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2.
BMC Geriatr ; 24(1): 442, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773457

RESUMO

BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of preoperative concurrent chemoradiotherapy (preCRT) for locally advanced rectal cancer in older people who were classified as "fit" by comprehensive geriatric assessment (CGA). METHODS: A single-arm, multicenter, phase II trial was designed. Patients were eligible for this study if they were aged 70 years or above and met the standards of "fit" (SIOG1) as evaluated by CGA and of the locally advanced risk category. The primary endpoint was 2-year disease-free survival (DFS). Patients were scheduled to receive preCRT (50 Gy) with raltitrexed (3 mg/m2 on days 1 and 22). RESULTS: One hundred and nine patients were evaluated by CGA, of whom eighty-six, eleven and twelve were classified into the fit, intermediate and frail category. Sixty-eight fit patients with a median age of 74 years were enrolled. Sixty-four patients (94.1%) finished radiotherapy without dose reduction. Fifty-four (79.3%) patients finished the prescribed raltitrexed therapy as planned. Serious toxicity (grade 3 or above) was observed in twenty-four patients (35.3%), and fourteen patients (20.6%) experienced non-hematological side effects. Within a median follow-up time of 36.0 months (range: 5.9-63.1 months), the 2-year overall survival (OS), cancer-specific survival (CSS) and disease-free survival (DFS) rates were 89.6% (95% CI: 82.3-96.9), 92.4% (95% CI: 85.9-98.9) and 75.6% (95% CI: 65.2-86.0), respectively. Forty-eight patients (70.6%) underwent surgery (R0 resection 95.8%, R1 resection 4.2%), the corresponding R0 resection rate among the patients with positive mesorectal fascia status was 76.6% (36/47). CONCLUSION: This phase II trial suggests that preCRT is efficient with tolerable toxicities in older rectal cancer patients who were evaluated as fit based on CGA. TRIAL REGISTRATION: The registration number on ClinicalTrials.gov was NCT02992886 (14/12/2016).


Assuntos
Quimiorradioterapia , Avaliação Geriátrica , Neoplasias Retais , Humanos , Idoso , Masculino , Feminino , Neoplasias Retais/terapia , Idoso de 80 Anos ou mais , Avaliação Geriátrica/métodos , Quimiorradioterapia/métodos , Intervalo Livre de Doença , Cuidados Pré-Operatórios/métodos , Tiofenos/administração & dosagem , Tiofenos/uso terapêutico , Equipe de Assistência ao Paciente , Quinazolinas/administração & dosagem , Quinazolinas/uso terapêutico
3.
Bone Res ; 12(1): 27, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714649

RESUMO

Tendon adhesion is a common complication after tendon injury with the development of accumulated fibrotic tissues without effective anti-fibrotic therapies, resulting in severe disability. Macrophages are widely recognized as a fibrotic trigger during peritendinous adhesion formation. However, different clusters of macrophages have various functions and receive multiple regulation, which are both still unknown. In our current study, multi-omics analysis including single-cell RNA sequencing and proteomics was performed on both human and mouse tendon adhesion tissue at different stages after tendon injury. The transcriptomes of over 74 000 human single cells were profiled. As results, we found that SPP1+ macrophages, RGCC+ endothelial cells, ACKR1+ endothelial cells and ADAM12+ fibroblasts participated in tendon adhesion formation. Interestingly, despite specific fibrotic clusters in tendon adhesion, FOLR2+ macrophages were identified as an antifibrotic cluster by in vitro experiments using human cells. Furthermore, ACKR1 was verified to regulate FOLR2+ macrophages migration at the injured peritendinous site by transplantation of bone marrow from Lysm-Cre;R26RtdTomato mice to lethally irradiated Ackr1-/- mice (Ackr1-/- chimeras; deficient in ACKR1) and control mice (WT chimeras). Compared with WT chimeras, the decline of FOLR2+ macrophages was also observed, indicating that ACKR1 was specifically involved in FOLR2+ macrophages migration. Taken together, our study not only characterized the fibrosis microenvironment landscape of tendon adhesion by multi-omics analysis, but also uncovered a novel antifibrotic cluster of macrophages and their origin. These results provide potential therapeutic targets against human tendon adhesion.


