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Metabolic syndrome (MetS) has a large clinical population nowadays, usually due to excessive energy intake and lack of exercise. During MetS, excess nutrients stress the mitochondria, resulting in relative hypoxia in tissues and organs, even when blood supply is not interrupted or reduced, making mitochondrial dysfunction a central pathogenesis of cardiovascular disease in the MetS. Sodium-glucose cotransporter 2 inhibitors were designed as a hyperglycemic drug that acts on the renal tubules to block sugar reabsorption in primary urine. Recently they have been shown to have anti-inflammatory and other protective effects on cardiomyocytes in MetS, and have also been recommended in the latest heart failure guidelines as a routine therapy. Among these inhibitors, empagliflozin shows better clinical promise due to less influence from glomerular filtration rate. This review focuses on the mitochondrial mechanisms of empagliflozin, which underlie the anti-inflammatory and recover cellular functions in MetS cardiomyocytes, including stabilizing calcium concentration, mediating metabolic reprogramming, maintaining homeostasis of mitochondrial quantity and quality, stable mitochondrial DNA copy number, and repairing damaged mitochondrial DNA.
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Compostos Benzidrílicos , Glucosídeos , Síndrome Metabólica , Miócitos Cardíacos , Inibidores do Transportador 2 de Sódio-Glicose , Animais , Humanos , Compostos Benzidrílicos/farmacologia , Cardiotônicos/farmacologia , Cardiotônicos/uso terapêutico , Glucosídeos/farmacologia , Glucosídeos/uso terapêutico , Síndrome Metabólica/tratamento farmacológico , Síndrome Metabólica/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias Cardíacas/efeitos dos fármacos , Mitocôndrias Cardíacas/metabolismo , Mitocôndrias Cardíacas/patologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Cálcio/metabolismo , Homeostase , Variações do Número de Cópias de DNARESUMO
BACKGROUND: While gastric cancer is generally declining globally, the temporal trend of young-onset (< 40 years) gastric cancer remains uncertain. We performed this analysis to determine the temporal trends of young-onset gastric cancer compared to late-onset cancer (≥ 40 years). METHODS: We extracted cross-sectional data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. The burden of gastric cancer from 1990 to 2019 was assessed through indicators including incidence and mortality rates, which were classified at global, national, and regional levels, and according to socio-demographic indexes (SDI) and age or sex groups. Joinpoint regression analysis was used to identify specific years with significant changes. The correlation between AAPC with countries' average SDI was tested by Pearson's Test. RESULTS: The global incidence rate of young-onset gastric cancer decreased from 2.20 (per 100,000) in 1990 to 1.65 in 2019 (AAPC: - 0.95; 95% confidence interval [CI] - 1.25 to - 0.65; P < 0.001). Late-onset cancer incidence also decreased from 59.53 (per 100,000) in 1990 to 41.26 in 2019 (AAPC: - 1.23; 95% CI - 1.39 to - 1.06, P < 0.001). Despite an overall decreasing trend, the incidence rate of young-onset cancer demonstrated a significant increase from 2015 to 2019 (annual percentage change [APC]: 1.39; 95% CI 0.06 to 2.74; P = 0.041), whereas no upward trend was observed in late-onset cancer. Mortality rates of young- and late-onset cancer both exhibited a significant decline during this period (AAPC: - 1.82; 95% CI - 2.15 to - 1.56; P < 0.001 and AAPC: - 1.69, 95% CI - 1.79 to - 1.59; P < 0.001). The male-to-female rate ratio for incidence and mortality in both age groups have been increasing since 1990. While countries with high SDI have had a greater decline in the incidence of late-onset gastric cancer (slope of AAPC change: - 0.20, P = 0.004), it was not observed in young-onset cancer (slope of AAPC change: - 0.11, P = 0.13). CONCLUSIONS: The global incidence and mortality rates of both young- and late-onset gastric cancer have decreased since 1990. However, the incidence rate of young-onset cancer has demonstrated a small but significant upward trend since 2015. There was disparity in the decline in young-onset gastric cancer among male and high SDI countries. These findings could help to inform future strategies in preventing gastric cancer in younger individuals.
