ABSTRACT
BACKGROUND: Epilepsy is a widespread central nervous system disorder with an estimated 50 million people affected globally. It is characterized by a bimodal incidence peak among infants and the elderly and is influenced by a variety of risk factors, including a significant genetic component. Despite the use of anti-epileptic drugs (AEDs), drug-refractory epilepsy develops in about one-third of patients, highlighting the need for alternative therapeutic approaches. AIMS: The primary aim of this study was to evaluate the neuroprotective effects of troglitazone (TGZ) in epilepsy and to explore the potential mechanisms underlying its action. METHODS: We employed both in vitro and in vivo models to assess TGZ's effects. The in vitro model involved glutamate-induced toxicity in HT22 mouse hippocampal neurons, while the in vivo model used kainic acid (KA) to induce epilepsy in mice. A range of methods, including Hoechst/PI staining, CCK-8 assay, flow cytometry, RT-PCR analysis, Nissl staining, scanning electron microscopy, and RNA sequencing, were utilized to assess various parameters such as cellular damage, viability, lipid-ROS levels, mitochondrial membrane potential, mRNA expression, seizure grade, and mitochondrial morphology. RESULTS: Our results indicate that TGZ, at doses of 5 or 20 mg/kg/day, significantly reduces KA-induced seizures and neuronal damage in mice by inhibiting the process of ferroptosis. Furthermore, TGZ was found to prevent changes in mitochondrial morphology. In the glutamate-induced HT22 cell damage model, 2.5 µM TGZ effectively suppressed neuronal ferroptosis, as shown by a reduction in lipid-ROS accumulation, a decrease in mitochondrial membrane potential, and an increase in PTGS2 expression. The anti-ferroptotic effect of TGZ was confirmed in an erastin-induced HT22 cell damage model as well. Additionally, TGZ reversed the upregulation of Plaur expression in HT22 cells treated with glutamate or erastin. The downregulation of Plaur expression was found to alleviate seizures and reduce neuronal damage in the mouse hippocampus. CONCLUSION: This study demonstrates that troglitazone has significant therapeutic potential in the treatment of epilepsy by reducing epileptic seizures and the associated brain damage through the inhibition of neuronal ferroptosis. The downregulation of Plaur expression plays a crucial role in TGZ's anti-ferroptotic effect, offering a promising avenue for the development of new epilepsy treatments.
Subject(s)
Epilepsy , Ferroptosis , Neuroprotective Agents , Troglitazone , Animals , Mice , Epilepsy/drug therapy , Epilepsy/chemically induced , Ferroptosis/drug effects , Ferroptosis/physiology , Neuroprotective Agents/pharmacology , Neurons/drug effects , Neurons/metabolism , Hippocampus/drug effects , Hippocampus/pathology , Hippocampus/metabolism , Glutamic Acid/metabolism , Male , Kainic Acid/toxicity , Mice, Inbred C57BL , Membrane Potential, Mitochondrial/drug effects , Anticonvulsants/pharmacology , Anticonvulsants/therapeutic useABSTRACT
BACKGROUND: Tuberculosis (TB) remains a pressing public health issue, posing a significant threat to individuals' well-being and lives. This study delves into the TB incidence in Chinese mainland during 2014-2021, aiming to gain deeper insights into their epidemiological characteristics and explore macro-level factors to enhance control and prevention. METHODS: TB incidence data in Chinese mainland from 2014 to 2021 were sourced from the National Notifiable Disease Reporting System (NNDRS). A two-stage distributed lag nonlinear model (DLNM) was constructed to evaluate the lag and non-linearity of daily average temperature (â, Atemp), average relative humidity (%, ARH), average wind speed (m/s, AWS), sunshine duration (h, SD) and precipitation (mm, PRE) on the TB incidence. A spatial panel data model was used to assess the impact of demographic, medical and health resource, and economic factors on TB incidence. RESULTS: A total of 6,587,439 TB cases were reported in Chinese mainland during 2014-2021, with an average annual incidence rate of 59.17/100,000. The TB incidence decreased from 67.05/100,000 in 2014 to 46.40/100,000 in 2021, notably declining from 2018 to 2021 (APC = -8.87%, 95% CI: -11.97, -6.85%). TB incidence rates were higher among males, farmers, and individuals aged 65 years and older. Spatiotemporal analysis revealed a significant cluster in