Integrating Data Mining with Metabolomics to Analyze the Mechanism of the "Pearl-Borneol" Pair in Promoting Healing of Diabetic Wounds.

INTRODUCTION: Chronic diabetic wounds pose a significant threat to the health of diabetic patients, representing severe and enduring complications. Globally, an estimated 2.5% to 15% of the annual health budget is associated with diabetes, with diabetic wounds accounting for a substantial share. Exploring new therapeutic agents and approaches to address delayed and impaired wound healing in diabetes becomes imperative. Traditional Chinese medicine (TCM) has a long history and remarkable efficacy in treating chronic wound healing. In this study, all topically applied proprietary Chinese medicines (pCMs) for wound healing officially approved by the National Medical Products Administration (NMPA) were collected from the NMPA TCM database. Data mining was employed to obtain a high-frequency TCM ingredients pair, Pearl-Borneol (1:1). METHOD: This study investigated the effect and molecular mechanism of the Pearl-Borneol pair on the healing of diabetic wounds by animal experiments and metabolomics. The results from animal experiments showed that the Pearl-Borneol pair significantly accelerated diabetic wound healing, exhibiting a more potent effect than the Pearl or Borneol treatment alone. Meanwhile, the metabolomics analysis identified significant differences in metabolic profiles in wounds between the model and normal groups, indicating that diabetic wounds had distinct metabolic characteristics from normal wounds. Moreover, Vaseline-treated wounds exhibited similar metabolic profiles to the wounds from the model group, suggesting that Vaseline might have a negligible impact on diabetic wound metabolism. In addition, wounds treated with Pearl, Borneol, and Pearl-Borneol pair displayed significantly different metabolic profiles from Vaseline-treated wounds, signifying the influence of these treatments on wound metabolism. Subsequent enrichment analysis of the metabolic pathway highlighted the involvement of the arginine metabolic pathway, closely associated with diabetic wounds, in the healing process under Pearl- Borneol pair treatment. Further analysis revealed elevated levels of arginine and citrulline, coupled with reduced nitric oxide (NO) in both the model and Vaseline-treated wounds compared to normal wounds, pointing to impaired arginine utilization in diabetic wounds. Interestingly, treatment with Pearl and Pearl-Borneol pair lowered arginine and citrulline levels while increasing NO content, suggesting that these treatments may promote the catabolism of arginine to generate NO, thereby facilitating faster wound closure. Additionally, borneol alone significantly elevated NO content in wounds, potentially due to its ability to directly reduce nitrates/nitrites to NO. Oxidative stress is a defining characteristic of impaired metabolism in diabetic wounds. RESULTS: The result showed that both Pearl and Pearl-Borneol pair decreased the oxidative stress biomarker methionine sulfoxide level in diabetic wounds compared to those treated with Vaseline, indicating that Pearl alone or combined with Borneol may enhance the oxidative stress microenvironment in diabetic wounds. CONCLUSION: In summary, the findings validate the effectiveness of the Pearl-Borneol pair in accelerating the healing of diabetic wounds, with effects on reducing oxidative stress, enhancing arginine metabolism, and increasing NO generation, providing a mechanistic basis for this therapeutic approach.

Direct synthesis of carbamates, thiocarbamates, and ureas from Boc-protected amines: a sustainable and efficient approach.

In the quest for sustainable and efficient synthetic methodologies within medicinal chemistry, the synthesis of carbamates and their derivatives holds a pivotal role due to their widespread application in bioactive compounds. This investigation unveils a novel methodology for the straightforward transformation of Boc-protected amines into carbamates, thiocarbamates, and ureas, utilizing tert-butoxide lithium as the sole base. This approach effectively obviates the necessity for hazardous reagents and metal catalysts, presenting marked enhancements compared to traditional synthetic pathways. Notably, the method demonstrates facile scalability to gram-level production. This study contributes to the advancement of sustainable synthetic methodologies, offering a more benign and efficient alternative for the synthesis of key chemical intermediates with implications for broad pharmaceutical and agrochemical applications.

Machine Learning Assisted Electronic/Ionic Skin Recognition of Thermal Stimuli and Mechanical Deformation for Soft Robots.

