Mutational Landscape of Gastric Adenocarcinoma of the Fundic Gland Type Revealed by Whole Genome Sequencing.

BACKGROUND: Gastric adenocarcinoma of the fundic gland type (GA-FG) is a newly described variant of gastric adenocarcinoma with lack of knowledges regarding its genetic features. METHODS: We performed whole-genome sequencing (WGS) in formalin-fixed paraffin-embedded (FFPE) tumor tissues and matched adjacent noncancerous specimens from 21 patients with GA-FG, and integrated published datasets from 1105 patients with traditional gastric adenocarcinoma with the purpose of dissecting genetic determinants both common to conventional gastric adenocarcinoma and unique to GA-FG disease. RESULTS: We characterized the genomic architecture of GA-FG disease, revealing the predominant proportion of C > T substitution among the six types of SNVs. GNAS was the most significantly mutated driver gene (14.29%). 42.8% of samples harbored "Kataegis." Distinct genomic alterations between GA-FG and conventional gastric cancer were identified. Specifically, low mutational burden and relatively moderate mutational frequencies of significantly mutated driver genes, coupled with the absence of non-silent alterations of formerly well-known drivers such as TP53, PIK3CA and KRAS were identified in GA-FG patients. Oncogenic signaling pathway analysis revealed mutational processes associated with focal adhesions and proteoglycans in cancer, highlighting both common and specific procedures during the development of GA-FG and conventional gastric cancer. CONCLUSION: Our study is the first to comprehensively depict the genomic landscape highlighting the multidimensional perturbations in GA-FG patients. These discoveries offered mechanistic insights for novel diagnostic and therapeutic strategies for patients with such disease.

ß-sitosterol alleviates pulmonary arterial hypertension by altering smooth muscle cell phenotype and DNA damage/cGAS/STING signaling.

BACKGROUND: Pulmonary arterial smooth muscle cells (PASMCs) have a neoplastic phenotype characterized by hyperproliferative and anti-apoptotic features that contribute to pulmonary hypertension (PH) development. DNA-sensing adapter protein stimulator of interferon genes (STING) regulate the phenotypic switch of vessel smooth muscle cells. ß-sitosterol (SITO) is a nutrient derived from plants that inhibits vascular smooth muscle cell proliferation without notable toxicity. However, the effect of SITO on cancer-like PH-associated pulmonary vascular remodeling and the specific mechanism has not yet be studied. PURPOSE: This study investigated the in vitro and in vivo effects of SITO against PH, and its underlying mechanisms. METHODS: The therapeutic efficacy of SITO was assessed, and its underlying mechanisms were explored in hypoxia-induced and platelet-derived growth factor (PDGF)-BB-stimulated primary PASMCs and in a monocrotaline (MCT)-induced preclinical PH rat model. SITO or sildenafil (SID) were administered after the MCT intraperitoneal injection. Pulmonary parameters, right heart function, morphology, and PASMCs were cultured for verification. The expression levels of DNA damage/cyclic GMP-AMP synthase (cGAS)/STING were determined using immunofluorescence and Western blotting. STING agonists that interfere with PASMCs were used to determine whether STING mediates the effects of SITO. RESULTS: SITO prevented PASMCs proliferation, promoted apoptosis and suppressed phenotypic switching in a dose-dependent manner in vitro and in vivo. In vivo results in rats demonstrated that four weeks of intragastric SITO administration effectively mitigated the MCT-induced elevation of hemodynamic parameters, improved right cardiac function, and reduced pulmonary arteries remodeling. Mechanistically, DNA damage and cGAS/STING/nuclear factor kappa-B signaling activation were observed in rats with PH and cultured PASMCs. SITO exhibited protective effects by suppressing the DNA damage, potentially via inhibiting the expression level of the cGAS/STING signaling pathway. Pharmacological overexpression of STING abolished the anti-proliferative effects of SITO treatment in hypoxia-induced and PDGF-stimulated PASMCs by downregulating PCNA. CONCLUSION: SITO may be an attractive agent for PH vascular remodeling by inhibiting proliferation and modulating the phenotypic switch in PASMCs via the DNA damage/cGAS/STING signaling pathway. This study provides a novel therapeutic agent and mediator of the pathological development of PASMCs and PH.

Kinesiophobia in patients after cardiac surgery: a scoping review.