Xinjiang, Qinghai, and Xizang from March 2017 to June 2019 (RR = 3.94, P < 0.001). From 2014 to 2021, the proportion of etiologically confirmed cases increased from 31.31% to 56.98%, and the time interval from TB onset to diagnosis shortened from 26 days (IQR: 10-56 days) to 19 days (IQR: 7-44 days). Specific meteorological conditions, including low temperature (< 16.69â), high relative humidity (> 71.73%), low sunshine duration (< 6.18 h) increased the risk of TB incidence, while extreme low wind speed (< 2.79 m/s) decreased the risk. The spatial Durbin model showed positive associations between TB incidence rates and sex ratio (ß = 1.98), number of beds in medical and health institutions per 10,000 population (ß = 0.90), and total health expenses (ß = 0.55). There were negative associations between TB incidence rates and population (ß = -1.14), population density (ß = -0.19), urbanization rate (ß = -0.62), number of medical and health institutions (ß = -0.23), and number of health technicians per 10,000 population (ß = -0.70). CONCLUSIONS: Significant progress has been made in TB control and prevention in China, but challenges persist among some populations and areas. Varied relationships were observed between TB incidence and factors from meteorological, demographic, medical and health resource, and economic aspects. These findings underscore the importance of ongoing efforts to strengthen TB control and implement digital/intelligent surveillance for early risk detection and comprehensive interventions.
Subject(s)
Tuberculosis , Humans , Incidence , China/epidemiology , Tuberculosis/epidemiology , Tuberculosis/prevention & control , Male , Female , Middle Aged , Adult , Aged , Child, Preschool , Child , Adolescent , Young Adult , Infant , Infant, Newborn , Aged, 80 and over , Risk Factors , East Asian PeopleABSTRACT
Whether stem-cell-like cancer cells avert ferroptosis to mediate therapy resistance remains unclear. In this study, using a soft fibrin gel culture system, we found that tumor-repopulating cells (TRCs) with stem-cell-like cancer cell characteristics resist chemotherapy and radiotherapy by decreasing ferroptosis sensitivity. Mechanistically, through quantitative mass spectrometry and lipidomic analysis, we determined that mitochondria metabolic kinase PCK2 phosphorylates and activates ACSL4 to drive ferroptosis-associated phospholipid remodeling. TRCs downregulate the PCK2 expression to confer themselves on a structural ferroptosis-resistant state. Notably, in addition to confirming the role of PCK2-pACSL4(T679) in multiple preclinical models, we discovered that higher PCK2 and pACSL4(T679) levels are correlated with better response to chemotherapy and radiotherapy as well as lower distant metastasis in nasopharyngeal carcinoma cohorts.
ABSTRACT
Peritoneal metastasis (PM) is considered one of the most dreaded forms of cancer metastases for both patients and physicians. Aggressive cytoreductive surgery (CRS) is the primary treatment for peritoneal metastasis. Unfortunately, this intensive treatment frequently causes clinical complications, such as postoperative recurrence, metastasis, and adhesion formation. Emerging evidence suggests that neutrophil extracellular traps (NETs) released by inflammatory neutrophils contribute to these complications. Effective NET-targeting strategies thus show considerable potential in counteracting these complications but remain challenging. Here, one type of sulfoxide-containing homopolymer, PMeSEA, with potent fouling-resistant and NET-inhibiting capabilities, is synthesized and screened. Hydrating sulfoxide groups endow PMeSEA with superior nonfouling ability, significantly inhibiting protein/cell adhesion. Besides, the polysulfoxides can be selectively oxidized by ClO- which is required to stabilize the NETs rather than H2O2, and ClO- scavenging effectively inhibits NETs formation without disturbing redox homeostasis in tumor cells and quiescent neutrophils. As a result, PMeSEA potently prevents postoperative adhesions, significantly suppresses peritoneal metastasis, and shows synergetic antitumor activity with chemotherapeutic 5-Fluorouracil. Moreover, coupling CRS with PMeSEA potently inhibits CRS-induced tumor metastatic relapse and postoperative adhesions. Notably, PMeSEA exhibits low in vivo acute and subacute toxicities, implying significant potential for clinical postoperative adjuvant treatment.
