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1.
Clin Sci (Lond) ; 2024 Oct 11.
Article in English | MEDLINE | ID: mdl-39392219

ABSTRACT

Previous studies have shown beneficial effects of empagliflozin (Empa), a selective inhibitor of the sodium-glucose cotransporter 2 (SGLT2), on diabetes and cardiovascular outcomes in patients with diabetes. However, whether Empa could ameliorate diabetes mellitus (DM)-induced male spermatogenesis dysfunction remains unclear. Our study aimed to investigate the effect of Empa in the development of DM-induced male spermatogenesis dysfunction and to reveal the molecular mechanisms. DM mice were orally treated with Empa to investigate the effects of Empa on DM-induced male mice spermatogenesis dysfunction. We employed a cardiac-specific C1q/tumor necrosis factor-related protein 9 (CTRP9)-deficient mouse model and a cardiac-specific CTRP9 overexpression mouse model to investigate its role in the protection of Empa against diabetes-induced male subfertility. We found that Empa treatment could improve DM-induced male mice subfertility. Interestingly, we discovered that cardiac-derived CTRP9 was decreased in DM mice and this decrease was prevented by Empa treatment. A CTRP9 blocking antibody or cardiac-specific depletion of CTRP9 abolished the protection of Empa on DM-induced male subfertility. Cardiac-specific CTRP9 overexpression ameliorated DM-induced male subfertility. Mechanistically, we identified that cardiac-derived CTRP9 increased steroidogenesis in mice with diabetes in a PKA-dependent manner. We also provided direct evidence that activation of AMP activated protein kinase α (AMPKα)/nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling pathway by CTRP9 was responsible for the attenuation of ferroptosis in Leydig cells. In conclusions, we supposed that Empa was a potential therapeutic agent against DM-induced male mice spermatogenesis dysfunction.

2.
BMC Psychiatry ; 24(1): 629, 2024 Sep 27.
Article in English | MEDLINE | ID: mdl-39334168

ABSTRACT

BACKGROUND: The incidence of non-suicidal self-injury (NSSI) is high and often occurs repeatedly. Psychiatric nurses play a vital role in the care and treatment of NSSI patients, as they have the most frequent contact with patients. The experiences and attitudes of nurses has a direct affect on the quality of care they provide to patients. Negative care experiences and attitudes of patient aversion on behalf of nurses may delay the observation and treatment of changes in the patient's condition, leading to irreversible risks. Although cross-sectional studies have investigated the attitudes of medical staff toward NSSI patients, quantitative research results cannot comprehensively reflect the emotional experiences and complex psychological changes of the study subjects. A few studies have focused on the psychiatric nurses' care experiences and attitudes toward patients with repeated NSSI. OBJECTIVE: This study aimed to explore psychiatric nurses' care experiences and attitudes toward patients during repeated NSSI. METHODS: A thematic analysis qualitative study was used. Using purposive sampling, 18 psychiatric nurses were recruited from a mental health center in Chengdu, China. Semi-structured interviews were conducted and audio-recorded. Audio-recordings were transcribed verbatim and analyzed using six-phase thematic analysis. RESULTS: Four themes emerged from the analysis: psychiatric nurses' care experiences, perceptions, care attitudes and coping style toward repeated NSSI patients. Psychiatric nurses have experienced negative care experiences and severe career burnout during the patient's repeated NSSI. Nurses' attitudes toward NSSI patients changed during repeated NSSI, from understanding to indifference to anger and resentment. At the same time, it was found that nurses' coping style with NSSI patients could be divided into three stages, namely, active coping, neglect and perfunctory, and criticism and punishment. CONCLUSIONS: The findings have implications for health care systems regarding interventions to improve nurses' care experiences and attitudes toward repeated NSSI patients. These findings suggest that enhancing nurses' understanding of NSSI, establishing standardized emergency response and intervention programs, guiding positive professional values and responsibility, and improving nurses' caring attitudes can promote the early detection and timely intervention of NSSI.