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Idade de Início , Carga Global da Doença , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/mortalidade , Masculino , Feminino , Carga Global da Doença/tendências , Incidência , Adulto , Estudos Transversais , Pessoa de Meia-Idade , Idoso , Fatores de Risco , Adulto Jovem , Saúde GlobalRESUMO
BACKGROUND AND AIMS: As global life expectancy rises and gastrointestinal tumor incidence increases, more elderly patients are undergoing endoscopic submucosal dissection (ESD) for tumor treatment. The current situation highlights the importance of sarcopenia assessment before ESD. This systematic review and meta-analysis aim to assess sarcopenia's role in predicting post-ESD adverse outcomes in the elderly. METHODS: We conducted a systematic review and meta-analysis to investigate the impact of sarcopenia on the prognosis of elderly patients undergoing ESD treatment. A comprehensive search was conducted across three databases (PubMed, Embase, Web of Science). We were using NEWCASTLE-OTTAWA ASSESSMENT SCALE for risk of bias assessment. The data were synthesized using Review Manager 5.3. RESULTS: A total of 9 reports were identified, analyzing 7 indicators, with a combined sample size of 6044. Through a series of analyses, we have derived several highly credible research findings: the overall OR and 95% CI for gastric and colorectal post-ESD perforation between sarcopenia and nonsarcopenia groups were 1.34 [0.92, 1.97], for CTCAE grade > 2 was 2.65 [1.45, 4.82], for upper gastrointestinal post-ESD pneumonia were 1.97 [1.30, 2.99], and for gastric post-ESD mortality within 5 years were 2.96 [1.33, 6.58]. CONCLUSIONS: Sarcopenia is a risk factor for increased incidence of complications (CTCAE > 2) after undergoing gastric and colorectal ESD, increased pneumonia rates, and higher mortality rates within five years following gastric ESD treatment in elderly patients. However, sarcopenia does not lead to an increased perforation rate in elderly patients undergoing gastric and colorectal ESD treatments. Registration and protocol: The protocol for this study was registered on the Open Science Framework in 2024 https://doi.org/10.17605/OSF.IO/7B2CZ . We also conducted pre-registration on PROSPERO (CRD42024532547).
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PURPOSE: The aim of this study is to identify the genetic cause of primary ciliary dyskinesia (PCD) and male infertility in two unrelated Han Chinese families. METHODS: We performed whole-exome sequencing in two unrelated male Han Chinese patients suffering from infertility and PCD to identify the pathogenic variants. Ultrastructural and immunostaining analyses of patient's spermatozoa were performed to characterize the effect of the variants. The pathogenicity of the variants was validated using patient's spermatozoa by western blotting and immunostaining analysis. Intracytoplasmic sperm injection (ICSI) was conducted in the affected families. RESULTS: Three variants in leucine-rich repeat containing 6 (LRRC6) [patient 1(compound heterozygote): NM_012472: c.538C > T, (p.R180*) and c.64dupT, (p.S22Ffs*19); patient 2 (homozygote): c.863C > A, (p.P288H)] were identified in two unrelated patients with PCD and male infertility. These variants were predicated deleterious and were absent or rare in human population genome data. LRRC6-mutant spermatozoa showed a highly aberrant morphology and ultrastructure with lacked inner and outer dynein arms. The LRRC6 protein was present along the normal sperm flagella, and was significantly decreased in the mutated spermatozoa. Interestingly, both patients were able to conceive through ICSI and birthed a healthy baby. CONCLUSION: Our results extend the LRRC6 variant spectrum and provide reproductive guidance to families suffering from PCD-linked infertility caused by LRRC6 variants.
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Transtornos da Motilidade Ciliar , Infertilidade Masculina , Humanos , Masculino , Transtornos da Motilidade Ciliar/genética , Proteínas do Citoesqueleto/genética , População do Leste Asiático , Infertilidade Masculina/genética , Mutação/genética , Proteínas/genética , Sêmen/metabolismo , Espermatozoides/metabolismo , ChinaRESUMO
BACKGROUND: Dissecting lymph nodes along the left recurrent laryngeal nerve (LRLN) is the most challenging step in thoracoscopic-assisted esophagectomy. To retract the proximal esophagus in the existing lymphadenectomy methods, either a special trocar is required to insert and take out endoscopic instruments or thoracic punctures are needed to externally retract the esophageal loop. Therefore, advanced skills for esophageal traction are important to facilitate the LRLN lymphadenectomy and to reduce the incidence of trauma to the chest wall. Herein, we present the magnetic anchoring and traction technique, a novel method for LRLN lymphadenectomy during thoracoscopic esophagectomy. METHODS: The magnetic anchoring traction system was successfully used to retract the upper thoracic esophagus and to help expose the upper mediastinum in 10 cases of thoracoscopic-assisted esophagectomy. When the external magnet was moved outside of body, the internal magnet was coupled with a magnetic force to pull the proximal esophagus to the appropriate direction, which helped to expose the LRLN and adjacent lymph nodes. The lymph nodes adjacent to the LRLN could then be dissected completely without any damage to the nerve. RESULTS: In all surgeries, the LRLN and adjacent lymph nodes were well visualized, and the number of trocars used to pass endoscopic instruments for retraction of the proximal esophagus or the number of thoracic punctures for external traction of the esophagus during the surgery were reduced. CONCLUSIONS: In thoracoscopic-assisted esophagectomy, the magnetic anchoring and traction technique can improve the exposure of the LRLN, facilitate LRLN lymphadenectomy, and reduce chest wall trauma.