Subject(s)
Extracellular Traps , Neutrophils , Extracellular Traps/metabolism , Extracellular Traps/drug effects , Animals , Mice , Neutrophils/drug effects , Neutrophils/metabolism , Humans , Tissue Adhesions/prevention & control , Cell Line, Tumor , Neoplasm Recurrence, Local/prevention & control , Biofouling/prevention & control , Polymers/chemistry , Peritoneal Neoplasms/secondary , Peritoneal Neoplasms/drug therapy , Peritoneal Neoplasms/prevention & control , Neoplasm Metastasis/prevention & control , Cell Adhesion/drug effects , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacologyABSTRACT
In recent years, the significant impact of lactate in the tumor microenvironment has been greatly documented. Acting not only as an energy substance in tumor metabolism, lactate is also an imperative signaling molecule. It plays key roles in metabolic remodeling, protein lactylation, immunosuppression, drug resistance, epigenetics and tumor metastasis, which has a tight relation with cancer patients' poor prognosis. This review illustrates the roles lactate plays in different aspects of tumor progression and drug resistance. From the comprehensive effects that lactate has on tumor metabolism and tumor immunity, the therapeutic targets related to it are expected to bring new hope for cancer therapy.
Subject(s)
Drug Resistance, Neoplasm , Lactic Acid , Neoplasms , Tumor Microenvironment , Humans , Clinical Relevance , Lactic Acid/metabolism , Neoplasms/metabolism , Neoplasms/pathology , Neoplasms/genetics , Neoplasms/drug therapy , Signal TransductionABSTRACT
Green hydrogen production through electrochemical overall water splitting has suffered from sluggish oxygen evolution reaction (OER) kinetics, inferior conversion efficiency, and high cost. Herein, ultrafine PtIr clusters are synthesized via an electrodeposition method and decorated on the Co3O4 nanoflowers assembled by nanowires (PtIr-Co3O4). The encouraging performances in electrochemical OER and hydrogen evolution reaction (HER) are achieved over the PtIr-Co3O4 catalyst, with the overpotentials as low as 410 and 237â mV at 100â mA cm-2, respectively, outperforming the commercial IrO2 and Pt/C catalysts. Due to the ultralow loading of PtIr clusters, the PtIr-Co3O4 catalyst exhibits 1270â A gIr -1 for OER at the overpotential of 400â mV. Our detailed analyses also show that the strong interactions between the ultrafine PtIr clusters and the Co3O4 nanoflowers enable the PtIr-Co3O4 catalyst to afford 10â mA cm-2 for the overall water splitting at the potential of 1.57â V, accompanied by high durability for 100â h.
ABSTRACT
Background: The coexistence of emphysema and lung nodules could interact with each other and then lead to potential higher lung cancer risk. The study aimed to explore the association between emphysema combined with lung nodules and lung cancer risk. Methods: A total of 21,949 participants from the National Lung Screening Trial (NLST) who underwent low-dose computed tomography (LDCT) examination were included. Participants were categorized into four groups (NENN group (non-emphysema and non-nodules), E group (emphysema without nodules), N group (nodules without emphysema), and E + N group (nodules with emphysema)) according to whether there were lung nodules and emphysema. Multivariable Cox regression and stratified analyses were performed to estimate the association between the four groups and lung cancer risk. Results: Among the 21,949 participants, there were 9,040 (41.2%), 5,819 (26.5%), 4,737 (21.6%), and 2,353 (10.7%) participants in the NENN group, E group, N group, and E + N group. The risk of lung cancer incidence increased in turn in NENN group, E group, N group and E + N group. Compared with NENN group, the age-adjusted hazard ratios (HRs) (95% confidence intervals (CIs)) of lung cancer incidence were 2.07 (1.69 - 2.54) for E group, 4.13 (3.47 - 5.05) for N group, and 6.26 (5.14 - 7.62) for E + N group. The association was robust to adjustment for potential confounders (1.83 (1.47 - 2.27) for E group, 3.97 (3.24 - 4.86) for N group, and 5.23 (4.28 - 6.48) for E + N group). Comparable results as the lung cancer incidence were observed for lung cancer mortality, whether in age-adjusted model (E group: 1.85 (1.39 - 2.46), N group: 2.49 (1.89 - 3.29), E + N group: 4.27 (3.21 - 5.68)) or fully adjusted model (E group: 1.56 (1.15 - 2.11), N group: 2.43 (1.81 - 3.26), E + N group: 3.39 (2.50 - 4.61)). However, the trend of all-cause mortality risk among the four groups was somewhat different from that of lung cancer risk, whether in age-adjusted model (1.37 (1.21 - 1.54) for E group, 1.06 (0.92 - 1.21) for N group, and 1.75 (1.51 - 2.02) for E + N group) or fully adjusted model (1.26 (1.10 - 1.44) for E group, 1.09 (0.94 - 1.27) for N group, and 1.52 (1.30 - 1.79) for E + N group). Conclusion: Based on a large-scale lung cancer screening trial in the United States, this study demonstrated that either emphysema or lung nodules can increase lung cancer risk, and lung nodules combined with emphysema can further increase the lung cancer risk and all-cause mortality. The significance of these findings for lung cancer screening should be evaluated.