Subject(s)
Attitude of Health Personnel , Psychiatric Nursing , Qualitative Research , Self-Injurious Behavior , Humans , Self-Injurious Behavior/psychology , Self-Injurious Behavior/nursing , Female , China , Adult , Male , Nurse-Patient Relations , Middle Aged , Nurses/psychology
3.
PhytoKeys ; 246: 229-236, 2024.
Article in English | MEDLINE | ID: mdl-39268084

ABSTRACT

Neomicrocalamus and Temochloa are closely-related genera for which 'inflorescence' structures were incompletely understood and difficult to reconcile. After re-examining the inflorescence morphology, the so-called 'spikelets' of both genera as described should instead be recognised as pseudospikelets with mostly inactive axillary buds. The new bamboo taxa, comprising two varieties of a new species, are placed in Temochloa, representing a new genus record for China and Vietnam.

4.
Trop Anim Health Prod ; 56(7): 233, 2024 Aug 03.
Article in English | MEDLINE | ID: mdl-39096351

ABSTRACT

Mosquitoes (Diptera: Culicidae) are one of the most studied groups of arthropods worldwide due to their high transmission capacity for pathogens, including viruses and parasites. During June to October 2022, the prevalence of mosquito species in 12 intensive pig farms from 12 representative administrative regions in Hunan province of China was investigated using traps with ultraviolet light. All collected mosquitoes were counted and identified to species according to morphological and molecular methods. A total of 4,443 mosquito specimens were collected in the pig farms, and they represented one family, four genera and nine species. Culex pipiens pipiens (24%) was the most common mosquito species, followed by Armigeres subalbatus (23.4%) and Culex tritaeniorhynchus (20.6%). Phylogenetic analyses based on mitochondrial cox1 sequences revealed all mosquito species from present study grouping into distinct monophyletic groups corresponding to nine known mosquito species with strongly supported. The results of the present investigation have implications for the ongoing control of mosquito infestation in pig farms in Hunan province, China. This is the first report of mosquito populations in intensive pig farms in Hunan province, China.


Subject(s)
Culicidae , Phylogeny , Animals , China/epidemiology , Culicidae/physiology , Culicidae/classification , Swine , Farms , Animal Husbandry , Sus scrofa
5.
Rev Cardiovasc Med ; 25(7): 262, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39139440

ABSTRACT

Cardiovascular disease (CVD), a leading cause of death and disability worldwide, and is associated with a wide range of risk factors, and genetically associated conditions. While many CVDs are preventable and early detection alongside treatment can significantly mitigate complication risks, current prediction models for CVDs need enhancements for better accuracy. Mendelian randomization (MR) offers a novel approach for estimating the causal relationship between exposure and outcome by using genetic variation in quasi-experimental data. This method minimizes the impact of confounding variables by leveraging the random allocation of genes during gamete formation, thereby facilitating the integration of new predictors into risk prediction models to refine the accuracy of prediction. In this review, we delve into the theory behind MR, as well as the strengths, applications, and limitations behind this emerging technology. A particular focus will be placed on MR application to CVD, and integration into CVD prediction frameworks. We conclude by discussing the inclusion of various populations and by offering insights into potential areas for future research and refinement.

6.
Ann Hematol ; 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38990296

ABSTRACT

Membranous nephropathy (MN) is a rare complication that can occur after allogeneic hematopoietic stem cell transplantation (allo-HSCT). MN patients may develop nephrotic syndrome or even kidney failure, which greatly affects their quality of life and prognosis. However, current knowledge regarding MN after allo-HSCT is limited. Thus, a multicenter nested case‒control study was conducted. Patients who had been diagnosed with MN after allo-HSCT were retrospectively identified at 8 HSCT centers. A total of 51 patients with MN after allo-HSCT were included. The median age of MN patients after allo-HSCT was 38 years, and the median duration from HSCT to MN was 18 months. The use of HLA-matched donors (P = 0.0102) and peripheral blood as the graft source (P = 0.0060) were identified as independent predisposing risk factors for the onset of MN after allo-HSCT. Compared to those in the control group, the incidence of extensive chronic graft-versus-host disease was greater in the MN patients (P = 0.0002). A total of 31 patients developed nephrotic syndrome. Patients receiving combination treatments of corticosteroids and immunosuppressants appeared to have better outcomes. In conclusion, MN is a rare but occasionally severe complication following HSCT and may require active treatment.