BACKGROUND: This paper reviews the scope of research on kinesiophobia in patients after cardiac surgery. Further, it reviews the current situation, evaluation tools, risk factors, adverse effects, and intervention methods of kinesiophobia to provide a reference for promoting early rehabilitation of patients after cardiac surgery. METHODS: Guided by the scoping methodology, the Web of Science, PubMed, CINAHL, Cochrane Library, China Biomedical Literature Database, VIP Database, Wanfang Database, CNKI, and other databases were searched from database inception until July 31, 2024. The studies obtained were screened, summarised and systematically analysed by two researchers. RESULTS: Eighteen studies (16 cross-sectional studies, one qualitative study, and one randomised controlled trial) were included. The incidence of kinesiophobia in patients after cardiac surgery was 39.20-82.57%, and the Tampa Scale for Kinesiophobia Heart (TSK-SV Heart) was used to evaluate this incidence. The influencing factors of kinesiophobia in patients after cardiac surgery included demographic characteristics, pain severity, frailty, exercise self-efficacy, disease-related factors, and psychosocial factors. Kinesiophobia led to adverse health outcomes such as reduced recovery, prolonged hospital stays, and decreased quality of life in patients after cardiac surgery, and there were few studies on intervention methods for postoperative kinesiophobia. CONCLUSION: The kinesiophobia assessment tools suitable for patients after cardiac surgery should be improved, and intervention methods to promote the early recovery of patients after major clinical surgery and those with difficult and critical diseases should be actively researched.

The correlation between healthy lifestyle habits and all-cause and cardiovascular mortality in Guangxi.

BACKGROUND: Adherence to healthy lifestyle habits has become a mainstream approach for lessening the burden of cardiovascular disease (CVD) during initial prevention efforts. The purpose of this study was to investigate the prevalence of four healthy lifestyle habits, the associated factors, and their impact on all-cause and cardiovascular mortality among residents of Guangxi Zhuang Autonomous Region. METHODS: From 2015 to 2019, individuals between the ages of 35 and 75 from Guangxi Zhuang Autonomous Region were recruited through the ChinaHeart Million Person Project. Our study examined four healthy lifestyle habits: not smoking, no or moderate amounts of alcohol, sufficient leisure time physical activity (LTPA) and a balanced diet. RESULTS: Out of the 19,969 individuals involved, the majority, 77.3% did not smoke, while 96.7% had limited alcohol intake, 24.5% engaged in sufficient LTPA, 5.5% followed a balanced diet, and merely 1.7% adhered to all four healthy lifestyle habits. Participants who were women, older, nonfarmers, living in cities, with a high income or level of education, or had hypertension or diabetes were more likely to follow all four healthy lifestyle habits (p < 0.001). People who followed the three healthy lifestyle habits had reduced chances of death from all cause (HR 0.34[95% CI:0.15,0.76]) and cardiovascular-related death (HR 0.23 [95% CI: 0.07, 0.68]) (p < 0.01) over a median period of 3.5 years. CONCLUSIONS: In Guangxi Province, the level of adherence to healthy lifestyle habits is very minimal. Therefore, population-specific health promotion strategies are urgently needed.

Incidence and influencing factors of olfactory dysfunction in patients 1 week after endoscopic transsphenoidal resection of pituitary tumor: a cross-sectional study of 158 patients.

Objective: To investigate the current situation of olfactory dysfunction in patients after endoscopic transsphenoidal resection of pituitary tumors, and analyze its influencing factors, to provide references for clinical nursing and rehabilitation. Methods: A cross-sectional study design and convenience sampling method were used to investigate 158 patients with pituitary tumors treated by endoscopic transsphenoidal pituitary tumor resection in the Department of Neurosurgery of three Grade-A general hospitals in Sichuan Province from January 2022 and June 2023. The olfactory function of patients was evaluated 1 week after surgery, and the general clinical data and olfactory related data of patients were collected, and the influencing factors of olfactory disorder were analyzed by logistic regression. Results: The incidence of olfactory dysfunction was 73.42%. analysis revealed that the formation of blood scabs, nasal cavity adhesion, cerebrospinal fluid leakage and operation time were independent risk factors for olfactory dysfunction in patients after transsphenoidal pituitary tumor resection (p < 0.05). Conclusion: The incidence of olfactory dysfunction is high in patients after endoscopic transsphenoidal resection of pituitary tumors, suggesting that medical staff should pay close attention to and identify patients with olfactory dysfunction based on the guidance of disease knowledge and skills, develop targeted nursing interventions, and promote the improvement of patients' olfactory function and quality of life.

STAU1-mediated CNBP mRNA degradation by LINC00665 alters stem cell characteristics in ovarian cancer.