Assuntos
Movimento Celular , Macrófagos , Regeneração , Humanos , Animais , Macrófagos/metabolismo , Camundongos , Tendões/metabolismo , Tendões/patologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Traumatismos dos Tendões/patologia , Traumatismos dos Tendões/metabolismo , Traumatismos dos Tendões/genética , Proteômica , Feminino , Multiômica
4.
Acta Pharmacol Sin ; 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589688

RESUMO

Lymphocyte activation gene 3 (LAG3), an immune checkpoint molecule expressed on activated T cells, functions as a negative regulator of immune responses. Persistent antigen exposure in the tumor microenvironment results in sustained LAG3 expression on T cells, contributing to T cell dysfunction. Fibrinogen-like protein 1 (FGL1) has been identified as a major ligand of LAG3, and FGL1/LAG3 interaction forms a novel immune checkpoint pathway that results in tumor immune evasion. In addition, ubiquitin-specific peptidase 7 (USP7) plays a crucial role in cancer development. In this study we investigated the role of USP7 in modulation of FGL1-mediated liver cancer immune evasion. We showed that knockdown of USP7 or treatment with USP7 inhibitor P5091 suppressed liver cancer growth by promoting CD8+ T cell activity in Hepa1-6 xenograft mice and in HepG2 or Huh7 cells co-cultured with T cells, whereas USP7 overexpression produced the opposite effect. We found that USP7 upregulated FGL1 in HepG2 and Huh7 cells by deubiquitination of transcriptional factor PR domain zinc finger protein 1 (PRDM1), which transcriptionally activated FGL1, and attenuated the CD8+ T cell activity, leading to the liver cancer growth. Interestingly, USP7 could be transcriptionally stimulated by PRDM1 as well in a positive feedback loop. P5091, an inhibitor of USP7, was able to downregulate FGL1 expression, thus enhancing CD8+ T cell activity. In an immunocompetent liver cancer mouse model, the dual blockade of USP7 and LAG3 resulted in a superior antitumor activity compared with anti-LAG3 therapy alone. We conclude that USP7 diminishes CD8+ T cell activity by a USP7/PRDM1 positive feedback loop on FGL1 production in liver cancer; USP7 might be a promising target for liver cancer immunotherapy.

5.
Hepatobiliary Surg Nutr ; 13(2): 258-272, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38617474

RESUMO

Background: Visceral pain induced by pancreatic cancer seriously affects patients' quality of life, and there is no effective treatment, because the mechanism of its neural circuit is unknown. Therefore, the aim of this study is to explore the main neural circuit mechanism regulating visceral pain induced by pancreatic cancer in mice. Methods: The mouse model of pancreatic cancer visceral pain was established on C57BL/6N mice by pancreatic injection of mPAKPC-luc cells. Abdominal mechanical hyperalgesia and hunch score were performed to assess visceral pain; the pseudorabies virus (PRV) was used to identify the brain regions innervating the pancreas; the c-fos co-labeling method was used to ascertain the types of activated neurons; in vitro electrophysiological patch-clamp technique was used to record the electrophysiological activity of specific neurons; the calcium imaging technique was used to determine the calcium activity of specific neurons; specific neuron destruction and chemogenetics methods were used to explore whether specific neurons were involved in visceral pain induced by pancreatic cancer. Results: The PRV injected into the pancreas was detected in the paraventricular nucleus of the hypothalamus (PVN). Immunofluorescence staining showed that the majority of c-fos were co-labeled with glutamatergic neurons in the PVN. In vitro electrophysiological results showed that the firing frequency of glutamatergic neurons in the PVN was increased. The calcium imaging results showed that the calcium activity of glutamatergic neurons in the PVN was enhanced. Both specific destruction of glutamatergic neurons and chemogenetics inhibition of glutamatergic neurons in the PVN alleviated visceral pain induced by pancreatic cancer. Conclusions: Glutamatergic neurons in the PVN participate in the regulation of visceral pain induced by pancreatic cancer in mice, providing new insights for the discovery of effective targets for the treatment of pancreatic cancer visceral pain.

