Histone modification-linked prognostic model for ovarian cancer reveals LBX2 as a novel growth promoter.

Ovarian cancer (OC) is a deadly disease with limited treatment options and poor overall survival rates. This study aimed to investigate the role of histone modification-related genes in predicting the prognosis of OC patients. Transcriptome data from multiple cohorts, including bulk RNA-Seq data and single-cell scRNA-Seq data, were collected. Gene set enrichment analysis was used to identify enriched gene sets in the histone modification pathway. Differentially expressed genes (DEGs) between histone modification-high and histone modification-low groups were identified using Lasso regression. A prognostic model was constructed using five selected prognostic genes from the DEGs in the TCGA-OV cohort. The study found enrichment of gene sets in the histone modification pathway and identified five prognostic genes associated with OC prognosis. The constructed risk score model based on histone modification-related genes was correlated with immune infiltration of T cells and M1 macrophages. Mutations are more prevalent in the high-risk group compared to the low-risk group. Several drugs were screened against the model genes. Through in vitro experiments, we confirmed the expression patterns of the model genes. LBX2 facilitates the proliferation of OC. Histone modification-related genes have the potential to serve as biomarkers for predicting OC prognosis. Targeting these genes may lead to the development of more effective therapies for OC. Additionally, LBX2 represents a novel cell proliferation promoter in OC carcinogenesis.

Nicotinamide mononucleotide induces autophagy and ferroptosis via AMPK/mTOR pathway in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common malignancy worldwide. Herein, we investigated the role of nicotinamide mononucleotide (NMN) in HCC progression. HCC cells were treated with NMN (125, 250, and 500 µM), and then nicotinamide adenine dinucleotide (NAD+ ) and NADH levels in HCC cells were measured to calculate NAD+ /NADH ratio. Cell proliferation, apoptosis, autophagy and ferroptosis were determined. AMPK was knocked down to confirm the involvement of AMPK/mTOR signaling. Furthermore, tumor-inhibitory effect of NMN was investigated in xenograft models. Exposure to NMN dose-dependently increased NAD+ level and NAD+ /NADH ratio in HCC cells. After NMN treatment, cell proliferation was inhibited, whereas apoptosis was enhanced in both cell lines. Additionally, NMN dose-dependently enhanced autophagy/ferroptosis and activated AMPK/mTOR pathway in HCC cells. AMPK knockdown partially rescued the effects of NMN in vitro. Furthermore, NMN treatment restrained tumor growth in nude mice, activated autophagy/ferroptosis, and promoted apoptosis and necrosis in tumor tissues. The results indicate that NMN inhibits HCC progression by inducing autophagy and ferroptosis via AMPK/mTOR signaling. NMN may serve as a promising agent for HCC treatment.

Prevalence and risk factors for kidney disease among hospitalized PLWH in China.

BACKGROUND: Kidney disease is an important comorbidity in people living with HIV(PLWH), and is associated with poor outcomes. However, data on renal function of PLWH are limited in China so far. In this study we assessed the prevalence of kidney disease in patients either on antiretroviral therapy (ART) or not respectively in a single center in China and explored the possible risk factors associated. METHODS: In the cross-sectional study, we recruited hospitalized adult PLWH. Demographic characteristics, clinical information and laboratory variables were collected. Kidney disease was defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2, and/or isolated hematuria, proteinuria, microalbuminuria. We calculated the prevalence of kidney disease and used logistic regression to assess its associated risk factors. RESULTS: A total of 501 adult PLWH were enrolled, 446 (89.0%) males and 55 (11.0%) females. The median age was 39 (IQR 30-50) years old. The prevalence of kidney disease was 19.0%, 22 (4.4%) patients with eGFR < 60 mL/min/1.73 m2, 53 (10.6%) patients with hematuria, 11 (2.2%) patients with proteinuria, and 40 (8.0%) patients with microalbuminuria. 297 (59.3%) patients were receiving ART. The patients on ART had a higher prevalence of renal disease than those had not been administrated with ART (22.6% vs. 13.7%, P = 0.013). On the multivariate logistic regression analysis among patients not on ART, lower haemoglobin (OR 0.994, 95%CI: 0.902-0.988, P = 0.013) were significantly associated with kidney disease. While among those on ART, older age (OR 1.034, 95%CI: 1.003-1.066, P = 0.032), lower haemoglobin (OR 0.968, 95%CI: 0.948-0.988, P = 0.002) and lower albumin (OR 0.912, 95%CI: 0.834-0.997, P = 0.044) were significantly associated with kidney disease. CONCLUSIONS: The prevalence of kidney disease among hospitalized PLWH in China is high, especially in patients on ART. A larger scale study on Chinese outpatient PLWH should be conducted, so as to precisely assess prevalence of kidney disease in general Chinese PLWH.