BACKGROUND: To investigate the role of lncRNA LINC00665 in modulating ovarian cancer stemness and its influence on treatment resistance and cancer development. METHODS: We isolated ovarian cancer stem cells (OCSCs) from the COC1 cell line using a combination of chemotherapeutic agents and growth factors, and verified their stemness through western blotting and immunofluorescence for stem cell markers. Employing bioinformatics, we identified lncRNAs associated with ovarian cancer, with a focus on LINC00665 and its interaction with the CNBP mRNA. In situ hybridization, immunohistochemistry, and qPCR were utilized to examine their expression and localization, alongside functional assays to determine the effects of LINC00665 on CNBP. RESULTS: LINC00665 employs its Alu elements to interact with the 3'-UTR of CNBP mRNA, targeting it for degradation. This molecular crosstalk enhances stemness by promoting the STAU1-mediated decay of CNBP mRNA, thereby modulating the Wnt and Notch signaling cascades that are pivotal for maintaining CSC characteristics and driving tumor progression. These mechanistic insights were corroborated by a series of in vitro assays and validated in vivo using tumor xenograft models. Furthermore, we established a positive correlation between elevated CNBP levels and increased disease-free survival in patients with ovarian cancer, underscoring the prognostic value of CNBP in this context. CONCLUSIONS: lncRNA LINC00665 enhances stemness in ovarian cancer by mediating the degradation of CNBP mRNA, thereby identifying LINC00665 as a potential therapeutic target to counteract drug resistance and tumor recurrence associated with CSCs.

Y4 RNA fragments from cardiosphere-derived cells ameliorate diabetic myocardial ischemia‒reperfusion injury by inhibiting protein kinase C ß-mediated macrophage polarization.

The specific pathophysiological pathways through which diabetes exacerbates myocardial ischemia/reperfusion (I/R) injury remain unclear; however, dysregulation of immune and inflammatory cells, potentially driven by abnormalities in their number and function due to diabetes, may play a significant role. In the present investigation, we simulated myocardial I/R injury by inducing ischemia through ligation of the left anterior descending coronary artery in mice for 40 min, followed by reperfusion for 24 h. Previous studies have indicated that protein kinase Cß (PKCß) is upregulated under hyperglycemic conditions and is implicated in the development of various diabetic complications. The Y4 RNA fragment is identified as the predominant small RNA component present in the extracellular vesicles of cardio sphere-derived cells (CDCs), exhibiting notable anti-inflammatory properties in the contexts of myocardial infarction and cardiac hypertrophy. Our investigation revealed that the administration of Y4 RNA into the ventricular cavity of db/db mice following myocardial I/R injury markedly enhanced cardiac function. Furthermore, Y4 RNA was observed to facilitate M2 macrophage polarization and interleukin-10 secretion through the suppression of PKCß activation. The mechanism by which Y4 RNA affects PKCß by regulating macrophage activation within the inflammatory environment involves the inhibition of ERK1/2 phosphorylation In our study, the role of PKCß in regulating macrophage polarization during myocardial I/R injury was investigated through the use of PKCß knockout mice. Our findings indicate that PKCß plays a crucial role in modulating the inflammatory response associated with macrophage activation in db/db mice experiencing myocardial I/R, with a notable exacerbation of this response observed upon significant upregulation of PKCß expression. In vitro studies further elucidated the protective mechanism by which Y4 RNA modulates the PKCß/ERK1/2 signaling pathway to induce M2 macrophage activation. Overall, our findings suggest that Y4 RNA plays an anti-inflammatory role in diabetic I/R injury, suggesting a novel therapeutic approach for managing myocardial I/R injury in diabetic individuals.

Risk factors affecting spinal fusion: A meta-analysis of 39 cohort studies.

PURPOSE: We performed a meta-analysis to identify risk factors affecting spinal fusion. METHODS: We systematically searched PubMed, Embase, and the Cochrane Library from inception to January 6, 2023, for articles that report risk factors affecting spinal fusion. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using fixed-effects models for each factor for which the interstudy heterogeneity I2 was < 50%, while random-effects models were used when the interstudy heterogeneity I2 was ≥ 50%. Using sample size, Egger's P value, and heterogeneity across studies as criteria, we categorized the quality of evidence from observational studies as high-quality (Class I), moderate-quality (Class II or III), or low-quality (Class IV). Furthermore, the trim-and-fill procedure and leave-one-out protocol were conducted to investigate potential sources of heterogeneity and verify result stability. RESULTS: Of the 1,257 citations screened, 39 unique cohort studies comprising 7,145 patients were included in the data synthesis. High-quality (Class I) evidence showed that patients with a smoking habit (OR, 1.57; 95% CI, 1.11 to 2.21) and without the use of bone morphogenetic protein-2 (BMP-2) (OR, 4.42; 95% CI, 3.33 to 5.86) were at higher risk for fusion failure. Moderate-quality (Class II or III) evidence showed that fusion failure was significantly associated with vitamin D deficiency (OR, 2.46; 95% CI, 1.24 to 4.90), diabetes (OR, 3.42; 95% CI, 1.59 to 7.36), allograft (OR, 1.82; 95% CI, 1.11 to 2.96), conventional pedicle screw (CPS) fixation (OR, 4.77; 95% CI, 2.23 to 10.20) and posterolateral fusion (OR, 3.63; 95% CI, 1.25 to 10.49). CONCLUSIONS: Conspicuous risk factors affecting spinal fusion include three patient-related risk factors (smoking, vitamin D deficiency, and diabetes) and four surgery-related risk factors (without the use of BMP-2, allograft, CPS fixation, and posterolateral fusion). These findings may help clinicians strengthen awareness for early intervention in patients at high risk of developing fusion failure.

