drug-loaded micelles OPDEA-PGED-5HA@Cur@Rg3 (PPH@CR) with pH response. In vitro cell experiments and in vivo animal experiments have proved that PPH@CR could not only promote the maturation of dendritic cells (DCs) and increase the CD4+ T cells and CD8+ T cells by inducing ICD in tumor cells but also reduce the expression of PD-L1 in tumor tissues, and reduce cancer stem cells and showed better anti-tumor effects and good biological safety compared with free double drugs, which is a promising cancer treatment strategy.

Heteroaggregation and deposition behaviors of carboxylated nanoplastics with different types of clay minerals in aquatic environments: Important role of calcium(II) ion-assisted bridging.

The widespread utilization of plastic products ineluctably leads to the ubiquity of nanoplastics (NPs), causing potential risks for aquatic environments. Interactions of NPs with mineral surfaces may affect NPs transport, fate and ecotoxicity. This study aims to investigate systematically the deposition and aggregation behaviors of carboxylated polystyrene nanoplastics (COOH-PSNPs) by four types of clay minerals (illite, kaolinite, Na-montmorillonite, and Ca-montmorillonite) under various solution chemistry conditions (pH, temperature, ionic strength and type). Results demonstrate that the deposition process was dominated by electrostatic interactions. Divalent cations (i.e., Ca2+, Mg2+, Cd2+, or Pb2+) were more efficient for screening surface negative charges and compressing the electrical double layer (EDL). Hence, there were significant increases in deposition rates of COOH-PSNPs with clay minerals in suspension containing divalent cations, whereas only slight increases in deposition rates of COOH-PSNPs were observed in monovalent cations (Na+, K+). Negligible deposition occurred in the presence of anions (F-, Cl-, NO3-, CO32-, SO42-, or PO43-). Divalent Ca2+ could incrementally facilitate the deposition of COOH-PSNPs through Ca2+-assisted bridging with increasing CaCl2 concentrations (0-100 mM). The weakened deposition of COOH-PSNPs with increasing pH (2.0-10.0) was primarily attributed to the reduce in positive charge density at the edges of clay minerals. In suspensions containing 2 mM CaCl2, increased Na+ ionic strength (0-100 mM) and temperature (15-55 ◦C) also favored the deposition of COOH-PSNPs. The ability of COOH-PSNPs deposited by four types of clay minerals followed the sequence of kaolinite > Na-montmorillonite > Ca-montmorillonite > illite, which was related to their structural and surface charge properties. This study revealed the deposition behaviors and mechanisms between NPs and clay minerals under environmentally representative conditions, which provided novel insights into the transport and fate of NPs in natural aquatic environments.

Inhibition of miR-9 Combined With Cisplatin Targeting APE1 Against Angiogenesis in Osteosarcoma.

Osteosarcoma (OS) is a highly malignant tumor, and chemotherapy resistance suggests poor prognosis in OS patients. In this study, the authors discovered that miR-9 has a pro-angiogenic role in OS. The anti-angiogenic effects of cisplatin were greatly increased when miR-9 was suppressed in OS. In addition, the authors demonstrated that miR-9 plays a pro-angiogenic role by targeting apoptosis-inducing factor 1 (APE1) in OS. Importantly, our in vivo experiments showed that inhibition of miR-9 combined with cisplatin could suppress xenograft tumor growth by targeting APE1 and decreasing angiogenesis in OS. In summary, our results suggest that miR-9 plays a role as a tumor promoter, and inhibiting miR-9 and APE1 is a new strategy for inhibiting OS angiogenesis and chemotherapy resistance.

The hue of temporomandibular joint arthroscopy under local versus general anaesthesia.