6.
BMC Cancer ; 24(1): 474, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622609

RESUMO

BACKGROUND AND PURPOSE: In recent years, there has been extensive research on the role of exercise as an adjunctive therapy for cancer. However, the potential mechanisms underlying the anti-tumor therapy of exercise in lung cancer remain to be fully elucidated. As such, our study aims to confirm whether exercise-induced elevation of epinephrine can accelerate CD8+ T cell recruitment through modulation of chemokines and thus ultimately inhibit tumor progression. METHOD: C57BL/6 mice were subcutaneously inoculated with Lewis lung cancer cells (LLCs) to establish a subcutaneous tumor model. The tumor mice were randomly divided into different groups to performed a moderate-intensity exercise program on a treadmill for 5 consecutive days a week, 45 min a day. The blood samples and tumor tissues were collected after exercise for IHC, RT-qPCR, ELISA and Western blot. In addition, another group of mice received daily epinephrine treatment for two weeks (0.05 mg/mL, 200 µL i.p.) (EPI, n = 8) to replicate the effects of exercise on tumors in vivo. Lewis lung cancer cells were treated with different concentrations of epinephrine (0, 5, 10, 20 µM) to detect the effect of epinephrine on chemokine levels via ELISA and RT-qPCR. RESULTS: This study reveals that both pre- and post-cancer exercise effectively impede the tumor progression. Exercise led to an increase in EPI levels and the infiltration of CD8+ T cell into the lung tumor. Exercise-induced elevation of EPI is involved in the regulation of Ccl5 and Cxcl10 levels further leading to enhanced CD8+ T cell infiltration and ultimately inhibiting tumor progression. CONCLUSION: Exercise training enhance the anti-tumor immunity of lung cancer individuals. These findings will provide valuable insights for the future application of exercise therapy in clinical practice.


Assuntos
Carcinoma Pulmonar de Lewis , Neoplasias Pulmonares , Animais , Camundongos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Camundongos Endogâmicos C57BL , Linfócitos T CD8-Positivos , Quimiocinas , Carcinoma Pulmonar de Lewis/terapia , Carcinoma Pulmonar de Lewis/patologia , Microambiente Tumoral , Linhagem Celular Tumoral
7.
Front Med (Lausanne) ; 11: 1354483, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38633312

RESUMO

Background: The use of multidisciplinary treatment programs in out-of-hospital healthcare is a new area of research. Little is known about the benefits of this method in the management of discharged patients undergoing cervical spondylosis surgery. Objective: This study aimed to explore the effect of a contracted-based, multidisciplinary follow-up plan in patients after cervical spondylosis surgery. Methods: This non-blinded non-randomized controlled study was conducted with 88 patients (44 in the intervention group, 44 in the control group). The clinical outcomes, including Neck Disability Index (NDI), pain score (VAS), Self-Efficacy for Managing Chronic Disease 6-item Scale (SECD-6), and 12-Item Short-Form Health Survey (SF-12) score were assessed at the time of discharge, 24-72 h, 1 month, and 3 months post-discharge. The complications, patient satisfaction, and economic indicators were assessed at the final follow-up (3 months). Results: Patients who received contracted follow-up showed greater improvement in neck dysfunction at 24-72 h, 1 month, and 3 months after discharge compared to those who received routine follow-up (p < 0.001). At 1 month after discharge, the intervention group exhibited better self-efficacy (p = 0.001) and quality of life (p < 0.001) than the control group, and these improvements lasted for 3 months. The intervention group reported lower pain scores at 24-72 h and 1 month (p = 0.008; p = 0.026) compared to the control group. The incidence of complications was significantly lower in the intervention group (11.4%) compared to the control group (40.9%). The total satisfaction score was significant difference between the two groups (p < 0.001). Additionally, the intervention group had lower direct medical costs (p < 0.001), direct non-medical costs (p = 0.035), and total costs (p = 0.04) compared to the control group. However, there was no statistically significant difference in indirect costs between the two groups (p = 0.59). Conclusion: A multidisciplinary contract follow-up plan has significant advantages regarding neck disability, self-efficacy, quality of life, postoperative complications, patient satisfaction, and direct costs compared with routine follow-up.