Longitudinal analysis of new-onset non-AIDS-defining diseases among people living with HIV: A real-world observational study.

OBJECTIVES: We aimed to analyze the incidence rates of new-onset diabetes, hypertriglyceridemia, hypercholesterolemia, liver injury, and renal injury during antiretroviral therapy (ART) among people living with HIV (PLWH) and determine the associated risk factors. METHODS: This study included PLWH enrolled from Beijing Ditan Hospital from November 11, 2004, to December 29, 2018. The incidence rates of new-onset diabetes, hypertriglyceridemia, hypercholesterolemia, liver injury, and renal injury were calculated and stratified based on ART regimen, CD4 count, and HIV-RNA. Risk factors were determined using Cox regression analysis. RESULTS: Overall, 6747 participants were included. Moreover, 4.5%, 43.3%, 25.4%, 11.2%, and 6.2% of patients developed new-onset diabetes, hypertriglyceridemia, hypercholesterolemia, liver injury, and renal injury, respectively, with incidence rates of 1.7, 26.9, 10.2, 3.9, and 5.5 per 100 person-years, respectively. Longitudinally, the incidence rates and percentages of these outcomes were highest in the first year of ART. The percentage of dyslipidemia was significantly higher in protease inhibitor (PI)-based regimen than in non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen. However, the percentage of liver injury was significantly higher in NNRTI-based regimen than in PI-based regimen. In multivariate Cox regression analysis, low CD4 count (<200 cells/µL, adjusted hazard ratio [aHR] = 1.34, 95% confidence interval [CI] 1.15-1.57) and high HIV-RNA (>105 copies/mL, aHR = 1.26, 95% CI 1.08-1.48) were risk factors for hypertriglyceridemia. CONCLUSIONS: Clinical outcomes, including new-onset diabetes, dyslipidemia, and liver and renal injuries, are common in PLWH. Regular glucose, lipid, liver, and renal function monitoring is required during ART, especially in high-risk patients.

Stroke among highly active antiretroviral therapy-naive people living with the human immunodeficiency virus in China: a retrospective study of the characteristics, risk factors, and prognosis.

BACKGROUND: We aimed to clarify the characteristics, risk factors, and prognosis of stroke among HAART-naive people living with HIV (PLWH) in China. METHODS: We selected HAART-naive PLWH admitted to Beijing Ditan Hospital, Capital Medical University, from 1 January 2009 to 31 December 2019. Demographic and clinical data were obtained by searching an anonymous electronic case system. Descriptive analysis and logistic regression and Cox proportional hazard models were used to determine the characteristics and predictors of stroke among all HAART-naive PLWH and evaluate the risk factors of mortality in HAART-naive PLWH with stroke. RESULTS: Stroke was diagnosed in 105 cases (3.7%) of 2867 HAART-naive PLWH. Multivariate logistic regression indicated that age of 30-55 years (OR 1.903, 95% CI 1.005-3.603, p = 0.048), age of ≥ 55 years (OR 4.104, 95% CI 1.928-8.737, p < 0.001), and CD4 count of < 200 cells/µL (OR 2.005, 95% CI 1.008-3.985, p = 0.047) were associated with increased odds of stroke. Diabetes (OR 3.268, 95% CI 1.744-6.125, p < 0.001), hypertension (OR 2.301, 95% CI 1.425-3.717, p = 0.001), syphilis (OR 2.003, 95% CI 1.300-3.089, p = 0.002), and complicated AIDS-defining CNS diseases (OR 7.719, 95% CI 4.348-13.703, p < 0.001) were risk factors for stroke. Of the 105 stroke patients, 12 (11.4%) died during hospitalisation, and the risk factors for mortality among patients with stroke were age of > 65 years (AHR: 8.783, 95% CI 1.522-50.668, p = 0.015), complicated severe pneumonia (AHR: 3.940, 95% CI 1.106-14.029, p = 0.034), and AIDS-defining CNS diseases (AHR: 19.766, 95% CI 3.586-108.961, p = 0.001). CONCLUSIONS: For HAART-naive people living with HIV (PLWH), stroke occurred in various age groups, and early screening for stroke, timely intervention for risk factors among patients in various age groups, and controlling the CD4 count are extremely important in reducing the burden of stroke.