7.
Am J Hematol ; 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38980207

ABSTRACT

Patients with steroid-resistant or relapsed immune thrombocytopenia (ITP) suffer increased bleeding risk and impaired quality of life. Baricitinib, an oral Janus-associated kinases (JAK) inhibitor, could alleviate both innate and adaptive immune disorders without inducing thrombocytopenia in several autoimmune diseases. Accordingly, an open-label, single-arm, phase 2 trial (NCT05446831) was initiated to explore the safety and efficacy of baricitinib in ITP. Eligible patients were adults with primary ITP who were refractory to corticosteroids and at least one subsequent treatment, and had platelet counts below 30 × 109/L at enrolment. Participants received baricitinib 4 mg daily for 6 months. The primary endpoint was durable response at the 6-month follow-up. A total of 35 patients were enrolled. Durable response was achieved in 20 patients (57.1%, 95% confidence interval, 39.9 to 74.4), and initial response in 23 (65.7%) patients. For patients responding to baricitinib, the median time to response was 12 (IQR 6-20) days, and the median peak platelet count was 94 (IQR 72-128) × 109/L. Among the 27 patients undergoing extend observation, 12 (44.4%) remained responsive for a median duration of approximately 20 weeks after baricitinib discontinuation. Adverse events were reported in 11 (31.4%) patients, including infections in 6 (17.1%) patients during the treatment period. Treatment discontinuation due to an adverse event was reported in 2 (5.7%) patients. Evidence from this pilot study suggested that baricitinib might be a novel candidate for the armamentarium of ITP-modifying agents. Future studies are warranted to validate the safety, efficacy, and optimal dosing of baricitinib in patients with ITP.

8.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 55(3): 739-743, 2024 May 20.
Article in Chinese | MEDLINE | ID: mdl-38948291

ABSTRACT

Objective: This study aims to investigate the agreement between the Huaxi Emotional Index (HEI) and the Nurses' Global Assessment of Suicide Risk (NGASR) in assessing high suicide risk and to explore the predictive value of HEI in identifying high suicide risk among patients with depression. Methods: Convenience sampling was used and 386 inpatients with depression were included in this cross-sectional study. All patients were admitted to the Mental Health Center, West China Hospital between June and December 2023. The inclusion criteria were as follows, a diagnosis of depression according to the International Classification of Diseases, Tenth Revision (ICD-10), age over 18, and completion of both NGASR and HEI assessments. According to the exclusion criteria, depression patients who had other comorbid mental disorders or those who had severe cognitive impairments and were unable to communicate effectively were excluded. The study was approved by the Biomedical Ethics Review Committee of West China Hospital (Approval No. 647, 2021). Demographic data such as age, sex, ethnicity, marital status, and educational attainment were collected using a self-designed questionnaire. Both the HEI and NGASR were applied to evaluate the patients. We conducted statistical analyses with SPSS 27, employing Spearman's rank correlation for correlation analysis, Kappa tests for consistency between the two instruments, and receiver operating characteristic (ROC) curves for evaluating the predictive performance of HEI scores for high suicide risk, with the optimal HEI cutoff value determined on the basis of the Youden Index. Results: The study included 386 depression inpatients with an average age of 32 years and an average length-of-stay of 14 days. Of these participants, 252 were female (65.3%) and 134 were male (34.7%). Regarding ethnicity, most of the participants were Han Chinese (89.4%), Tibetans accounted for 7.3%, and other minorities, 3.3%. Regarding marital status, 51.3% of the participants were married, 41.2% single, 6.5% divorced, and 1.0% widowed. Regarding educational attainment, 26.2% had an undergraduate or graduate education, 20.7% had junior college education, 24.8% had high school or secondary technical school education, and 28.2% had middle school education or less. The NGASR identified 57.3% of the participants as being at high suicide risk, while the HEI identified 53.6% as having severe emotional distress. There was a moderate agreement between the HEI and the NGASR scores, with a Kappa value of 0.518 ( P<0.001), indicating statistically significant differences. At an HEI score of 17, the Youden Index peaked at 0.52, predicting high suicide risk with a specificity of 76.36%, a sensitivity of 76.02%, and an area under the ROC curve of 0.829 (95% CI: 0.787-0.871), demonstrating statistically significant differences. Conclusion: HEI and NGASR demonstrate moderate agreement in assessing high suicide risk among depression patients. The HEI questionnaire effectively predicts high suicide risk in patients with depression, with 17 being the optimal cutoff value for assessing high suicide risk.


