Diabetic cardiomyopathy （DCM） is one of the most common complications of diabetes mellitus and is a major threat to global health. As a key mechanism in the occurrence and progression of DCM， the inflammatory response persists throughout the entire course of the DCM. The Gaozhuo theory suggests that the basic pathogenesis of inflammatory injury in DCM is the Qi deficiency of spleen and kidney and Gaozhuo invasion， and divides the pathological process into three phases： Gaozhuo invasion， turbid heat damage to the channels， and turbid blood stasis and heat junction. Among them， the Qi deficiency of spleen and kidney and the endogenous formation of Gaozhuo represent the process of inflammatory factor formation induced by glucose metabolism disorders. Turbid heat damage to the channels refers to the process of myocardial inflammatory injury mediated by inflammatory factors， and turbid blood stasis and heat junction are the process of myocardial injury developing toward myocardial fibrosis and ventricular remodeling. As the disease continues to progress， it eventually develops into a depletion of the heart Yang， leading to the ultimate regression of heart failure. According to the theory of Gaozhuo， traditional Chinese medicine （TCM） should regulate inflammatory injury in DCM by strengthening the spleen and tonifying the kidney to address the root cause， and resolving dampness and lowering turbidity to treat the symptoms. If the turbidity has been stored for a long time and turns into heat， strengthening the spleen and tonifying the kidney， and clearing heat and resolving turbidity should be the therapy. If the turbidity， stasis， and heat are knotted in the heart and collaterals， strengthening the spleen and tonifying the kidney， and resolving stasis and lowering turbidity should be the therapy. TCM compounds and monomers can regulate the inflammatory response in DCM. TCM compounds can be divided into the categories for benefiting Qi to resolve turbidity， benefiting Qi and clearing heat to resolve turbidity， and benefiting Qi and activating blood to reduce turbidity. The compounds can inhibit upstream signals of inflammation and expression of inflammatory factors， improve the inflammatory damage to myocardium and blood vessels， myocardial fibrosis， and cardiac systole and diastole， and thus slow down the onset and progression of DCM.

Objective: To reveal the molecular biological mechanism of a rare Dc-variant individual using PacBio third-generation sequencing technology. Methods: ABO and Rh blood type identification, DAT, unexpected antibody screening and D antigen enhancement test were conducted by serological testing. The absorption-elution test was used to detect the e antigen. RHCE gene typing was performed by PCR-SSP, and the 1-10 exons of RHCE were sequenced by Sanger sequencing. The full-length sequences of RHCE, RHD and RHAG were detected by PacBio third-generation sequencing technology. Results: Serological findings: Blood type O, Dc-phenotype, DAT negative, unexpected antibody screening negative; enhanced D antigen expression; no detection of e antigen in the absorption-elution test. PCR-SSP genotyping indicated the presence of only the RHCE c allele. Sanger sequencing results: Exons 5-9 of RHCE were deleted, exon 1 had a heterozygous mutation at c. 48G/C, and exon 2 had five heterozygous mutations at c. 150C/T, c. 178C/A, c. 201A/G, c. 203A/G and c. 307C/T. Third-generation sequencing results: RHCE genotype was RHCE 02N. 08/RHCE-D(5-9)-CE; RHD genotype was RHD 01/RHD 01; RHAG genotype was RHAG 01/RHAG 01 (c. 808G>A and c. 861G>A). Conclusion: This Dc-individual carries the allele RHCE 02N. 08 and the novel allele RHCE-D(5-9)-CE. The findings of this study provide data support and a theoretical basis for elucidating the molecular mechanisms underlying RhCE deficiency phenotypes.

BACKGROUND: Epidermal growth factor receptor (EGFR) sensitive mutation is one of the effective targets of targeted therapy for non-small cell lung cancer (NSCLC). However, due to the difficulty of obtaining some primary tissues and the economic factors in some underdeveloped areas, some patients cannot undergo traditional genetic testing. The aim of this study is to establish a machine learning (ML) model using non-invasive peripheral blood markers to explore the biomarkers closely related to EGFR mutation status in NSCLC and evaluate their potential prognostic value. METHODS: 2642 lung cancer patients who visited Jiangsu Cancer Hospital from November 2016 to May 2023 were retrospectively enrolled and finally 175 NSCLC patients with complete follow-up data were included in the study. The ML model was constructed based on peripheral blood indicators and divided into training set and test set according to the ratio of 8:2. Unsupervised learning algorithms were used for clustering blood features and mutual information method for feature selection, and an ensemble learning algorithm based on Shapley value was designed to calculate the contribution of each feature to the model prediction result. The receiver operating characteristic (ROC) curve was used to evaluate the predictive ability of the model. RESULTS: Through the feature extraction and contribution analysis of the predictive results of the interpretable ML model based on the Shapley value, the top ten indicators with the highest contribution were: pathological type, phosphorus, eosinophils, monocyte count, activated partial thromboplastin time, potassium, total bilirubin, sodium, eosinophil percentage, and total cholesterol. The area under the curve (AUC) of the model was 0.80. In addition, patients with hyponatremia and squamous cell carcinoma group had a poor prognosis (P<0.05). CONCLUSIONS The interpretable model constructed in this study provides a new approach for the prediction of EGFR mutation status in NSCLC patients, which provides a scientific basis for the diagnosis and treatment of patients who cannot undergo genetic testing.
Humans ; Carcinoma, Non-Small-Cell Lung/diagnosis* ; Machine Learning ; Lung Neoplasms/diagnosis* ; Male ; Female ; Mutation ; Middle Aged ; ErbB Receptors/genetics* ; Prognosis ; Aged ; Retrospective Studies ; Adult ; Biomarkers, Tumor/genetics*