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Neoplasias Esofágicas , Nervo Laríngeo Recorrente , Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Humanos , Excisão de Linfonodo/métodos , Fenômenos Magnéticos , Mediastino/patologia , Nervo Laríngeo Recorrente/patologia , Estudos Retrospectivos , TraçãoRESUMO
BACKGROUND: By hindering energy supply pathway for cancer cells, an alternative therapeutic strategy modality is put forward: tumor starvation therapy. And yet only in this blockade of glucose supply which is far from enough to result in sheer apoptosis of cancer cells. RESULTS: In an effort to boost nutrient starvation-dominated cancer therapy, here a novel mitochondrial Ca2+ modulator Alg@CaP were tailor-made for the immobilization of Glucose oxidase for depriving the intra-tumoral glucose, followed by the loading of Curcumin to augment mitochondrial Ca2+ overload to maximize the therapeutic efficiency of cancer starvation therapy via mitochondrial dysfunctions. Also, autophagy inhibitors Obatoclax were synchronously incorporated in this nano-modulator to highlight autophagy inhibition. CONCLUSION: Here, a promising complementary modality for the trebling additive efficacy of starvation therapy was described for cutting off the existing energy sources in starvation therapy through Curcumin-augmented mitochondrial Ca2+ overload and Obatoclax-mediated autophagy inhibition.
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Curcumina , Neoplasias , Inanição , Apoptose , Autofagia , Linhagem Celular Tumoral , Curcumina/farmacologia , Curcumina/uso terapêutico , Glucose , Humanos , Indóis , Neoplasias/terapia , Nutrientes , PirróisRESUMO
An off-axis common-path digital holography is built up by inserting a 45° tilted cube beam splitter (CBS) into a 4f system that is described in this paper. Two apertures are set as the input of the 4f system, where one supports the object, and the other is vacant. The CBS divides the incoming beam into two copies, which are symmetrical with each other along the semi-reflecting layer. Due to the separation of two beams in a Fourier plane and the flipping of the field of view induced by the CBS, an off-axis hologram can be captured. Moreover, the carrier frequency can be easily modulated by translating the CBS perpendicular to the optical axis. The new proposed scheme has high light utilization, a compact setup, and high temporal stability. The experiments are carried out to demonstrate the validity and stability of the proposed method.
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BACKGROUND: Transanal endoscopic microsurgery (TEM) has been accepted worldwide for the treatment of local rectal lesions. We aimed to assess the efficacy and safety of TEM in the treatment of rectal neuroendocrine tumors (RNET). METHODS: A retrospective study of patients who had undergone TEM for RNET at our institution between December 2006 and June 2019 was performed. Demographic and tumor characteristics, operative and pathological details, complications, anal function questionnaires, and follow-up data were included. RESULTS: A total of 144 patients was included. TEM was performed as primary excision in 54 patients, after endoscopic forceps biopsy in 57 patients, and after incomplete resection by endoscopic excision in 33 patients. The median size of all primary tumors was 0.6 cm (range, 0.3-2.0 cm), and the negative resection margin was achieved in 142 (98.6%) patients. Postoperative complications (referring to only bleeding) occurred in 3 (2.1%) patients and was successfully managed with conservative method. After a median follow-up of 75.5 months after surgery, 3 patients died of other causes, and 2 patients suffered metastasis. An anal function questionnaire was posted 24 months after TEM. Among the results, 3 (2.1%) patients complained of major low anterior resection syndrome (LARS), including 1 (0.7%) who suffered from complete incontinence, while 6 (4.2%) patients had minor LARS. CONCLUSIONS: TEM has satisfying long-term outcomes and relatively low anal function disturbance as for the treatment of small RNET. TEM also acts as a preferred salvage treatment for incomplete endoscopic excision.