Subject(s)
Depression , Inpatients , Suicide , Humans , Female , Male , Depression/diagnosis , Depression/etiology , Cross-Sectional Studies , Surveys and Questionnaires , Suicide/psychology , Suicide/statistics & numerical data , China/epidemiology , Risk Assessment/methods , Emotions , Adult , Risk Factors , Middle Aged , Predictive Value of Tests
9.
J Hematol Oncol ; 17(1): 52, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39026311

ABSTRACT

Recent developments in menin inhibitors for relapsed or refractory acute myeloid leukemia (AML) were highlighted at the 2023 ASH Annual Meeting. Notably, revumenib showed promising efficacy, achieving a 100% ORR when combined with decitabine/cedazuridine and venetoclax. These findings underscore the potential of menin inhibitors in transforming AML treatment, particularly in genetically defined subgroups, offering hope for improved patient outcomes. Ongoing studies, like KOMET-008, further explore the synergistic potential of menin inhibitors in combination regimens, shaping future AML management strategies.


Subject(s)
Leukemia, Myeloid, Acute , Proto-Oncogene Proteins , Humans , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/pharmacology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Leukemia, Myeloid, Acute/drug therapy , Proto-Oncogene Proteins/antagonists & inhibitors
10.
Phys Rev Lett ; 132(16): 161604, 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38701468

ABSTRACT

We consider Majorana lattices with two-site interactions consisting of a general function of the fermion bilinear. The models are exactly solvable in the limit of a large number of on-site fermions. The four-site chain exhibits a quantum phase transition controlled by the hopping parameters and manifests itself in a discontinuous entanglement entropy, obtained by constraining the one-sided modular Hamiltonian. Inspired by recent work within the AdS/CFT correspondence, we identify transitions between types of von Neumann operator algebras throughout the phase diagram. We find transitions of the form II_{1}↔III↔I_{∞} that reduce to II_{1}↔I_{∞} in the strongly interacting limit, where they connect nonfactorized and factorized ground states. Our results provide novel realizations of such transitions in a controlled many-body model.

12.
J Am Heart Assoc ; 13(10): e028006, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38726894

ABSTRACT

BACKGROUND: S100a8/9 (S100 calcium binding protein a8/9) belongs to the S100 family and has gained a lot of interest as a critical regulator of inflammatory response. Our previous study found that S100a8/9 homolog promoted aortic valve sclerosis in mice with chronic kidney disease. However, the role of S100a8/9 in pressure overload-induced cardiac hypertrophy remains unclear. The present study was to explore the role of S100a8/9 in cardiac hypertrophy. METHODS AND RESULTS: Cardiomyocyte-specific S100a9 loss or gain of function was achieved using an adeno-associated virus system, and the model of cardiac hypertrophy was established by aortic banding-induced pressure overload. The results indicate that S100a8/9 expression was increased in response to pressure overload. S100a9 deficiency alleviated pressure overload-induced hypertrophic response, whereas S100a9 overexpression accelerated cardiac hypertrophy. S100a9-overexpressed mice showed increased FGF23 (fibroblast growth factor 23) expression in the hearts after exposure to pressure overload, which activated calcineurin/NFAT (nuclear factor of activated T cells) signaling in cardiac myocytes and thus promoted hypertrophic response. A specific antibody that blocks FGFR4 (FGF receptor 4) largely abolished the prohypertrophic response of S100a9 in mice. CONCLUSIONS: In conclusion, S100a8/9 promoted the development of cardiac hypertrophy in mice. Targeting S100a8/9 may be a promising therapeutic approach to treat cardiac hypertrophy.


Subject(s)
Calgranulin A , Calgranulin B , Fibroblast Growth Factor-23 , NFATC Transcription Factors , Up-Regulation , Animals , Male , Mice , Calcineurin/metabolism , Calgranulin A/metabolism , Calgranulin A/genetics , Calgranulin B/metabolism , Calgranulin B/genetics , Cardiomegaly/metabolism , Cardiomegaly/pathology , Disease Models, Animal , Fibroblast Growth Factor-23/metabolism , Hypertrophy, Left Ventricular/genetics , Hypertrophy, Left Ventricular/pathology , Mice, Inbred C57BL , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , NFATC Transcription Factors/metabolism , NFATC Transcription Factors/genetics , Signal Transduction
13.
Bioorg Med Chem Lett ; 104: 129711, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38521175