Loss-of-function variants in CSDE1 have been strongly linked to neuropsychiatric disorders, yet the precise role of CSDE1 in neurogenesis remains elusive. In this study, we demonstrate that knockout of Csde1 during cortical development in mice results in impaired neural progenitor proliferation, leading to abnormal cortical lamination and embryonic lethality. Transcriptomic analysis revealed that Csde1 upregulates the transcription of genes involved in the cell cycle network. Applying a dual thymidine-labelling approach, we further revealed prolonged cell cycle durations of neuronal progenitors in Csde1-knockout mice, with a notable extension of the G1 phase. Intersection with CLIP-seq data demonstrated that Csde1 binds to the 3' untranslated region (UTR) of mRNA transcripts encoding cell cycle genes. Particularly, we uncovered that Csde1 directly binds to the 3' UTR of mRNA transcripts encoding Cdk6, a pivotal gene in regulating the transition from the G1 to S phases of the cell cycle, thereby maintaining its stability. Collectively, this study elucidates Csde1 as a novel regulator of Cdk6, sheds new light on its critical roles in orchestrating brain development, and underscores how mutations in Csde1 may contribute to the pathogenesis of neuropsychiatric disorders.
Animals ; Neurogenesis/genetics* ; Cell Cycle/genetics* ; Mice, Knockout ; Mice ; Neural Stem Cells/metabolism* ; DNA-Binding Proteins/metabolism* ; Cyclin-Dependent Kinase 6/genetics* ; Cell Proliferation ; 3' Untranslated Regions ; Cerebral Cortex/embryology* ; RNA-Binding Proteins ; Mice, Inbred C57BL

Sepsis is a life-threatening organ dysfunction syndrome caused by a dysregulated host response to infection. Septic acute kidney injury (SAKI) is one of the most common complications of sepsis, and the occurrence of acute kidney injury (AKI) indicates that the patient's condition is critical with a poor prognosis. The traditional view holds that the main mechanism of SAKI is the reduction of renal blood flow, inadequate renal perfusion, inflammatory response, and microcirculatory dysfunction caused by sepsis, which subsequently leads to ischemia and necrosis of renal tubular cells. Recent research findings indicate that processes such as autophagy and other forms of programmed cell death play an increasingly important role. Autophagy is a programmed intracellular degradation process and is a form of programmed cell death. Cells degrade their cytoplasmic components via lysosomes, breaking down and recycling intracellular constituents to meet their metabolic needs, maintain intracellular homeostasis, and renew organelles. During SAKI, autophagy plays a crucial protective role through various mechanisms, including regulating inflammation and immune responses, clearing damaged organelles, and maintaining stability in the intracellular environment. In recent years, the role of autophagy in the pathogenesis and treatment of SAKI has received widespread attention. Research has confirmed that various intracellular signaling pathways and signaling molecules targeting autophagy [such as mammalian target of rapamycin (mTOR) signaling pathway, AMP-activated protein kinase (AMPK) signaling pathway, nuclear factor-κB (NF-κB) signaling pathway, and Sirtuins (SIRT), autophagy associated factor Beclin-1, and Toll-like receptor (TLR)] are involved in the development of SAKI. Due to the complex pathogenesis of SAKI, current treatment strategies include fluid management, infection control, maintenance of internal environment balance, and renal replacement therapy; however, the mortality remains high. In recent years, it has been found that autophagy plays a critical protective role in sepsis-mediated AKI. As a result, an increasing number of drugs are being developed to alleviate SAKI by regulating autophagy. This article reviews the latest advances in the role of autophagy in the pathogenesis and treatment of SAKI, with the aim of providing insights for the development of new drugs for SAKI patients.
Humans ; Acute Kidney Injury/etiology* ; Autophagy ; Sepsis/complications* ; Signal Transduction