Soft robots have the advantage of adaptability and flexibility in various scenarios and tasks due to their inherent flexibility and mouldability, which makes them highly promising for real-world applications. The development of electronic skin (E-skin) perception systems is crucial for the advancement of soft robots. However, achieving both exteroceptive and proprioceptive capabilities in E-skins, particularly in terms of decoupling and classifying sensing signals, remains a challenge. This study presents an E-skin with mixed electronic and ionic conductivity that can simultaneously achieve exteroceptive and proprioceptive, based on the resistance response of conductive hydrogels. It is integrated with soft robots to enable state perception, with the sensed signals further decoded using the machine learning model of decision trees and random forest algorithms. The results demonstrate that the newly developed hydrogel sensing system can accurately predict attitude changes in soft robots when subjected to varying degrees of pressing, hot pressing, bending, twisting, and stretching. These findings that multifunctional hydrogels combine with machine learning to decode signals may serve as a basis for improving the sensing capabilities of intelligent soft robots in future advancements.

Choline suppresses hepatocellular carcinoma progression by attenuating AMPK/mTOR-mediated autophagy via choline transporter SLC5A7 activation.

Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-associated death. Emerging evidence suggests that autophagy plays a critical role in HCC tumorigenesis, metastasis, and prognosis. Choline is an essential nutrient related to prolonged survival and reduced risk of HCC. However, it remains unclear whether this phenomenon is mediated by autophagy. Methods: Two HCC cell lines (HUH-7 and Hep3B) were used in the present study. Cell growth was evaluated by cell counting kit 8 (CCK-8), colony formation, and in vivo mouse xenografts assays. Cell motility was calculated by wound healing and transwell assays. Autophagosomes were measured by transmission electron microscope (TEM), and autophagy flux was detected by mRFP-GFP-labeled LC3 protein. The mRNA level of genes was measured by quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels were detected by Western blotting (WB). Results: We found that choline inhibited the proliferation, migration, and invasion of HCC cells by downregulating autophagy in vitro and in vivo. Upregulated expression of the solute carrier family 5 member 7 (SLC5A7), a specific choline transporter, correlated with better HCC prognosis. We further discovered that choline could promote SLC5A7 expression, upregulate cytoplasm p53 expression to impair the AMPK/mTOR pathway, and attenuate autophagy. Finally, we found that choline acted synergistically with sorafenib to attenuate HCC development in vitro and in vivo. Conclusions: Our findings provide novel insights into choline-mediated autophagy in HCC, providing the foothold for its future application in HCC treatment.

Sodium-glucose cotransporter 2 inhibitors attenuate vascular calcification by suppressing endoplasmic reticulum protein thioredoxin domain containing 5 dependent osteogenic reprogramming.

AIMS: Vascular calcification is strongly linked to the development of major adverse cardiovascular events, but effective treatments are lacking. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are an emerging category of oral hypoglycemic drugs that have displayed marked effects on metabolic and cardiovascular diseases, including recently reported vascular medial calcification. However, the roles and underlying mechanisms of SGLT2 inhibitors in vascular calcification have not been fully elucidated. Thus, we aimed to further determine whether SGLT2 inhibitors protect against vascular calcification and to investigate the mechanisms involved. METHODS AND RESULTS: A computed tomography angiography investigation of coronary arteries from 1554 patients with type 2 diabetes revealed that SGLT2 inhibitor use was correlated with a lower Agatston calcification score. In the vitamin D3 overdose, 5/6 nephrectomy chronic kidney disease-induced medial calcification and Western diet-induced atherosclerotic intimal calcification models, dapagliflozin (DAPA) substantially alleviated vascular calcification in the aorta. Furthermore, we showed that DAPA reduced vascular calcification via Runx2-dependent osteogenic transdifferentiation in vascular smooth muscle cells (VSMCs). Transcriptome profiling revealed that thioredoxin domain containing 5 (TXNDC5) was involved in the attenuation of vascular calcification by DAPA. Rescue experiments showed that DAPA-induced TXNDC5 downregulation in VSMCs blocked the protective effect on vascular calcification. Furthermore, TXNDC5 downregulation disrupted protein folding-dependent Runx2 stability and promoted subsequent proteasomal degradation. Moreover, DAPA downregulated TXNDC5 expression via amelioration of oxidative stress and ATF6-dependent endoplasmic reticulum stress. Consistently, the class effects of SGLT2 inhibitors on vascular calcification were validated with empagliflozin in intimal and medial calcification models. CONCLUSIONS: SGLT2 inhibitors ameliorate vascular calcification through blocking endoplasmic reticulum stress-dependent TXNDC5 upregulation and promoting subsequent Runx2 proteasomal degradation, suggesting that SGLT2 inhibitors are potentially beneficial for vascular calcification treatment and prevention.