8.
Orthop Surg ; 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38664223

RESUMO

OBJECTIVES: Multi-planar external fixation has been used for the management of segmental tibial fractures with severe soft tissue injuries. However, fewer specialized studies have been reported. The primary aim of this study was to describe our experience of treating fractures of this type using the Taylor Spatial Frame and Ilizarov external fixation methods. METHODS: We retrospectively analyzed 33 patients with segmental tibial fracture treated at our institution between January 2016 and December 2020. The patients were divided into double Taylor Spatial Frame (D-TSF) and Ilizarov groups based on the external fixation structure. Baseline demographic data included sex, age, injury side and cause, open or closed fracture, time from injury to surgery, complications, and external frame removal and fracture healing time. The hip-knee-ankle angle (HKA) was measured from preoperative, immediate postoperative, and final follow-up full-length X-rays of bilateral lower limbs. We determined the degree of deviation in the HKA by calculating the difference between the measured angle and the ideal value of 180°; the absolute value was used to assess recovery of the lower limb force line. At the final follow-up, Johner-Wruhs tibial fracture outcome criteria (J-W TFOC) were used to classify the postoperative function of the affected limb as excellent, good, moderate, or poor. Count data were analyzed with the chi-square test or Fisher's exact test; the Mann-Whitney U test was used for rank data. RESULTS: No statistically significant differences were observed between the two groups in terms of sex, age, side of injury, cause of injury, closed or open fracture, or time between injury and surgery, which indicates that the groups were comparable (p > 0.05). A statistically significant difference was observed in external frame removal and fracture healing time between the D-TSF and Ilizarov groups (36.24 ± 8.34 vs 45.42 ± 10.21 weeks, p = 0.009; 33.33 ± 8.21 vs 42.00 ± 9.78 weeks, p = 0.011). The Johner-Wruhs criteria were used to assess the function of the affected limb, the D-TSF group performed better in correcting the lower limb force line than the Ilizarov group. A statistically significant difference in terms of excellent ratings was observed between the two groups (18/2/1/0 vs 5/5/1/1, p = 0.010). Postoperative follow-up X-rays demonstrated a significant improvement in the HKA in both groups immediately after surgery and at the final follow-up compared to the angle before surgery. At the final follow-up, a statistically significant difference was observed in the degree of deviation in the HKA between the two groups (1.58° ± 0.84° vs 2.37° ± 1.00°, p = 0.023). CONCLUSION: The D-TSF treatment is associated with minimal secondary damage to soft tissue, a straightforward and minimally invasive procedure, multiplanar stable fracture fixation, and optimization of fracture alignment and lower limb force lines, therefore, it is highly effective therapeutic option for segmental tibial fracture.

9.
Funct Integr Genomics ; 24(2): 75, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38600341

RESUMO

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality globally. Many herbal medicines and their bioactive compounds have shown anti-tumor properties. This study was conducted to examine the effect of psilostachyin C (PSC), a sesquiterpenoid lactone isolated from Artemisia vulgaris L., in the malignant properties of HCC cells. CCK-8, flow cytometry, wound healing, and Transwell assays revealed that 25 µM PSC treatment significantly suppressed proliferation, cell cycle progression, migration, and invasion of two HCC cell lines (Hep 3B and Huh7) while promoting cell apoptosis. Bioinformatics prediction suggests CREB binding protein (CREBBP) as a promising target of PSC. CREBBP activated transcription of GATA zinc finger domain containing 2B (GATAD2B) by binding to its promoter. CREBBP and GATAD2B were highly expressed in clinical HCC tissues and the acquired HCC cell lines, but their expression was reduced by PSC. Either upregulation of CREBBP or GATAD2B restored the malignant properties of HCC cells blocked by PSC. Collectively, this evidence demonstrates that PSC pocessess anti-tumor functions in HCC cells by blocking CREBBP-mediated transcription of GATAD2B.


Assuntos
Carcinoma Hepatocelular , Compostos Heterocíclicos com 3 Anéis , Neoplasias Hepáticas , Pironas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Proteína de Ligação a CREB/genética , Proteína de Ligação a CREB/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica
10.
Pharmacol Biochem Behav ; 239: 173757, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38574898

RESUMO

Depression is a major chronic mental illness worldwide, characterized by anhedonia and pessimism. Exposed to the same stressful stimuli, some people behave normally, while others exhibit negative behaviors and psychology. The exact molecular mechanisms linking stress-induced depressive susceptibility and resilience remain unclear. Connexin 43 (Cx43) forms gap junction channels between the astrocytes, acting as a crucial role in the pathogenesis of depression. Cx43 dysfunction could lead to depressive behaviors, and depression down-regulates the expression of Cx43 in the prefrontal cortex (PFC). Besides, accumulating evidence indicates that inflammation is one of the most common pathological features of the central nervous system dysfunction. However, the roles of Cx43 and peripheral inflammation in stress-susceptible and stress-resilient individuals have rarely been investigated. Thus, animals were classified into the chronic unpredictable stress (CUS)-susceptible group and the CUS-resilient group based on the performance of behavioral tests following the CUS protocol in this study. The protein expression of Cx43 in the PFC, the Cx43 functional changes in the PFC, and the expression levels including interleukin (IL)-1ß, tumor necrosis factor-α, IL-6, IL-2, IL-10, and IL-18 in the peripheral serum were detected. Here, we found that stress exposure triggered a significant reduction in Cx43 protein expression in the CUS-susceptible mice but not in the CUS-resilient mice accompanied by various Cx43 phosphorylation expression and the changes of inflammatory signals. Stress resilience is associated with Cx43 in the PFC and fluctuation in inflammatory signaling, showing that therapeutic targeting of these pathways might promote stress resilience.