Performance of Xpert MTB/RIF for Diagnosis of Tuberculosis in HIV-Infected People in China: A Retrospective, Single-Center Study.

BACKGROUND There are few studies of GeneXpert MTB/RIF (hereafter referred to as Xpert) detection technology in HIV-infected people in China. Therefore, this study aimed to evaluate the value of Xpert in HIV/TB co-infected patients and to provide reference and guidance for the diagnosis of TB in HIV-infected populations. MATERIAL AND METHODS This study reviewed medical records of human immunodeficiency virus (HIV) patients hospitalized at the Infection Center of Beijing Ditan Hospital affiliated to Capital Medical University from January 2018 to May 2020, and patients diagnosed with pulmonary and extrapulmonary tuberculosis were screened as study subjects. Sensitivity and specificity of Xpert were analyzed using ROC curves. RESULTS Of the 413 HIV patients, 177 patients met the entry criteria, of which the diagnosis was active pulmonary tuberculosis (PTB): 145 and extrapulmonary tuberculosis (EPTB): 32. The sensitivity of Xpert for PTB and EPTB was 82.0% and 100%, higher than that of acid-fast bacilli (AFB) (61.0% and 58.3%), and slightly lower than that of T-SPOT.TB (91.0% and 100%); the specificity was 83.7% and 93.5%, higher than that of AFB (72.6%, 87.1%) and T-SPOT.TB (16.6%, 21.2%). The sensitivity of Xpert was 100% in bronchoalveolar lavage fluid (BALF) and 80.0% in sputum; in patients with CD4⁺ <200 cells/mm³, the sensitivity of Xpert was 90.0% and specificity was 84.8%, higher than that of AFB (60.0%, 75.5%) and T-SPOT.TB (90.0%, 21.5%). CONCLUSIONS Xpert has a high accuracy in HIV/TB co-infected patients, and Xpert still shows a high sensitivity and specificity even in HIV patients with CD4⁺ <200 cells/mm³. Xpert is recommended for the diagnosis of tuberculosis in HIV-infected patients.

Risk factors of in-stent restenosis among coronary artery disease patients with syphilis undergoing percutaneous coronary intervention: a retrospective study.

BACKGROUND: The risk factors of in-stent restenosis (ISR) among coronary artery disease (CAD) patients with syphilis after percutaneous coronary intervention (PCI) are not fully understood. Therefore, this study aimed to elucidate not only the risk factors of ISR among CAD patients with syphilis after performing PCI, but also the population attributable risk percentage (PAR%), which is used to quantify the proportion of ISR that could be eliminated if particular risk factors are not present. METHODS: Evaluation of the prevalence, risk factors, and their PAR% for ISR among CAD patients with syphilis undergoing PCI was conducted retrospectively at Beijing Ditan Hospital. CAD patients with syphilis underwent PCI from August 2010 to August 2019 and received a diagnosis, coronary angiography, PCI, and periodical follow-up. The clinical, laboratory, and imaging data were reviewed and summarised anonymously from electronic medical records. The chi-square or Fisher exact test was used in data analysis. RESULTS: Among 114 CAD patients with syphilis undergoing PCI, ISR occurred in 18 patients (15.78%). The multivariate Cox regression model indicated that average stent length ≥ 35 mm (adjusted hazard ratio [HR] = 4.47, 95% confidence interval [CI] = 1.30-15.44, p = 0.018) and titres of the toluidine red unheated serum test (TRUST) > 1:16 (adjusted HR = 3.72, 95% CI = 1.22-11.36, p = 0.021) were associated with an increased risk of ISR, while successful antisyphilitic treatment (adjusted HR = 0.12, 95% CI = 0.02-0.95, p = 0.045) was protective predictor of ISR among these patients. The PAR% values of particular risk factors associated with ISR including average stent length ≥ 35 mm, titres of TRUST > 1:16, and successful antisyphilitic treatment were 12.2%, 24.0%, and -39.6%, respectively, among these patients. CONCLUSIONS: Preventing the occurrence of ISR among CAD patients with syphilis undergoing PCI requires clinical intervention. Our results indicated that carefully evaluating the length of the vessel lesion to determine whether the stent length is < 35 mm, prioritising the clinical intervention for titres of TRUST > 1:16, and providing successful antisyphilitic treatment could reduce the risk of ISR occurrence.