Anomalous origin of the coronary artery: prevalence and coronary artery disease in adults undergoing coronary tomographic angiography.

BACKGROUND: Anomalous aortic origin of a coronary artery (AAOCA) is a rare congenital coronary anomaly with the potential to cause adverse cardiac events. However, there is limited data on the association between AAOCA and coronary artery disease (CAD). Therefore, the aim of this study is to determine the prevalence and symptoms of patients with AAOCA, as well as investigate the correlation between AAOCA and CAD in a population referred for coronary computed tomographic angiography (CTA). METHODS AND RESULTS: All consecutive patients who underwent CTA from 2010 to 2021 were included. Characteristics, symptoms, coronary related adverse events and CTA information were reviewed by medical records. Separate multivariable cumulative logistic regressions were performed, using the stenosis severity in each of the four coronaries as individual responses and as a combined patient clustered response. Finally, we identified 207 adult patients with AAOCA, the prevalence of AAOCA is 0.23% (207/90,501). Moreover, this study found no significant association between AAOCA and CAD. AAOCA did not contribute to higher rates of hospitalization or adverse cardiac events, including calcification. CONCLUSION: AAOCA is a rare congenital disease that is not associated with increased presence of obstructive CAD in adults.

Metagenomic Analysis Reveals A Gut Microbiota Structure and Function Alteration between Healthy and Diarrheic Juvenile Yaks.

Diarrhea-induced mortality among juvenile yaks is highly prevalent in the pastoral areas of the Qinghai-Tibet plateau. Although numerous diseases have been linked to the gut microbial community, little is known about how diarrhea affects the gut microbiota in yaks. In this work, we investigated and compared changes in the gut microbiota of juvenile yaks with diarrhea. The results demonstrated a considerable drop in the alpha diversity of the gut microbiota in diarrheic yaks, accompanied by Eysipelatoclostridium, Parabacteroides, and Escherichia-Shigella, which significantly increased during diarrhea. Furthermore, a PICRust analysis verified the elevation of the gut-microbial metabolic pathways in diarrhea groups, including glycine, serine, and threonine metabolism, alanine, aspartate, oxidative phosphorylation, glutamate metabolism, antibiotic biosynthesis, and secondary metabolite biosynthesis. Taken together, our study showed that the harmful bacteria increased, and beneficial bacteria decreased significantly in the gut microbiota of yaks with diarrhea. Moreover, these results also indicated that the dysbiosis of the gut microbiota may be a significant driving factor of diarrhea in yaks.

Biochanin A inhibits endothelial dysfunction induced by IL­6­stimulated endothelial microparticles in Perthes disease via the NFκB pathway.

Endothelial dysfunction caused by the stimulation of endothelial microparticles (EMPs) by the inflammatory factor IL-6 is one of the pathogenic pathways associated with Perthes disease. The natural active product biochanin A (BCA) has an anti-inflammatory effect; however, whether it can alleviate endothelial dysfunction in Perthes disease is not known. The present in vitro experiments on human umbilical vein endothelial cells showed that 0-100 pg/ml IL-6-EMPs could induce endothelial dysfunction in a concentration-dependent manner, and the results of the Cell Counting Kit 8 assay revealed that, at concentrations of <20 µM, BCA had no cytotoxic effect. Reverse transcription-quantitative PCR demonstrated that BCA reduced the expression levels of the endothelial dysfunction indexes E-selectin and intercellular cell adhesion molecule-1 (ICAM-1) in a concentration-dependent manner. Immunofluorescence and western blotting illustrated that BCA increased the expression levels of zonula occludens-1 and decreased those of ICAM-1. Mechanistic studies showed that BCA inhibited activation of the NFκB pathway. In vivo experiments demonstrated that IL-6 was significantly increased in the rat model of ischemic necrosis of the femoral head, whereas BCA inhibited IL-6 production. Therefore, in Perthes disease, BCA may inhibit the NFκB pathway to suppress IL-6-EMP-induced endothelial dysfunction, and could thus be regarded as a potential treatment for Perthes disease.