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Tumores Neuroendócrinos , Neoplasias Retais , Microcirurgia Endoscópica Transanal , Humanos , Microcirurgia , Tumores Neuroendócrinos/cirurgia , Complicações Pós-Operatórias/epidemiologia , Neoplasias Retais/cirurgia , Estudos Retrospectivos , Síndrome , Resultado do TratamentoRESUMO
Despite advances in the development of tumor treatments, mortality from cancer continues to increase. Nanotechnology is expected to provide an innovative anti-cancer therapy, to combat challenges such as multidrug resistance and tumor recurrence. Nevertheless, tumors can greatly rely on autophagy as an alternative source for metabolites, and which desensitizes cancer cells to therapeutic stress, hindering the success of any current treatment paradigm. Autophagy is a conserved process by which cells turn over their own constituents to maintain cellular homeostasis. The multistep autophagic pathway provides potentially druggable targets to inhibit pro-survival autophagy under various therapeutic stimuli. In this review, we focus on autophagy inhibition based on functional nanoplatforms, which may be a potential strategy to increase therapeutic sensitivity in combinational cancer therapies, including chemotherapy, radiotherapy, phototherapy, sonodynamic therapy, and immunotherapy.
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Autofagia , Neoplasias/terapia , Antineoplásicos/uso terapêutico , Autofagia/efeitos dos fármacos , Autofagia/efeitos da radiação , Terapia Combinada , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos da radiação , Humanos , NanopartículasRESUMO
Tumor angiogenesis has been identified as an important factor in the development and progression of tumors, and anti-angiogenesis therapy has been recognized as an effective tumor therapy pattern. The unique characteristics of nanodiamonds (NDs) have been explored for photothermal therapy (PTT) against cancer, while the efficiency of mild PTT mediated by bare NDs was limited. The combination of different therapies into a single nanoplatform has shown great potential for synergistic cancer treatment. In this investigation, we integrated hydrophobic antiangiogenesis agent combretastatin A4 (CA4) into the protamine sulfate (PS) functionalized NDs hybrids (NDs@PS) with a noncovalent self-assembling method (CA4-NDs@PS) for potential combined anti-angiogenesis and mild PTT in liver cancer. The resulted CA4-NDs@PS NDs exhibited high drug loading ability, good dispersibility and colloidal stability. The near-infrared (NIR) laser irradiation could trigger the release of CA4 from CA4-NDs@PS NDs and elevate the temperature of CA4-NDs@PS NDs aqueous solution.In vitroresults illustrated that CA4-NDs@PS coupled with laser irradiation could remarkably enhance HepG-2 cells killing efficiency, leading to an enhanced photocytotoxicity. Furthermore,in vivoexperiments revealed that CA4-NDs@PS exhibited a highly synergistic anticancer efficacy with NIR laser irradiation in HepG-2 tumor-bearing mice. Altogether, our present study fabricated a novel NDs@PS-based nanoplatform for combined anti-tumor angiogenesis and mild PTT against liver cancer.
