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2.
PhytoKeys ; 241: 191-200, 2024.
Article En | MEDLINE | ID: mdl-38721013

A new spleenwort species, Aspleniumguodanum, was found and described from Danxia landform region in Guangdong, China. The new species has close resemblance to A.subcrenatum Ching ex S.H.Wu in morphology, but can be distinguished by having plants small, stipes and rachises not covered with fibrous scales, relatively fewer pairs of pinnae, pinnae short, pinna margin weakly biserrate, pinna apex acute and lower pinnae obviously reduced. Phylogenetic analyses, based on six plastid markers (atpB, rbcL, rps4 & rps4-trnS and trnL & trnL-F) of the new species and its relatives, support a close relationship between A.guodanum and A.subcrenatum. Only one population with no more than 50 individuals were found and, therefore, it is recommended to be classified as Critically Endangered (CR) following IUCN Red List Criteria.

3.
Mol Oncol ; 2024 May 21.
Article En | MEDLINE | ID: mdl-38770553

Accumulation of abnormal chondroitin sulfate (CS) chains in breast cancer tissue is correlated with poor prognosis. However, the biological functions of these CS chains in cancer progression remain largely unknown, impeding the development of targeted treatment focused on CS. Previous studies identified chondroitin polymerizing factor (CHPF; also known as chondroitin sulfate synthase 2) is the critical enzyme regulating CS accumulation in breast cancer tissue. We then assessed the association between CHPF-associated proteoglycans (PGs) and signaling pathways in breast cancer datasets. The regulation between CHPF and syndecan 1 (SDC1) was examined at both the protein and RNA levels. Confocal microscopy and image flow cytometry were employed to quantify macropinocytosis. The effects of the 6-O-sulfated CS-binding peptide (C6S-p) on blocking CS functions were tested in vitro and in vivo. Results indicated that the expression of CHPF and SDC1 was tightly associated within primary breast cancer tissue, and high expression of both genes exacerbated patient prognosis. Transforming growth factor beta (TGF-ß) signaling was implicated in the regulation of CHPF and SDC1 in breast cancer cells. CHPF supported CS-SDC1 stabilization on the cell surface, modulating macropinocytotic activity in breast cancer cells under nutrient-deprived conditions. Furthermore, C6S-p demonstrated the ability to bind CS-SDC1, increase SDC1 degradation, suppress macropinocytosis of breast cancer cells, and inhibit tumor growth in vivo. Although other PGs may also be involved in CHPF-regulated breast cancer malignancy, this study provides the first evidence that a CS synthase participates in the regulation of macropinocytosis in cancer cells by supporting SDC1 expression on cancer cells.

4.
Mol Med Rep ; 30(1)2024 07.
Article En | MEDLINE | ID: mdl-38757301

Psoriasis is a chronic inflammatory dermatological disease, and there is a lack of understanding of the genetic factors involved in psoriasis in Taiwan. To establish associations between genetic variations and psoriasis, a genome­wide association study was performed in a cohort of 2,248 individuals with psoriasis and 67,440 individuals without psoriasis. Using the ingenuity pathway analysis software, biological networks were constructed. Human leukocyte antigen (HLA) diplotypes and haplotypes were analyzed using Attribute Bagging (HIBAG)­R software and chi­square analysis. The present study aimed to assess the potential risks associated with psoriasis using a polygenic risk score (PRS) analysis. The genetic association between single nucleotide polymorphisms (SNPs) in psoriasis and various human diseases was assessed by phenome­wide association study. METAL software was used to analyze datasets from China Medical University Hospital (CMUH) and BioBank Japan (BBJ). The results of the present study revealed 8,585 SNPs with a significance threshold of P<5x10­8, located within 153 genes strongly associated with the psoriasis phenotype, particularly on chromosomes 5 and 6. This specific genomic region has been identified by analyzing the biological networks associated with numerous pathways, including immune responses and inflammatory signaling. HLA genotype analysis indicated a strong association between HLA­A*02:07 and HLA­C*06:02 in a Taiwanese population. Based on our PRS analysis, the risk of psoriasis associated with the SNPs identified in the present study was quantified. These SNPs are associated with various dermatological, circulatory, endocrine, metabolic, musculoskeletal, hematopoietic and infectious diseases. The meta­analysis results indicated successful replication of a study conducted on psoriasis in the BBJ. Several genetic loci are significantly associated with susceptibility to psoriasis in Taiwanese individuals. The present study contributes to our understanding of the genetic determinants that play a role in susceptibility to psoriasis. Furthermore, it provides valuable insights into the underlying etiology of psoriasis in the Taiwanese community.