Soil bacterial community in a photovoltaic system adopted different survival strategies to cope with small-scale light stress under different vegetation restoration modes.

Solar photovoltaic (PV) power generation is a major carbon reduction technology that is rapidly developing worldwide. However, the impact of PV plant construction on subsurface microecosystems is currently understudied. We conducted a systematic investigation into the effects of small-scale light stress caused by shading of PV panels and sampling depth on the composition, diversity, survival strategy, and key driving factors of soil bacterial communities (SBCs) under two vegetation restoration modes, i.e., Euryops pectinatus (EP) and Loropetalum chinense var. rubrum (LC). The study revealed that light stress had a greater impact on rare species with relative abundances below 0.01% than on high-abundance species, regardless of the vegetation restoration pattern. Additionally, PV shadowing increased SBCs' biomass by 20-30% but had varying negative effects on the numbers of Operational Taxonomic Unit (OTU), Shannon diversity, abundance-based coverage estimator (ACE), and Chao1 richness index. Co-occurrence and correlation network analysis revealed that symbiotic relationships dominated the key SBCs in the LC sample plots, with Chloroflexi and Actinobacteriota being the most ecologically important. In contrast, competitive relationships were significantly increased in the EP sample plots, with Actinobacteriota having the most ecological importance. In the EP sample plot, SBCs were found to be more tightly linked and had more stable ecological networks. This suggests that EP is more conducive to the stability and health of underground ecosystems in vulnerable areas when compared with LC. These findings offer new insights into the effects of small-scale light stress on subsurface microorganisms under different vegetation restoration patterns. Moreover, they may provide a reference for optimizing ecological restoration patterns in fragile areas.

Stop codon variant in EFEMP1 is associated with primary open-angle glaucoma due to impaired regulation of aqueous humor outflow.

It is known that the actin cytoskeleton and its associated cellular interactions in the trabecular meshwork (TM) and juxtacanalicular tissues mainly contribute to the formation of resistance to aqueous outflow of the eye. Fibulin-3, encoded by EFEMP1 gene, has a role in extracellular matrix (ECM) modulation, and interacts with enzymatic ECM regulators, but the effects of fibulin-3 on TM cells has not been explored. Here, we report a stop codon variant (c.T1480C, p.X494Q) of EFEMP1 that co-segregates with primary open angle glaucoma (POAG) in a Chinese pedigree. In the human TM cells, overexpression of wild-type fibulin-3 reduced intracellular actin stress fibers formation and the extracellular fibronectin levels by inhibiting Rho/ROCK signaling. TGFß1 up-regulated fibulin-3 protein levels in human TM cells by activating Rho/ROCK signaling. In rat eyes, overexpression of wild-type fibulin-3 decreased the intraocular pressure and the fibronectin expression of TM, however, overexpression of mutant fibulin-3 (c.T1480C, p.X494Q) showed opposite effects in cells and rat eyes. Taken together, the EFEMP1 variant may impair the regulatory capacity of fibulin-3 which has a role for modulating the cell contractile activity and ECM synthesis in TM cells, and in turn may maintain normal resistance of aqueous humor outflow. This study contributes to the understanding of the important role of fibulin-3 in TM pathophysiology and provides a new possible POAG therapeutic approach.

The effect of cognition in combination with an ACBT on dyspnea-related kinesiophobia in patients with moderate to severe COPD: Quasirandomized controlled trial study.