BACKGROUND: Temporomandibular joint arthroscopy (TMJA) is often performed under general anaesthesia (GA) worldwide on an inpatient basis, whereas local anaesthesia (LA) is not equally considered as the standard procedure. OBJECTIVES: To compare the efficacy between LA and GA when performing TMJA. METHODS: This study retrospectively reviewed a total of 182 patients in LA group and 91 patients in GA group who underwent TMJA for the management of disc displacement. Patients were divided into two groups based on type of anaesthesia used for surgery; LA group and GA group. Comparisons were made based on operative time, intubation and extubation time (for GA only), hospital stay duration, total cost and post-operative clinical and radiological outcomes. RESULTS: The demographics and pre-operative clinical assessments were matched in both groups. No post-operative significant difference was found in outcomes when performing TMJA under LA compared to GA in terms of pain reduction (p = .016) and improvement in mouth opening (p = .866). The median operative time and hospital stay duration for LA group were significantly less compared to GA group (p < .001). GA group required an additional intubation and extubation time, whereas LA group patients were waived from it. TMJA for LA group was performed in the minor procedure setup, which reduced the costs for surgery (p < .001). Post-operative disc position was excellent and good with an overall success rate of 95%. CONCLUSION: The use of LA performing TMJA reduces operating time, costs, hospital stay and recovery room time than GA group. Furthermore, TMJA performed under LA shared similar post-operative clinical and radiological outcomes with those performed under GA.

Evaluation of the efficacy and quality of life in patients with temporomandibular joint disorders treated with Kovacs digital occlusal splint: a pilot study.

BACKGROUND: Few studies have been conducted on treating temporomandibular disorders (TMDs) with new digital occlusal splints, which has increasingly attracted wide attention. METHODS: To evaluate the clinical efficacy and quality of life (QoL) of Kovacs digital occlusal splint (KDOS) treatment in patients with TMD. MATERIALS AND METHODS: Eighty-nine patients with TMD who were treated using KDOS were analyzed. The patients were divided into three groups according to the Wilkes stage. The clinical symptoms and QoL scores of the patients in each group were recorded before and at least three months after treatment, and the data were statistically analyzed and compared. The relationships between the disease severity, sex, age, and level of QoL before treatment and improvement in the clinical symptoms were analyzed using binary logistic regression. RESULTS: The mean age and follow-up period of the patients were 28.0 ± 10.4 years and 4.9 ± 2.1 months, respectively. After KDOS treatment, the improvement rates of joint noise and pain were 80.4% and 69.8%, respectively. Additionally, the patients' maximum mouth opening and global QoL mean scores significantly improved compared to those before treatment (p < 0.001). Binary logistic regression analysis revealed that the factors affecting the improvement in the clinical symptoms were disease severity and level of QoL before treatment. CONCLUSIONS: KDOS can improve the clinical symptoms and QoL of patients with TMD. Moreover, patients without osteoarthritis and with low pretreatment QoL levels are more likely to demonstrate clinical improvement. TRIAL REGISTRATION: The trial was registered with Chinese Clinical Trial Registry (ChiCTR) (ID: ChiCTR2300076518) on 11/10/2023.

Mapping of Lymph Node Metastasis and Efficacy Index in Thoracic Esophageal Squamous Cell Carcinoma: A Large-Scale Retrospective Analysis.

BACKGROUND: Esophageal squamous cell carcinoma has a high mortality rate in China. The metastatic pattern in the lymph nodes and the value of their dissection on the overall survival of these patients remain controversial. The primary aim of this study was to provide a basis for accurate staging of esophageal cancer and to identify the relationship between esophageal cancer surgery, lymph node dissection, and overall survival rates. METHODS: We utilized our hospital database to retrospectively review the data of 1727 patients with esophageal cancer who underwent R0 esophagectomy from January 2010 to December 2017. The lymph nodes were defined according to Japanese Classification of Esophageal Cancer, 11th Edition. The Efficacy Index (EI) was calculated by multiplying the frequency (%) of metastases to a zone and the 5-year survival rate (%) of patients with metastases to that zone, and then dividing by 100. RESULTS: The EI was high in the supraclavicular and mediastinal zones in patients with upper esophageal tumors, and the EI of 101R was 17.39, which was the highest among the lymph node stations. In patients with middle esophageal tumors, the EI was highest in the mediastinal zone, followed by the celiac and supraclavicular zones. Furthermore, the EI was highest in the celiac zone, followed by the mediastinal zones in patients with lower esophageal tumors. CONCLUSIONS: The EI of resected lymph nodes was found to vary between stations and was related to the primary location of the tumor.

Nucleolar protein treacle ribosome biogenesis factor 1 maintains gastric cancer cell proliferation by regulating R-loop associated DNA replication stress.