Genetic Predisposition to Disease , Genome-Wide Association Study , Multifactorial Inheritance , Phenotype , Polymorphism, Single Nucleotide , Psoriasis , Humans , Psoriasis/genetics , Taiwan/epidemiology , Male , Female , Middle Aged , Adult , Risk Factors , Haplotypes , Genotype , HLA Antigens/genetics , Aged , Genetic Risk Score
5.
Arch Dermatol Res ; 316(6): 234, 2024 May 25.
Article En | MEDLINE | ID: mdl-38795240

In the field of alopecia areata research, various focuses including risk factors, epidemiology, molecular pathways, and treatment were constantly improving. However, to date, a bibliometric analysis summarizing the research trend is not available to date. The main objective of this study was to provide researchers with an overview of the research trend on alopecia areata in the past two decades. In Web of Science database, screening and extraction of studies related to alopecia areata has been performed. Within studies related to alopecia areata, the most cited 100 studies were appraised and the information of articles, including the citation amounts, keywords and publication types, was extracted for analyses. On average, each study in the top 100 list was cited 104.72 times. Within the top 100 list, the most focused fields were on the management of alopecia areata (34%), molecular mechanisms (28%) and epidemiological issues (23%). Approximately one third of the management-associated studies focused on Janus kinase (JAK) inhibitors (10 studies) and 5 studies focused on the efficacy of corticosteroids for alopecia areata. According to the results of the keyword analysis, JAK inhibitors had become the most mentioned keywords in the field of alopecia areata research since 2016. The top 100 most referenced papers in the field of alopecia areata mostly focused on essential aspects such as treatment options, pathogenesis, risk factors, and comorbidities. The results of the current study could be considered a potential resource for future research and patient care information.


Alopecia Areata , Bibliometrics , Alopecia Areata/epidemiology , Alopecia Areata/drug therapy , Humans , Cross-Sectional Studies , Janus Kinase Inhibitors/therapeutic use , Adrenal Cortex Hormones/therapeutic use , Biomedical Research/trends , Biomedical Research/statistics & numerical data
6.
J Hazard Mater ; 472: 134459, 2024 Jul 05.
Article En | MEDLINE | ID: mdl-38691999

Bioaerosols are widely distributed in urban air and can be transmitted across the atmosphere, biosphere, and anthroposphere, resulting in infectious diseases. Automobile air conditioning (AAC) filters can trap airborne microbes. In this study, AAC filters were used to investigate the abundance and pathogenicity of airborne microorganisms in typical Chinese and European cities. Culturable bacteria and fungi concentrations were determined using microbial culturing. High-throughput sequencing was employed to analyze microbial community structures. The levels of culturable bioaerosols in Chinese and European cities exhibited disparities (Analysis of Variance, P < 0.01). The most dominant pathogenic bacteria and fungi were similar in Chinese (Mycobacterium: 18.2-18.9 %; Cladosporium: 23.0-30.2 %) and European cities (Mycobacterium: 15.4-37.7 %; Cladosporium: 18.1-29.3 %). Bartonella, Bordetella, Alternaria, and Aspergillus were also widely identified. BugBase analysis showed that microbiomes in China exhibited higher abundances of mobile genetic elements (MGEs) and biofilm formation capacity than those in Europe, indicating higher health risks. Through co-occurrence network analysis, heavy metals such as zinc were found to correlate with microorganism abundance; most bacteria were inversely associated, while fungi exhibited greater tolerance, indicating that heavy metals affect the growth and reproduction of bioaerosol microorganisms. This study elucidates the influence of social and environmental factors on shaping microbial community structures, offering practical insights for preventing and controlling regional bioaerosol pollution.


