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591 result(s) for "Chen, Tingyu"
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Identification of biomarkers related to γ-aminobutyric acid-associated genes in membranous nephropathy based on transcriptome data and clinical experiments
Background Membranous nephropathy (MN) is a leading cause of nephrotic syndrome in adults, being driven by incompletely understood autoimmune mechanisms. Emerging evidence suggests that γ-aminobutyric acid (GABA), traditionally considered a neurotransmitter, also functions as a critical immunomodulator in peripheral tissues. Dysregulation of GABAergic signaling has been linked to altered immune cell trafficking and metabolic stress in renal pathologies. However, its specific role and signature genes in MN pathogenesis have not been systematically characterized. This study aimed to identify novel GABA-associated biomarkers for MN and elucidate their potential mechanistic roles. Results By integrating differential expression analysis, weighted gene coexpression network analysis, and machine learning algorithms on public transcriptomic datasets, we identified three robust GABA-associated candidate biomarkers: AP2S1 , STXBP1 , and GNGT2 . These genes were consistently upregulated in patients with MN across both the training and validation cohorts. Functional enrichment analysis revealed their significant involvement in vesicle trafficking, cytochrome P450 metabolism, and cell adhesion pathways. Immune infiltration analysis demonstrated that these biomarkers had strong positive correlations with central memory CD4 + T cells and myeloid-derived suppressor cells. Furthermore, molecular docking simulations indicated high binding affinities between these targets and potential therapeutic compounds, including valproic acid and genistein. Crucially, reverse transcription quantitative polymerase chain reaction validation in an independent clinical cohort ( n  = 10) confirmed significantly elevated expression of AP2S1 , STXBP1 , and GNGT2 in the peripheral blood of patients with MN versus healthy controls ( P  < 0.05). Conclusion This study established a distinct GABAergic signature in MN, highlighting AP2S1 , STXBP1 , and GNGT2 as promising noninvasive diagnostic biomarkers. Our findings suggested that GABA-related vesicle trafficking and metabolic pathways contribute to the autoimmune microenvironment in MN. These genes offer new avenues for early diagnosis and represent potential therapeutic targets for precision medicine strategies in managing MN.
A novel APOL1 membrane-addressing domain mutation ( p.T272I ) in Chinese twins with FSGS: implications for podocyte injury and ion channel disruption
Apolipoprotein L1 (APOL1) risk variants are strongly associated with kidney diseases, including focal segmental glomerulosclerosis (FSGS), though known mutations (G1/G2) are primarily observed in African populations. This study reports a novel APOL1 mutation (p.T272I) identified in a pair of Chinese twins with FSGS, expanding the genetic spectrum of APOL1-related nephropathies. Whole exome sequencing detected the APOL1 mutation in the twins and excluded parental inheritance. Functional studies demonstrated that transfection of mutant APOL1 into human podocytes and HEK293T cells led to cytoplasmic lysis, disrupted F-actin organization, and reduced expression of nephrin and synaptopodin. The variant also induced mitochondrial dysfunction, increased the LC3-II/I ratio, activated p38 MAPK signaling, and altered chloride channel activity. Structural modeling AlphaFold2 suggested conformational disturbance within the membrane-addressing domain. These findings reveal the first de novo APOL1 mutation in the Chinese population, implicating podocyte injury through cytoskeletal collapse, mitochondrial damage, altered autophagic markers, and ion channel dysfunction in FSGS pathogenesis. This study expands the spectrum of APOL1-related variants beyond G1/G2 and highlights underlying mechanisms for potential therapeutic targeting.
Experimental Research on the Flow and Heat Transfer Characteristics of Subcritical and Supercritical Water in the Vertical Upward Smooth and Rifled Tubes
Experiments were conducted to investigate the heat transfer and flow characteristics of the vertical upward smooth and rifled tubes from subcritical to supercritical pressure. The distributions of wall temperature and heat transfer coefficient (HTC) were obtained, and the HTC correlations and friction resistance coefficient correlations were fitted with experimental data. In addition, the influences of heat flux and type of tube on heat transfer performance were analyzed. The research shows that heat flux has different influences on the heat transfer characteristics under different pressures. The increase in heat flux improves the heat transfer characteristics in the nucleate boiling region, yet it leads to the advance in heat transfer deterioration. However, for supercritical water, the increase in heat flux reduces the heat transfer ability. In addition, using the rifled tube not only improves the heat transfer performance, but also inhibits the occurrence of heat transfer deterioration. The fitted correlations have great predictive ability for the heat transfer coefficient and friction resistance coefficient, and the average relative fitting errors are limited to 20%.