System-wide identification of novel de-ubiquitination targets for USP10 in gastric cancer metastasis through multi-omics screening.

OBJECTIVE: Ubiquitin-specific peptidase 10 (USP10), a typical de-ubiquitinase, has been found to play a double-edged role in human cancers. Previously, we reported that the expression of USP10 was negatively correlated with the depth of gastric wall invasion, lymph node metastasis, and prognosis in gastric cancer (GC) patients. However, it remains unclear whether USP10 can regulate the metastasis of GC cells through its de-ubiquitination function. METHODS: In this study, proteome, ubiquitinome, and transcriptome analyses were conducted to comprehensively identify novel de-ubiquitination targets for USP10 in GC cells. Subsequently, a series of validation experiments, including in vitro cell culture studies, in vivo metastatic tumor models, and clinical sample analyses, were performed to elucidate the regulatory mechanism of USP10 and its de-ubiquitination targets in GC metastasis. RESULTS: After overexpression of USP10 in GC cells, 146 proteins, 489 ubiquitin sites, and 61 mRNAs exhibited differential expression. By integrating the results of multi-omics, we ultimately screened 9 potential substrates of USP10, including TNFRSF10B, SLC2A3, CD44, CSTF2, RPS27, TPD52, GPS1, RNF185, and MED16. Among them, TNFRSF10B was further verified as a direct de-ubiquitination target for USP10 by Co-IP and protein stabilization assays. The dysregulation of USP10 or TNFRSF10B affected the migration and invasion of GC cells in vitro and in vivo models. Molecular mechanism studies showed that USP10 inhibited the epithelial-mesenchymal transition (EMT) process by increasing the stability of TNFRSF10B protein, thereby regulating the migration and invasion of GC cells. Finally, the retrospective clinical sample studies demonstrated that the downregulation of TNFRSF10B expression was associated with poor survival among 4 of 7 GC cohorts, and the expression of TNFRSF10B protein was significantly negatively correlated with the incidence of distant metastasis, diffuse type, and poorly cohesive carcinoma. CONCLUSIONS: Our study established a high-throughput strategy for screening de-ubiquitination targets for USP10 and further confirmed that inhibiting the ubiquitination of TNFRSF10B might be a promising therapeutic strategy for GC metastasis.

Subchronic Toxicity Evaluation of Idesia polycarpa Fruit Oil by 90-Day Oral Exposure in Wistar Rats.

Idesia polycarpa, belonging to the Flacourtiaceae family, is a tall deciduous tree, widely distributed in some Asian countries. It is famous for its high yield of fruit known as oil grape, which is rich of linoleic acid and linolenic acid, and so on. To provide evidences for its safe use as food, subchronic toxicity of I. polycarpa fruit oil and no observed adverse effect level were performed in male and female specific pathogen-free Wistar rats. Based on the Organization for Economic Co-operation and Development guidelines, the oil was orally administered to rats by gavage at 0, 1.0, 2.0, and 4.0mL/kg.bw/day for 90 days, followed by a 28-day recovery period. The results showed that no sign of oil-related toxicity, clinically or histologically, was observed in both male and female rats. Although there was a slight increase or decrease in some indicators such as hematology, serum chemistry, and so on, those changes were all within the normal ranges, and as presented in the 90-day study, the oil exhibited no toxic effect compared to the control rats. I. polycarpa might be a potential excellent and healthy vegetable oil resource.

Effect of screening colonoscopy frequency on colorectal cancer mortality in patients with a family history of colorectal cancer.