Air Conditioning , Air Microbiology , Automobiles , Bacteria , Cities , Fungi , China , Europe , Bacteria/genetics , Bacteria/isolation & purification , Fungi/isolation & purification , Fungi/pathogenicity , Fungi/genetics , Air Filters/microbiology , Air Pollutants/analysis , Microbiota , Environmental Monitoring
7.
Complement Ther Med ; 82: 103049, 2024 Jun.
Article En | MEDLINE | ID: mdl-38729273

BACKGROUND AND PURPOSE: Acupuncture exerts an anti-inflammatory effect and is recommended by the World Health Organization as a complementary therapy for stroke. This study investigated the improvement in neurological function outcome in acute-stage intervention of acute ischemic stroke (AIS), and the anti-inflammatory effect of early acupuncture. METHODS: Fifty patients with AIS were randomly assigned to either a control group (CG, 25 patients, received sham acupuncture) or treatment group (TG, 25 patients, received acupuncture treatment). Acupuncture intervention was administered twice a week for a total of 8 sessions over 4 consecutive weeks. The primary outcome was the changes in the National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), and Barthel Index (BI) scores. The secondary outcome was the changes in serum inflammation-related biomarker levels.(ANAIS trial) RESULTS: A total of 35 patients (18 patients in the CG and 17 patients in the TG) completed the trial. The reduction in NIHSS scores was greater in the TG than in the CG between V2 (second assessment administered after acupuncture intervention) and V1 (first assessment administered before acupuncture intervention; 4.33 ± 1.91 vs. 2.68 ± 1.42, p = 0.005) and between V3 (third assessment administered 28 days after last acupuncture intervention) and V1 (6.00 ± 2.53 vs. 3.83 ± 2.31, p = 0.012). The increase in BI scores was greater in the TG than in the CG between V2 and V1 (28.89 ± 15.39 vs. 14.21 ± 19.38, p = 0.016) and between V3 and V1 (39.41 ± 20.98 vs. 25.00 ± 18.47, p = 0.038). Among participants with high inflammation, the increase in serum IL-12p70 level between V2 and V1 was greater in the TG than in the CG (0.20 ± 0.19 vs. -0.14 ± 0.30, pg/mL p = 0.006). CONCLUSIONS: Acupuncture improved the neurological function of patients with AIS, and the relationship between acupuncture improving neurological function and anti-inflammatory effect needs further study. In addition, studies with larger sample sizes and longer follow-ups as well as multicenter clinical trials are expected in the future.


Acupuncture Therapy , Ischemic Stroke , Humans , Acupuncture Therapy/methods , Male , Female , Ischemic Stroke/therapy , Middle Aged , Aged , Double-Blind Method , Treatment Outcome , Biomarkers/blood
8.
Ren Fail ; 46(1): 2337290, 2024 Dec.
Article En | MEDLINE | ID: mdl-38575339

Background: The aim of our study was to evaluate the effectiveness of Global Leadership Initiative on Malnutrition (GLIM) criteria in assessing malnutrition within the peritoneal dialysis (PD) population.Methods: We conducted a retrospective analysis involving 1057 PD patients across multiple institutions, characterized by an age of 56.1 ± 14.4 years, 464 (43.9%) female, and a median follow-up of 45 (25, 68) months. Malnutrition was diagnosed according to GLIM criteria. The endpoint event was overall mortality. The survival rate and hazard ratio (HR) of death between malnutrition and well-nourished were analyzed in all patients and various subgroups. Receiver operator characteristic curve and integrated discrimination improvement (IDI) were used to distinguish the efficacy of the nutritional tools prediction model.Results: According to the GLIM criteria, the prevalence of malnutrition among the study population was 34.9%. The adjusted HR of overall mortality was 2.91 (2.39 - 3.54, p < 0.001) for malnutrition versus well-nourished. In sensitivity analyses, the HR remained robust except the cardiovascular disease subgroup. The area under the curve of GLIM predicting 5-year mortality was 0.65 (0.62-0.68, p < 0.001). As a complex model for forecast the long-term mortality, the performance of adjusted factors combined with GLIM was poorer than combined malnutrition inflammation score (MIS) (IDI >0, p < 0.001), but fitter than combined geriatric nutritional risk index (GNRI) (IDI <0, p < 0.001).Conclusions: The GLIM criteria provide a viable tool for nutritional assessment in patients with PD, and malnutrition defined according to the GLIM can predict prognosis with an acceptable performance.


