Volume 12, Issue 4

Diabetes is a significant independent risk factor for atherosclerotic cardiovascular disease (ASCVD), with dyslipidemia playing a critical role in the initiation and progression of ASCVD in diabetic patients. In China, the current prevalence of dyslipidemia in diabetes is high, but the control rate remains low. Therefore, to enhance lipid management in patients with diabetes, the Endocrinology and Metabolism Physician Branch of the Chinese Medical Doctor Association, in collaboration with the Experts’ Committee of the National Society of Cardiometabolic Medicine, has convened experts to develop a consensus on the management of dyslipidemia in patients with type 1 or type 2 diabetes. The development of this consensus is informed by existing practices in lipid management among Chinese diabetic patients, incorporating contemporary evidence-based findings and guidelines from national and international sources. The consensus encompasses lipid profile characteristics, the current epidemiological status of dyslipidemia, ASCVD risk stratification, and lipid management procedures in diabetic patients. For the first time, both low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol have been recommended as primary targets for lipid intervention in diabetic patients. The consensus also includes a summary and recommendations for lipid management strategies in special diabetic populations, including children and adolescents, individuals aged 75 years and older, patients with chronic kidney disease, metabolic-associated fatty liver disease, and those who are pregnant. This comprehensive consensus aims to improve cardiovascular outcomes in diabetic patients by contributing to the dissemination of key clinical advancements and guiding clinical practice.

Hepatitis viral infection can cause severe complications, even mortality in pregnant women and their offspring. Multiple studies have shown that vertical transmission can cause viral hepatitis infections in newborns, especially in hepatitis B, C, and E. Screening for hepatitis viral infection in pregnant women is essential. Once infected, pregnant women should be given timely antiviral treatments, which could effectively alleviate the disease progression and reduce adverse outcomes. Besides, the mechanism of viral hepatitis mediating adverse pregnancy outcomes has been a hot topic. Hepatitis B virus has been found to mediate both mother-to-child and parent-child transmission. Liver injury in hepatitis C virus infection is associated with immune-mediated mechanisms, which can be regulated by hormonal factors as well. The mediating mechanism of adverse maternal and infant outcomes caused by hepatitis E virus infection is mainly related to viral replication in the placenta and changes in cytokine and estrogen. Nevertheless, the specific mechanisms related to hepatitis A virus and hepatitis D virus remain unclear, and more research is needed. This review shows that the existence of viral hepatitis during pregnancy can pose certain risks for pregnant women and infants, and different interventions have been used to treat pregnant women infected with viral hepatitis. It may provide deep insight into adverse pregnancy outcomes caused by viral hepatitis and give guidance on treatment.

Background and Objectives Symptom-based subtyping for functional gastrointestinal disorders (FGIDs) has limited value in identifying underlying mechanisms and guiding therapeutic strategies. Small intestinal dysbiosis is implicated in the development of FGIDs. We tested if machine learning (ML) algorithms utilizing both gastrointestinal (GI) symptom characteristics and lactulose breath tests could provide distinct clusters. Materials and Methods This was a prospective cohort study. We performed lactulose hydrogen methane breath tests and hydrogen sulfide breath tests in 508 patients with GI symptoms. An unsupervised ML algorithm was used to categorize subjects by integrating GI symptoms and breath gas characteristics. Generalized Estimating Equation (GEE) models were used to examine the longitudinal associations between cluster patterns and breath gas time profiles. An ML-based prediction model for identifying excessive gas production in FGIDs patients was developed and internal validation was performed. Results FGIDs were confirmed in 300 patients. K-means clustering identified 4 distinct clusters. Cluster 2, 3, and 4 showed enrichments for abdominal distention and diarrhea with a high proportion of excessive gas production, whereas Cluster 1 was characterized by moderate lower abdominal discomforts with the most psychological complaints and the lowest proportion of excessive gas production. GEE models showed that breath gas concentrations varied among different clusters over time. We further sought to develop an ML-based prediction model to determine excessive gas production. The model exhibited good predictive capabilities. Conclusion ML-based phenogroups and prediction model approaches could provide distinct FGIDs subsets and efficiently determine FGIDs subsets with greater gas production, thereby facilitating clinical decision-making and guiding treatment.