BACKGROUND: Colorectal cancer is a common malignant tumor in China, and its incidence in the elderly is increasing annually. Inflammatory bowel disease is a group of chronic non-specific intestinal inflammatory diseases, including ulcerative colitis and Crohn's disease. AIM: To assess the effect of screening colonoscopy frequency on colorectal cancer mortality. METHODS: We included the clinicopathological and follow-up data of patients with colorectal cancer who underwent laparoscopic colectomy or open colectomy at our Gastrointestinal Department between January 2019 and December 2022. Surgical indicators, oncological indicators, and survival rates were compared between the groups. The results of 104 patients who met the above criteria were extracted from the database (laparoscopic colectomy group = 63, open colectomy group = 41), and there were no statistically significant differences in the baseline data or follow-up time between the two groups. RESULTS: Intraoperative blood loss, time to first ambulation, and time to first fluid intake were significantly lower in the laparoscopic colectomy group than in the open colectomy group. The differences in overall mortality, tumor-related mortality, and recurrence rates between the two groups were not statistically significant, and survival analysis showed that the differences in the cumulative overall survival, tumor-related survival, and cumulative recurrence-free rates between the two groups were not statistically significant. CONCLUSION: In elderly patients with colorectal cancer, laparoscopic colectomy has better short-term outcomes than open colectomy, and laparoscopic colectomy has superior long-term survival outcomes compared with open colectomy.

Predictors of quitting support from nonsmoking mothers for smoking fathers: a cross-sectional study from Chinese pupils' families.

BACKGROUND: Quitting support from smokers' partners can predict quit attempts and smoking abstinence but research on factors that predict such support has been limited. To add more evidence for partner support and the improved interventions for smoking cessation, we analyzed some new potential predictors of quitting support from smokers' spouses. METHOD: This cross-sectional study was conducted in in 2022 and 2023, selecting the students' families in which fathers smoked and mothers didn't smoke from grade 1-5 of 13 primary schools in Qingdao, China. Parents who met the criteria completed the online questionnaires and 1018 families were included in the analysis. We measured personal information related to smokers and their spouses such as age, education and nicotine dependence, and variables related to family and marital relationship such as family functioning, perceived responsiveness and power in decision-making of quitting smoking. Quitting support from smokers' spouses was measured by Partner Interaction Questionnaire and generalized linear model was used to explore the potential predictors of partner support. RESULTS: In this study, the mean age of smokers was 39.97(SD = 5.57) and the mean age of smokers' spouses was 38.24(SD = 4.59). The regression analysis showed that for smokers and their spouses, the older age groups showed the lower ratio of positive/negative support(P < 0.05) and smokers with high education showed the less positive and negative partner support(P < 0.05). Nicotine dependence was positively associated with negative support (ß = 0.120, P < 0.01), and perceived responsiveness (ß = 0.124, P < 0.05) as well as family functioning (ß = 0.059, P < 0.05) was positively associated with positive support. These three factors were associated with ratio of positive/negative support(P < 0.05). In addition, power of smoker's spouse in decision-making of quitting smoking was positively associated with the positive (ß = 0.087, P < 0.001) and negative support (ß = 0.084, P < 0.001). CONCLUSIONS: Nicotine dependence, family functioning, power in decision-making of quitting smoking and perceived responsiveness were found to be the predictors of quitting support from smokers' spouses. By incorporating predictors of partner support and integrating some established theories that can improve family functioning and marital relationships, smoking cessation interventions can be further improved.

Prognostic implication of residual inflammatory trajectories in acute type I aortic dissection: dual-center prospective cohort study.

BACKGROUND: Peripheral platelet-white blood cell ratio (PWR) integrating systemic inflammatory and coagulopathic pathways is a key residual inflammatory measurement in the management of acute DeBakey type I aortic dissection (AAD); however, trajectories of PWR in AAD is poorly defined. METHODS: Two AAD cohorts were included in two cardiovascular centers (2020-2022) if patients underwent emergency total arch replacement with frozen elephant trunk implantation. PWR data were collected over time at baseline and five consecutive days after surgery. Trajectory patterns of PWR were determined using the latent class mixed modelling (LCMM). Cox regression was used to determine independent risk factors. By adding PWR Trajectory, a user-friendly nomogram was developed for predicting mortality after surgery. RESULTS: Two hundred forty-six patients with AAD were included with a median follow-up of 26 (IRQ 20-37) months. Three trajectories of PWR were identified [cluster α 45(18.3%), ß105 (42.7%), and γ 96 (39.0%)]. Cluster γ was associated with higher risk of mortality at follow-up (crude HR, 3.763; 95% CI: 1.126-12.574; P =0.031) than cluster α. By the addition of PWR trajectories, an inflammatory nomogram, composed of age, hemoglobin, estimated glomerular filtration rate, and cardiopulmonary time was developed and internally validated, with adequate discrimination [the area under the receiver-operating characteristic curve 0.765, 95% CI: 0.660-0.869)], calibration, and clinical utility. CONCLUSION: Based on PWR trajectories, three distinct clusters were identified with short-term outcomes, and longitudinal residual inflammatory shed some light to individualize treatment strategies for AAD.