Patients with moderate to severe COPD frequently experience dyspnea, which causes these patients to acquire a fear of dyspnea and a fear of activity. This study developed a cognitive intervention combined with active cycle of breathing technique (ACBT) intervention program based on the fear-avoidance model, with the goal of evaluating the program's effectiveness in improving dyspnea-related kinesiophobia in patients with moderate to severe COPD. This study had a total of 106 participants. For 8 weeks, the intervention group (N=53) received cognitive combined with ACBT, while the control group (N=53) received standard care. The findings of the four times the dyspnea belief questionnaire were collected indicated that the combined intervention had a better impact on reducing dyspnea-related kinesiophobia than did routine nursing (P<0.05), and the impact persisted even after the intervention. Additionally, it may enhance dyspnea and quality of life, increase exercise capacity, and lower the BODE index.

Strong, tough and anisotropic bioinspired hydrogels.

Soft materials are widely used in tissue engineering, soft robots, wearable electronics, etc. However, it remains a challenge to fabricate soft materials, such as hydrogels, with both high strength and toughness that are comparable to biological tissues. Inspired by the anisotropic structure of biological tissues, a novel solvent-exchange-assisted wet-stretching strategy is proposed to prepare anisotropic polyvinyl alcohol (PVA) hydrogels by tuning the macromolecular chain movement and optimizing the polymer network. The reinforcing and toughening mechanisms are found to be "macromolecule crystallization and nanofibril formation". These hydrogels exhibit excellent mechanical properties, such as extremely high fracture stress (12.8 ± 0.7 MPa) and fracture strain (1719 ± 77%), excellent modulus (4.51 ± 0.76 MPa), high work of fracture (134.47 ± 9.29 MJ m-3), and fracture toughness (305.04 kJ m-2) compared with other strong hydrogels and even natural tendons. In addition, excellent conductivity, strain sensing capability, water retention, freezing resistance, swelling resistance, and biocompatibility can also be achieved. This work provides a new and effective method to fabricate multifunctional anisotropic hydrogels with high tunable strength and toughness with potential applications in the fields of regenerative medicine, flexible sensors, and soft robotics.

Acetate Ions Facilitated Immobilization of Highly Dispersed Transition Metal Oxide Nanoclusters in Mesoporous Silica.

The immobilization of tiny active species within inert mesoporous silica imparts a range of functions, enhancing their applicability. A significant obstacle is the spontaneous migration and aggregation of these species within the mesopores, which threaten their uniform distribution. To address this, we propose a postmodification method that involves grafting transition metal oxide nanoclusters into silica mesopores via interfacial condensation, catalyzed by acetate ions. Specifically, CuO nanoclusters, in the form of oligomeric [O1-x-Cu2-(OH) 2x]n2+, have a strong interaction with the silica framework. This interaction inhibits their growth and prevents mesopore blockage. Theoretical calculation results reveal that the acetate ion promotes proton transfer among various hydroxy species, lowering the free energy and thereby facilitating the formation of Cu-O-Si bonds. This technique has also been successfully applied to the encapsulation of four other types of transition metal oxide nanoclusters. Our encapsulation strategy effectively addresses the challenge of dispersing transition metal oxides in mesoporous silica, offering a straightforward and widely applicable method for enhancing the functionality of mesoporous materials.

B-type natriuretic peptide levels at admission predict the prognosis of patients with infective endocarditis undergoing cardiac surgery.

Purpose: The objective of this study was to explore the relationship between elevated B-type natriuretic peptide (BNP) levels and the prognosis of patients with infective endocarditis (IE) undergoing cardiac surgery. Methods: In total, 162 IE patients with recorded BNP levels upon admission were included in the present study. The primary end point was all-cause mortality. Results: Multivariate Cox analysis revealed a significant association between log BNP and all-cause mortality. Kaplan-Meier analysis revealed a poorer prognosis for patients with BNP levels ≥ the 75th percentile. Furthermore, the linear trend test indicated a significant link between BNP quartiles and the primary end point within the models. Conclusion: Elevated BNP levels upon admission could predict all-cause mortality in IE patients undergoing cardiac surgery.