ABSTRACT
Dysregulated hematopoietic niches remodeled by leukemia cells lead to imbalances in immunological mediators that support leukemogenesis and drug resistance. Targeting immune niches may ameliorate disease progression and tyrosine kinase inhibitor (TKI) resistance in Philadelphia chromosome-positive B-ALL (Ph+ B-ALL). Here, we show that T helper type 17 (Th17) cells and IL-17A expression are distinctively elevated in Ph+ B-ALL patients. IL-17A promotes the progression of Ph+ B-ALL. Mechanistically, IL-17A activates BCR-ABL, IL6/JAK/STAT3, and NF-kB signalling pathways in Ph+ B-ALL cells, resulting in robust cell proliferation and survival. In addition, IL-17A-activated Ph+ B-ALL cells secrete the chemokine CXCL16, which in turn promotes Th17 differentiation, attracts Th17 cells and forms a positive feedback loop supporting leukemia progression. These data demonstrate an involvement of Th17 cells in Ph+ B-ALL progression and suggest potential therapeutic options for Ph+ B-ALL with Th17-enriched niches.
Subject(s)
Philadelphia Chromosome , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Humans , Imatinib Mesylate/pharmacology , Imatinib Mesylate/therapeutic use , Fusion Proteins, bcr-abl/genetics , Interleukin-17/genetics , Drug Resistance, Neoplasm/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , Acute DiseaseABSTRACT
Cancer-associated fibroblast (CAF) has emerged as a key contributor to the remodeling of tumor microenvironment through the expression and secretion of extracellular matrix (ECM) proteins, thereby promoting carcinogenesis. However, the precise contribution of ECM proteins from CAFs to gastric carcinogenesis remains poorly understood. In this study, we find that matrilin-3 (MATN3), an upregulated ECM protein associated with poorer prognosis in gastric cancer patients, originates from CAFs in gastric cancer tissues. Ectopic expression of MATN3 in CAFs significantly promotes the invasion of gastric cancer cells, which can be attenuated by neutralizing MATN3 with its antibody. Notably, a portion of MATN3 protein is found to form puncta in gastric cancer tissues ECM. MATN3 undergoes phase separation, which is mediated by its low complexity (LC) and coiled-coil (CC) domains. Moreover, overexpression of MATN3 deleted with either LC or CC in CAFs is unable to promote the invasion of gastric cancer cells, suggesting that LC or CC domain is required for the effect of CAF-secreted MATN3 in gastric cancer cell invasion. Additionally, orthotopic co-injection of gastric cancer cells and CAFs expressing MATN3, but not its ΔLC and ΔCC mutants, leads to enhanced gastric cancer cell invasion in mouse models. Collectively, our works suggest that MATN3 is secreted by CAFs and undergoes phase separation, which promotes gastric cancer invasion.