A preliminary single-center investigation of percutaneous biliary stenting in malignant hilar biliary obstruction: what impacts the clinical success and the long-term outcomes?

PURPOSE: The purpose of this study is to investigate the influencing factors that may impact the clinical success, jaundice-free time, and overall survival in patients of malignant hilar biliary obstruction (MHBO) treated with a self-expanding metallic stent (SEMS). MATERIALS AND METHODS: Patients diagnosed with MHBO and treated with SEMS through percutaneous access from 1 Jul. 2013 to 1 Jul. 2018 were enrolled in this monocentric study. Demographic information, disease baseline measurements, and interventional strategies were collected and examined. Bilirubin was measured 1-3 days before and 3-7 days after stenting using the unit of "µmol/L." The bilirubin reduction ratio was compared between different study groups, which were separated by specific characteristics. Univariate and multivariate analyses were performed to evaluate each characteristic's impact on jaundice-free time (JF) and overall survival time (OS). Statistical analyses were conducted using SPSS 14.0, p < 0.05 indicated significance. RESULTS: Eighty patients were enrolled. Direct bilirubin (DB) and indirect bilirubin (IB) both significantly decreased after stenting (U = 1575.0, p < 0.001; U = 1541.0, p < 0.001). The DB reduction ratio of the "nearby lymph metastases" group was significantly higher (U = 566.0, p = 0.037). The IB reduction ratio in the "single stent" group was significantly higher (U = 554.0, p = 0.018). Sixty-six cases reached jaundice recurrence, the median JF was 6 months, and the 95% confidence interval was 4.411 ~ 7.589 months. Fifty-eight cases ended in death, the median OS was 7 months, and the 95% confidence interval was 5.759 ~ 8.241 months. "Nearby lymph metastases" and "distant metastases" independently impacted OS (OR = 2.344, p = 0.013; OR = 3.239, p = 0.042). "IB reduction ratio" independently impacted both JF and OS (OR = 0.422, p = 0.021; OR = 0.315, p = 0.001). CONCLUSION: The goal of treatment in patients with MHBO is to recover liver function. However, the overall survival is greatly impacted by the presence of metastases. Managing to obtain adequate liver function recovery may improve the long-term outcomes in affected patients.

Efficacy of transarterial chemoembolization compared with radiofrequency ablation for the treatment of recurrent hepatocellular carcinoma after radiofrequency ablation.

Purpose: To compare the efficacy and outcome of transarterial chemoembolization (TACE) with radiofrequency ablation (RFA) in the treatment of recurrent hepatocellular carcinoma (HCC) after initial RFA.Material and methods: From January 2008 to December 2014, 199 consecutive patients with primary HCC underwent percutaneous RFA as initial treatment. One hundred and fourteen patients developed intrahepatic recurrent HCC after initial RFA. The patients with recurrent tumor size ≤3 cm and tumor numbers ≤3 who underwent RFA (n = 47) or TACE (n = 31) were included in study. Progression-free survival (PFS), tumor response to treatment and overall survival (OS) were assessed. Prognostic factors for OS were analyzed using multivariate Cox proportional hazard models.Results: The baseline data of initial HCC and the first recurrence of HCC were comparable in both groups. The complete response (CR) rate in the RFA group and the TACE group was 95.7% and 50%, respectively (p < .001). The PFS time in the RFA group and the TACE group was 424 days and 275 days, respectively (p = .004). The one-year and three-year cumulative overall survival rate was 93.5% and 45% in the TACE group, 91.3% and 68.8% in the RFA group (p = .49), respectively. Significant predictive factors for OS were tumor size (HR = 1.951, 95%CI 1.061-3.687, p = .032), prothrombin time (HR = 1.59, 95%CI 1.012-2.498, p = .044) and response to treatment (HR = 0.267, 95%CI 0.092-0.78, p = .016).Conclusion: Repeated RFA is still considered to be the first treatment choice for patients with post-RFA intrahepatic recurrence. However, TACE should also be considered due to comparable overall survival benefits. The advantages of being less invasive and highly repeatable may render TACE to be a preferred treatment for some patients with recurrent HCC after RFA.