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Inibidores da Angiogênese/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Nanodiamantes/uso terapêutico , Protaminas/farmacologia , Estilbenos/farmacologia , Animais , Linhagem Celular Tumoral , Feminino , Células Hep G2 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Fototerapia/métodos , Terapia Fototérmica/métodosRESUMO
BACKGROUND: Transanal endoscopic microsurgery (TEM) is widely used in the treatment of local rectal lesions and helps avoid radical surgery. This study evaluated the management and outcome in a long-term followed cohort of patients with localized rectal GIST underwent TEM with alternative neodajuvant imatinib (nIM). METHODS: A retrospective cohort study was undertaken of patients identified from a case database at Department of General Surgery, Peking Union Medical College Hospital (PUMCH) over a continuous period, from January 2006 to December 2017. RESULTS: Over 12 years, 42 patients presented with a primary rectal GIST in PUMCH. Median age was 49 (range 27-77) years. Neoadjuvant imatinib (nIM) therapy was used in 16 patients, significantly reducing mean tumor size from 4.41 to 2.46 cm (p < 0.001) and mitotic index (p = 0.041). All of these patients underwent TEM with no tumor rupture, nIM therapy enabled sphincter-preserving surgery to be undertaken in 16 (16/42) patients who would otherwise have required abdominoperineal resection or pelvic exenteration for tumor clearance and all patients (42/42) achieve R0 resection and negative margin. Imatinib was also used as postoperative adjuvant treatment in 15 patients with high-risk GIST. Median follow-up was 77 (range 14-144) and overall survival is 100%. In 42 patients, Local recurrence (LR) occurred in 3 of 42 patients and 1 of 42 patients developed distant metastasis (DM) in 112 months after TEM. In the univariate analysis, mitotic index (p = 0.028), NIH risk categories (p = 0.047) were predictive feature of local relapse. CONCLUSION: The application of nIM significantly decreased tumor size in large localized rectal GIST, which permitted TEM to preserve sphincter. The TEM procedure with alternative neoadjuvant imatinib therapy is a practicable treatment for patients with rectal GIST to preserve anus and have satisfied anal function.
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Tumores do Estroma Gastrointestinal , Neoplasias Retais , Microcirurgia Endoscópica Transanal , Adulto , Idoso , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/cirurgia , Humanos , Mesilato de Imatinib , Microcirurgia , Pessoa de Meia-Idade , Terapia Neoadjuvante , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Cancer synergistic therapy strategy in combination with therapeutic gene and small molecule drug offers the possibility to amplify anticancer efficiency. Colon cancer-associated transcript-1 (CCAT1) is a well identified oncogenic long noncoding RNA (lncRNA) exerting tumorigenic effects in a variety of cancers including colorectal cancer (CRC). RESULTS: In the present work, curcumin (Cur) and small interfering RNA targeting lncRNA CCAT1(siCCAT1) were co-incorporated into polymeric hybrid nanoparticles (CSNP), which was constructed by self-assembling method with two amphiphilic copolymers, polyethyleneimine-poly (D, L-lactide) (PEI-PDLLA) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol) (DSPE-mPEG). Owing to the multicolor fluorescence characteristics of PEI-PDLLA, the constructed CSNP could be served as a theranostic nanomedicine for synchronous therapy and imaging both in vitro and in vivo. Resultantly, proliferation and migration of HT-29 cells were efficiently inhibited, and the highest apoptosis ratio was induced by CSNP with coordination patterns. Effective knockdown of lncRNA CCAT1 and concurrent regulation of relevant downstream genes could be observed. Furthermore, CSNP triggered conspicuous anti-tumor efficacy in the HT-29 subcutaneous xenografts model with good biosafety and biocompatibility during the treatment. CONCLUSION: On the whole, our studies demonstrated that the collaborative lncRNA CCAT1 silencing and Cur delivery based on CSNP might emerge as a preferable and promising strategy for synergetic anti-CRC therapy.
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Curcumina/farmacologia , Nanopartículas/química , RNA Longo não Codificante/genética , RNA Longo não Codificante/farmacologia , Animais , Apoptose/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Combinação de Medicamentos , Sistemas de Liberação de Medicamentos/métodos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HT29 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Polímeros , Medicina de Precisão , Interferência de RNA , RNA Longo não Codificante/química , RNA Interferente Pequeno/genéticaRESUMO
BACKGROUND: Gastric cancer is the fifth most common cancer globally, with about 75% of cases occurring in Asia. While chronic atrophic gastritis (CAG) and intestinal metaplasia (IM) are well-recognized preneoplastic gastric lesions, we determined the prevalence and temporal trend of CAG and IM in Asia over the past 50 years. METHODS: In this systematic review and meta-analysis, we searched PubMed, Embase, MEDLINE, Scopus, and Web of Science for studies reporting the prevalence of CAG and IM in Asia (according to the United Nations geoscheme) published between 1970 and 2022. Heterogeneity was assessed by the I2 index and Cochran Q test. We adopted the random effects model to estimate the pooled prevalence and 95% confidence interval (CI). The slope of prevalence was estimated as a function of time in simple linear regression and weighted meta-regression models to demonstrate the temporal trend. Studies that reported the odds ratio (OR) of Helicobacter pylori infection and CAG/IM were analyzed separately to compile a pooled OR with a 95% CI. This study was registered in INPLASY2022120028. RESULTS: Of the 81 studies from 19 Asian countries identified, the pooled prevalence for CAG and IM in Asia was 26.1% (95%CI: 22.7-30.0) and 22.9% (95%CI: 19.7-26.6), respectively. Over the past 5 decades, there was a significant decline in the prevalence of IM (slope in adjusted meta-regression models: -0.79 [95%CI: -1.28 to -0.26], P = 0.003), but there was no significant change in the pooled prevalence of CAG. Within Asia, the prevalence varied significantly among different regions. Southern Asia reported the highest pooled prevalence of CAG (42.9%, 95%CI: 27.5%-67.1%), while Western Asia reported the lowest level (12.7%, 95%CI: 5.0%-32.3%). For IM, Eastern Asia reported the highest prevalence (27.1%, 95%CI: 21.1-34.9), with the lowest prevalence reported in Western Asia (3.1%; 95% CI 1.2%-8.0%). H. pylori infection was linked to CAG and IM with OR of 2.16 (95%CI: 2.09-2.22) and 1.64 (95%CI: 1.57-1.72), respectively. CONCLUSION: This updated meta-analysis showed that up to 26% of study individuals in Asia harbored preneoplastic gastric lesions. There was a declining temporal trend in the prevalence of IM, but not for CAG, in Asia.