Subject(s)
Cancer-Associated Fibroblasts , Matrilin Proteins , Stomach Neoplasms , Animals , Humans , Mice , Carcinogenesis , Matrilin Proteins/genetics , Neoplasm Invasiveness , Phase Separation , Stomach Neoplasms/genetics , Tumor MicroenvironmentABSTRACT
Emerging electrochemical disinfection techniques provide a promising pathway to the biofouling control of reverse osmosis (RO) process. However, the comparative effectiveness and mechanism of it under flow-through conditions with low voltage remains unclear. This study investigated the effect of a flow-through electrode system (FES) with both direct current (DC) and alternating pulse current (AC) on RO biofouling control compared with chlorine disinfection. At the initial stage of biofouling development, the normalized flux of AC-FES (67% on Day 5) was saliently higher than the control group (56% on Day 5). Subsequently, the normalized fluxes of each group tended similarity in their differences until the 20th day. After mild chemical cleaning, the RO membrane in the AC-FES group reached the highest chemical cleaning efficiency of 58%, implying its foulant was more readily removable and the biofouling was more reversible. The biofouling layer in the DC-FES group was also found to be easily cleanable. Morphological analysis suggested that the thickness and compactness of the fouling layers were the major reasons for the fouling behavior difference. The abundance of 4 fouling-related abundant genera (>1%), which were Pseudomonas, Thiobacillus, Sphingopyxis, and Mycobacterium exhibited a salient correlation with the biofouling degree. The operating cost of FES was also lower than that of chlorine disinfection. In summary, AC-FES is a promising alternative to chlorine disinfection in RO biofouling control, as it caused less and easy-cleaning biofouling layer mainly due to two advantages: a) reducing the regrowth potential after disinfection of the bacteria, leading to alleviated initial fouling, (b) reshaping the microbial community to those with weaker biofilm formation capacity.
Subject(s)
Biofouling , Water Purification , Wastewater , Biofouling/prevention & control , Chlorine , Membranes, Artificial , Osmosis , Water Purification/methodsABSTRACT
Objective:To explore the relationship between the expressions of P21,P27 and proliferating cell nuclear antigen(PCNA)in glomerular mesangial tissue and poor renal prognosis in patients with immunoglobulin A(IgA)nephropathy.Methods:A total of 145 patients with IgA nephropathy treated in Xiaogan Central Hospital from April 2017 to August 2019 were selected as the research object.The expressions of P21,P27 and PCNA in glomerular mesangial tissue were detected by immunohistochemistry.All patients were followed up for 24 months,and the prognosis were counted.The expressions of P21,P27 and PCNA in glomerular mesangial tissue of patients with different prognosis were compared and the influencing factors of poor prognosis in patients with IgA nephropathy were analyzed by Logistic regression analysis.Results:The expression rates of P21,P27 and PCNA positive cells in glomerular mesangial tissue of patients with IgA nephropathy were(38.69±6.83)%,(55.94±8.08)%,(33.47±5.72)%,respectively.The incidence rete of poor prognosis in patients with IgA nephropathy was 17.24%,and the expression rates of P21 and PCNA positive cells in glomerular mesangial tissue of patients with poor prognosis were higher than those in good prognosis group(P<0.05),while the expression rate of P27 positive cells was lower than that in good prognosis group(P<0.05).Logistic multiple regression analysis showed that elevated diastolic blood pressure,increased 24 h proteinuria,mesangial cell proliferation,segmental glomerulosclerosis,renal tubular atrophy/interstitial fibrosis,crescentic body,increased expression rates of P21 and PCNA positive cells and decreased expression rate of P27 positive cells were all risk factors affecting the poor prognosis of patients with IgA nephropathy(P<0.05).Conclusion:There are positive expressions of P21,P27 and PCNA in glomerular mesangial tissue of IgA nephropathy.The expression rates of P21 and PCNA positive cells in glomerular mesangial tissue of of patients with poor prognosis of IgA nephropathy are higher than those with good prognosis,while the expression rate of P27 protein positive cells is lower than those with good prognosis,which are risk factors for poor prognosis of patients with IgA nephropathy.
