Erratum to "PGAM5-Mediated PHB2 Dephosphorylation Contributes to Diabetic Cardiomyopathy by Disrupting Mitochondrial Quality Surveillance".

[This corrects the article DOI: 10.34133/research.0001.].

ChatGPT in medicine: prospects and challenges: a review article.

It has been a year since the launch of Chat Generator Pre-Trained Transformer (ChatGPT), a generative artificial intelligence (AI) program. The introduction of this cross-generational product initially brought a huge shock to people with its incredible potential, and then aroused increasing concerns among people. In the field of medicine, researchers have extensively explored the possible applications of ChatGPT and achieved numerous satisfactory results. However, opportunities and issues always come together. Problems have also been exposed during the applications of ChatGPT, requiring cautious handling, thorough consideration and further guidelines for safe use. Here, we summarized the potential applications of ChatGPT in the medical field, including revolutionizing healthcare consultation, assisting patient management and treatment, transforming medical education and facilitating clinical research. Meanwhile, we also enumerated researchers' concerns arising along with its broad and satisfactory applications. As it is irreversible that AI will gradually permeate every aspect of modern life, we hope that this review can not only promote people's understanding of the potential applications of ChatGPT in the future, but also remind them to be more cautious about this "Pandora's Box" in the medical field. It is necessary to establish normative guidelines for its safe use in the medical field as soon as possible.

The DNA-dependent protein kinase catalytic subunit exacerbates endotoxemia-induced myocardial microvascular injury by disrupting the MOTS-c/JNK pathway and inducing profilin-mediated lamellipodia degradation.

Rationale: The DNA-dependent protein kinase catalytic subunit (DNA-PKcs) promotes pathological mitochondrial fission during septic acute kidney injury. The mitochondrial open reading frame of the 12S rRNA type-c (MOTS-c) is a mitochondria-derived peptide that exhibits anti-inflammatory properties during cardiovascular illnesses. We explored whether endotoxemia-induced myocardial microvascular injury involved DNA-PKcs and MOTS-c dysregulation. Methods: To induce endotoxemia in vivo, endothelial cell-specific DNA-PKcs-knockout mice were injected intraperitoneally with a single dose of lipopolysaccharide (10 mg/kg) and evaluated after 72 h. Results: Lipopolysaccharide exposure increased DNA-PKcs activity in cardiac microvascular endothelial cells, while pharmacological inhibition or endothelial cell-specific genetic ablation of DNA-PKcs reduced lipopolysaccharide-induced myocardial microvascular dysfunction. Proteomic analyses showed that endothelial DNA-PKcs ablation primarily altered mitochondrial protein expression. Verification assays confirmed that DNA-PKcs drastically repressed MOTS-c transcription by inducing mtDNA breaks via pathological mitochondrial fission. Inhibiting MOTS-c neutralized the endothelial protective effects of DNA-PKcs ablation, whereas MOTS-c supplementation enhanced endothelial barrier function and myocardial microvascular homeostasis under lipopolysaccharide stress. In molecular studies, MOTS-c downregulation disinhibited c-Jun N-terminal kinase (JNK), allowing JNK to phosphorylate profilin-S173. Inhibiting JNK or transfecting cells with a profilin phosphorylation-defective mutant improved endothelial barrier function by preventing F-actin depolymerization and lamellipodial degradation following lipopolysaccharide treatment. Conclusions: DNA-PKcs inactivation during endotoxemia could be a worthwhile therapeutic strategy to restore MOTS-c expression, prevent JNK-induced profilin phosphorylation, improve F-actin polymerization, and enhance lamellipodial integrity, ultimately ameliorating endothelial barrier function and reducing myocardial microvascular injury.

Prevalence, incidence density and standardized morbidity rate of melanoma among patients with congenital melanocytic nevi: A systematic review.