Background and Objectives Systemic lupus erythematosus (SLE) is distinguished by dysregulated immune system activity, resulting in a spectrum of clinical manifestations, with lupus nephritis being particularly prominent. This study endeavors to discern novel targets as potential therapeutic markers for this condition. Methods Weighted correlation network analysis (WGCNA) was used to construct the network and select the key hub genes in the co-expression module based on the gene expression dataset GSE81622. Subsequently, functional enrichment and pathway analysis were performed for SLE and lupus nephritis. In addition, also identify genes and differences in SLE with lupus nephritis and methylation site. Finally, qRT-PCR and western blot were used to verify the up-regulated expression levels of the selected key genes. Results Within the co-expression modules constructed by WGCNA, the MElightcyan module exhibited the strongest positive correlation with lupus nephritis (0.4, P = 0.003), while showing a weaker correlation with the control group SLE (0.058) and a negative correlation with the control group (-0.41, P = 0.002). Additionally, the MEgreenyellow module displayed the highest positive correlation with SLE (0.25), but its P value was 0.06, which did not reach statistical significance(P > 0.05). Furthermore, it had a negative correlation with the control group was (-0.38, P = 0.004). The module associated with lupus nephritis was characterized by processes such as neutrophil activation (neutrophil_activation), neutrophil degranulation (neutrophil_degranulation), neutrophil activation involved in immune response (neutrophil_activation_involved_in_immune_response), neutrophils mediated immune (neutrophil_mediated_immunity) and white blood cells degranulation (leukocyte_degranulation) and so on the adjustment of the process. Secondly, in the analysis of SLE samples, the identification of differentially expressed genes revealed 125 genes, with 49 being up-regulated and 76 down-regulated. In the case of lupus nephritis samples, 156 differentially expressed genes were discerned, include in 70 up-regulated and 86 down-regulated genes. When examining differential methylation sites, we observed 12432 such sites in the SLE sample analysis, encompassing 2260 hypermethylation sites and 10172 hypomethylation sites. In the lupus nephritis samples analysis, 9613 differential methylation sites were identified, comprising 4542 hypermethylation sites and 5071 hypomethylation sites. Substantiating our findings, experimental validation of the up-regulated genes in lupus nephritis confirmed increased levels of gene expression and protein expression for CEACAM1 and SLC2A5. Conclusions We have identified several genes, notably CEACAM1 and SLC2A5, as potential markers for lupus nephritis. Their elevated expression levels and reduced DNA methylation in lupus nephritis contribute to a more comprehensive understanding of the aberrant epigenetic regulation of expression in this condition. These findings hold significant implications for the diagnosis and therapeutic strategies of lupus nephritis.

Background and Objectives Autologous skin graft (ASG) transplantation is a challenging approach but a promising option for patients to prevent postoperative esophageal stricture. Nonetheless, the current strategies require improvement. We aimed to investigate the effectiveness of the injection of platelet-rich plasma (PRP) before skin graft transplantation for extensive esophageal defects after endoscopic resection. Methods Standardized complete circular endoscopic resection (5 cm in length) was performed in 27 pigs allocated into 3 groups. The artificial ulcers were treated with a fully covered esophageal stent (control group), ASG (ASG group), and submucosal injection of PRP with ASG (PRP-ASG group). Macroscopic evaluation and histological analysis of the remolded esophagus were performed 7, 14, and 28 days after surgery. Results The macroscopic evaluation indicated that submucosal injection of PRP before transplantation effectively promoted the survival rate of skin grafts and decreased the rate of mucosal contraction compared with those treated with ASG or stent alone. Histological analysis of submucosal tissue showed that this modified strategy significantly promoted wound healing of reconstructed tissues by enhancing angiogenesis, facilitating collagen deposition, and decreasing inflammation and fibrogenesis. Conclusions These findings suggested that PRP might be used as a biological supplement to increase the esophageal skin graft survival rate and improve submucosal tissue remolding in a clinically relevant porcine model. With extremely low mucosal contraction, this novel combination strategy showed the potential to effectively prevent stenosis in extensive esophageal ulcers.

Background Renal inflammation plays key roles in the pathogenesis of diabetic kidney disease (DKD). Immune cell infiltration is the main pathological feature in the progression of DKD. Sodium glucose cotransporter 2 inhibitor (SGLT2i) were reported to have antiinflammatory effects on DKD. While the heterogeneity and molecular basis of the pathogenesis and treatment with SGLT2i in DKD remains poorly understood. Methods To address this question, we performed a single-cell transcriptomics data analysis and cell cross-talk analysis based on the database (GSE181382). The single-cell transcriptome analysis findings were validated using multiplex immunostaining. Results A total of 58760 cells are categorized into 25 distinct cell types. A subset of macrophages with anti-inflammatory potential was identified. We found that Ccl3+ (S100a8/a9 high) macrophages with anti-inflammatory and antimicrobial in the pathogenesis of DKD decreased and reversed the dapagliflozin treatment. Besides, dapagliflozin treatment enhanced the accumulation of Pck1+ macrophage, characterized by gluconeogenesis signaling pathway. Cell-cross talk analysis showed the GRN/SORT1 pair and CD74 related signaling pathways were enriched in the interactions between tubular epithelial cells and immune cells. Conclusions Our study depicts the heterogeneity of macrophages and clarifies a new possible explanation of dapagliflozin treatment, showing the metabolism shifts toward gluconeogenesis in macrophages, fueling the anti-inflammatory function of M2 macrophages, highlighting the new molecular features and signaling pathways and potential therapeutic targets, which has provided an important reference for the study of immune-related mechanisms in the progression of the disease.