Objective To compare the efficacy and tolerability of the novel bowel-cleansing agent TCIC-001 and the traditional polyethylene glycol (PEG) regimen for bowel preparation prior to colonoscopy. Methods Prospective inclusion of 62 patients who were scheduled to undergo colonoscopy at Zhongshan Hospital, Fudan University from July 2021 to July 2022. They were randomly divided into TCIC-001 group (n=31) and PEG group (n=31) using a random number table method. The TCIC-001 group took TCIC-001 orally, drinking water in stages, with a total liquid intake of 1 500 mL; the PEG group took PEG orally, taking it in 4 doses, with a total liquid intake of 3 000 mL. The primary endpoint indicator is the quality of intestinal hygiene evaluated by the Boston Bowel Preparation Scale (BBPS), the secondary endpoint indicators were medication adherence, medication duration, frequency of bowel movements, duration of bowel movements, and incidence of adverse events between two groups. Results No significant differences were observed in sex, age, or defecation frequency between the two groups. For efficacy, both groups achieved equivalent bowel cleanliness, with a “good preparation” rate of 93.55% and comparable BBPS score of each intestinal segment and total scores. For tolerability, the TCIC-001 group had a shorter medication duration compared to the PEG group ([48.8±25.9] min vs [82.8±28.4] min, P<0.001), a longer defecation duration ([288.6±74.0] min vs [236.5±74.3] min, P<0.001), and a lower incidence of first defecation before medication completion (9.68% vs 41.94%, P=0.004). Regarding safety, no significant differences were observed between the TCIC-001 group and the PEG group in incidences of chloride disturbances (0% vs 9.68%) and calcium disturbances (3.23% vs 6.45%), and no other adverse events. Conclusions TCIC-001 demonstrated comparable bowel-cleansing efficacy to PEG while significantly improving tolerability (reduced medication time and lower risk of premature defecation) and maintaining favorable safety.

Objective:To explore the potential categories of post-traumatic stress disorder (PTSD) trajectories in women with multiple in vitro fertilization-embryo transfer (IVF-ET) failures, and to analyze the effects of different demographic characteristics and psychological factors on the potential categories of PTSD trajectories.Methods:This was a prospective empirical research, from May 2021 to October 2022, women with IVF-ET failure ≥ 2 times in the reproductive department of Shanghai First People′s Hospital from May 2021 to October 2022 were selected as the research objects. Post-traumatic stress disorder civilian version scale was used for 4 follow-ups at 3 d (T1), 10 d (T2), 20 d (T3) after the last transplantation failure and 3 d before the next transplantation cycle (T4). Telephone follow-up and online follow-up were combined to obtain the PTSD level at 4 time points. Potential categories of PTSD score trajectories at four time points were identified using a latent category growth model, and analyze influencing factors using unordered multi classification logistic analysis.Results:Totally 196 IVF-ET women were admitted, aged (29.42 ± 4.13) years. Three PTSD trajectories were fitted in this study, including 82 cases (42%) in non-PTSD group, 61 cases (31%) in mild PTSD group and 53 cases (27%) in elevated PTSD group. Logistic regression analysis showed that age, education level, fertility pressure and marital adjustment level were the predictors of PTSD trajectory in women with multiple IVF-ET failures. Compared with the non-PTSD group, women aged ≥35 years, with lower education level and marital adjustment level were more likely to enter the elevated PTSD group ( OR=4.570, 8.540, 0.949, all P<0.05). Women aged 35 years and with greater reproductive pressure were more likely to enter the mild PTSD group ( OR=3.871, 1.063, both P<0.05). Conclusions:There is group heterogeneity in the trajectories of PTSD in women with multiple IVF-ET failures in the next transplantation cycle. Old age, low education level, high fertility pressure and poor marital adjustment can predict the trajectories of PTSD. Fertility stress and marriage adjustment are changeable variables. Medical staff can relieve women′s fertility pressure through health education and mindfulness intervention, promote a good state of marriage adjustment, and minimize the adverse effects of PTSD on the next cycle of conception.