Malnutrition , Peritoneal Dialysis , Humans , Female , Aged , Adult , Middle Aged , Male , Nutrition Assessment , Leadership , Retrospective Studies , Malnutrition/diagnosis , Malnutrition/epidemiology , Malnutrition/etiology , Peritoneal Dialysis/adverse effects , Nutritional Status
9.
Orphanet J Rare Dis ; 19(1): 144, 2024 Apr 04.
Article En | MEDLINE | ID: mdl-38575988

BACKGROUND: Osteoporosis and its primary complication, fragility fractures, contribute to substantial global morbidity and mortality. Gaucher disease (GD) is caused by glucocerebrosidase (GBA1) deficiency, leading to skeletal complications. This study aimed to investigate the impact of the GBA1 gene on osteoporosis progression in GD patients and the specific populations. METHODS: We selected 8115 patients with osteoporosis (T-score ≤ - 2.5) and 55,942 healthy individuals (T-score > - 1) from a clinical database (N = 95,223). Monocytes from GD patients were evaluated in relation to endoplasmic reticulum (ER) stress, inflammasome activation, and osteoclastogenesis. An in vitro model of GD patient's cells treated with adeno-associated virus 9 (AAV9)-GBA1 to assess GBA1 enzyme activity, chitotriosidase activity, ER stress, and osteoclast differentiation. Longitudinal dual-energy X-ray absorptiometry (DXA) data tracking bone density in patients with Gaucher disease (GD) undergoing enzyme replacement therapy (ERT) over an extended period. RESULTS: The GBA1 gene variant rs11264345 was significantly associated [P < 0.002, Odds Ratio (OR) = 1.06] with an increased risk of bone disease. Upregulation of Calnexin, NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) and Apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC) was positively associated with osteoclastogenesis in patients with GD. In vitro AAV9-GBA1 treatment of GD patient cells led to enhanced GBA1 enzyme activity, reduced chitotriosidase activity, diminished ER stress, and decreased osteoclast differentiation. Long-term bone density data suggests that initiating ERT earlier in GD leads to greater improvements in bone density. CONCLUSIONS: Elevated ER stress and inflammasome activation are indicative of osteoporosis development, suggesting the need for clinical monitoring of patients with GD. Furthermore, disease-associated variant in the GBA1 gene may constitute a risk factor predisposing specific populations to osteoporosis.


Gaucher Disease , Osteoporosis , Humans , Bone Density/genetics , Gaucher Disease/drug therapy , Glucosylceramidase/therapeutic use , Inflammasomes , Osteoporosis/genetics , Osteoporosis/drug therapy
10.
JMIR Serious Games ; 12: e44025, 2024 Apr 16.
Article En | MEDLINE | ID: mdl-38634461

Background: Surgery is an essential treatment for early-stage breast cancer. However, various side effects of breast cancer surgery, such as arm dysfunction and lymphedema, remain causes for concern. Rehabilitation exercises to prevent such side effects should be initiated within 24 hours after surgery. Virtual reality (VR) can assist the process of rehabilitation; however, the feasibility of applying VR for rehabilitation must be explored, in addition to experiences of this application. Objective: This study explored patients' attitudes toward and experiences of using VR for their rehabilitation to determine the feasibility of such VR use and to identify potential barriers. Methods: A phenomenological qualitative study was conducted from September to December 2021. A total of 18 patients with breast cancer who had undergone surgical treatment were interviewed using open-ended questions. The Colaizzi 7-step procedure for phenomenological analysis was used for data analysis. To ensure high study reliability, this study followed previously reported quality criteria for trustworthiness. Results: Three themes were identified: (1) VR was powerful in facilitating rehabilitation, (2) early and repetitive upper limb movements were an advantage of VR rehabilitation, and (3) extensive VR use had challenges to be overcome. Most of the interviewed patients reported positive experiences of using VR for rehabilitation. Specifically, VR helped these patients identify appropriate motion and angle limits while exercising; in other words, knowledge gained through VR can play a key role in the rehabilitation process. In addition, the patients reported that the use of VR provided them company, similar to when a physiotherapist is present. Finally, the gamified nature of the VR system seemed to make VR-based rehabilitation more engaging than traditional rehabilitation, particularly with respect to early rehabilitation; however, the high cost of VR equipment made VR-based rehabilitation difficult to implement at home. Conclusions: The interviewed patients with breast cancer had positive experiences in using VR for rehabilitation. The high cost of both VR equipment and software development presents a challenge for applying VR-based rehabilitation.