Congenital melanocytic nevi (CMN) are the result of aberrations in the mitogen-activated protein kinase signal transduction pathway. The risk of melanoma is the most important concern among patients with CMN for its poor prognosis. However, due to the great variability between studies, the reported risk of melanoma varied considerably, making it difficult to provide reliable information. To evaluate the prevalence, incidence density and standardized morbidity ratio (SMR) of melanoma among patients with CMN, we conducted a systematic literature search of studies providing data on the risk of melanoma in CMN patients following our registered and published protocol (PROSPERO ID# CRD42022383009). Overall, twenty-seven studies with a total of 11480 CMN patients and 82 melanoma cases were included for analysis. The prevalence of melanoma was 1.84% [95% confidence interval (CI) 1.13%-2.99%] in CMN patients and 2.73% (95% CI 1.67%-4.33%) in patients with large CMN (LCMN). The incidence density of melanoma was 237.56 (95% CI 97.79-575.96) per 100,000 person-years (P-Y) in CMN patients and 585.73 (95% CI 315.39-1085.29) per 100,000 P-Y in the LCMN subgroup. The SMR of melanoma was 122.27 (95% CI 11.84-1262.88) among all CMN patients and 285.97 (95% CI 50.65-1614.59) in patients with LCMN. Our research suggests that the risk of melanoma in the CMN population seems to be overestimated by previous studies, but still significantly higher than that in the normal population. In addition to the risk of melanoma, aesthetic improvement and mental health should also be taken into account when making management decisions.

A clinical and biologic review of congenital melanocytic nevi.

Congenital melanocytic nevi (CMN) are the result of aberrations in the mitogen-activated protein kinase signal transduction pathway caused by postzygotic somatic mutations. The estimated incidence of newborns with CMN is 1%-2%. The main complications of CMN include proliferative nodules, melanomas, and neurocutaneous melanosis, and the latter two are the most troublesome issues to address. Treatments are primarily taken into account for aesthetic purposes and the reduction of melanoma risk. Due to the much lower incidence of malignant transformation observed in recent studies than in previous data, clinical management paradigms for CMN patients have gradually shifted towards conservative observation and close monitoring. Surgery and lasers are still the main treatments, and targeted therapy may be a promising strategy to help manage complications. With the increase in awareness of mental health, increasing focus has been placed on the quality of life (QoL) and psychological issues of both CMN patients and their parents. Recent studies have revealed that families coping with CMN might endure intense pressure, a major loss in QoL, and psychological problems after diagnosis and during treatment. Here, we sought to present an overview of genetic basis, complications, treatments, and psychological issues related to CMN and hope to provide better management for patients with CMN.

Risk factors associated with surgical site infections in patients undergoing cardiothoracic surgery: A systematic review and meta-analysis.

Surgical site infections (SSIs) following cardiothoracic surgery can pose significant challenges to patient recovery and outcome. This systematic review and meta-analysis aim to identify and quantify the risk factors associated with SSIs in patients undergoing cardiothoracic surgery. A comprehensive literature search adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and based on the PICO paradigm was conducted across four databases: PubMed, Embase, Web of Science and the Cochrane Library, without any temporal restrictions. The meta-analysis incorporated studies detailing the risk factors for post-operative sternal infections, especially those reporting odds ratios (OR) or relative risks with 95% confidence intervals (CI). Quality assessment of the studies was done using the Newcastle-Ottawa Scale. Statistical analysis was executed using the chi-square tests for inter-study heterogeneity, with further analyses depending on I2 values. Sensitivity analyses were performed, and potential publication bias was also assessed. An initial dataset of 2442 articles was refined to 21 articles after thorough evaluations based on inclusion and exclusion criteria. Patients with diabetes mellitus have an OR of 1.80 (95% CI: 1.40-2.20) for the incidence of SSIs, while obese patients demonstrate an OR of 1.63 (95% CI: 1.40-1.87). Individuals who undergo intraoperative blood transfusion present an OR of 1.13 (95% CI: 1.07-1.18), and smokers manifest an OR of 1.32 (95% CI: 1.03-1.60). These findings unequivocally indicate a pronounced association between these factors and an elevated risk of SSIs post-operatively. This meta-analysis confirms that diabetes, obesity, intraoperative transfusion and smoking heighten the risk of SSIs post-cardiac surgery. Clinicians should be alert to these factors to optimise patient outcomes.

Case report: Concomitant EGFR mutation and ALK rearrangement in non-small cell lung cancer.