Development and application of a qPCR assay for Lawsonia intracellularis in Tibetan pigs
This study developed a rapid, sensitive, and specific TaqMan MGB based qPCR assay for detecting in Tibetan pigs by targeting the gene. The method showed no cross-reactivity with other common porcine enteric pathogens, and exhibited high sensitivity (detection limit: 7.056 copies/μL) and excellent repeatability (CV < 2%). A standard curve with good linearity (R² = 0.998) and 110.95% amplification efficiency was established. The assay was applied to 237 fecal samples collected from Tibetan pigs across eight townships in Xiangcheng County, Sichuan Province, in parallel with a national standard method. Results indicated a 19% overall positivity rate (45/237), with regional rates ranging from 11.11% to 26.67%. The established qPCR provides a reliable tool for field surveillance, and findings underscore the need to integrate monitoring into local prevention systems to support healthy Tibetan pig production.
Safety and efficacy of pharmacotherapy containing INSTIs and chemotherapy drugs in people living with HIV and concomitant colorectal cancer
Background Previous clinical data have shown that raltegravir-based antiretroviral therapy (ART) with fewer drug-drug interactions (DDIs) and adverse events (AEs) is a good regimen in patients with HIV infection who need cancer chemotherapy. There are currently few data on ART regimens that include Integrase inhibitors (INSTIs) other than RAL among this patient subgroup. Methods We evaluated the safety and efficacy of different kinds of INSTI-based regimens among patients with HIV and concomitant colorectal cancer (CRC) who received antineoplastic agents. Results From January 2020 to November 2021, 66 patients were enrolled. The patients were divided into three groups: 20 patients treated with dolutegravir (DTG)/lamivudine (3TC)/tenofovir (TDF) (group I), 24 patients treated with DTG/albuvirtide (ABT) (group II), and 22 patients treated with bictegravir (BIC)/tenofovir alafenamide (TAF)/emtricitabine (FTC) (group III). The majority of AEs during treatment were of grade 1–2. Treatment‐related AEs of grade 3–4 occurred in 6 patients (9.09%), and no grade 5 AEs occurred. The most common AEs were nausea (100%) and neutrophils (84.85%) attributed to anticancer agents, and there was no significant difference in the incidence of these AEs among the three groups (P > 0.05). Viral load rebound was not observed among pretreated patients during chemotherapy. The viral load of untreated patients who started their ART concomitant with chemotherapy almost decreased to the lower limit of detection 6 months after ART initiation (only one patient in group III had a viral load of 102 copies/ml). At the 6th month, the CD4 count in group I decreased significantly from baseline (P < 0.05). However, the change in CD4 count was not significant in group II (P = 0.457) or group III (P = 0.748). Conclusions DTG- or BIC-containing regimens are good options for patients with HIV and concomitant CRC.