11.
Int J Mol Sci ; 25(6)2024 Mar 12.
Article En | MEDLINE | ID: mdl-38542204

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly worldwide. The prevalence and phenotypes of AMD differ among populations, including between people in Taiwan and other regions. We performed a genome-wide association study to identify genetic variants and to develop genetic models to predict the risk of AMD development and progression in the Taiwanese population. In total, 4039 patients with AMD and 16,488 non-AMD controls (aged ≥ 65 years) were included. We identified 31 AMD-associated variants (p < 5 × 10-8) on chromosome 10q26, surrounding PLEKHA1-ARMS2-HTRA1. Two genetic models were constructed using the clump and threshold method. Model 1 included the single nucleotide polymorphism rs11200630 and showed a 1.31-fold increase in the risk of AMD per risk allele (95% confidence interval (CI) = 1.20-1.43, p < 0.001). In model 2, 1412 single-nucleotide polymorphisms were selected to construct a polygenic risk score (PRS). Individuals with the top 5% PRS had a 1.40-fold higher AMD risk compared with that of individuals with a PRS in the bottom quartile (95% CI = 1.04-1.89, p = 0.025). Moreover, the PRS in the upper quartile was related to a decreased age at AMD diagnosis by 0.62 years (95% CI = -1.15, -0.09, p = 0.023). Both genetic models provide useful predictive power for populations at high risk of AMD, affording a basis for identifying patients requiring close follow-up and early intervention.


Macular Degeneration , Proteins , Aged , Humans , Proteins/genetics , Genome-Wide Association Study , Macular Degeneration/diagnosis , Macular Degeneration/epidemiology , Macular Degeneration/genetics , High-Temperature Requirement A Serine Peptidase 1/genetics , Polymorphism, Single Nucleotide , Early Diagnosis , Genetic Predisposition to Disease , Risk Factors , Genotype
12.
Nutrition ; 117: 112227, 2024 Jan.
Article En | MEDLINE | ID: mdl-38486479

OBJECTIVE: Radiation for locally advanced esophageal squamous cell carcinoma often is accompanied by radiation esophagitis, which interferes with oral intake. We aimed to develop a nomogram model to identify initially inoperable patients with relative and absolute weight loss who need prophylactic nutritional supplementation. METHODS: A total of 365 initially inoperable patients with locally advanced esophageal squamous cell carcinoma receiving radiotherapy between January 2018 and December 2022 were included in the study, which was divided into discovery and validation cohorts. Receiver operating characteristic and Kaplan-Meier curve analyses were performed to compare the areas under the curve and survival benefits. RESULTS: A total of 42.2% (154 of 365) of the patients had been diagnosed with cancer cachexia. The malnourished group had a higher interruption rate of radiotherapy and number of complication diseases (P < 0.05). Meanwhile, patients with malnutrition had lower lymphocytes and prognostic nutritional index (P < 0.05). The combined index showed a higher area under the curve value (0.67; P < 0.001) than number of complication diseases (area under the curve = 0.52) and prognostic nutritional index (area under the curve = 0.49) for relative weight loss (≥ 5%). Similarly, the combined index had a higher area under the curve value (0.79; P < 0.001) than number of complication diseases (area under the curve = 0.56), treatment regimens (area under the curve = 0.56), subcutaneous fat thickness (area under the curve = 0.60), pretreatment body weight (area under the curve = 0.61), neutrophils (area under the curve = 0.56), and prognostic nutritional index (area under the curve = 0.50) for absolute weight loss (≥ 5 kg). Absolute and relative weight loss remained independent prognostic factors, with short overall survival rates compared with the normal group (P < 0.05). Patients with high nomogram scores supported by nutritional intervention had less weight loss, better nutrition scores, and increased plasma CD8+ T cells, and interferon gamma. CONCLUSIONS: We developed a nomogram model that was intended to estimate relative and absolute weight loss in initially inoperable patients with locally advanced esophageal squamous cell carcinoma during radiotherapy, which might help facilitate an objective decision on prophylactic nutritional supplementation.


Carcinoma, Squamous Cell , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Humans , Esophageal Squamous Cell Carcinoma/radiotherapy , Nomograms , Esophageal Neoplasms/complications , Esophageal Neoplasms/radiotherapy , Carcinoma, Squamous Cell/radiotherapy , Carcinoma, Squamous Cell/drug therapy , Weight Loss
13.
J Obstet Gynaecol ; 44(1): 2320844, 2024 Dec.
Article En | MEDLINE | ID: mdl-38466187

