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Abstract Objective Explore the feasibility of a mobile health(mHealth) and virtual reality (VR) based nutrition-exercise-psychology integrated rehabilitation model in Chinese cancer patients. Methods We recruited cancer patients in the Oncology department of the Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University from October 2022 to April 2023. The rehabilitation program was provided by a team of medical oncologists, dietitians, psychotherapists, and oncology specialist nurses. Participants received standard anti-cancer therapy and integrated intervention including hospitalized group-based exercise classes, at-home physical activity prescription, behavior change education, oral nutrition supplements, and psychological counseling. An effective intervention course includes two consecutive hospitalization and two periods of home-based rehabilitation (8 weeks). Access the feasibility as well as changes in aspects of physical, nutritional, and psychological status. Results At the cutoff date of April 2023, the recruitment rate was 75% (123/165). 11.4%patients were lost to follow-up, and 3.25% withdrew halfway. Respectively, the completion rate of nutrition, exercise, and psychology were 85%,55%, and 63%. Nutrition interventions show the highest compliance. The parameters in nutrition, psychology, muscle mass, and quality of life after the rehabilitation showed significant improvements (P .05) in handgrip strength and 6-minute walking speed. Conclusion It is feasible to conduct mHealth and VR-based nutrition-exercise-psychology integrated rehabilitation model in Chinese cancer patients. A larger multi-center trial is warranted in the future. Trial registration ChiCTR2200065748 Registered 14 November 2022.

Abstract Background To investigate related factors for postoperative pathological upgrading of cervical biopsy to cervical cancer (CC) in patients with cervical intraepithelial neoplasia (CIN)3 after conical resection. Methods This retrospective study collected data from patients diagnosed with CIN3 by cervical biopsies at the author’s Hospital between January 2012 and December 2022. The primary outcome was the pathological results of patients after conical resection. The pathological findings were categorized into the pathological upgrading group if postoperative pathology indicated CC, while those with normal, inflammatory, or cervical precancerous lesions were classified into the pathological non-upgrading group. The factors associated with upgrading were identified using multivariable logistic regression analysis. Results Among 511 patients, there were 125 patients in the pathological upgrading group (24.46%). The patients in the upgrading group were younger (47.68 ± 9.46 vs. 52.11 ± 7.02, P

Abstract Background Myocardial ischemia–reperfusion injury (MIRI) is widespread in the treatment of ischemic heart disease, and its treatment options are currently limited. Adiponectin (APN) is an adipocytokine with cardioprotective properties; however, the mechanisms of APN in MIRI are unclear. Therefore, based on preclinical (animal model) evidence, the cardioprotective effects of APN and the underlying mechanisms were explored. Methods The literature was searched for the protective effect of APN on MIRI in six databases until 16 November 2023, and data were extracted according to selection criteria. The outcomes were the size of the myocardial necrosis area and hemodynamics. Markers of oxidation, apoptosis, and inflammation were secondary outcome indicators. The quality evaluation was performed using the animal study evaluation scale recommended by the Systematic Review Center for Laboratory animal Experimentation statement. Stata/MP 14.0 software was used for the summary analysis. Results In total, 20 papers with 426 animals were included in this study. The pooled analysis revealed that APN significantly reduced myocardial infarct size [weighted mean difference (WMD) = 16.67 (95% confidence interval (CI) = 13.18 to 20.16, P