ABSTRACT
Tumor-associated macrophages play pivotal roles in tumor progression and metastasis. Macrophage-mediated clearance of apoptotic cells (efferocytosis) supports inflammation resolution, contributing to immune evasion in colorectal cancers. To reverse this immunosuppressive process, we propose a readily translatable RNA therapy to selectively inhibit macrophage-mediated efferocytosis in tumor microenvironment. A clinically approved lipid nanoparticle platform (LNP) is employed to encapsulate siRNA for the phagocytic receptor MerTK (siMerTK), enabling selective MerTK inhibition in the diseased organ. Decreased MerTK expression in tumor-associated macrophages results in apoptotic cell accumulation and immune activation in tumor microenvironment, leading to suppressed tumor growth and better survival in both liver and peritoneal metastasis models of colorectal cancers. siMerTK delivery combined with PD-1 blockade further produces enhanced antimetastatic efficacy with reactivated intratumoral immune milieu. Collectively, LNP-based siMerTK delivery combined with immune checkpoint therapy may present a feasible modality for metastatic colorectal cancer therapy.
Subject(s)
Colonic Neoplasms , Efferocytosis , Humans , c-Mer Tyrosine Kinase , Macrophages , RNA, Small Interfering , Tumor MicroenvironmentABSTRACT
OBJECTIVE: There is no consensus regarding the best interval time between transurethral resection of a bladder tumor and Bacillus Calmette-Guerin (BCG) perfusion. This study was to explore whether the interval time has an impact on the prognosis and adverse effects. METHODS: We retrospectively reviewed the clinical data of patients who received BCG intravesical perfusion at Sun Yat-sen University Cancer Center (SYSUCC) from September 2015 to October 2021. Recurrence-free survival (RFS) and progression-free survival were the primary endpoints. Cox regression was used to explore independent predictors. The association between interval time and adverse effect grade was detected by logistic regression. Propensity score matching (PSM) was performed. RESULTS: A total of 403 patients were enrolled, the median interval time was 24 days (6-163 days), and the follow-up was 28 months (7-82 months). Eighty-eight (20.9%) patients relapsed, and 40 patients (10.0%) suffered progression. The multivariate Cox regression analysis confirmed that interval time was an independent predictor of RFS (p = 0.017). Notably, when the interval time was less than or equal to 26 days, there was a trend toward better RFS, PSM resulted in 65 matched pairs in each group, and Kaplan-Meier analysis showed that there was a significant difference in RFS between groups (p = 0.009). The logistic regression analysis showed that there was no correlation between interval time and adverse effects and their grades (p > 0.05). CONCLUSIONS: We considered that the first BCG perfusion could be performed within 2-4 weeks after surgery.
Subject(s)
BCG Vaccine , Urinary Bladder Neoplasms , Humans , BCG Vaccine/adverse effects , Retrospective Studies , Transurethral Resection of Bladder , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/surgery , Perfusion , Neoplasm Recurrence, Local/pathology , Neoplasm Invasiveness/pathologyABSTRACT
BACKGROUND: Respiratory infectious diseases (RIDs) remain a pressing public health concern, posing a significant threat to the well-being and lives of individuals. This study delves into the incidence of seven primary RIDs during the period 2017-2021, aiming to gain deeper insights into their epidemiological characteristics for the purpose of enhancing control and prevention strategies. METHODS: Data pertaining to seven notifiable RIDs, namely, seasonal influenza, pulmonary tuberculosis (PTB), mumps, scarlet fever, pertussis, rubella and measles, in the mainland of China between 2017 and 2021 were obtained from the National Notifiable Disease Reporting System (NNDRS). Joinpoint regression software was utilized to analyze temporal trends, while SaTScan software with a Poisson probability model was used to assess seasonal and spatial patterns. RESULTS: A total of 11,963,886 cases of the seven RIDs were reported during 2017-2021, and yielding a five-year average incidence rate of 170.73 per 100,000 individuals. Among these RIDs, seasonal influenza exhibited the highest average incidence rate (94.14 per 100,000), followed by PTB (55.52 per 100,000), mumps (15.16 per 100,000), scarlet fever (4.02 per 100,000), pertussis (1.10 per 100,000), rubella (0.59 per 100,000), and measles (0.21 per 100,000). Males experienced higher incidence rates across all seven RIDs. PTB incidence was notably elevated among farmers and individuals aged over 65, whereas the other RIDs primarily affected children and students under 15 years of age. The incidences of PTB and measles exhibited a declining trend from 2017 to 2021 (APC = -7.53%, P = 0.009; APC = -40.87%, P = 0.02), while the other five RIDs peaked in 2019. Concerning seasonal and spatial distribution, the seven RIDs displayed distinct characteristics, with variations observed for the same RIDs across different regions. The proportion of laboratory-confirmed cases fluctuated among the seven RIDs from 2017 to 2021, with measles and rubella exhibiting higher proportions and mumps and scarlet fever showing lower proportions. CONCLUSIONS: The incidence of PTB and measles demonstrated a decrease in the mainland of China between 2017 and 2021, while the remaining five RIDs reached a peak in 2019. Overall, RIDs continue to pose a significant public health challenge. Urgent action is required to bolster capacity-building efforts and enhance control and prevention strategies for RIDs, taking into account regional disparities and epidemiological nuances. With the rapid advancement of high-tech solutions, the development and effective implementation of a digital/intelligent RIDs control and prevention system are imperative to facilitate precise surveillance, early warnings, and swift responses.