Perioperative Antiretroviral Regimen for HIV/AIDS Patients Who Underwent Abdominal Surgery
Background A short interruption of antiretroviral therapy (ART) and reduced oral bioavailability of antiretroviral medications could occur in perioperative human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) patients who undergo abdominal surgery. Therefore, we focused on the changes in HIV viral load and CD4 + T lymphocyte count in HIV/AIDS patients after surgery and explored whether the perioperative use of intravenous antiretroviral drugs is beneficial in lowering the viral load and increasing the safety of the surgery. Methods We prospectively collected data from HIV/AIDS patients who underwent abdominal surgery at our institution from January 2019 and April 2019. According to the use of different antiretroviral medications during the perioperative period, the HIV/AIDS patients were divided into four groups: Group I: Patients continued their original antiretroviral medications; Group II: Patients received their original antiretroviral medications plus intravenous administration of the fusion inhibitor albuvirtide (ABT); Group III: Patients received ABT alone; and Group IV: Patients did not receive ART. The primary outcomes considered were the changes in HIV load and CD4 + T lymphocyte count and the postoperative complications in the four groups. Results A total of 64 HIV/AIDS patients were enrolled, and their data were analyzed descriptively. There were no differences between group I and group II in terms of the changes in viral load. The viral load continued to decrease in group III within 30 days after surgery, especially from D7 to D30 ( t  = 2.179, p  = 0.043). However, the viral load showed an upward trend after surgery in group IV. There were statistically significant differences between the two groups in the changes in viral load after surgery ( p  = 0.022). However, there were no statistically significant differences between group III and group IV in the postoperative changes in the CD4 + T lymphocyte count. Seven out of 64 patients had postoperative infective complications. The incidence of complications from high to low was as follows: group IV > group I > group III > group II ( p  < 0.05). Conclusions A short perioperative interruption of ART may have a small impact on viral load in HIV/AIDS patients on virologic suppression after abdominal surgery. For patients with a detectable viral load, an intravenous injection of ABT in the perioperative period can reduce the viral load quickly, lower the occurrence of postoperative complications, and increase operation safety for both the HIV/AIDS patient and the surgeons.
Psychological Experiences of Pregnant Women with Fetal Growth Restriction in China: A Qualitative Study
Fetal growth restriction is a global public health concern. This study aimed to explore the psychological experiences of pregnant women with fetal growth restriction to develop evidence-based and effective psychological intervention strategies. A qualitative descriptive study was conducted at Fujian Maternity and Child Health Hospital, China, from November 2024 to April 2025. Socio-demographic and clinical characteristic data were collected. Interview questions were developed following a pre-survey with three women and refined through input from three clinical nursing experts. Subsequently, in-depth semi-structured interviews were conducted with 20 pregnant women diagnosed with fetal growth restriction. The interviews were audio-recorded and analyzed using Colaizzi's seven-step method. Themes and sub-themes were identified and examined. Five major themes emerged: (1) unknown fetal outcomes and generalized anxiety (persistent anxiety over fetal health; catastrophic associations related to fetal outcomes), (2) imbalanced medical information and coping dilemmas (overwhelming information; ineffective coping strategies), (3) maternal responsibility discipline and family conflict (maternal attribution of responsibility; counterproductive family support), (4) medical decision-making dilemmas and trust crisis (conflicts in medical interventions; lack of trust in healthcare providers), and (5) social support and improvement of psychological resilience (empathic peer support; buffered family support; trusted medical support). Pregnant women with fetal growth restriction may experience a range of psychological responses. Future research needs to further explore the specific biological mechanism between psychological factors and occurrence and development of FGR in pregnant women. At the same time, more personalized and effective psychological intervention programs need to be developed and validated, and integrated into the clinical FGR management, in order to improve the overall health outcomes of FGR pregnant women and their offspring. In addition, future research should also explore the dynamic trajectories of psychological experiences among pregnant women with FGR.
Deep brain stimulation in the globus pallidus alleviates motor activity defects and abnormal electrical activities of the parafascicular nucleus in parkinsonian rats
Deep brain stimulation (DBS) is an effective treatment for Parkinson's disease (PD). The most common sites targeted for DBS in PD are the globus pallidus internal (GPi) and subthalamic nucleus (STN). However, STN-DBS and GPi-DBS have limited improvement in some symptoms and even aggravate disease symptoms. Therefore, discovering new targets is more helpful for treating refractory symptoms of PD. Therefore, our study selected a new brain region, the lateral globus pallidus (GP), as the target of DBS, and the study found that GP-DBS can improve motor symptoms. It has been reported that the thalamic parafascicular (PF) nucleus is strongly related to PD pathology. Moreover, the PF nucleus and GP have very close direct and indirect fiber connections. However, whether GP-DBS can change the activity of the PF remains unclear. Therefore, in this study, we monitored the activity changes in the PF nucleus in PD rats during a quiet awake state after GP-DBS. We found that GP-DBS could reverse the electrical activity of the PF nucleus in PD model rats, including the discharge pattern of the neurons and the local field potential (0.7–12 and 12–70 Hz). Based on the results mentioned above, PF activity in PD model rats could be changed by GP-DBS. Thus, the normalization of PF neuronal activity may be a potential mechanism for GP-DBS in the treatment of PD; these findings lay the foundation for PD treatment strategies.