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Gastrite Atrófica , Infecções por Helicobacter , Helicobacter pylori , Humanos , Prevalência , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/patologia , Gastrite Atrófica/epidemiologia , Gastrite Atrófica/patologia , Ásia/epidemiologiaRESUMO
BACKGROUND: Neoadjuvant chemotherapy, used to shrink tumors before surgery, is increasingly applied in clinical practice. However, retrospective studies indicate that it may increase sarcopenia rates and consequently result in an elevated occurrence rate of postoperative severe complications such as severe surgical incision infection, severe respiratory failure, and severe postoperative hemorrhage, especially in the elderly population. Currently, no systematic analysis examines the association between neoadjuvant chemotherapy and sarcopenia. This study aims to fill this gap with a comprehensive meta-analysis focused on this critical aspect of the field. METHODS: A systematic literature search was conducted in the PubMed and Web of Science databases from their inception to January 2024. The included studies encompassed patients who received neoadjuvant chemotherapy and underwent computed tomography (CT) scans both before and after treatment to calculate skeletal muscle index (SMI) or categorize them for the presence of sarcopenia. The determination of sarcopenia status was based on well-established and validated threshold criteria. Data extraction was performed independently by two reviewers. A meta-analysis was employed to estimate the pooled odds ratio (OR) and its corresponding 95% confidence interval (95% CI) to assess the risk of neoadjuvant chemotherapy-induced muscle reduction. RESULTS: In the 14 studies with complete categorical variable data, comprising 1853 patients, 773 patients were identified as having sarcopenia before neoadjuvant treatment and 941 patients had sarcopenia after neoadjuvant therapy. The OR and its 95% CI was calculated as 1.51 [1.31, 1.73]. Among these, 719 patients had digestive system cancer, with 357 patients having sarcopenia before neoadjuvant treatment and 447 patients after, resulting in an OR of 1.74 [1.40, 2.17]. In the remaining 1134 patients with non-digestive system cancers, 416 were identified as having sarcopenia before neoadjuvant treatment, and 494 patients had sarcopenia after, with an OR of 1.37 [1.15, 1.63]. Additionally, in seven studies with complete continuous variable data, including 1228 patients, the mean difference in the change of SMI before and after neoadjuvant treatment was - 1.13 [- 1.65, - 0.62]. After excluding low-quality small-sample studies with fewer than 50 patients, the same trend was observed in the analysis. CONCLUSION: The risk of muscle reduction significantly increases in cancer patients after neoadjuvant chemotherapy and digestive system cancers tend to have a higher risk of developing sarcopenia post-treatment compared to non-digestive system cancers.