BACKGROUND: The Menstrual Distress Questionnaire (MDQ) is a commonly used questionnaire that assesses various symptoms and distress associated with the menstrual cycle in women. However, the questionnaire has not been completely translated into Chinese with rigorous reliability and validity testing. METHODS: This study translated the Menstrual Distress Questionnaire Form Cycle (MDQC) from English into Chinese: MDQCC in two stages. First, it was translated forward and backward using Jones' model; second, to test the validity and reliability, 210 Chinese-speaking women were recruited through online announcements and posters posted between June 2019 and May 2020. Expert validity, construct validity, convergent validity, and factorial validity were determined using content validity index (CVI), intraclass correlation coefficient (ICC), composite reliability (CR), and exploratory factor analysis, respectively. For concurrent criterion validity, MDQCC score was compared with three existing pain scales. Reliability was evaluated using internal consistency across items and two-week test-retest reliability over time. RESULTS: The CVI for content validity was .92. Item-CVI for expert validities among the 46 items ranged from .50 - 1; scale-CVI for the eight subscales, from .87 - 1; ICC, from .650 - .897; and CRs, from .303 - .881. Pearson correlation coefficients between MDQCC and short-form McGill pain questionnaire, present pain intensity, and visual analog scale scores were .640, .519, and .575, respectively. Cronbach's α for internal consistency was satisfactory (.932). ICC for test-retest reliability was .852 for the entire MDQCC. CONCLUSION: MDQCC was valid and reliable for Mandarin Chinese-speaking women. It can be used to evaluate female psychiatric symptoms related to the menstrual cycle in future work.


The Menstrual Distress Questionnaire has been used to evaluate menstrual distress, including dysmenorrhoea and premenstrual syndrome. This questionnaire has been translated into Persian, Korean, Japanese, and Cantonese, rendering it to be used more and more widely all over the world. The study translated all 46 items of the Menstrual Distress Questionnaire from English to Mandarin Chinese using a two-stage strategy. The Chinese version of this questionnaire developed by the present study was found to be a valid and reliable tool in Chinese Mandarin-speaking female populations. It could be used to evaluate women's physical and psychiatric symptoms related to the menstrual cycle in future works.


Asian People , Menstrual Cycle , Female , Humans , Correlation of Data , Factor Analysis, Statistical , Reproducibility of Results
14.
Nat Med ; 30(4): 1035-1043, 2024 Apr.
Article En | MEDLINE | ID: mdl-38438735

Epigenetic modifications of chromatin, including histone acetylation, and tumor angiogenesis play pivotal roles in creating an immunosuppressive tumor microenvironment. In the randomized phase 2 CAPability-01 trial, we investigated the potential efficacy of combining the programmed cell death protein-1 (PD-1) monoclonal antibody sintilimab with the histone deacetylase inhibitor (HDACi) chidamide with or without the anti-vascular endothelial growth factor (VEGF) monoclonal antibody bevacizumab in patients with unresectable chemotherapy-refractory locally advanced or metastatic microsatellite stable/proficient mismatch repair (MSS/pMMR) colorectal cancer. Forty-eight patients were randomly assigned to either the doublet arm (sintilimab and chidamide, n = 23) or the triplet arm (sintilimab, chidamide and bevacizumab, n = 25). The primary endpoint of progression-free survival (PFS) rate at 18 weeks (18wPFS rate) was met with a rate of 43.8% (21 of 48) for the entire study population. Secondary endpoint results include a median PFS of 3.7 months, an overall response rate of 29.2% (14 of 48), a disease control rate of 56.3% (27 of 48) and a median duration of response of 12.0 months. The secondary endpoint of median overall survival time was not mature. The triplet arm exhibited significantly improved outcomes compared to the doublet arm, with a greater 18wPFS rate (64.0% versus 21.7%, P = 0.003), higher overall response rate (44.0% versus 13.0%, P = 0.027) and longer median PFS rate (7.3 months versus 1.5 months, P = 0.006). The most common treatment-emergent adverse events observed in both the triplet and doublet arms included proteinuria, thrombocytopenia, neutropenia, anemia, leukopenia and diarrhea. There were two treatment-related fatalities (hepatic failure and pneumonitis). Analysis of bulk RNA sequencing data from the patients suggested that the triplet combination enhanced CD8+ T cell infiltration, resulting in a more immunologically active tumor microenvironment. Our study suggests that the combination of a PD-1 antibody, an HDACi, and a VEGF antibody could be a promising treatment regimen for patients with MSS/pMMR advanced colorectal cancer. ClinicalTrials.gov registration: NCT04724239 .