BACKGROUND AND AIM: Gastric cancer (GC) is a common malignant neoplasm in the gastrointestinal tract, accounting for high mortality globally. Treacle ribosome biogenesis factor 1 (TCOF1) is a nucleolar protein, which has been reported to be implicated in the pathogenesis of Treacher Collins syndrome and the development of several types of human cancer. However, the role of TCOF1 in GC is not known. METHODS: Immunohistochemistry was carried out to determine TCOF1 expression in GC tissues. Immunofluorescence, co-IP, and DNA fiber assays were conducted to investigate the function of TCOF1 in GC-derived BGC-823 and SGC-7901 cell lines. RESULTS: TCOF1 expression was aberrantly increased in GC tissues compared with adjacent normal tissues. In addition, we found that TCOF1 left the nucleolus and localized to R-loops (DNA/RNA hybrids) during S phase in GC cells. Furthermore, TCOF1 interacted with DDX5 and suppressed R-loop levels. Knockdown of TCOF1 led to increased nucleoplasmic R-loops specifically during S phase, which restrained DNA replication and cell proliferation. Overexpression of R-loop eraser RNaseH1 rescued the DNA synthesis defects and decreased DNA damage caused by TCOF1 depletion. CONCLUSION: These findings demonstrate a novel role of TCOF1 in maintaining GC cell proliferation by alleviating R-loop associated DNA replication stress.

Prevalent falls, fall frequencies and health-related quality of life among community-dwelling older Chinese adults.

PURPOSE: Fall is a serious health hazard to older adults. The aim of our study was to investigate the relationship between falls and health-related quality of life (HRQOL) in mainland China. METHODS: Data from 4579 Chinese community-dwelling older adults was analyzed. Data of falls was self-reported by participants, the HRQOL of older adults was measured by the 3-Level EQ-5D (EQ-5D-3L, 3L). Regression models were built to explore the associations of falls (experience and frequency) with the 3L data (index score, EQ-VAS score and health problems). The potential interaction effects between falls and gender on HRQOL were assessed using a likelihood ratio test, sex-stratified analysis was also performed to separately investigate the associations in men and women. RESULTS: A total of 368 (8.0%) participants had the experience of fall during the last year. Falls (experience and frequency) were significantly related to EQ-5D-3L index and EQ-VAS scores, fall experience contributed to pain/discomfort and anxiety/depression problems, while fall frequency was associated with physical-related problems and pain/discomfort. Significant interactions between falls and sex in several EQ-5D measures were also observed, and men had lager magnitude of associations than women. CONCLUSION: Falls were negative associated with overall HRQOL as well as separate HRQOL dimensions among older adults. It also appears that the HRQOL influence on older men is more evident than older women.

Association between alcohol use and frailty among elder adults in three Chinese cities.

BACKGROUND: Frailty is often described as a condition of the elderly and alcohol use is associated with frailty. The aim of this study is to examine the associations between alcohol use and frailty in three cities in elder adults. METHODS: A cross-sectional study was conducted in three cities in China from June 2017 to October 2018. In total, 2888 residents aged ≥65 years old were selected by using a multi-level stage sampling procedure. Alcohol use was assessed by Focusing on Cutting down, Annoyance by criticism, Guilty feeling, and Eye-openers (CAGE) four-item questionnaire. Frailty was measured by a validated Chinese version of the Fatigue, Resistance, Ambulation, Illness, and Loss of weight (FRAIL) scale. Multinomial logistic regressions were used to examine the association of alcohol use with pre-frailty and frailty after controlling for varied covariates. RESULTS: In general, the prevalence of pre-frailty and frailty was 38.64 and 20.26%, respectively. After controlling for covariates and interaction of age and problematic drinking, non-problematic drinkers neither had association with pre-frailty (OR: 1.15, 95%CI:0.86-1.52) nor with frailty (OR:0.90, 95%CI:0.60-1.36), and problematic drinkers neither had association with frailty (OR: 1.21, 95%CI:0.83-1.76), while problematic drinkers had high odd ratios of frailty (OR:3.28, 95%CI:2.02-5.33) compared with zero-drinker. CONCLUSIONS: Our study found a positive association between problematic drinking and frailty, no relationship between non-problematic drinking and (pre-)frailty compared with zero-drinking among Chinese elder adults. Based on previous findings and ours, we conclude it is important for the prevention of frailty to advocate no problematic drinking among elder adults.

Durable response to afatinib in advanced lung adenocarcinoma harboring a novel NPTN-NRG1 fusion: a case report.