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Terapia Neoadjuvante , Neoplasias , Sarcopenia , Sarcopenia/induzido quimicamente , Humanos , Terapia Neoadjuvante/efeitos adversos , Neoplasias/tratamento farmacológico , Neoplasias/complicações , Quimioterapia Adjuvante/efeitos adversos , Complicações Pós-Operatórias , Músculo Esquelético/patologiaRESUMO
This study aimed to isolate marine bacteria to investigate their stress response, inhibition mechanisms, and degradation processes under high-load conditions of salinity and enrofloxacin (ENR). The results demonstrated that marine bacteria exhibited efficient pollutant removal efficiency even under high ENR stress (up to 10 mg/L), with chemical oxygen demand (COD), total phosphorus (TP), total nitrogen (TN) and ENR removal efficiencies reaching approximately 88%, 83%, 61%, and 73%, respectively. The predominant families of marine bacteria were Bacillaceae (50.46%), Alcanivoracaceae (32.30%), and Rhodobacteraceae (13.36%). They responded to ENR removal by altering cell membrane properties, stimulating the activity of xenobiotic-metabolizing enzymes and antioxidant systems, and mitigating ENR stress through the secretion of extracellular polymeric substance (EPS). The marine bacteria exhibited robust adaptability to environmental factors and effective detoxification of ENR, simultaneously removing carbon, nitrogen, phosphorus, and antibiotics from the wastewater. The attapulgite carrier enhanced the bacteria's resistance to the environment. When treating actual mariculture wastewater, the removal efficiencies of COD and TN exceeded 80%, TP removal efficiency exceeded 90%, and ENR removal efficiency approached 100%, significantly higher than reported values in similar salinity reactors. Combining the constructed physical and mathematical models of tolerant bacterial, this study will promote the practical implementation of marine bacterial-based biotechnologies in high-loading saline wastewater treatment.
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Antibacterianos , Enrofloxacina , Nitrogênio , Fósforo , Águas Residuárias , Poluentes Químicos da Água , Águas Residuárias/química , Enrofloxacina/metabolismo , Poluentes Químicos da Água/metabolismo , Antibacterianos/metabolismo , Fósforo/metabolismo , Fósforo/química , Nitrogênio/metabolismo , Biodegradação Ambiental , Bactérias/metabolismo , Aquicultura , Eliminação de Resíduos Líquidos/métodosRESUMO
Hybrid transformer-based segmentation approaches have shown great promise in medical image analysis. However, they typically require considerable computational power and resources during both training and inference stages, posing a challenge for resource-limited medical applications common in the field. To address this issue, we present an innovative framework called Slim UNETR, designed to achieve a balance between accuracy and efficiency by leveraging the advantages of both convolutional neural networks and transformers. Our method features the Slim UNETR Block as a core component, which effectively enables information exchange through self-attention mechanism decomposition and cost-effective representation aggregation. Additionally, we utilize the throughput metric as an efficiency indicator to provide feedback on model resource consumption. Our experiments demonstrate that Slim UNETR outperforms state-of-the-art models in terms of accuracy, model size, and efficiency when deployed on resource-constrained devices. Remarkably, Slim UNETR achieves 92.44% dice accuracy on BraTS2021 while being 34.6x smaller and 13.4x faster during inference compared to Swin UNETR. Code: https://github.com/aigzhusmart/Slim-UNETR.
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Processamento de Imagem Assistida por Computador , Redes Neurais de ComputaçãoRESUMO
Iodide (I-) vacancy defects are strongly related to the stability of perovskite optoelectronic devices. The I- vacancy in lead iodide perovskites is normally considered to exist in the form of a single isolated defect. However, we determined that the I- vacancies cluster in pairs in specific ways in the typical perovskite of tetragonal CsPbI3. This I- vacancy-vacancy dimer is energetically more favorable than two isolated I- monovacancies. It breaks the symmetry of the Pb-I octahedron, resulting in lattice distortion. Its origin lies in the special lattice distortion effect caused by the electron orbital interaction of the perovskite material. Furthermore, the I- vacancy-vacancy dimer and the associated lattice distortion increase the carrier lifetime by 1.3 times compared to that of the system with two isolated I- monovacancies, but they also compromise its structural stability. This new insight into the I- vacancy defect will enhance our understanding of perovskite optoelectronic devices.