Aminopyridines , Benzamides , Colorectal Neoplasms , Histone Deacetylase Inhibitors , Humans , Antibodies, Monoclonal/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bevacizumab/adverse effects , Bevacizumab/therapeutic use , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Histone Deacetylase Inhibitors/adverse effects , Histone Deacetylase Inhibitors/therapeutic use , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Programmed Cell Death 1 Receptor/metabolism , Tumor Microenvironment , Vascular Endothelial Growth Factor A
15.
World J Clin Cases ; 12(6): 1144-1149, 2024 Feb 26.
Article En | MEDLINE | ID: mdl-38464923

BACKGROUND: This study presents a case of rapidly developing respiratory failure due to antisynthetase syndrome (AS) following coronavirus disease 2019 (COVID-19) in a 33-year-old man diagnosed with Klinefelter syndrome (KS). CASE SUMMARY: A 33-year-old man with a diagnosis of KS was admitted to the Department of Pulmonary and Critical Care Medicine of a tertiary hospital in China for fever and shortness of breath 2 wk after the onset of COVID-19. Computed tomography of both lungs revealed diffuse multiple patchy heightened shadows in both lungs, accompanied by signs of partial bronchial inflation. Metagenomic next-generation sequencing of the bronchoalveolar lavage fluid suggested absence of pathogen. A biopsy specimen revealed organizing pneumonia with alveolar septal thickening. Additionally, extensive auto-antibody tests showed strong positivity for anti-SSA, anti-SSB, anti-Jo-1, and anti-Ro-52. Following multidisciplinary discussions, the patient received a final diagnosis of AS, leading to rapidly progressing respiratory failure. CONCLUSION: This study underscores the clinical progression of AS-associated interstitial lung disease subsequent to viral infections such as COVID-19 in patients diagnosed with KS.

16.
Cancers (Basel) ; 16(3)2024 Feb 03.
Article En | MEDLINE | ID: mdl-38339408

Hypoxia-inducible factor 1α (HIF-1α) plays a pivotal role in the survival, metastasis, and response to treatment of solid tumors. Autophagy serves as a mechanism for tumor cells to eliminate misfolded proteins and damaged organelles, thus promoting invasiveness, metastasis, and resistance to treatment under hypoxic conditions. MicroRNA (miRNA) research underscores the significance of these non-coding molecules in regulating cancer-related protein synthesis across diverse contexts. However, there is limited reporting on miRNA-mediated gene expression studies, especially with respect to epithelial-mesenchymal transition (EMT) and autophagy in the context of hypoxic breast cancer. Our study reveals decreased levels of miRNA-622 (miR-622) and miRNA-30a (miR-30a) in invasive breast cancer cells compared to their non-invasive counterparts. Inducing miR-622 suppresses HIF-1α protein expression, subsequently activating miR-30a transcription. This cascade results in reduced invasiveness and migration of breast cancer cells by inhibiting EMT markers, such as Snail, Slug, and vimentin. Furthermore, miR-30a negatively regulates beclin 1, ATG5, and LC3-II and inhibits Akt protein phosphorylation. Consequently, this improves the sensitivity of invasive MDA-MB-231 cells to docetaxel treatment. In conclusion, our study highlights the therapeutic potential of inducing miR-622 to promote miR-30a expression and thus disrupt HIF-1α-associated EMT and autophagy pathways. This innovative strategy presents a promising approach to the treatment of aggressive breast cancer.

17.
Am J Physiol Endocrinol Metab ; 326(5): E547-E554, 2024 May 01.
Article En | MEDLINE | ID: mdl-38363735

Type 2 diabetes (T2D) prevalence in adults at a younger age has increased but the disease status may go unnoticed. This study aimed to determine whether the onset age and subsequent diabetic complications can be attributed to the polygenic architecture of T2D in the Taiwan Han population. A total of 9,627 cases with T2D and 85,606 controls from the Taiwan Biobank were enrolled. Three diabetic polygenic risk scores (PRSs), PRS_EAS and PRS_EUR, and a trans-ancestry PRS (PRS_META), calculated using summary statistic from East Asian and European populations. The onset age was identified by linking to the National Taiwan Insurance Research Database, and the incidence of different diabetic complications during follow-up was recorded. PRS_META (7.4%) explained a higher variation for T2D status. And the higher percentile of PRS is also correlated with higher percentage of T2D family history and prediabetes status. More, the PRS was negatively associated with onset age (ß = -0.91 yr), and this was more evident among males (ß = -1.11 vs. -0.76 for males and females, respectively). The hazard ratio of diabetic retinopathy (DR) and diabetic foot were significantly associated with PRS_EAS and PRS_META, respectively. However, the PRS was not associated with other diabetic complications, including diabetic nephropathy, cardiovascular disease, and hypertension. Our findings indicated that diabetic PRS which combined susceptibility variants from cross-population could be used as a tool for early screening of T2D, especially for high-risk populations, such as individuals with high genetic risk, and may be associated with the risk of complications in subjects with T2D. NEW & NOTEWORTHY Our findings indicated that diabetic polygenic risk score (PRS) which combined susceptibility variants from Asian and European population affect the onset age of type 2 diabetes (T2D) and could be used as a tool for early screening of T2D, especially for individuals with high genetic risk, and may be associated with the risk of diabetic complications among people in Taiwan.