Analysis of genetic profiling, pathomics signature, and prognostic features of primary lymphoepithelioma‐like carcinoma of the renal pelvis
The genetic features of primary lymphoepithelioma‐like carcinoma (LELC) of the upper urinary tract have not been systematically explored. In this study, tumor mutation profiling was performed using whole‐genome sequencing in two patients with LELC of the renal pelvis. Novel candidate variants relevant to known disease genes were selected using rare‐variant burden analysis. Subsequently, a population‐based study was performed using the Surveillance, Epidemiology, and End Results (SEER), PubMed, MEDLINE, Embase, and Scopus databases to explore clinical features and prognostic risk factors. Immunohistochemical analysis revealed seven positive cytokeratin‐associated markers in tumor cells and five positive lymphocyte‐associated markers in and around the tumor area. Sub‐sequently, we identified KDM6A as the susceptibility gene and LEPR as the driver gene by Sanger sequencing in case 2 of LELC of the renal pelvis. Three mutation sites of the existing targeted drugs were screened: CA9, a therapeutic target for zonisamide; ARVCF, a therapeutic target for bupropion; and PLOD3, a therapeutic target for vitamin C. In a population‐based study, patients with primary LELC of the upper urinary tract had clinical outcomes similar to those of patients with primary upper urinary tract urothelial carcinoma (UUT‐UC) before and after propensity score matching at 1 : 5. Focal subtype was an independent prognostic factor for the overall survival of patients with LELC of the upper urinary tract. The carcinogenesis of primary LELC may be due to different genetic variations, including single‐nucleotide variants, insertion and deletions, structural variations, and repeat regions, which may provide the basis for clinical diagnosis and treatment. The prognosis of LELC in the upper urinary tract is similar to that of UUT‐UC. We suggest that the focal subtype can serve as a prognostic factor for LELC of the upper urinary tract; however, further studies are required to confirm this. Here, the genetic, pathological and prognostic features of primary lymphoepithelioma‐like carcinoma (LELC) of the renal pelvis are explored. Mutations in the driver gene LEPR and susceptibility gene KDM6A might be associated with LELC of the renal pelvis. The prognosis of LELC of the upper urinary tract is similar to that of UUT‐UC.
Leaf Plasticity and Biomass Allocation of Arundo donax Under Combined Irrigation and Nitrogen Conditions in Salinized Soil
Arundo donax L. (giant reed) is a perennial rhizomatous grass with high drought and salinity tolerance, making it a promising low-input bioenergy crop. However, the understanding of the combined effects of irrigation and nitrogen application in salinized soil on physiological adaptations and biomass allocation is still limited. In this study, we conducted a three-factor orthogonal pot experiment with four levels per factor in 2023 and 2024 as follows: salinity (S0: non-saline, S1: low salinity, S2: moderate salinity, S3: high salinity); irrigation amount (W0: 605, W1: 770, W2: 935, W3: 1100 mm); and nitrogen application (N0: 0, N1: 60, N2: 120, N3: 180 kg/ha). This resulted in 14 irrigation-nitrogen-salinity combined treatments. The results showed the following: (1) Irrigation, nitrogen and salinity significantly affected leaf dimensions, photosynthetic rate, plant height, biomass allocation and dry matter of the total plant (p < 0.05). (2) Significant coupling interactions were observed between salinity and irrigation, as well as between nitrogen and irrigation, affecting leaf morphology, plant height, leaf dry matter and total biomass accumulation; a coupling interaction of salinity and nitrogen was found to affect the leaf area, root, stem and leaf dry weight. (3) The S0N2W2 treatment produced the highest dry biomass, which was 2.2 times higher than for the S3N2W2 treatment. (4) Under moderate-salinity conditions (S2), biomass allocation favored stems and leaves, whereas under high-salinity conditions (S3) biomass allocation shifted towards leaves, followed by stems and roots. A combination of 935 mm irrigation amount and 120 kg/ha nitrogen (N2W2) under S1 and S2 is recommended to optimize biomass production. Our study provides practical irrigation and nitrogen management strategies to enhance A. donax cultivation on marginal saline lands, supporting climate-resilient bio-economy initiatives.