Subject(s)
Communicable Diseases , Influenza, Human , Measles , Mumps , Rubella , Scarlet Fever , Tuberculosis, Pulmonary , Whooping Cough , Child , Male , Humans , Aged , Mumps/epidemiology , Mumps/prevention & control , Scarlet Fever/epidemiology , Influenza, Human/epidemiology , Communicable Diseases/epidemiology , Measles/prevention & control , Rubella/epidemiology , China/epidemiology , IncidenceABSTRACT
PURPOSE: Urachal cancer is similar to gastrointestinal adenocarcinoma in histology, and gastroscopy/colonoscopy is often administered during perioperative evaluation. However, gastroscopy and colonoscopy have corresponding disadvantages. This study discusses whether gastroscopy/colonoscopy is truly necessary for patients with urachal cancer. PATIENTS AND METHODS: A total of 166 bladder adenocarcinoma cases diagnosed at Sun Yat-sen University Cancer Center were retrospectively reviewed and divided into two groups (urachal cancer and nonurachal cancer), and perioperative evaluations were retrieved. RESULTS: There were 78 patients with urachal cancer, the median age was 48 years, and 59 were male. Perioperative gastroscopy/colonoscopy revealed 5 intestinal polyps and 1 adenoma during these evaluations, and no primary gastrointestinal cancer was found. Meanwhile, preoperative imaging evaluation did not detect significant gastrointestinal lesions. For 88 patients with nonurachal cancer, including primary bladder adenocarcinoma and metastatic tumors from gastrointestinal cancer, the median age was 56 years, and 64 were male. Preoperative imaging evaluation demonstrated 36 cases of gastrointestinal lesions, and 32 were confirmed by gastroscopy/colonoscopy; the other 4 were negative. Another 4 cases of colon cancer were detected by regular colonoscopy for suspected primary bladder adenocarcinoma. In all, 35 cases of colon cancer and 1 case of gastric cancer were identified by endoscopic examination. The diagnostic consistency of imaging and gastrointestinal endoscopy was favorable (P < 0.001), and the negative predictive value and diagnostic efficiency of imaging were 96.9% and 94.6%, respectively. CONCLUSIONS: The vast majority of gastrointestinal cancer cases can be identified by assessment of the patient's clinical symptoms, meticulous physical examination, and imaging evaluation. We recommend that gastroscopy/colonoscopy only be applied to patients with urachal cancer when the above examinations are positive.