Abstract Background Multimorbidity is better prevented in younger ages than in older ages. This study aims to identify the differences in comorbidity patterns in middle-aged inpatients from China and the United Kingdom (UK). Methods We utilized 184,133 and 180,497 baseline hospitalization records in middle-aged populations (40–59 years) from Shaanxi, China, and UK Biobank. Logistic regression was used to calculate odds ratios and P values for 43,110 unique comorbidity patterns in Chinese inpatients and 21,026 unique comorbidity patterns in UK inpatients. We included the statistically significant (P values adjusted by Bonferroni correction) and common comorbidity patterns (the pattern with prevalence > 1/10,000 in each dataset) and employed network analysis to construct multimorbidity networks and compare feature differences in multimorbidity networks for Chinese and UK inpatients, respectively. We defined hub diseases as diseases having the top 10 highest number of unique comorbidity patterns in the multimorbidity network. Results We reported that 57.12% of Chinese inpatients had multimorbidity, substantially higher than 30.39% of UK inpatients. The complete multimorbidity network for Chinese inpatients consisted of 1367 comorbidities of 341 diseases and was 2.93 × more complex than that of 467 comorbidities of 215 diseases in the UK. In males, the complexity of the multimorbidity network in China was 2.69 × more than their UK counterparts, while the ratio was 2.63 × in females. Comorbidities associated with hub diseases represented 68.26% of comorbidity frequencies in the complete multimorbidity network in Chinese inpatients and 55.61% in UK inpatients. Essential hypertension, dyslipidemia, type 2 diabetes mellitus, and gastritis and duodenitis were the hub diseases in both populations. The Chinese inpatients consistently demonstrated a higher frequency of comorbidities related to circulatory and endocrine/nutritional/metabolic diseases. In the UK, aside from these comorbidities, comorbidities related to digestive and genitourinary diseases were also prevalent, particularly the latter among female inpatients. Conclusions Chinese inpatients exhibit higher multimorbidity prevalence and more complex networks compared to their UK counterparts. Multimorbidity with circulatory and endocrine/nutritional/metabolic diseases among both Chinese and UK inpatients necessitates tailored surveillance, prevention, and intervention approaches. Targeted interventions for digestive and genitourinary diseases are warranted for the UK.

Abstract Background Improving feed efficiency is the most important goal for modern animal production. The regulatory mechanisms of controlling feed efficiency traits are extremely complex and include the functions related to host genetics and gut microbiota. Short-chain fatty acids (SCFAs), as significant metabolites of microbiota, could be used to refine the combined effect of host genetics and gut microbiota. However, the association of SCFAs with the gut microbiota and host genetics for regulating feed efficiency is far from understood. Results In this study, 464 broilers were housed for RFI measuring and examining the host genome sequence. And 300 broilers were examined for cecal microbial data and SCFA concentration. Genome-wide association studies (GWAS) showed that four out of seven SCFAs had significant associations with genome variants. One locus (chr4: 29414391–29417189), located near or inside the genes MAML3, SETD7, and MGST2, was significantly associated with propionate and had a modest effect on feed efficiency traits and the microbiota. The genetic effect of the top SNP explained 8.43% variance of propionate. Individuals with genotype AA had significantly different propionate concentrations (0.074 vs. 0.131 μg/mg), feed efficiency (FCR: 1.658 vs. 1.685), and relative abundance of 14 taxa compared to those with the GG genotype. Christensenellaceae and Christensenellaceae_R-7_group were associated with feed efficiency, propionate concentration, the top SNP genotypes, and lipid metabolism. Individuals with a higher cecal abundance of these taxa showed better feed efficiency and lower concentrations of caecal SCFAs. Conclusion Our study provides strong evidence of the pathway that host genome variants affect the cecal SCFA by influencing caecal microbiota and then regulating feed efficiency. The cecal taxa Christensenellaceae and Christensenellaceae_R-7_group were identified as representative taxa contributing to the combined effect of host genetics and SCFAs on chicken feed efficiency. These findings provided strong evidence of the combined effect of host genetics and gut microbial SCFAs in regulating feed efficiency traits. Video Abstract

Abstract Brain–heart interaction has raised up increasing attentions. Nuclear receptors (NRs) are abundantly expressed in the brain, and emerging evidence indicates that a number of these brain NRs regulate multiple aspects of cardiovascular diseases (CVDs), including hypertension, heart failure, atherosclerosis, etc. In this review, we will elaborate recent findings that have established the physiological relevance of brain NRs in the context of cardiovascular function. In addition, we will discuss the currently available evidence regarding the distinct neuronal populations that respond to brain NRs in the cardiovascular control. These findings suggest connections between cardiac control and brain dynamics through NR signaling, which may lead to novel tools for the treatment of pathological changes in the CVDs.