Background and Objectives Actin-related protein 2/3 complex subunit 1B (ARPC1B) is an essential subunit of the actin-related protein 2/3 (Arp2/3) complex. While there have been numerous research reports on Arp2/3 in relation to tumors, there needs to be more research on ARPC1B and its role in tumors, particularly at the pan-cancer level. Methods Utilizing data from the cancer genome atlas (TCGA) and genotype-tissue expression (GTEx) databases, we analyzed ARPC1B expression differences in normal, tumor, and adjacent tissues, investigating its correlation with prognosis and clinical stages in various cancers. We conducted gene enrichment analysis and explored ARPC1B’s connection to the tumor immune microenvironment and its impact on anti-tumor drug resistance. In addition, in vivo and in vitro experiments have also been carried out to find the mechanism of ARPC1B on ovarian cancer (OV) proliferation and invasion. Results ARPC1B was highly expressed in 33 tumor types, suggesting its role as a tumor-promoting factor. Its expression correlated with poor prognosis and served as a clinical staging marker in over 10 tumor types. ARPC1B is implicated in various biological processes and signaling pathways, uniquely associated with tumor immunity, indicating immunosuppressive conditions in high-expression cases. High ARPC1B expression was linked to resistance to six anti-tumor drugs. Further experiments showed that ARPC1B can affect the proliferation, apoptosis, migration, and invasion of OV cells through the AKT/PI3K/mTOR pathway. Conclusion ARPC1B is a biomarker for immune suppression, prognosis, clinical staging, and drug resistance, providing new insights for cancer therapeutics.

Background and Objectives Local hyperthermia at 44°C can clear multiple human papillomavirus (HPV)-infected skin lesions (warts) by targeting a single lesion, which is considered as a success of inducing antiviral immunity in the human body. However, approximately 30% of the patients had a lower response to this intervention. To identify novel molecular targets for anti-HPV immunity induction to improve local hyperthermia efficacy, we conducted a lysine succinylome assay in HaCaT cells (subjected to 44°C and 37°C water baths for 30 min). Methods The succinylome analysis was conducted on HaCaT subjected to 44°C and 37°C water bath for 30 min using antibody affinity enrichment together with liquid chromatography-tandem mass spectrometry (LC-MS/MS). The results were validated by western blot (WB), immunoprecipitation (IP), and co-immunoprecipitation (Co-IP). Then, bioinformatic analysis including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, motif characterization, secondary structure, and protein-protein interaction (PPI) was performed. Results A total of 119 proteins with 197 succinylated sites were upregulated in 44°C-treated HaCaT cells. GO annotation demonstrated that differential proteins were involved in the immune system process and viral transcription. Succinylation was significantly upregulated in annexin A2. We found that hyperthermia upregulated the succinylated level of global proteins in HaCaT cells by downregulating the desuccinylase sirtuin7 (SIRT7), which can interact with annexin A2. Conclusions Taken together, these data indicated that succinylation of annexin A2 may serve as a new drug target, which could be intervened in combination with local hyperthermia for better treatment of cutaneous warts.

Background and Objective Chronic thromboembolic pulmonary hypertension (CTEPH) is a lethal complication of pulmonary embolism involving pulmonary artery occlusion and microvascular disease. The glucose metabolism and reactive oxygen species (ROS) production may be perturbed in CTEPH, but the precise mechanisms are unclear. This study investigated glucose metabolism in CTEPH employing pulmonary endarterectomy (PEA)-derived pulmonary artery smooth muscle cells (PASMCs) and characterized the roles of pyruvate kinase M2 (PKM2) and its regulation by heterogeneous nuclear ribonucleoproteins A1 (hnRNPA1) and ROS in CTEPH. Methods PEA tissues and blood samples of CTEPH patients were collected to study the levels of PKM2. Primary PASMCs were isolated from PEA tissues. We used small interfering RNAs to knock down PKM2 and hnRNPAI , and applied antioxidant N-acetylcysteine (NAC) and mito-TEMPO to reduce ROS production. The expression of glucometabolic genes, ROS production, glycolysis rate and proliferative and migratory activities were analyzed in PEA-derived PASMCs. Results PKM2 levels in serum and PEA tissues of CTEPH patients were higher than that of the healthy controls. Compared to the control PASMCs, PEA-derived PASMCs showed increased PKM2 expression and ROS production. The rates of glycolysis, proliferation and migration were increased in PEA-PASMCs and could be mitigated by PKM2 downregulation through hnRNPA1 or ROS inhibition. Conclusions Increased glycolysis and PKM2 expression were found in PEA-PASMCs. Inhibition of hnRNPA1 or ROS corrected the aberrant glycolysis, cell proliferation and migration by downregulating PKM2. Regulation of the hnRNPA1/PKM2 axis represents a potential therapeutic target for the treatment of CTEPH.