ABSTRACT

WRN helicase is a critical protein involved in maintaining genomic stability, utilizing ATP hydrolysis to dissolve DNA secondary structures. It has been identified as a promising synthetic lethal target for microsatellite instable (MSI) cancers. However, few WRN helicase inhibitors have been discovered, and their potential binding sites remain unexplored. In this study, we analyzed potential binding sites for WRN inhibitors and focused on the ATP-binding site for screening new inhibitors. Through molecular dynamics-enhanced virtual screening, we identified two compounds, h6 and h15, which effectively inhibited WRN's helicase and ATPase activity in vitro. Importantly, these compounds selectively targeted WRN's ATPase activity, setting them apart from other non-homologous proteins with ATPase activity. In comparison to the homologous protein BLM, h6 exhibits some degree of selectivity towards WRN. We also investigated the binding mode of these compounds to WRN's ATP-binding sites. These findings offer a promising strategy for discovering new WRN inhibitors and present two novel scaffolds, which might be potential for the development of MSI cancer treatment.


Subject(s)
Adenosine Triphosphate , Antineoplastic Agents , Enzyme Inhibitors , Molecular Dynamics Simulation , Werner Syndrome Helicase , Adenosine Triphosphate/chemistry , Binding Sites , Werner Syndrome Helicase/antagonists & inhibitors , Werner Syndrome Helicase/chemistry , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Drug Screening Assays, Antitumor , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Microsatellite Instability/drug effects , Neoplasms/genetics , Humans
14.
Asian J Psychiatr ; 95: 103997, 2024 May.
Article in English | MEDLINE | ID: mdl-38492442

ABSTRACT

BACKGROUND: Depression is a prevalent mood disorder during the perioperative period, with both preoperative concurrent depression and new-onset postoperative depression impacting postoperative recovery. Recent studies have indicated that the dissociative anesthetic esketamine may alleviate perioperative depressive symptoms. OBJECTIVE: This meta-analysis aimed to assess the efficacy and safety of esketamine in treating perioperative depression. METHODS: We selected randomized controlled trials comparing esketamine to placebo in terms of postoperative depressive symptoms. The primary outcome was postoperative depression scores, with secondary outcomes including the prevalence of postoperative depression, pain scores using the Visual Analogue Scale or Numeric Rating Scale, and incidences of adverse reactions such as nausea/vomiting, dizziness, dreams/nightmares, hallucinations. RESULTS: We enrolled a total of 17 studies involving 2462 patients. The esketamine group demonstrated a significant reduction in postoperative depression scores within one week after surgery (SMD -0.47, 95% CI (-0.66, -0.27), P < 0.001) and over the long term (SMD -0.44, 95% CI (-0.79, -0.09), P = 0.01). Furthermore, esketamine significantly decreased the prevalence of postoperative depression both within one week (RR 0.46, 95% CI (0.33, 0.63), P < 0.001) and over the long term (RR 0.50, 95% CI (0.36, 0.70), P < 0.001). Additionally, esketamine effectively relieved pain on the first postoperative day compared to control. However, it also increased the risks of dizziness and hallucinations for a short time. CONCLUSION: This meta-analysis suggests that the intraoperative or postoperative application of esketamine could be a potentially effective treatment for perioperative depression, although the increased risk of adverse reactions should be considered.


Subject(s)
Elective Surgical Procedures , Ketamine , Randomized Controlled Trials as Topic , Humans , Ketamine/administration & dosage , Ketamine/adverse effects , Elective Surgical Procedures/adverse effects , Postoperative Complications/prevention & control , Depression/drug therapy , Perioperative Period
15.
J Nanobiotechnology ; 22(1): 136, 2024 Mar 29.
Article in English | MEDLINE | ID: mdl-38553716

ABSTRACT

Pulmonary fibrosis (PF) threatens millions of people worldwide with its irreversible progression. Although the underlying pathogenesis of PF is not fully understood, there is evidence to suggest that the disease can be blocked at various stages. Inhalation therapy has been applied for lung diseases such as asthma and chronic obstructive pulmonary disease, and its application for treating PF is currently under consideration. New techniques in inhalation therapy, such as the application of microparticles and nanoparticles, traditional Chinese medicine monomers, gene therapy, inhibitors, or agonists of signaling pathways, extracellular vesicle interventions, and other specific drugs, are effective in treating PF. However, the safety and effectiveness of these therapeutic techniques are influenced by the properties of inhaled particles, biological and pathological barriers, and the type of inhalation device used. This review provides a comprehensive overview of the pharmacological, pharmaceutical, technical, preclinical, and clinical experimental aspects of novel inhalation therapy for treating PF and focus on therapeutic methods that significantly improve existing technologies or expand the range of drugs that can be administered via inhalation. Although inhalation therapy for PF has some limitations, the advantages are significant, and further research and innovation about new inhalation techniques and drugs are encouraged.