In non-small cell lung cancer (NSCLC), two key genetic alterations, epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements, are commonly believed to be mutually exclusive. Studies have reported that concurrent EGFR/ALK co-mutation in non-small cell lung cancer patients is rare, with a prevalence ranging from 0.1% to 1.6%. However, the clinical and pathological characteristics of these patients are not well-defined, and the optimal treatment approach for such cases remains controversial. In this report, we present a case of stage IV lung adenocarcinoma with both epidermal growth factor receptor and anaplastic lymphoma kinase mutations, along with high PD-L1 expression. The patient initially received treatment with epidermal growth factor receptor tyrosine kinase inhibitors (TKIs), but the disease progressed. However, following a switch to ALK-TKI therapy and local radiotherapy, the lesion showed regression. Our report also provides a comprehensive summary of the clinical and pathological features, as well as treatment strategies, for non-small cell lung cancer patients with concurrent epidermal growth factor receptor mutation and anaplastic lymphoma kinase rearrangement.

Single-cell transcriptomics reveals zinc and copper ions homeostasis in epicardial adipose tissue of heart failure.

Epicardial adipose tissue (EAT) is a unique visceral fat reservoir that shares an immune microenvironment without a distinct boundary with myocardium. Increasingly, visceral fat has been studied as a secondary immune organ, and EAT is no exception in this regard. Cellular subsets of EAT are associated with disease development. In heart failure (HF) patients, however, the immune characteristics of EAT have rarely been studied, especially those non-immune cells related to the immune microenvironment. Herein, an analysis of seven EAT samples by single-cell RNA sequencing (scRNA-Seq) is presented here, including 1 neonate, 1 infant, 1 child, 2 adults with heart failure (Adults-HF) and 2 adult heart transplant donors as non-heart failure control (Adults-Non HF). Analysis of 51730 high-quality cells revealed eleven major cell types in EAT. For the first time, the pseudo-temporal reconstruction technique was employed to plot the cell trajectories of various major cell types (such as T lymphocytes, fibroblasts, endothelial cells, monocytes, and smooth muscle cells) in EAT across different developmental stages, achieving a single-cell resolution. The dynamic gene expression patterns of major cell types presented the immune characteristics of metabolism disorder of zinc and copper ions, and downregulated immune-related pathways in EAT of adult patients with HF. These data provide insights regarding HF immune dysregulation at the cellular level.

Case report: Highly differentiated endometrial adenocarcinoma that collided with uterine cervical carcinosarcoma.

Uterine collision tumor is a rare pathological type composed of two or more malignant tumors. The components of these malignant tumors do not have histological mixing and are separated by the normal mesenchyme. Collision cancer is very rare, with uterine collision tumors being even rarer. Only a few cases have been reported in relation to uterine collision tumors. At present, there is no standard treatment guideline for uterine collision tumors, and a comprehensive treatment composed of surgery, radiotherapy, and chemotherapy is suggested. In this study, we report a 54-year-old female patient diagnosed with highly differentiated endometrial adenocarcinoma with cervical carcinosarcoma. The endometrial adenocarcinoma component invaded the deep myometrium (> 1/2 layer), involving the cervical glands and interstitium. The regional lymph node metastasis from endometrial adenocarcinoma was also detected. The patient underwent "transabdominal tumor cytoreduction (total hysterectomy + right adnexal resection + greater omentectomy + pelvic lymph node dissection + para-aortic lymph node dissection) + pelvic adhesion release." In addition, she has completed adjuvant radiotherapy and chemotherapy. After reviewing previous reports of collision tumors in different positions of the uterus, we found that collision tumors between the cervix and uterine body are very uncommon. In addition, we have not found any reports on the metastasis of sarcoid components, no matter what the composition is.

Reconstruction of aortic sinus using patches in patients with acute type A aortic dissection.