Diabetes Mellitus, Type 2 , Diabetic Retinopathy , Male , Adult , Female , Humans , Diabetes Mellitus, Type 2/genetics , Genetic Risk Score , Taiwan , Genetic Predisposition to Disease , Age of Onset , Polymorphism, Single Nucleotide , Genome-Wide Association Study , Risk Factors
18.
PhytoKeys ; 237: 245-255, 2024.
Article En | MEDLINE | ID: mdl-38333589

A new species of the genus Camellia (Theaceae), Camelliazijinica, discovered in the Danxia landscape from Guangdong Province, China, is characterized and illustrated. Phylogenetic analysis based on chloroplast genomes suggested its affinity with C.drupifera, C.oleifera and C.fluviatilis, however, it morphologically differs from all of the latter by leaf shape and size. Phonologically, it most closely resembles C.microphylla, but can be distinguished from the latter by its young branchlets glabrous (vs. densely pubescent), fewer bracteoles and sepals, diverse leaf shape, midvein raised slightly with sparsely pubescent or glabrous (vs. prominently with densely pubescent) and leaf adaxially matt (vs. vernicose) when dried. By morphological and molecular analyses, Camelliazijinica represented a distinct new species of C.sect.Paracamellia.

19.
PhytoKeys ; 237: 257-268, 2024.
Article En | MEDLINE | ID: mdl-38333592

Lysimachiadanxiashanensis, a new Primulaceae species, endemic to the Danxia landscape in Guangdong Province, China, is described and illustrated. This new species is morphologically similar to L.pseudohenryi, L.phyllocephala, L.congestiflora and L.kwangtungensis, but it differs from the similar species by its purplish-red plants, petiole without wings, calyx with orange glandular and the corolla margin serrated on upper half with orange-red glandular punctates. This new species belongs to Lysimachiasubgen.Lysimachiasect.Nummularia. Phylogenetic analysis confirmed that L.danxiashanensis is a distinct clade, based on the combined data of ITS and rbcL sequences. The conservation status of the new species was evaluated as Endangered (EN) according to IUCN Red List Categories and Criteria.

20.
World Neurosurg ; 185: 115-125, 2024 May.
Article En | MEDLINE | ID: mdl-38237801

BACKGROUND: Noncontiguous 2-level cervical disc herniation (NCT-CDH) is a common condition that often requires surgical intervention. In this study, we developed a surgical approach for the treatment of NCT-CDH using anterior percutaneous full-endoscopic single incision through the vertebral body. We provide a brief overview of its safety, efficacy, and feasibility, along with a description of our relevant surgical experience. METHODS: A retrospective study was conducted, involving 30 patients who were followed up for at least 12 months. Preoperative and postoperative visual analog scale, Japanese Orthopedic Association scores, Nurick scores, intervertebral disc height, and modified Macnab criteria were recorded. Patients underwent regular radiological evaluations throughout the follow-up period. RESULTS: Postoperative computed tomography, magnetic resonance imaging, and X-ray examinations revealed bone tunnel healing, intact drilled vertebral bodies without collapse, adequate decompression of the spinal canal, and normal cervical mobility. There was a significant improvement in postoperative visual analog scale, Japanese Orthopedic Association scores, Nurick scores, and modified Macnab criteria compared to the preoperative values (P < 0.05). CONCLUSIONS: Our study revealed that the anterior percutaneous full-endoscopic transcorporeal with single-incision treatment for NCT-CDH is a safe and feasible surgical method. Therefore, it can be considered as a viable treatment option for patients with NCT-CDH.


Cervical Vertebrae , Intervertebral Disc Displacement , Humans , Intervertebral Disc Displacement/surgery , Intervertebral Disc Displacement/diagnostic imaging , Male , Female , Middle Aged , Cervical Vertebrae/surgery , Cervical Vertebrae/diagnostic imaging , Retrospective Studies , Adult , Follow-Up Studies , Treatment Outcome , Aged , Endoscopy/methods , Diskectomy, Percutaneous/methods
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