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Multiobject tracking (MOT) is a fundamental problem in computer vision with numerous applications, such as intelligent surveillance and automated driving. Despite the significant progress made in MOT, pedestrian attributes, such as gender, hairstyle, body shape, and clothing features, which contain rich and high-level information, have been less explored. To address this gap, we propose a simple, effective, and generic method to predict pedestrian attributes to support general reidentification (Re-ID) embedding. We first introduce attribute multi-object tracking (AttMOT), a large, highly enriched synthetic dataset for pedestrian tracking, containing over 80k frames and six million pedestrian identity switches (IDs) with different times, weather conditions, and scenarios. To the best of authors' knowledge, AttMOT is the first MOT dataset with semantic attributes. Subsequently, we explore different approaches to fuse Re-ID embedding and pedestrian attributes, including attention mechanisms, which we hope will stimulate the development of attribute-assisted MOT. The proposed method attribute-assisted method (AAM) demonstrates its effectiveness and generality on several representative pedestrian MOT benchmarks, including MOT17 and MOT20, through experiments on the AttMOT dataset. When applied to the state-of-the-art trackers, AAM achieves consistent improvements in multi-object tracking accuracy (MOTA), higher order tracking accuracy (HOTA), association accuracy (AssA), IDs, and IDF1 scores. For instance, on MOT17, the proposed method yields a + 1.1 MOTA, + 1.7 HOTA, and + 1.8 IDF1 improvement when used with FairMOT. To further encourage related research, we release the data and code at https://github.com/HengLan/AttMOT.
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Amyotrophic lateral sclerosis (ALS) stands as a rare, yet severely debilitating disorder marked by the deterioration of motor neurons (MNs) within the brain and spinal cord, which is accompanied by degenerated corticobulbar/corticospinal tracts and denervation in skeletal muscles. Despite ongoing research efforts, ALS remains incurable, attributed to its intricate pathogenic mechanisms. A notable feature in the pathology of ALS is the prevalence of TAR DNA-binding protein 43 (TDP-43) proteinopathy, detected in approximately 97% of ALS cases, underscoring its significance in the disease's progression. As a result, strategies targeting the aberrant TDP-43 protein have garnered attention as a potential avenue for ALS therapy. This review delves into the existing drug screening systems aimed at TDP-43 proteinopathy and the models employed for drug efficacy validation. It also explores the hurdles encountered in the quest to develop potent medications against TDP-43 proteinopathy, offering insights into the intricacies of drug discovery and development for ALS. Through this comprehensive analysis, the review sheds light on the critical aspects of identifying and advancing therapeutic solutions for ALS.
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INTRODUCTION: The characteristics of gastric carcinoma in young individuals differ from that in older individuals. We conducted a systematic review and meta-analysis to explore the clinicopathological features and risk factors associated with young-onset (younger than 50 years) gastric carcinoma. METHODS: We searched for studies published between January 1, 1990, and September 1, 2023, on patients with young-onset gastric carcinoma in PubMed, EMBASE, Web of Science, and MEDLINE to explore clinicopathological characteristics among this specific patient group. Extracted information included the proportion of patients with symptoms or family history of gastric cancer, tumor location, and histological features such as Lauren or World Health Organization histological classification and degree of differentiation. Additional analyses were conducted on risk factors such as positive family history, Helicobacter pylori infection, or high-risk nutritional or behavioral factors. The estimates were derived using random or fixed-effect models and included subgroup analyses based on different sex and age groups. This study was registered in PROSPERO (CRD42023466131). RESULTS: We identified 5,696 records, 1,292 were included in the quality assessment stage. Finally, 84 studies from 18 countries or regions including 89,447 patients with young-onset gastric carcinoma were included. Young-onset gastric carcinoma has slight female predominance (53.7%, 95% confidence interval [CI]: 51.6-55.7%), with most having symptoms (87.0%, 95% CI: 82.4%-91.7%). Family history was reported in 12.1% (95% CI: 9.5%-14.7%). H. pylori infection was detected in 60.0% of cases (95% CI: 47.1%-72.8%). Most of these carcinomas were in the non-cardia region (89.6%, 95% CI: 82.4%-96.8%), exhibiting Lauren diffuse-type histology (71.1%, 95% CI: 66.8%-75.3%) and poor/undifferentiated features (81.9%, 95% CI%: 79.7-84.2%). A positive family history of gastric cancer was the most important risk factor associated with the development of gastric carcinoma in young individuals (pooled odds ratios 4.0, 95% CI: 2.8-5.2), followed by H. pylori infection (odds ratio 2.3; 95% CI: 1.4-3.2) and dietary and other lifestyle risk factors. DISCUSSION: Young-onset gastric carcinoma exhibits specific clinicopathological characteristics, with positive family history being the most important risk factor. Most of the patients were symptomatic at diagnosis. These findings could help to inform future strategies for the early detection of gastric carcinoma among young individuals.