OBJECTIVES: Acute type A aortic dissection involving the aortic sinus is often combined with varying degrees of aortic regurgitation, while the structure of the aortic valve is often undamaged. The aim of this study was to evaluate the clinical effects of reconstruction of the aortic sinus using patches in patients with acute type A aortic dissection. METHODS: From January 2016 to December 2019, 52 patients with acute type A aortic dissection involving the aortic sinus were treated with aortic sinus reconstruction using pericardial or artificial vascular patches. The clinical and follow-up data were summarized. RESULTS: Bovine pericardial patches were used in 31 cases and artificial vascular patches were used in 21 cases for aortic sinus reconstruction. Cardiopulmonary bypass time was (250.4 ± 65.7) min, aortic cross clamp time was (143.7 ± 42.3) min, and hypothermic circulatory arrest time was (9.6 ± 8.1) min. Three patients died in hospital, with a mortality rate of 5.8%. Fifteen patients (28.8%) had mild postoperative aortic regurgitation. The follow-up duration was 40 ± 12 (range, 21-66) months. Five patients (10.2%) developed moderate to severe aortic regurgitation and 3 (6.1%) died during the follow-up period. CONCLUSIONS: The application of patches for aortic sinus reconstruction is a relatively easy method in aortic valve-sparing root reconstruction for acute type A aortic dissection involving the aortic sinus. The clinical and follow-up results are favorable.

The role of neutrophil extracellular traps in cancer progression, metastasis and therapy.

Neutrophil extracellular traps (NETs) released by activated neutrophils typically consist of DNA-histone complexes and granule proteins. NETs were originally identified as a host defense system against foreign pathogens and are strongly associated with autoimmune diseases. However, a novel and predominant role of NETs in cancer is emerging. Increasing evidence has confirmed that many stimuli can facilitate NET formation in an NADPH oxidase (NOX)-dependent/NOX-independent manner. In cancer, NETs have been linked to cancer progression, metastasis, and cancer-associated thrombosis. In this review, we aimed to summarize the current available knowledge regarding NET formation and focused on the role of NETs in cancer biological behaviors. The potential target for cancer therapy will be further discussed.

A circular network of purine metabolism as coregulators of dilated cardiomyopathy.

BACKGROUND: The crosstalk of purine biosynthesis and metabolism exists to balance the cell energy production, proliferation, survival and cytoplasmic environment stability, but disorganized mechanics of with respect to developing heart failure (HF) is currently unknown. METHODS: We conducted a multi-omics wide analysis, including microarray-based transcriptomes, and full spectrum metabolomics with respect to chronic HF. Based on expression profiling by array, we applied a bioinformatics platform of quantifiable metabolic pathway changes based on gene set enrichment analysis (GSEA), gene set variation analysis (GSVA), Shapley Additive Explanations (SHAP), and Xtreme Gradient Boosting (XGBoost) algorithms to comprehensively analyze the dynamic changes of metabolic pathways and circular network in the HF development. Additionally, left ventricular tissue from patients undergoing myocardial biopsy and transplantation were collected to perform the protein and full spectrum metabolic mass spectrometry. RESULTS: Systematic bioinformatics analysis showed the purine metabolism reprogramming was significantly detected in dilated cardiomyopathy. In addition, this result was also demonstrated in metabolomic mass spectrometry. And the differentially expressed metabolites analysis showing the guanine, urea, and xanthine were significantly detected. Hub markers, includes IMPDH1, ENTPD2, AK7, AK2, and CANT1, also significantly identified based on XGBoost, SHAP model and PPI network. CONCLUSION: The crosstalk in the reactions involved in purine metabolism may involving in DCM metabolism reprogramming, and as coregulators of development of HF, which may identify as potential therapeutic targets. And the markers of IMPDH1, ENTPD2, AK7, AK2, and CANT1, and metabolites involved in purine metabolism shown an important role.

Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model.