TFAB002s, novel CD20-targeting T cell-dependent bispecific Fab-FabCH3 antibodies, exhibit potent antitumor efficacy against malignant B-cell lymphoma.

B-cell lymphoma, clinically, comprises a heterogeneous group of malignancies that encompass various subtypes. CD20 is an optimal target for therapeutic antibodies in B-cell lymphoma immunotherapy since approximately 90% of B-cell malignancies typically exhibit CD20 expression on their surface, while its presence is limited in normal tissues. In this study, we have developed a series of novel non-IgG-like T cell-dependent bispecific antibodies by constructing Fab-FabCH3, referred to as Tandem Antigen-binding Fragment 002 (TFAB002), which specifically target CD20 for the treatment of malignant B-cell lymphoma. TFAB002s display strong binding affinity with CD20 and moderate binding affinity with CD3, thereby triggering target-specific T-cell activation, cytokine release, and tumor cell lysis in vitro. Furthermore, TFAB002s exhibit potent cytotoxicity against B-cell malignancies that express varying levels of CD20. Besides, the TFAB002s show potent pharmacodynamic activity in vivo in the WIL2-S cells CDX mouse model. Collectively, these results underscore the potential of TFAB002s as a highly promising therapeutic approach for selectively depleting CD20-positive B cells, thereby warranting further clinical evaluation as a viable treatment option for CD20-expressing B-cell malignancies.

Bridging across the ampulla with metal stents: evidences for intestinal bile reflux.

BACKGROUND/AIMS: To investigate the early intestinal bile reflux following the implantation of metal stent across the ampulla and the mechanism of reflux cholangitis. METHODOLOGY: Twenty-three patients with implantation of metal stent across the ampulla were recruited. Prior to the implantation, the white blood cell count, neutrophil percentage, total blood bilirubin, direct bilirubin and the trypsin content in the bile were recorded; 2-5 days after implantation these indices were measured again, as well as the 99mTc -DTPA radioactivity. RESULTS: A high percentage (82.61%) of patients showed 99mTc in the bile in 2 hours, which accounts for 1.73% of total intake. In 4 cases the radioactivity was not found. Bile lipase and amylase levels were significantly higher than that in prior to the stent implantation. There were no changes in the white blood cell count and neutrophil percentage after stent implantation. Additionally, the total blood bilirubin and direct bilirubin decreased. CONCLUSIONS: After the implantation of metal stent across the ampulla, there is evidence for the early intestinal bile reflux, without signs for the reflux cholangitis.

Clinical application of percutaneous drainage in treating hepatocellular carcinoma with bile duct tumor thrombus.

AIM OF THE STUDY: This study aimed to evaluate the effect of percutaneous interventional treatment on obstructive jaundice caused by hepatocellular carcinoma with bile duct tumor thrombus. MATERIAL AND METHODS: A total of 16 patients with bile duct tumor thrombus were included in the current retrospective study. All the patients were subjected to percutaneous transhepatic biliary drainage (PTBD). Treatment included permanent external drainage, internal drainage and routine tube adjustment, and covered stents according to the patients' clinical manifestations. RESULTS: The success rate of PTBD was 100%. Among all the patients, two were treated with permanent external drainage, seven were treated with internal drainage and routine tube adjustment, and seven were treated with detaining covered stents. All the drainage tubes were successfully pulled out from the patients receiving covered stents. Among all the 16 patients, the clinical symptoms and life quality of 12 patients (12/16, 75%) were improved. The average survival time of all the patients was 203.7 days (ranging from 30 days to 391 days) with the median survival time of 199.5 days. CONCLUSIONS: Percutaneous interventional therapy for obstructive jaundice caused by hepatocellular carcinoma with bile duct tumor thrombus is a good choice. It improves patients' life quality. Permanent external drainage, internal drainage, and covered stents are alternative methods which should be chosen according to the patient's condition.