Subject(s)
Asthma , Pulmonary Disease, Chronic Obstructive , Pulmonary Fibrosis , Humans , Pulmonary Fibrosis/drug therapy , Administration, Inhalation , Pulmonary Disease, Chronic Obstructive/drug therapy , Asthma/drug therapy , Respiratory Therapy
16.
Psychopharmacology (Berl) ; 241(5): 1093-1099, 2024 May.
Article in English | MEDLINE | ID: mdl-38286858

ABSTRACT

OBJECTIVE: The objective of this study was to observe the changes in the levels of indoleamine 2, 3-dioxygenase (IDO) and tryptophan-2, 3-dioxygenase (TDO) in patients with major depressive disorder (MDD) and investigate their potential role as novel biomarkers for diagnosing MDD. METHODS: A total of 55 MDD patients and 55 healthy controls (HC) were enrolled in the study. The severity of MDD was assessed using the 24-item Hamilton Depression Rating Scale (HAMD-24) before and after treatment. The serum concentrations of IDO and TDO were measured at baseline and after treatment. The correlations between the serum levels of IDO and TDO and HAMD-24 scores were evaluated using Pearson's correlation test. Receiver operating characteristic (ROC) curve analysis was used to evaluate the area under the curve (AUC) of serum levels of IDO and TDO for discriminating MDD patients from HC. RESULTS: The serum IDO and TDO concentrations were significantly higher in patients with MDD at baseline than in healthy controls, and decreased significantly after 2 weeks or 1 month of treatment. The levels of IDO and TDO were significantly positively correlated with HAMD-24 scores. Furthermore, the AUC values for IDO and TDO were 0.999 and 0.966, respectively. CONCLUSION: The study suggests that serum IDO and TDO may serve as novel biomarkers for diagnosing MDD. These findings may lead to a better understanding of the pathogenesis of MDD and the development of new therapeutic targets.


Subject(s)
Depressive Disorder, Major , Tryptophan , Humans , Depressive Disorder, Major/diagnosis , Tryptophan Oxygenase , Indoleamine-Pyrrole 2,3,-Dioxygenase , Biomarkers
17.
J Clin Rheumatol ; 30(2): 73-78, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38268091

ABSTRACT

OBJECTIVE: The purpose of this research was to ascertain the effectiveness of the newly established criteria for classifying IgG4-related disease (IgG4-RD), as applied to a large Chinese cohort in real-world clinical settings. METHODS: Patient data were procured from the digital health records of 4 prominent academic hospitals. The criterion standard for identifying IgG4-RD patients was from a seasoned rheumatologist. The control group consisted of individuals with other ailments such as cancer, other forms of pancreatitis, infectious diseases, and illnesses that mimic IgG4-RD. RESULTS: A total of 605 IgG4-RD patients and 760 mimickers were available for analysis. The 2019 EULAR/ACR criteria have a sensitivity of 69.1% and a specificity of 90.9% in this large Chinese cohort. IgG4-RD had a greater proportion of males (55.89% vs 36.25%, p < 0.001), an older average age at diagnosis (54.91 ± 13.44 vs 48.91 ± 15.71, p < 0.001), more pancreatic (29.59% vs 6.12%, p < 0.001) and salivary gland (63.30% vs 27.50%, p < 0.001) involvement, and a larger number of organ involvement (3.431 ± 2.054 vs 2.062 ± 1.748, p < 0.001) compared with mimickers. CONCLUSIONS: The 2019 EULAR/ACR criteria are effective in classifying IgG4-RD in Chinese patients, demonstrating high specificity and moderate sensitivity.