Favorable Outcomes of Liver Transplantation for Hepatopulmonary Syndrome.

BACKGROUND: Hepatopulmonary syndrome (HPS) is a pulmonary vascular complication of chronic liver disease, which develops insidiously as a result of chronic liver disease. The prognosis for untreated patients with HPS is extremely poor, and liver transplantation (LT) serves as the only effective means for treating this condition. Here, we performed a retrospective analysis to evaluate the efficacy of LT on the survival and long-term prognosis of patients with HPS. METHODS: Clinical data, including survival and postoperative efficacy, from patients with HPS from records as obtained over the period from January 1 to December 31, 2022. All records were from a waiting list for LT at the Beijing Friendship Hospital Affiliated with Capital Medical University. RESULTS: Among the 274 patients on the LT waiting list, 37 were diagnosed with HPS (13.50%) and were enrolled. Survival rates of patients with HPS receiving an LT were greater, whereas a statistically significant difference was obtained between patients with LT vs non-LT with moderate to severe HPS (P = .003). The overall time until death without LT was 4-72 days after their initial HPS diagnosis. Patients with HPS receiving an LT showed a significant improvement in the state of oxygenation after surgery (P = .001). CONCLUSION: Comprehensive preoperative screening of patients on the waiting list for LT is critical to identify those patients with HPS who would maximally benefit from LT. Survival rates of patients with moderate to severe HPS are significantly increased after LT, a procedure that should be performed as soon as possible in these patients with HPS.

[Early effectiveness of arthroscopic tri-anchor double-pulley suture-bridge repair of medium-size supraspinatus tendon tears].

Objective: To explore the early effectiveness of arthroscopic tri-anchor double-pulley suture-bridge in treatment of medium-size supraspinatus tendon tears. Methods: Between December 2020 and January 2023, 40 patients with medium-size supraspinatus tendon tears were treated with arthroscopic tri-anchor double-pulley suture-bridge. There were 18 males and 22 females, with an average age of 62.6 years (mean, 45-73 years). Among them, 17 patients had trauma history. The main clinical symptom was shoulder pain with hug resistance test (+). The interval from symptom onset to operation was 10.7 months on average (range, 3-36 months). Visual analogue scale (VAS) score, University of California Los Angeles (UCLA) score, American Shoulder and Elbow Surgeons (ASES) score, and shoulder range of motion (ROM) of forward flexion, abduction, and external rotation were used to evaluate shoulder function. MRI was performed to assess the structural integrity and tension of reattached tendon. Patient satisfactions were calculated at last follow-up. Results: All incisions healed by first intention, no complications such as incision infection or nerve injury occurred. All patients were followed up 12-37 months (mean, 18.2 months). At 12 months after operation, VAS score, UCLA score, and ASES score significantly improved when compared with the preoperative scores ( P<0.05). At 3 and 12 months after operation, the ROM of external rotation significantly improved when compared with preoperative one ( P<0.05), and further improved at 12 months after operation ( P<0.05). However, the ROMs of abduction and forward flexion did not improve at 3 months after operation when compared with those before operation ( P>0.05), but significantly improved at 12 months after operation ( P<0.05). Twenty-six patients underwent MRI at 3-6 months, of which 23 patients possessed intact structural integrity, good tendon tension, and tendon healing; 3 patients underwent tendon re-tear. The self-rated satisfaction rate was 92.5% at last follow-up. Conclusion: Arthroscopic tri-anchor double-pulley suture-bridge in treatment of medium-size supraspinatus tendon tears can maximize the tendon-bone contact area, obtain satisfied early effectiveness with high satisfaction rate and low incidence of tendon re-tear. However, the function of abduction is limited at 3 months after operation, and patients need to adhere to rehabilitation training to further improve the joint activity.

[Short-term effectiveness of arthroscopic repair via modified subacromial viewing portal in treatment of Lafosse â subscapularis tendon tears].