Potential roles of exosomes in the initiation and metastatic progression of lung cancer.

Lung cancer (LC) incidence and mortality continue to increase annually worldwide. LC is insidious and readily metastasizes and relapses. Except for its early diagnosis and surgical resection, there is no effective cure for advanced metastatic LC, and the prognosis remains dismal. Exosomes, a class of nano-sized extracellular vesicles produced by healthy or diseased cells, are coated with a bilayer lipid membrane and contain various functional molecules such as proteins, lipids, and nucleic acids. They can be used for intracellular or intercellular signaling or the transportation of biological substances. A growing body of evidence supports that exosomes play multiple crucial roles in the occurrence and metastatic progression of many malignancies, including LC. The elucidation of the potential roles of exosomes in the initiation, invasion, and metastasis of LC and their underlying molecular mechanisms may contribute to improved early diagnosis and treatment.

The therapeutic potential of exosomes in lung cancer.

BACKGROUND: Lung cancer (LC) is one of the most common malignancies globally. Besides early detection and surgical resection, there is currently no effective curative treatment for metastatic advanced LC. Exosomes are endogenous nano-extracellular vesicles produced by somatic cells that play an important role in the development and maintenance of normal physiology. Exosomes can carry proteins, peptides, lipids, nucleic acids, and various small molecules for intra- and intercellular material transport or signal transduction. LC cells can maintain their survival, proliferation, migration, invasion, and metastasis, by producing or interacting with exosomes. Basic and clinical data also show that exosomes can be used to suppress LC cell proliferation and viability, induce apoptosis, and enhance treatment sensitivity. Due to the high stability and target specificity, good biocompatibility, and low immunogenicity of exosomes, they show promise as vehicles of LC therapy. CONCLUSION: We have written this comprehensive review to communicate the LC treatment potential of exosomes and their underlying molecular mechanisms. We found that overall, LC cells can exchange substances or crosstalk with themselves or various other cells in the surrounding TME or distant organs through exosomes. Through this, they can modulate their survival, proliferation, stemness, migration, and invasion, EMT, metastasis, and apoptotic resistance.

Leveraging diverse cell-death patterns to predict the clinical outcome of immune checkpoint therapy in lung adenocarcinoma: Based on muti-omics analysis and vitro assay.

Advanced LUAD shows limited response to treatment including immune therapy. With the development of sequencing omics, it is urgent to combine high-throughput multi-omics data to identify new immune checkpoint therapeutic response markers. Using GSE72094 (n = 386) and GSE31210 (n = 226) gene expression profile data in the GEO database, we identified genes associated with lung adenocarcinoma (LUAD) death using tools such as "edgeR" and "maftools" and visualized the characteristics of these genes using the "circlize" R package. We constructed a prognostic model based on death-related genes and optimized the model using LASSO-Cox regression methods. By calculating the cell death index (CDI) of each individual, we divided LUAD patients into high and low CDI groups and examined the relationship between CDI and overall survival time by principal component analysis (PCA) and Kaplan-Meier analysis. We also used the "ConsensusClusterPlus" tool for unsupervised clustering of LUAD subtypes based on model genes. In addition, we collected data on the expression of immunomodulatory genes and model genes for each cohort and performed tumor microenvironment analyses. We also used the TIDE algorithm to predict immunotherapy responses in the CDI cohort. Finally, we studied the effect of PRKCD on the proliferation and migration of LUAD cells through cell culture experiments. The study utilized the TCGA-LUAD cohort (n = 493) and identified 2,901 genes that are differentially expressed in patients with LUAD. Through KEGG and GO enrichment analysis, these genes were found to be involved in a wide range of biological pathways. The study also used univariate Cox regression models and LASSO regression analyses to identify 17 candidate genes that were best associated with mortality prognostic risk scores. By comparing the overall survival (OS) outcomes of patients with different CDI values, it was found that increased CDI levels were significantly associated with lower OS rates. In addition, the study used unsupervised cluster analysis to divide 115 LUAD patients into two distinct clusters with significant differences in OS timing. Finally, a prognostic indicator called CDI was established and its feasibility as an independent prognostic indicator was evaluated by Cox proportional risk regression analysis. The immunotherapy efficacy was more sensitive in the group with high expression of programmed cell death models. Relationship between programmed cell death (PCD) signature models and drug reactivity. After evaluating the median inhibitory concentration (IC50) of various drugs in LUAD samples, statistically significant differences in IC50 values were found in cohorts with high and low CDI status. Specifically, Gefitinib and Lapatinib had higher IC50 values in the high-CDI cohort, while Olaparib, Oxaliplatin, SB216763, and Axitinib had lower values. These results suggest that individuals with high CDI levels are sensitive to tyrosine kinase inhibitors and may be resistant to conventional chemotherapy. Therefore, this study constructed a gene model that can evaluate patient immunotherapy by using programmed cell death-related genes based on muti-omics. The CDI index composed of these programmed cell death-related genes reveals the heterogeneity of lung adenocarcinoma tumors and serves as a prognostic indicator for patients.