Subject(s)
Adenocarcinoma , Colonic Neoplasms , Gastrointestinal Neoplasms , Humans , Male , Middle Aged , Female , Gastroscopy , Retrospective Studies , Colonoscopy , Adenocarcinoma/diagnostic imaging , Adenocarcinoma/surgeryABSTRACT
Benefiting from the massive labeled samples, deep learning-based segmentation methods have achieved great success for two dimensional natural images. However, it is still a challenging task to segment high dimensional medical volumes and sequences, due to the considerable efforts for clinical expertise to make large scale annotations. Self/semi-supervised learning methods have been shown to improve the performance by exploiting unlabeled data. However, they are still lack of mining local semantic discrimination and exploitation of volume/sequence structures. In this work, we propose a semi-supervised representation learning method with two novel modules to enhance the features in the encoder and decoder, respectively. For the encoder, based on the continuity between slices/frames and the common spatial layout of organs across subjects, we propose an asymmetric network with an attention-guided predictor to enable prediction between feature maps of different slices of unlabeled data. For the decoder, based on the semantic consistency between labeled data and unlabeled data, we introduce a novel semantic contrastive learning to regularize the feature maps in the decoder. The two parts are trained jointly with both labeled and unlabeled volumes/sequences in a semi-supervised manner. When evaluated on three benchmark datasets of medical volumes and sequences, our model outperforms existing methods with a large margin of 7.3% DSC on ACDC, 6.5% on Prostate, and 3.2% on CAMUS when only a few labeled data is available. Further, results on the M&M dataset show that the proposed method yields improvement without using any domain adaption techniques for data from unknown domain. Intensive evaluations reveal the effectiveness of representation mining, and superiority on performance of our method. The code is available at https://github.com/CcchenzJ/BootstrapRepresentation.
Subject(s)
Pelvis , Prostate , Male , Humans , Semantics , Supervised Machine Learning , Image Processing, Computer-AssistedABSTRACT
In this study, bacterial cellulose/gum Arabic composite (BC/GA) was synthesized by in-situ modification from lavender residue hydrolysate for the first time. The in-situ modification with GA adding showed great beneficial effect for BC/GA synthesis. Both the product (BC or BC/GA) yield and the product (BC or BC/GA) production per sugars consumption increased greatly by the in-situ modification when compared with the fermentation without GA adding (2.90 g/L vs. 0.91 g/L, and 0.461 g/g vs. 0.138 g/g). It is hypothesized that the combination of BC and GA is the main mechanism for the beneficial effect of the in-situ modification, and the scanning electron microscope (SEM) images confirmed this hypothesis. GA adding showed little effect on the rheological properties of lavender residue hydrolysate, and this environment was suitable for the combination of BC and GA. The in-situ modification had an obvious influence on the crystallinity index and the thermal stability of BC/GA, but affected little on its functional groups and cellulose structural framework. Besides BC/GA synthesis and structure, the in-situ modification could also alter the texture properties of BC/GA. Overall, this study can offer some useful information for the biochemical conversion from green and cost-effective lavender residue hydrolysate to attractive biomaterial BC/GA.
Subject(s)
Cellulose , Lavandula , Cellulose/chemistry , Gum Arabic , Fermentation , Carbohydrate Metabolism , Bacteria/metabolismABSTRACT
Enantiomerically pure acyclic O,O-acetal compounds (up to 97 %â ee) have been accessed through chemo-, regio- and enantioselective palladium-catalyzed addition of oximes to alkoxyallenes. DFT calculations support that a protonative hydropalladation pathway is favourable, in which the hydrogen bonding interaction between the amide group of the diphosphine ligand and the alkoxyallene is critical for the highly stereoselective formation of the dioxygenated stereogenic center.
ABSTRACT
Tumor-derived exosomes play an important role in the tumor micro-environment. The exosome-derived non-coding RNAs are transmitted in the tumor microenvironment in three ways, communication between tumor cells, normal cells affecting tumor cells, and tumor cells affecting normal cells. Through these three ways, exosomal non-coding RNAs are involved in the regulation of tumor progression, affecting tumor angiogenesis, tumor invasiveness, drug resistance, stemness, tumor metabolic repro-gramming and immune escape, resulting in dual roles in promoting or inhibiting tumor development. Exosomes have a membranous structure and their contents are resistant to degradation by extracellular proteases and remain highly stable in body fluids, thus exosome-derived non-coding RNAs are expected to serve as diagnostic and prognostic indicators for a variety of cancers. In addition, exosomes can be used to deliver non-coding RNAs for targeted therapy, or to knock down or modify tumor-promoting non-coding RNAs for tumor therapy. This article reviews the function and communication mechanism of exosomal non-coding RNAs in the tumor microenvironment, including their pathways of action, effects, potential values for tumor biomarkers and treatment targets. This article also points out the issues that need to be further studied in order to promote the progress of extracellular non-coding RNAs in cancer research and their application in tumor diagnosis and treatment.