Subject(s)
Immunoglobulin G4-Related Disease , Pancreatitis , Humans , Male , Asian People , China , Immunoglobulin G4-Related Disease/diagnosis , Pancreatitis/diagnosis , Salivary Glands , Female
18.
J Med Chem ; 67(3): 1961-1981, 2024 02 08.
Article in English | MEDLINE | ID: mdl-38272464

ABSTRACT

Hyperactivated KRAS mutations fuel tumorigenesis and represent attractive targets for cancer treatment. While covalent inhibitors have shown clinical benefits against the KRASG12C mutant, advancements for non-G12C mutants remain limited, highlighting the urgent demand for pan-KRAS inhibitors. RNA G-quadruplexes (rG4s) in the 5'-untranslated region of KRAS mRNA can regulate KRAS translation, making them promising targets for pan-KRAS inhibitor development. Herein, we designed and synthesized 50 novel coumarin-quinolinium derivatives, leveraging our previously developed rG4-specific ligand, QUMA-1. Notably, several compounds exhibited potent antiproliferative activity against cancer cells as pan-KRAS translation inhibitors. Among them, 15a displayed exceptional capability in stabilizing KRAS rG4s, suppressing KRAS translation, and consequently modulating MAPK and PI3K-AKT pathways. 15a induced cell cycle arrest, prompted apoptosis in KRAS-driven cancer cells, and effectively inhibited tumor growth in a KRAS mutant xenograft model. These findings underscore the potential of 15a as a pan-KRAS translation inhibitor, offering a novel and promising approach to target various KRAS-driven cancers.


Subject(s)
G-Quadruplexes , Proto-Oncogene Proteins p21(ras) , Humans , Cell Line, Tumor , Proto-Oncogene Proteins p21(ras)/genetics , Proto-Oncogene Proteins p21(ras)/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Protein Synthesis Inhibitors , Mutation
19.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1019069

ABSTRACT

Objects To explore the effectiveness and safety of using the Cardio-O-Fix Plug occluder in the treatment of muscular ventricular septal defect(mVSD)in children.Methods 14 patients with mVSD were taken to the cardiology department of First Affiliated Hospital of Kunming Medical University from July 2015 to June 2021 as research subjects.They were divided into two groups:14 children who received Cardi-O-Fix Plug occluder as the experimental group,and 10 children who received Cardi-O-O-Fix mVSD occluder as the control group.Electrocardiogram and transthoracic echocardiography were used to evaluate the occlusive efficacy and incidence of complications 1 day after surgery and 1 month,3 months,and 6 months of follow-up.Results Among the 24 pediatric patients,22 cases were successfully occluded,and 2 cases were unsuccessful(1 in the experi-mental group and 1 in the control group).The success rate of the experimental group was 92.8%(13/14),while the success rate of the control group was 90.0%(9/10).The average surgical duration of the experimental group was(71.93±14.85)minutes,while the average surgical duration of the control group was(90.70±19.78)minutes.There was a significant statistical difference between the two groups(P<0.05).Both the experimental group and the control group did not experience serious complications during surgery and follow-up.There was no significant difference in cardiac ultrasound indicators(including left ventricular ejection fraction,left ventricular end-diastolic diameter,and pulmonary artery pressure)between the two groups at different time points(P>0.05).Conclusion Trans-catheter closure of mVSD using Cardi-O-Fix Plug occluder in children is both safe and effective.The incidence of arrhythmia is low in the short,medium and long term.

20.
Front Plant Sci ; 14: 1274337, 2023.
Article in English | MEDLINE | ID: mdl-38111884

ABSTRACT

Neomicrocalamus and Temochloa are closely related to bamboo genera. However, when considered with newly discovered and morphologically similar material from China and Vietnam, the phylogenetic relationship among these three groups was ambiguous in the analyses based on DNA regions. Here, as a means of investigating the relationships among the three bamboo groups and exploring potential sources of genomic conflicts, we present a phylogenomic examination based on the whole plastome, single-nucleotide polymorphism (SNP), and single-copy nuclear (SCN) gene datasets. Three different phylogenetic hypotheses were found. The inconsistency is attributed to the combination of incomplete lineage sorting and introgression. The origin of newly discovered bamboos is from introgressive hybridization between Temochloa liliana (which contributed 80.7% of the genome) and Neomicrocalamus prainii (19.3%), indicating that the newly discovered bamboos are closer to T. liliana in genetics. The more similar morphology and closer distribution elevation also imply a closer relationship between Temochloa and newly discovered bamboos.

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