Familial hypertrophic cardiomyopathy (HCM, OMIM: 613690) is the most common cardiomyopathy in China. However, the underlying genetic etiology of HCM remains elusive. We previously identified a myosin heavy chain 7 (MYH7) gene heterozygous variant, NM_000257.4: c.G2468A (p.G823E), in a large Chinese Han family with HCM. In this family, variant G823E cosegregates with an autosomal dominant disorder. This variant is located in the lever arm domain of the neck region of the MYH7 protein and is highly conserved among homologous myosins and species. To verify the pathogenicity of the G823E variant, we produced a C57BL/6N mouse model with a point mutation (G823E) at the mouse MYH7 locus with CRISPR/Cas9-mediated genome engineering. We designed gRNA targeting vectors and donor oligonucleotides (with targeting sequences flanked by 134 bp of homology). The p.G823E (GGG to GAG) site in the donor oligonucleotide was introduced into exon 23 of MYH7 by homology-directed repair. A silenced p.R819 (AGG to CGA) was also inserted to prevent gRNA binding and re-cleavage of the sequence after homology-directed repair. Echocardiography revealed left ventricular posterior wall (LVPW) hypertrophy with systole in MYH7 G823E/- mice at 2 months of age. These results were likewise validated by histological analysis (Figure 3). These results demonstrate that the G823E variant plays an important role in the pathogenesis of HCM. Our findings enrich the spectrum of MYH7 variants linked to familial HCM and may provide guidance for genetic counseling and prenatal diagnosis in this Chinese family.

The Research Progress of Antiangiogenic Therapy, Immune Therapy and Tumor Microenvironment.

Anti-angiogenesis therapy, a promising strategy against cancer progression, is limited by drug-resistance, which could be attributed to changes within the tumor microenvironment. Studies have increasingly shown that combining anti-angiogenesis drugs with immunotherapy synergistically inhibits tumor growth and progression. Combination of anti-angiogenesis therapy and immunotherapy are well-established therapeutic options among solid tumors, such as non-small cell lung cancer, hepatic cell carcinoma, and renal cell carcinoma. However, this combination has achieved an unsatisfactory effect among some tumors, such as breast cancer, glioblastoma, and pancreatic ductal adenocarcinoma. Therefore, resistance to anti-angiogenesis agents, as well as a lack of biomarkers, remains a challenge. In this review, the current anti-angiogenesis therapies and corresponding drug-resistance, the relationship between tumor microenvironment and immunotherapy, and the latest progress on the combination of both therapeutic modalities are discussed. The aim of this review is to discuss whether the combination of anti-angiogenesis therapy and immunotherapy can exert synergistic antitumor effects, which can provide a basis to exploring new targets and developing more advanced strategies.

Aortic Repair Through a Left Thoracotomy in a 12-Year-Old Child with Traumatic Aortic Pseudoaneurysm: A Case Report.

Traumatic pseudoaneurysm of the descending aorta is a rare but life-threatening disease, especially in children. Open surgical replacement and thoracic endovascular repair in treating traumatic pseudoaneurysm to prevent aortic rupture rarely have been reported in children. Here, we present a rare case of aortic pseudoaneurysm caused by trauma in a 12-year-old child treated with an alternative surgical strategy. Aortic repair without an implant assisted by distal perfusion was performed through a left thoracotomy. The child satisfactorily recovered, was discharged, and remained in a good condition during the follow-up period.

Identification of two novel poleroviruses and the occurrence of Tobacco bushy top disease causal agents in natural plants.

Tobacco bushy top disease (TBTD) is a devastating tobacco disease in the southwestern region of China. TBTD in the Yunnan Province is often caused by co-infections of several plant viruses: tobacco bushy top virus (TBTV), tobacco vein distorting virus (TVDV), tobacco bushy top virus satellite RNA (TBTVsatRNA) and tobacco vein distorting virus-associated RNA (TVDVaRNA). Through this study, two new poleroviruses were identified in two TBTD symptomatic tobacco plants and these two novel viruses are tentatively named as tobacco polerovirus 1 (TPV1) and tobacco polerovirus 2 (TPV2), respectively. Analyses of 244 tobacco samples collected from tobacco fields in the Yunnan Province through RT-PCR showed that a total of 80 samples were infected with TPV1 and/or TPV2, and the infection rates of TPV1 and TPV2 were 8.61% and 29.51%, respectively. Thirty-three TPV1 and/or TPV2-infected tobacco samples were selected for further test for TBTV, TVDV, TBTVsatRNA and TVDVaRNA infections. The results showed that many TPV1 and/or TPV2-infected plants were also infected with two or more other assayed viruses. In this study, we also surveyed TBTV, TVDV, TBTVsatRNA and TVDVaRNA infections in a total of 1713 leaf samples collected from field plants belonging to 29 plant species in 13 plant families and from 11 provinces/autonomous regions in China. TVDV had the highest infection rates of 37.5%, while TVDVaRNA, TBTV and TBTVsatRNA were found to be at 23.0%, 12.4% and 8.1%, respectively. In addition, TVDV, TBTV, TBTVsatRNA and TVDVaRNA were firstly detected of co-infection on 10 plants such as broad bean, pea, oilseed rape, pumpkin, tomato, crofton weed etc., and 1 to 4 of the TBTD causal agents were present in the samples collected from Guizhou, Hainan, Henan, Liaoning, Inner mongolia and Tibet autonomous regions. The results indicated that TBTD causal agents are expanding its host range and posing a risk to other crop in the field.