Objective:The status quo and related factors of human papillomavirus (HPV) infection in multiple parts of men who have sex with men (MSM) in Tianjin were analyzed.Methods:Using the cross-sectional survey method, a total of 600 MSM were recruited in Tianjin from September to December 2023, including 200 (18-26 years old), 300 (27-45 years old), and 100 (≥46 years old) stratificaed by age group. Questionnaire survey was used to collect knowledge and behavioral information related to demography and STD prevention and treatment. Exfoliated cells from genital, perianal and oral cavity were collected for HPV typing detection. Logistic regression model was used to analyze the related factors of HPV infection.Results:The infection rate of HPV was 53.67% (322/600) in MSM, with high-risk type as 41.17% (247/600), low-risk type as 27.17% (163/600). The infection rate of HPV in both multiple and single types was 26.83% (161/600).The infection rates of genotypes covered by nine-valent HPV vaccine, quadrivalent HPV vaccine and bivalent HPV vaccine were 36.83% (221/600), 25.17% (151/600) and 9.50% (57/600), respectively.The infection rates of genital HPV, high-risk or low-risk types were 24.67% (148/600), 16.67% (100/600) and 11.00% (66/600), respectively. The infection rates of perianal HPV, high-risk or low-risk types were 42.00% (252/600), 30.17% (181/600) and 20.50% (123/600), respectively. The infection rates of oral HPV high-risk and low-risk types were 3.17% (19/600), 2.33% (14/600) and 1.17% (7/600), respectively. Divorce or widowhood (a OR=2.38, 95% CI: 1.26-4.50), history of homosexual anal intercourse in the past 6 months (a OR=2.28, 95% CI: 1.00-5.50), and use of dependent drugs (including new psychoactive substances) (a OR=1.62, 95% CI: 1.02-2.58) were risk factors for genital HPV infection. College degree/university degree or above (a OR=0.36, 95% CI: 0.16-0.81) was a protective factor for perianal HPV infection, and a history of drug dependence (a OR=1.85, 95% CI: 1.19-2.88) was a risk factor. Conclusions:MSM in Tianjin was a high-risk group for HPV infection, and the HPV infection in the perianal area was more severe than in the genital area and oral area.Marital status, education level, history of homosexual anal sex in the past 6 months, and history of drug dependence were related factors of HPV infection among MSM.

Background::Triple-negative breast cancer (TNBC) is a type of highly invasive breast cancer with a poor prognosis. According to new research, long noncoding RNAs (lncRNAs) play a significant role in the progression of cancer. Although the role of lncRNAs in breast cancer has been well reported, few studies have focused on TNBC. This study aimed to explore the biological function and clinical significance of forkhead box C1 promoter upstream transcript (FOXCUT) in triple-negative breast cancer.Methods::Based on a bioinformatic analysis of the cancer genome atlas (TCGA) database, we detected that the lncRNA FOXCUT was overexpressed in TNBC tissues, which was further validated in an external cohort of tissues from the General Surgery Department of the First Affiliated Hospital of Nanjing Medical University. The functions of FOXCUT in proliferation, migration, and invasion were detected in vitro or in vivo. Luciferase assays and RNA immunoprecipitation (RIP) were performed to reveal that FOXCUT acted as a competitive endogenous RNA (ceRNA) for the microRNA miR-24-3p and consequently inhibited the degradation of p38. Results::lncRNA FOXCUT was markedly highly expressed in breast cancer, which was associated with poor prognosis in some cases. Knockdown of FOXCUT significantly inhibited cancer growth and metastasis in vitro or in vivo. Mechanistically, FOXCUT competitively bounded to miR-24-3p to prevent the degradation of p38, which might act as an oncogene in breast cancer. Conclusion::Collectively, this research revealed a novel FOXCUT/miR-24-3p/p38 axis that affected breast cancer progression and suggested that the lncRNA FOXCUT could be a diagnostic marker and therapeutic target for breast cancer.

[Abstract] [Objective] To evaluate the immunogenicity of red blood cell blood group antigens in the population of Xi'an. [Methods] Data on blood group antigens of voluntary blood donors from the Shaanxi Province Blood Center and unexpected antibody detection results from clinically submitted cases between January 2019 and May 2024 were analyzed. The Giblett blood group antigen immunogenicity calculation formula was used to calculate the immunogenicity of blood group antigens based on the frequency of unexpected antibodies and the probability of antigen-negative patients receiving antigen-positive red blood cells. The relative immunogenicity of each blood group antigen was obtained by multiplying the immunogenicity of the K antigen (0.095). [Results] A total of 30 921 individuals were included for red blood cell blood group antigen analysis, with 511 cases of unexpected antibody identification. The ranking of red blood cell blood group antigen immunogenicity for the overall population was: Wr^a>E>Di^b>Fy^a>K>C>e>c>Di^a>Jk^a>M>Le^a>Jk^b>Le^b>Fy^b>S, while for males, it was: Di^b>Wr^a>E>K>Fy^a>C>e>c>M>Di^a>Jk^a>Fy^b>Le^a>Le^b>Jk^b>S. [Conclusion] Based on the immunogenicity ranking from strong to weak of red blood cell antigens in the population of Xi'an, this study provides theoretical support for the expansion and matching of antigens, and technical support for achieving precise red blood cell transfusions to improve transfusion efficacy and safety.