Infective endocarditis (IE) refers to an infection affecting the heart lining, heart valves or blood vessels. Despite advancements in medical and surgical interventions, the overall mortality rate remains high among IE patients after surgery. B-type natriuretic peptide (BNP) is a peptide released in response to increased stress on the ventricular and atrial walls and is commonly used as a biomarker for heart failure. This study was aimed to assess the potential of BNP in predicting all-cause mortality in IE patients. The results indicate that elevated BNP levels upon admission could predict a worse prognosis following endocarditis surgery. Additionally, elevated BNP levels upon admission were associated with an increased risk of death.

Betaine alleviates cognitive impairment induced by homocysteine through attenuating NLRP3-mediated microglial pyroptosis in an m6A-YTHDF2-dependent manner.

Dementia, with homocysteine (Hcy) as an important risk factor, is a severe public health problem in the aging society. Betaine serves as a methyl donor and plays an important role in reducing Hcy. However, the effects and mechanisms of betaine on Hcy-induced cognitive impairment remain unclear. Firstly, SD rats were injected with Hcy (400 µg/kg) through vena caudalis, and betaine (2.5 % w/v) was supplemented via drinking water for 14 days. Betaine supplementation could attenuate Hcy-induced cognitive impairment in the Y maze and novel object recognition tests by repairing brain injury. Meanwhile, microglial activation was observed to be inhibited by betaine supplementation using immunofluorescence and sholl analysis. Secondly, HMC3 cells were treated with betaine, which was found to decrease the ROS level, ameliorate cell membrane rupture, reduce the release of LDH, IL-18 and IL-1ß, and attenuate the damage of microglia to neurons. Mechanistically, betaine alleviates cognitive impairment by inhibiting microglial pyroptosis via reducing the expressions of NLRP3, ASC, pro-caspase-1, cleaved-caspase-1, GSDMD, GSDMD-N, IL-18 and IL-1ß. Betaine treatment can increase SAM/SAH ratio, confirming its enhancement on methylation capacity. Furthermore, betaine treatment was found to enhance N6-methyladenosine (m6A) modification of NLRP3 mRNA, and reduced the NLRP3 mRNA stability through increasing the expression of the m6A reader YTH N6-methyladenosine RNA binding protein 2 (YTHDF2). Finally, silencing YTHDF2 could reverse the inhibitory effect of betaine on pyroptosis. Our data demonstrated that betaine attenuated Hcy-induced cognitive impairment by suppressing microglia pyroptosis via inhibiting the NLRP3/caspase-1/GSDMD pathway in an m6A-YTHDF2-dependent manner.

Embodied Conversational Agents for Chronic Diseases: Scoping Review.

BACKGROUND: Embodied conversational agents (ECAs) are computer-generated animated humanlike characters that interact with users through verbal and nonverbal behavioral cues. They are increasingly used in a range of fields, including health care. OBJECTIVE: This scoping review aims to identify the current practice in the development and evaluation of ECAs for chronic diseases. METHODS: We applied a methodological framework in this review. A total of 6 databases (ie, PubMed, Embase, CINAHL, ACM Digital Library, IEEE Xplore Digital Library, and Web of Science) were searched using a combination of terms related to ECAs and health in October 2023. Two independent reviewers selected the studies and extracted the data. This review followed the PRISMA-ScR (Preferred Reporting Items of Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) statement. RESULTS: The literature search found 6332 papers, of which 36 (0.57%) met the inclusion criteria. Among the 36 studies, 27 (75%) originated from the United States, and 28 (78%) were published from 2020 onward. The reported ECAs covered a wide range of chronic diseases, with a focus on cancers, atrial fibrillation, and type 2 diabetes, primarily to promote screening and self-management. Most ECAs were depicted as middle-aged women based on screenshots and communicated with users through voice and nonverbal behavior. The most frequently reported evaluation outcomes were acceptability and effectiveness. CONCLUSIONS: This scoping review provides valuable insights for technology developers and health care professionals regarding the development and implementation of ECAs. It emphasizes the importance of technological advances in the embodiment, personalized strategy, and communication modality and requires in-depth knowledge of user preferences regarding appearance, animation, and intervention content. Future studies should incorporate measures of cost, efficiency, and productivity to provide a comprehensive evaluation of the benefits of using ECAs in health care.