Anlotinib Exerts Anti-Cancer Effects on KRAS-Mutated Lung Cancer Cell Through Suppressing the MEK/ERK Pathway.

BACKGROUND: With a high frequency of 30%, KRAS mutations in patients with non-small cell lung cancer (NSCLC) often lead to their poor response to most anti-cancer therapies. As a multi-target tyrosine kinase inhibitor, Anlotinib shows clinical efficacy against several types of cancer. However, its effects on KRAS mutant NSCLC and the underlying molecular mechanisms remain unclear. MATERIALS AND METHODS: Cell counting Kit-8 assay, colony formation assay, flow cytometry analysis, wound healing scratch assay, Transwell assay and xenograft mouse model were used to evaluate the anti-cancer effects of Anlotinib. The potential molecular mechanisms were determined by immunohistochemistry (IHC) and Western blotting. RESULTS: Anlotinib inhibited proliferation of KRAS mutant lung cancer cells and induced apoptosis in vitro. In addition, the migration and invasion abilities of these cells were also decreased after treatment with Anlotinib. It significantly suppressed tumor growth in vivo and prolonged the survival of the xenograft-bearing mice, which correlated to lower expression levels of Ki67 in the tumor tissues. Mechanistically, Anlotinib downregulated MEK and ERK as well as their phosphorylated forms in the KRAS mutant lung cancer cells. CONCLUSION: Anlotinib inhibits the growth of KRAS mutant lung cancer cells partly via the suppression of the MEK/ERK pathway. Our findings provide novel insights into treating recalcitrant KRAS mutated NSCLC.

Molecular characterization of a novel potyvirus infecting noni.

The complete genomic sequence of a novel potyvirus from a noni plant in China (Morinda citrifolia) with foliar mosaic and chlorotic symptoms was determined. The genomic RNA consists of 9645 nucleotides (nt) excluding the poly(A) tail, containing the typical open reading frame (ORF) of potyviruses and encoding a large putative polyprotein of 3077 amino acids (aa). Pairwise comparisons showed that the virus shares 48.8%-58.5% sequence identity at the genome sequence level, and 38.5%-53.4% identity at the polyprotein sequence level with other members of the genus Potyvirus. Phylogenetic analysis indicated that the virus is most closely related to jasmine virus T and plum pox virus in the genus Potyvirus. These results suggest that this virus should be considered a distinct member of the genus Potyvirus, and it was tentatively named "noni mosaic virus" (NoMV).

Complete genome sequence of yam chlorotic necrosis virus, a novel macluravirus infecting yam.

The complete genome sequence of a novel member of the genus Macluravirus was determined from yam plants with chlorotic and necrotic symptoms in China. The genomic RNA consists of 8,261 nucleotides (nt) excluding the 3'-terminal poly(A) tail, containing one long open reading frame (ORF) encoding a large putative polyprotein of 2,627 amino acids. Its genomic structure is typical of macluraviruses, which lack the P1 protein, N-terminal HC-Pro, and D-A-G motif for aphid transmission that are found in potyviruses. The virus shares 56.3-63.8% sequence identity at the genome sequence level and 49.7-63.9% at the polyprotein sequence level with other members of the genus Macluravirus. Phylogenetic analysis based on the complete polyprotein sequence of representative members of the family Potyviridae clearly places the virus within the genus Macluravirus. These results suggest that the virus, tentatively named "yam chlorotic necrosis virus" (YCNV), should be considered a member of a novel species in the genus Macluravirus.