Abstract Background Pro-opiomelanocortin (POMC) neurons play a sexually dimorphic role in body weight and glucose balance. However, the mechanisms for the sex differences in POMC neuron functions are not fully understood. Results We detected small conductance calcium-activated potassium (SK) current in POMC neurons. Secondary analysis of published single-cell RNA-Seq data showed that POMC neurons abundantly express SK3, one SK channel subunit. To test whether SK3 in POMC neurons regulates POMC neuron functions on energy and glucose homeostasis, we used a Cre-loxP strategy to delete SK3 specifically from mature POMC neurons. POMC-specific deletion of SK3 did not affect body weight in either male or female mice. Interestingly, male mutant mice showed not only decreased food intake but also decreased physical activity, resulting in unchanged body weight. Further, POMC-specific SK3 deficiency impaired glucose balance specifically in female mice but not in male mice. Finally, no sex differences were detected in the expression of SK3 and SK current in total POMC neurons. However, we found higher SK current but lower SK3 positive neuron population in male POMC neurons co-expressing estrogen receptor α (ERα) compared to that in females. Conclusion These results revealed a sexually dimorphic role of SK3 in POMC neurons in both energy and glucose homeostasis independent of body weight control, which was associated with the sex difference of SK current in a subpopulation of POMC + ERα + neurons.

Abstract Background Accumulating evidence suggests a strong association between polycystic ovary syndrome (PCOS) and ovarian cancer (OC), but the potential molecular mechanism remains unclear. In this study, we identified previously unrecognized genes that are significantly correlated with PCOS and OC via bioinformatics. Materials and methods Multiple bioinformatic analyses, such as differential expression analysis, univariate Cox analysis, functional and pathway enrichment analysis, protein–protein interaction (PPI) network construction, survival analysis, and immune infiltration analysis, were utilized. We further evaluated the effect of OGN on FSHR expression via immunofluorescence. Results TCGA-OC, GSE140082 (for OC) and GSE34526 (for PCOS) datasets were downloaded. Twelve genes, including RNF144B, LPAR3, CRISPLD2, JCHAIN, OR7E14P, IL27RA, PTPRD, STAT1, NR4A1, OGN, GALNT6 and CXCL11, were identified as signature genes. Drug sensitivity analysis showed that OGN might represent a hub gene in the progression of PCOS and OC. Experimental analysis found that OGN could increase FSHR expression, indicating that OGN could regulate the hormonal response in PCOS and OC. Furthermore, correlation analysis indicated that OGN function might be closely related to m6A and ferroptosis. Conclusions Our study identified a 12-gene signature that might be involved in the prognostic significance of OC. Furthermore, the hub gene OGN represent a significant gene involved in OC and PCOS progression by regulating the hormonal response.

Abstract Background Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides (nt) that are involved in the pathogenesis and development of various cancers including B cell acute lymphoblastic leukemia (B–ALL). To determine the potential roles of lncRNAs involved in pathogenesis of B-ALL, we analyzed the expression profile of lncRNAs and mRNAs in B-ALL, respectively, and constructed lncRNAs/mRNAs interaction network. Methods We performed RNA sequencing of 10 non-leukemic blood disease donors and 10 B-ALL patients for Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Interactions among mRNAs were predicted using the STRING database. Quantitative real time PCR (qRT-PCR) was performed to verify the RNA-seq data of lncRNAs and mRNAs. Potential functions of subtype-specific lncRNAs were determined by using coexpression-based analysis on distally (trans-pattern) located protein-coding genes. Results A total of 1813 differentially expressed transcripts (DETs) and 2203 lncRNAs were identified. Moreover, 10 dysregulated lncRNAs and 10 mRNAs were randomly selected, and further assessed by RT-qPCR in vitro. Go and KEGG analysis demonstrated that the differentially expressed mRNAs were most closely associated with myeloid leukocyte activation and in transcriptional misregulation in cancer, respectively. In addition, co-expression analysis demonstrated that these lncRNAs, including MSTRG.27994.3, MSTRG.21740.1, ENST00000456341, MSTRG.14224.1 and MSTRG.20153.1, may mediate the pathogenesis and development of B-ALL via lncRNA-mRNA network interactions. Conclusions These results showed that several mRNAs and lncRNAs are aberrantly expressed in the bone marrow of B-ALL patients and play potential roles in B-ALL development, and be useful for diagnostic and/or prognostic purposes in pediatric B–ALL. Data availability The datasets used during our study are available through HARVARD Dataverse Persistent ID doi: https://doi.org/10.7910/DVN/LK9T4Z .