Objective: To investigate short-term effectiveness of arthroscopic repair via modified subacromial viewing portal (hereinafter referred to as modified viewing portal) in treatment of LafosseⅠsubscapularis tendon tears. Methods: A clinical data of 52 patients with LafosseⅠsubscapularis tendon tears, who underwent the arthroscopic repair via modified viewing portal between October 2020 and November 2022 and met the selective criteria, was retrospectively analyzed. There were 15 males and 37 females with an average age of 63.4 years (range, 41-76 years). Twelve patients had trauma history and the other 40 patients had no obvious inducement. The main clinical symptom was shoulder pain and the hug resistance tests were positive in all patients. The interval between symptom onset and admission ranged from 3 to 26 months (mean, 7.2 months). The shoulder pain and function were evaluated by visual analogue scale (VAS) score, American Shoulder and Elbow Surgeons (ASES) score, and University of California Los Angeles (UCLA) score before operation and at 12 months after operation. The shoulder range of motion (ROM) of forward flexion, abduction, and external rotation and the internal rotation strength were measured before operation and at 3 and 12 months after operation. MRI was performed at 3-6 months after operation to assess the tendon healing and the structural integrity and tension of reattached tendon. Patient's satisfactions were calculated at last follow-up. Results: All incisions healed by first intention, no complication such as incision infection or nerve injury occurred. All patients were followed up 12-37 months (mean, 18.5 months). The VAS, UCLA, and ASES scores at 12 months after operation significantly improved when compared with those before operation ( P<0.05). The ROMs of abduction and forward flexion and the internal rotation strength at 3 and 12 months significantly improved when compared with those before operation ( P<0.05); and the ROMs at 12 months significantly improved compared to that at 3 months ( P<0.05). However, there was no significant difference ( P>0.05) in the ROM of external rotation at 3 months compared to that before operation; but the ROM at 12 months significantly improved compared to that before operation and at 3 months after operation ( P<0.05). Thirty-one patients underwent MRI at 3-6 months, of which 28 patients possessed intact structural integrity, good tendon tension and tendon healing; 3 patients underwent tendon re-tear. At last follow-up, 41 patients (78.8%) were very satisfied with the effectiveness, 7 were satisfied (13.5%), and 4 were dissatisfied (7.7%). Conclusion: Arthroscopic repair via modified viewing portal for Lafosse Ⅰsubscapularis tendon tears, which can achieve the satisfactory visualization and working space, can obtain good short-term effectiveness with low overall re-tear risk.

Propranolol inhibits EMT and metastasis in breast cancer through miR-499-5p-mediated Sox6.

PURPOSE: This study will focus on 4T1 cells, a murine mammary adenocarcinoma cell line, as the primary research subject. We aim to investigate the inhibitory effects and mechanisms of propranolol on epithelial-mesenchymal transition (EMT) in breast cancer cells, aiming to elucidate this phenomenon at the miRNA level. METHODS: In this study, the EMT inhibitory effect of propranolol was observed through in vitro and animal experiments. For the screening of potential target miRNAs and downstream target genes, second-generation sequencing (SGS) and bioinformatics analysis were conducted. Following the screening process, the identified target miRNAs and their respective target genes were confirmed using various experimental methods. To confirm the target miRNAs and target genes, Western Blot (WB), reverse transcription polymerase chain reaction (RT-PCR), and immunofluorescence experiments were performed. RESULTS: In this study, we found that propranolol significantly reduced lung metastasis in 4T1 murine breast cancer cells (p < 0.05). In vitro and in vivo experiments demonstrated that propranolol inhibited the epithelial-mesenchymal transition (EMT) as evidenced by Western Blot analysis (p < 0.05). Through next-generation sequencing (SGS), subsequent bioinformatics analysis, and PCR validation, we identified a marked downregulation of miR-499-5p (p < 0.05), suggesting its potential involvement in mediating the suppressive effects of propranolol on EMT. Overexpression of miR-499-5p promoted EMT, migration, and invasion of 4T1 cells, and these effects were not reversed or attenuated by propranolol (Validated via Western Blot, wound healing assay, transwell migration, and invasion assays, p < 0.05). Sox6 was identified as a functional target of miR-499-5p, with its downregulation correlating with the observed EMT changes (p < 0.05). Silencing Sox6 or overexpressing miR-499-5p inhibited Sox6 expression, further promoting the processes of EMT, invasion, and migration in 4T1 cells. Notably, these effects were not alleviated by propranolol (validated via Western Blot, wound healing assay, transwell migration, and invasion assays, p < 0.05). The direct interaction between miR-499-5p and Sox6 mRNA was confirmed by dual-luciferase reporter gene assay. CONCLUSION: These results suggest that propranolol may have potential as a therapeutic agent for breast cancer treatment by targeting EMT and its regulatory mechanisms.

Conventional and multi-omics assessments of subacute inhalation toxicity due to propylene glycol and vegetable glycerin aerosol produced by electronic cigarettes.