Artificial intelligence-based models enabling accurate diagnosis of ovarian cancer using laboratory tests in China: a multicentre, retrospective cohort study.

BACKGROUND: Ovarian cancer is the most lethal gynecological malignancy. Timely diagnosis of ovarian cancer is difficult due to the lack of effective biomarkers. Laboratory tests are widely applied in clinical practice, and some have shown diagnostic and prognostic relevance to ovarian cancer. We aimed to systematically evaluate the value of routine laboratory tests on the prediction of ovarian cancer, and develop a robust and generalisable ensemble artificial intelligence (AI) model to assist in identifying patients with ovarian cancer. METHODS: In this multicentre, retrospective cohort study, we collected 98 laboratory tests and clinical features of women with or without ovarian cancer admitted to three hospitals in China during Jan 1, 2012 and April 4, 2021. A multi-criteria decision making-based classification fusion (MCF) risk prediction framework was used to make a model that combined estimations from 20 AI classification models to reach an integrated prediction tool developed for ovarian cancer diagnosis. It was evaluated on an internal validation set (3007 individuals) and two external validation sets (5641 and 2344 individuals). The primary outcome was the prediction accuracy of the model in identifying ovarian cancer. FINDINGS: Based on 52 features (51 laboratory tests and age), the MCF achieved an area under the receiver-operating characteristic curve (AUC) of 0·949 (95% CI 0·948-0·950) in the internal validation set, and AUCs of 0·882 (0·880-0·885) and 0·884 (0·882-0·887) in the two external validation sets. The model showed higher AUC and sensitivity compared with CA125 and HE4 in identifying ovarian cancer, especially in patients with early-stage ovarian cancer. The MCF also yielded acceptable prediction accuracy with the exclusion of highly ranked laboratory tests that indicate ovarian cancer, such as CA125 and other tumour markers, and outperformed state-of-the-art models in ovarian cancer prediction. The MCF was wrapped as an ovarian cancer prediction tool, and made publicly available to provide estimated probability of ovarian cancer with input laboratory test values. INTERPRETATION: The MCF model consistently achieved satisfactory performance in ovarian cancer prediction when using laboratory tests from the three validation sets. This model offers a low-cost, easily accessible, and accurate diagnostic tool for ovarian cancer. The included laboratory tests, not only CA125 which was the highest ranked laboratory test in importance of diagnostic assistance, contributed to the characterisation of patients with ovarian cancer. FUNDING: Ministry of Science and Technology of China; National Natural Science Foundation of China; Natural Science Foundation of Guangdong Province, China; and Science and Technology Project of Guangzhou, China. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Effectiveness of acupuncture for postoperative gastrointestinal recovery in patients undergoing thoracoscopic surgery: a prospective randomized controlled study.

BACKGROUND: Postoperative gastrointestinal dysfunction (PGD) is one of the most common complications among patients who have undergone thoracic surgery. Acupuncture has long been used in traditional Chinese medicine to treat gastrointestinal diseases and has shown benefit as an alternative therapy for the management of digestive ailments. This study aimed to explore the therapeutic effectiveness of acupuncture as a means to aid postoperative recovery of gastrointestinal function in patients undergoing thoracoscopic surgery. METHODS: In total, 112 patients aged 18-70 years undergoing thoracoscopic surgery between 15 June 2022 and 30 August 2022 were randomized into two groups. Patients in the acupuncture group (AG) first received acupuncture treatment 4 h after surgery, and treatment was repeated at 24 and 48 h. Patients in the control group (CG) did not receive any acupuncture treatment. Both groups received the same anesthetic protocol. Ultrasound-guided thoracic paravertebral block (TPVB) was performed in the paravertebral spaces between T4 and T5 with administration of 20 mL of 0.33% ropivacaine. All patients received patient-controlled intravenous analgesia (PCIA) after surgery. RESULTS: Median time to first flatus [interquartile range] in the AG was significantly less than in the CG (23.25 [18.13, 29.75] vs 30.75 [24.13, 45.38] h, p < 0.001). Time to first fluid intake after surgery was significantly less in the AG, as compared with the CG (4 [3, 7] vs 6.5 [4.13, 10.75] h, p = 0.003). Static pain, measured by visual analog scale (VAS) score, was significantly different on the third day after surgery (p = 0.018). Dynamic pain VAS scores were lower in the AG versus CG on the first three postoperative days (p = 0.014, 0.003 and 0.041, respectively). CONCLUSION: Addition of acupuncture appeared to improve recovery of postoperative gastrointestinal function and alleviate posteoperative pain in patients undergoing thoracoscopic surgery. Acupuncture may represent a feasible strategy for the prevention of PGD occurrence. TRIAL REGISTRATION NUMBER: ChiCTR2200060888 (Chinese Clinical Trial Registry).