CD70-induced differentiation of proinflammatory Th1/17/22/GM lymphocytes associated with disease progression and immune reconstitution during HIV infection.

Immune overactivation is a hallmark of chronic HIV infection, which is critical to HIV pathogenesis and disease progression. The imbalance of helper T cell (Th) differentiation and subsequent cytokine dysregulation are generally considered to be the major drivers of excessive activation and inflammatory disorders in HIV infection. However, the accurate factors driving HIV-associated Th changes remained to be established. CD70, which was a costimulatory molecule, was found to increase on CD4+ T cells during HIV infection. Overexpression of CD70 on CD4+ T cells was recently reported to associate with highly pathogenic proinflammatory Th1/Th17 polarization in multiple sclerosis. Thus, the role of CD70 in the imbalance of Th polarization and immune overactivation during HIV infection needs to be investigated. Here, we found that the elevated frequency of CD70 + CD4+ T cells was negatively correlated with CD4 count and positively associated with immune activation in treatment-naïve people living with HIV (PLWH). More importantly, CD70 expression defined a population of proinflammatory Th1/17/22/GM subsets in PLWH. Blocking CD70 decreased the mRNA expression of subset-specific markers during Th1/17/22/GM polarization. Furthermore, we demonstrated that CD70 influenced the differentiation of these Th cells through STAT pathway. Finally, it was revealed that patients with a high baseline level of CD70 on CD4+ T cells exhibited a greater risk of poor immune reconstitution after antiretroviral therapy (ART) than those with low CD70. In general, our data highlighted the role of CD70 in Th1/17/22/GM differentiation during HIV infection and provided evidence for CD70 as a potential biomarker for predicting immune recovery.

Reasons, safety and efficacy analysis for conversion of HAART to TAF/FTC/BIC among HIV-infected patients.

BACKGROUND: This study aimed to determine the reasons for conversion and elucidate the safety and efficacy of transition to tenofovir alafenamide/emtricitabine/bictegravir sodium (TAF/FTC/BIC) in highly active antiretroviral therapy (HAART)-experienced HIV-infected patients in real-world settings. METHODS: We conducted a retrospective cohort study. The treatment conversion rationales, safety, and effectiveness in 1684 HIV-infected patients with previous HAART experience who switched to TAF/FTC/BIC were evaluated at Beijing Ditan Hospital from September 2021 to Auguest 2022. RESULTS: Regimen simplification (990/1684, 58.79%) was the most common reason for switching, followed by osteoporosis or osteopenia (375/1684, 22.27%), liver dysfunction (231/1684, 13.72%), decline in tenofovir alafenamide/emtricitabine/elvitegravir/cobicistat (TAF/FTC/EVG/c) with food restriction (215/1684, 12.77%), virological failure (116/1684, 6.89%), and renal dysfunction (90/1684, 5.34%). In patients receiving non-nucleotide reverse transcriptase inhibitors (NNRTI)-containing regimens, lipid panel changes 1 year after switching indicated a difference of 3.27 ± 1.10 mmol/L vs . 3.40 ± 1.59 mmol/L in triglyceride ( P  = 0.014), 4.82 ± 0.74 mmol/L vs . 4.88 ± 0.72 mmol/L in total cholesterol ( P  = 0.038), 3.09 ± 0.70 mmol/L vs . 3.18 ± 0.66 mmol/L in low-density lipoprotein ( P  <0.001), and 0.99 ± 0.11 mmol/L vs . 0.95 ± 0.10 mmol/L in high-density lipoprotein ( P  <0.001). Conversely, among patients receiving booster-containing regimens, including TAF/FTC/EVG/c and lopinavir/ritonavir (LPV/r), lipid panel changes presented decreased trends. We also observed an improved trend in viral load suppression, and alanine transaminase (ALT), aspartate transaminase (AST), estimated glomerular filtration rate (eGFR), and serum creatinine levels after the transition ( P  <0.001). CONCLUSION: The transition to TAF/FTC/BIC demonstrated good treatment potency. Furthermore, this study elucidates the motivations behind the adoption of TAF/FTC/BIC in real-world scenarios, providing clinical evidence supporting the stable conversion to TAF/FTC/BIC for HAART-experienced patients.