Abstract Background Bridging integrator 1 (BIN1) has showed outstanding tumor-suppressive potential via inhibiting c-MYC-mediated tumorigenesis. However, a frequent phosphorylation of c-MYC at Ser-62 site could block the BIN1/c-MYC interaction and limits the tumor-suppressive effect of BIN1. Cyclin-dependent kinase 5 (CDK5), a generally dysregulated protein in various carcinomas, can mediate c-MYC phosphorylation at Ser-62 site. However, whether the existence of CDK5 could block the BIN1/c-MYC interaction remains unclear. Materials and methods The expression of CDK5 and BIN1 in non-small cell lung cancer (NSCLC) cell lines were measured. CDK5 was knocked down and overexpressed in H460 and PC9 cells, respectively. CCK-8, wound healing and transwell were used to detect the proliferation, migration and invasion ability of NSCLC cells. Tumor-bearing nude mouse model was built with H460 cells. Dinaciclib was added to realize the effect of CDK5 inhibition in vivo. NSCLC and matched para-carcinoma specimens were collected from 153 patients who underwent radical operation. IHC was performed to determine the expression of CDK5 in the specimens. Kaplan–Meier analysis was used to analyze the correlation between the postoperative survival and CDK5 expression. Results CDK5 was highly expressed in H460 cells, and knockdown of CDK5 could restore the BIN1/c-MYC interaction. Meanwhile, low expression of CDK5 was observed in PC9 cells, and overexpression of CDK5 blocked the BIN1/c-MYC interaction. Consequently, the growth, migration, invasion and epithelial mesenchymal transition (EMT) ability of H460 and PC9 cells could be facilitated by CDK5. The addition of CDK5 inhibitor Dinaciclib significantly suppressed the tumorigenesis ability of NSCLC cells in tumor-bearing mouse model. Furthermore, high expression of CDK5, along with low expression of BIN1, could predict poor postoperative prognosis of NSCLC patients. The patients with high expression of CDK5 and low expression of BIN1 showed similar prognosis, indicating that CDK5 could neutralize the tumor suppressing effect of BIN1 in clinical situation. Conclusions CDK5 blocked the interaction of BIN1 and c-MYC via promoting phosphorylation of c-MYC at ser-62 site, ultimately facilitated the progression of NSCLC.

Abstract Background While a large number of well-known knowledge bases (KBs) in life science have been published as Linked Open Data, there are few KBs in Chinese. However, KBs in Chinese are necessary when we want to automatically process and analyze electronic medical records (EMRs) in Chinese. Of all, the symptom KB in Chinese is the most seriously in need, since symptoms are the starting point of clinical diagnosis. Results We publish a public KB of symptoms in Chinese, including symptoms, departments, diseases, medicines, and examinations as well as relations between symptoms and the above related entities. To the best of our knowledge, there is no such KB focusing on symptoms in Chinese, and the KB is an important supplement to existing medical resources. Our KB is constructed by fusing data automatically extracted from eight mainstream healthcare websites, three Chinese encyclopedia sites, and symptoms extracted from a larger number of EMRs as supplements. Methods Firstly, we design data schema manually by reference to the Unified Medical Language System (UMLS). Secondly, we extract entities from eight mainstream healthcare websites, which are fed as seeds to train a multi-class classifier and classify entities from encyclopedia sites and train a Conditional Random Field (CRF) model to extract symptoms from EMRs. Thirdly, we fuse data to solve the large-scale duplication between different data sources according to entity type alignment, entity mapping, and attribute mapping. Finally, we link our KB to UMLS to investigate similarities and differences between symptoms in Chinese and English. Conclusions As a result, the KB has more than 26,000 distinct symptoms in Chinese including 3968 symptoms in traditional Chinese medicine and 1029 synonym pairs for symptoms. The KB also includes concepts such as diseases and medicines as well as relations between symptoms and the above related entities. We also link our KB to the Unified Medical Language System and analyze the differences between symptoms in the two KBs. We released the KB as Linked Open Data and a demo at https://datahub.io/dataset/symptoms-in-chinese .