Folate deficiency promotes cervical squamous carcinoma SiHa cells progression by targeting miR-375/FZD4/ß-catenin signaling.

Epidemiological studies suggest an association between folate deficiency (FD) and cervical squamous cell carcinoma (SCC) progression. However, the underlying mechanism is unclear. Our study showed that FD-driven downregulation of miR-375 promoted proliferation of SCC SiHa cells and progression of xenograft tumors developed from SiHa; however, the exact mechanism of this process remained unclear. The current study aimed to elucidate the underlying mechanisms by which FD promotes the progression of SiHa cells by downregulating miR-375 expression. The results showed that miR-375 acted as a suppressor of SCC and inhibited the proliferation, migration, and invasion of SiHa cells. The FZD4 gene was identified as a target gene of miR-375, which can reverse the anti-onco effect of miR-375 and promote the proliferation and migration of SiHa cells. Furthermore, the regulatory effects of miR-375 and FZD4 on SiHa cells may be achieved by activating the ß-catenin signaling pathway. Moreover, FD may regulate the expression of miR-375 by regulating its DNA methylation level in the promoter region. In conclusion, our study reveals that FD regulates the miR-375/FZD4 axis by increasing the methylation of the miR-375 promoter, thereby activating ß-catenin signaling to promote SiHa cells progression. This study may provide new insights into the role of folic acid in the prevention and treatment of SCC.

Betaine attenuates age-related suppression in autophagy via Mettl21c/p97/VCP axis to delay muscle loss.

Age-related impairment of autophagy accelerates muscle loss and lead to sarcopenia. Betaine can delay muscle loss as a dietary methyl donor via increasing S-adenosyl-L-methionine (SAM, a crucial metabolite for autophagy regulation) in methionion cycle. However, whether betaine can regulate autophagy level to attenuate degeneration in aging muscle remains unclear. Herein, male C57BL/6J young mice (YOU, 2-month-old), old mice (OLD, 15-month-old), and 2%-betaine-treated old mice (BET, 15-month-old) were employed and raised for 12 weeks. All mice underwent body composition examination and grip strength test before being sacrificed. Betaine alleviated age-related decline in muscle mass and strength. Meanwhile, betaine preserved the expression autophagy markers (Atg5, Atg7, LC3-II, and Beclin1) both at transcriptional and translational level during the aging process. RNA-sequencing results generated from mice gastrocnemius muscle found Mettl21c, a SAM-dependent autophagy-regulating methyltransferase, was significantly higher expressed in BET and YOU group. Results were further validated by qPCR and western bloting. In vitro, C2C12 cells with or without Mettl21c RNA interference were treated different concentration of betaine (0 mM, 10 mM) under methionine-starved condition. Compared with control group, betaine upregulated autophagy markers expression and autophagy flux. By increasing the SAM level, betaine facilitated trimethylation of p97 (Mettl21c downstream effector) into valosin-containing protein (VCP). Increased VCP promoted autophagic turnover of cellular components, ATP production, and cell differentiation. Knock-down of Metthl21c dismissed improvements mentioned above. Collectively, betaine could enhance aged skeletal muscle autophagy level via Mettl21c/p97/VCP axis to delay muscle loss.