Supervised machine learning algorithms to predict the duration and risk of long-term hospitalization in HIV-infected individuals: a retrospective study.

Objective: The study aimed to use supervised machine learning models to predict the length and risk of prolonged hospitalization in PLWHs to help physicians timely clinical intervention and avoid waste of health resources. Methods: Regression models were established based on RF, KNN, SVM, and XGB to predict the length of hospital stay using RMSE, MAE, MAPE, and R2, while classification models were established based on RF, KNN, SVM, NN, and XGB to predict risk of prolonged hospital stay using accuracy, PPV, NPV, specificity, sensitivity, and kappa, and visualization evaluation based on AUROC, AUPRC, calibration curves and decision curves of all models were used for internally validation. Results: In regression models, XGB model performed best in the internal validation (RMSE = 16.81, MAE = 10.39, MAPE = 0.98, R2 = 0.47) to predict the length of hospital stay, while in classification models, NN model presented good fitting and stable features and performed best in testing sets, with excellent accuracy (0.7623), PPV (0.7853), NPV (0.7092), sensitivity (0.8754), specificity (0.5882), and kappa (0.4672), and further visualization evaluation indicated that the largest AUROC (0.9779), AUPRC (0.773) and well-performed calibration curve and decision curve in the internal validation. Conclusion: This study showed that XGB model was effective in predicting the length of hospital stay, while NN model was effective in predicting the risk of prolonged hospitalization in PLWH. Based on predictive models, an intelligent medical prediction system may be developed to effectively predict the length of stay and risk of HIV patients according to their medical records, which helped reduce the waste of healthcare resources.

Subgroup detection-based dental caries status and inequalities trend exploration: A nationwide, 10-year-repeated cross-sectional study.

Background: The goal of this study was to identify potentially important factors for the dental health though heterogeneous effects of risk factors within Chinese adolescent populations with different characteristics by analyzing the repeated cross-sectional data collected in the 3rd (2005) and 4th (2015) National Oral Health Survey. Methods: We studied the relationships between the decayed, missing and filled permanent teeth (DMFT) score, which was a discrete value, with the caries risk factors (region, census type, gender, only child or not, parents' education level, tooth bushing, dentist visit history, knowledge score, sugar intake, and pit-and-fissure sealants status), though the Poisson mixture regression model, which could identify subgroups among the full population and estimate the heterogeneous effects of risk factors simultaneously. We performed a series of tests and trend analysis based on the model fitting results to explore the primary causes for the dental caries issue clearly and intuitively. Results: A total of 39,049 teenagers aged 12 years were involved in the analysis. The Poisson mixture regression model clustered all individuals into three subgroups, where the mean values (standard deviations) of DMFT were 0.18 (0.56), 1.31 (1.49), and 2.91 (1.89), respectively. Model fitting results indicated that the heterogeneous effects of the involved risk factors were significant. In addition, we also found significant differences in the distributions and trends of DMFT within different categories of selected risk factors (region, census type, gender and dentist visiting history) from the projection analysis results. The estimated and projected proportions showed that the proportion of high caries risk population in the southwestern region increased by 31.8%, and will become even more severe as it will be the major component of high caries risk population in 2025. Conclusions: We found that the trends for the developments and changes of dental caries within populations with different characteristics were inequality. The regional difference is the primary factor for diversified changes in DMFT. The findings in this study provide support for intervention and prevention policies for the deterioration of dental caries risk within different adolescent populations.