BACKGROUND: NRG1 fusions are rare oncogenic drivers in solid tumors, and the incidence of NRG1 fusions in non-small cell lung cancer (NSCLC) was 0.26%. It is essential to explore potential therapeutic strategies and efficacy predictors for NRG1 fusion-positive cancers. CASE PRESENTATION: We report an advanced lung adenocarcinoma patient harboring a novel NPTN-NRG1 fusion identified by RNA-based next-generation sequencing (NGS), which was not detected by DNA-based NGS at initial diagnosis. Transcriptomics data of the tissue biopsy showed NRG1α isoform accounted for 30% of total NRG1 reads, and NRG1ß isoform was undetectable. The patient received afatinib as fourth-line treatment and received a progression-free survival (PFS) of 14 months. CONCLUSIONS: This report supports afatinib can provide potential benefit for NRG1 fusion patients, and RNA-based NGS is an accurate and cost-effective strategy for fusion detection and isoform identification.

Garcinone E suppresses breast cancer growth and metastasis by modulating tumor-associated macrophages polarization via STAT6 signaling.

Cancer metastasis remains the most common cause of death in breast cancer patients. Tumor-associated macrophages (TAMs) are a novel therapeutic target for the treatment of metastatic breast cancer. Despite the good anti-cancer activity of garcinone E (GE), there are no reports on its therapeutic effects on breast cancer metastasis. The objective of this study was to examine the anti-cancer effects of GE on metastatic breast cancer. RAW 264.7 and THP-1 cells were polarized to M2 macrophages by IL-4/IL-13 in vitro. A 4T1 mouse breast cancer model and the tail vein breast cancer metastasis model were used to explore the effect of GE on breast cancer growth and metastasis in vivo. In vitro studies showed that GE dose-dependently suppressed IL-4 + IL-13-induced expression of CD206 in both RAW 264.7 cells and differentiated THP-1 macrophages. However, GE did not affect the LPS + IFN-γ-induced polarization to the M1-like macrophages in vitro. GE inhibited the expression of the M2 macrophage specific genes in RAW 264.7 cells, and simultaneously impaired M2 macrophage-induced breast cancer cell proliferation and migration, and angiogenesis. In animal studies, GE significantly suppressed tumor growth, angiogenesis, and lung metastasis in 4T1 tumor-bearing mice, without causing toxicity. In both tumor and lung tissues, the proportion of M2-like TAMs was significantly decreased while the proportion of M1-like TAMs was markedly increased by GE treatment. Mechanistically, GE inhibited phosphorylation of STAT6 in vitro and in vivo. Our results demonstrate for the first time that GE suppresses breast cancer growth and pulmonary metastasis by modulating M2-like macrophage polarization through the STAT6 signaling pathway.

Analysis of preoperative influential factors and construction of a predictive nomogram of difficult thyroidectomy.

OBJECTIVE: To explore the preoperative influential factors of difficult thyroidectomy and establish a preoperative nomogram for predicting the difficulty of thyroidectomy. METHODS: A total of 753 patients who underwent total thyroidectomy with central lymph node dissection between January 2018 and December 2021 were retrospectively enrolled in this study and randomly divided into training and validation groups at a ratio of 8:2. In both subgroups, the patients were divided into difficult thyroidectomy and nondifficult thyroidectomy groups based on the operation time. Patient age, sex, body mass index (BMI), thyroid ultrasound, thyroid function, preoperative fine needle aspiration (FNA), postoperative complications and other data were collected. Logistic regression analysis was performed to identify the predictors of difficult thyroidectomy, and a nomogram predicting surgical difficulty was created. RESULTS: Multivariate logistic regression analysis demonstrated that male sex (OR = 2.138, 95% CI 1.055-4.336, p = 0.035), age (OR = 0.954, 95% CI 0.932-0.976, p < 0.001), BMI (OR = 1.233, 95% CI 1.106-1.375, p < 0.001), thyroid volume (OR = 1.177, 95% CI 1.104-1.254, p < 0.001) and TPO-Ab (OR = 1.001, 95% CI 1.001-1.002, p = 0.001) were independent risk factors for difficult thyroidectomy. The nomogram model incorporating the above predictors performed well in both the training and validation sets. A higher postoperative complication rate was found in the difficult thyroidectomy group than in the nondifficult thyroidectomy group. CONCLUSION: This study identified independent risk factors for difficult thyroidectomy and created a predictive nomogram for difficult thyroidectomy. This nomogram may help to objectively and individually predict surgical difficulty before surgery and provide optimal treatment.