Propylene glycol (PG) and vegetable glycerin (VG) are the most common solvents used in electronic cigarette liquids. No long-term inhalation toxicity assessments have been performed combining conventional and multi-omics approaches on the potential respiratory effects of the solvents in vivo. In this study, the systemic toxicity of aerosol generated from a ceramic heating coil-based e-cigarette was evaluated. First, the aerosol properties were characterized, including carbonyl emissions, the particle size distribution, and aerosol temperatures. To determine toxicological effects, rats were exposed, through their nose only, to filtered air or a propylene glycol (PG)/ glycerin (VG) (50:50, %W/W) aerosol mixture at the target concentration of 3 mg/L for six hours daily over a continuous 28-day period. Compared with the air group, female rats in the PG/VG group exhibited significantly lower body weights during both the exposure period and recovery period, and this was linked to a reduced food intake. Male rats in the PG/VG group also experienced a significant decline in body weight during the exposure period. Importantly, rats exposed to the PG/VG aerosol showed only minimal biological effects compared to those with only air exposure, with no signs of toxicity. Moreover, the transcriptomic, proteomic, and metabolomic analyses of the rat lung tissues following aerosol exposure revealed a series of candidate pathways linking aerosol inhalation to altered lung functions, especially the inflammatory response and disease. Dysregulated pathways of arachidonic acids, the neuroactive ligand-receptor interaction, and the hematopoietic cell lineage were revealed through integrated multi-omics analysis. Therefore, our integrated multi-omics approach offers novel systemic insights and early evidence of environmental-related health hazards associated with an e-cigarette aerosol using two carrier solvents in a rat model.

Bowel Stiffness Assessed by Shear-Wave Ultrasound Elastography Predicts Disease Behavior Progression in Patients With Crohn's Disease.

INTRODUCTION: There is a lack of reliable predictors of disease behavior progression in patients with Crohn's disease (CD). Real-time shear-wave elastography (SWE) is a novel method for evaluating tissue stiffness. However, its value for assessing CD has not yet been investigated. We aimed to explore the value of SWE and other ultrasound parameters at diagnosis in predicting CD behavior progression. METHODS: We retrospectively collected data from patients with CD with the nonstenotic nonpenetrating disease (B1 phenotype based on the Montreal classification). All patients underwent intestinal ultrasound at baseline and were followed up. The end point was defined as disease behavior progression to stricturing (B2) or penetrating (B3) disease. Cox regression analysis was performed for the association between baseline characteristics and subsequent end points. In addition, a multivariate nomogram was established to predict the risk of disease behavior progression quantitatively. RESULTS: A total of 130 patients with CD with B1 phenotype were enrolled. Twenty-seven patients (20.8%) developed B2 or B3 disease, with a median follow-up of 33 months. Multivariate analysis identified that SWE was the only independent predictor of disease behavior progression (hazard ratio 1.08, 95% confidence interval 1.03-1.12, P = 0.001). A reverse of the HR appeared at the cutoff 12.75 kPa. The nomogram incorporating SWE and other clinical characteristics showed a good prediction performance (area under the curve = 0.792). DISCUSSION: Intestinal stiffness assessed using SWE is an independent predictor of disease behavior progression in patients with CD. Patients with CD with SWE >12.75 kPa at diagnosis are prone to progress toward stricturing or penetrating diseases.

Single-Cell Atlas of Human Ovaries Reveals The Role Of The Pyroptotic Macrophage in Ovarian Aging.

Female fecundity declines in a nonlinear manner with age during the reproductive years, even as ovulatory cycles continue, which reduces female fertility, disrupts metabolic homeostasis, and eventually induces various chronic diseases. Despite this, the aging-related cellular and molecular changes in human ovaries that occur during these reproductive years have not been elucidated. Here, single-cell RNA sequencing (scRNA-seq) of human ovaries is performed from different childbearing ages and reveals that the activation of the pyroptosis pathway increased with age, mainly in macrophages. The enrichment of pyroptotic macrophages leads to a switch from a tissue-resident macrophage (TRM)-involve immunoregulatory microenvironment in young ovaries to a pyroptotic monocyte-derived macrophage (MDM)-involved proinflammatory microenvironment in middle-aged ovaries. This remolded ovarian immuno-microenvironment further promotes stromal cell senescence and accelerated reproductive decline. This hypothesis is validated in a series of cell and animal experiments using GSDMD-KO mice. In conclusion, the work expands the current understanding of the ovarian aging process by illustrating a pyroptotic macrophage-involved immune mechanism, which has important implications for the development of novel strategies to delay senescence and promote reproductive health.