Assuntos
Conexina 43 , Inflamação , Córtex Pré-Frontal , Estresse Psicológico , Animais , Córtex Pré-Frontal/metabolismo , Conexina 43/metabolismo , Camundongos , Estresse Psicológico/metabolismo , Masculino , Inflamação/metabolismo , Resiliência Psicológica , Camundongos Endogâmicos C57BL , Depressão/metabolismo , Citocinas/metabolismo , Suscetibilidade a Doenças , Comportamento Animal
11.
Zhongguo Zhong Yao Za Zhi ; 49(6): 1455-1466, 2024 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-38621929

RESUMO

Ulcerative colitis is a chronic, recurrent, and nonspecific intestinal inflammatory disease, which is difficult to cure and has the risk of deterioration into related tumors. Long-term chronic inflammatory stimulation can increase the risk of cancerization. With the signaling pathway as a key link in the regulation of tumor microenvironments, nuclear factor-kappa B(NF-κB) is an important regulator of intestinal inflammation. It can also be co-regulated as downstream factors of other signaling pathways, such as TLR4, MAPK, STAT, PI3K, and so on. At present, a large number of animal experiments have proved that traditional Chinese medicine(TCM) can reduce inflammation by interfering with NF-κB-related signaling pathways, improve intestinal inflammation, and inhibit the progression of inflammation to tumors. This article reviewed the relationship between NF-κB-related signaling pathways and the intervention mechanism of TCM, so as to provide a reference for the clinical treatment of ulcerative colitis and the optimization of related cancer prevention strategies.


Assuntos
Colite Ulcerativa , Neoplasias Colorretais , Animais , Colite Ulcerativa/complicações , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/genética , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Modelos Animais de Doenças , Inflamação , Medicina Tradicional Chinesa , NF-kappa B/genética , NF-kappa B/metabolismo , Transdução de Sinais , Microambiente Tumoral
12.
BMC Nurs ; 23(1): 217, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38549159

RESUMO

BACKGROUND: Patients in spine surgery often have emotional disorders which is caused by multi-factors. Therefore, a multidisciplinary and multimodal intervention program is required to improve emotional disorders during the perioperative period. However, related studies were rare. This study aimed to confirm that the multidisciplinary-based psychological management leading by nurses was effective in treating emotional disorders and show the assignments of the members of the multidisciplinary team with the orientations of nurses. DESIGN: A retrospective, comparative study. METHOD: This study was a retrospective cohort research and compared the results between the intervention group and control group using the Huaxi Emotional Distress Index (HEI) which was used to evaluate emotional disorders. The intervention group consisted of patients who underwent surgery between January 2018 and December 2020 after psychological management was implemented. The control group consisted of patients with regular care who underwent surgery between January 2015 and December 2017. To improve comparability between the two groups, baseline data from the recruited patients were analyzed using propensity-score-matching (PSM) based on age, sex, marital status, education, and disease region. RESULTS: A total of 539 (11.5%) people developed emotional disorders, of which 319 (6.8%), 151 (3.2%) and 69 (1.5%) had mild, moderate mood and severe emotional disorders, respectively. 2107 pairs of patients were matched after PSM. Scores of HEI in the intervention group were heightened compared with those in the control group (P<0.001) after matching. Moreover, the incidence of emotional disorders in patients decreased after implementing psychological management (P = 0.001). The severity of emotional disorders was alleviated with statistical significance as well (P = 0.010). CONCLUSIONS: Nurses-led Multidisciplinary-Based psychological management was able to reduce the incidence of emotional disorders and improve the severity of these in spine surgery patients.

13.
Sci Rep ; 14(1): 7522, 2024 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-38553594

RESUMO

To investigate the safety and efficacy of the neoadjuvant chemoradiotherapy (NCRT) followed by neoadjuvant consolidation chemotherapy (NCCT) and surgery for locally advanced gastric cancer (GC) or gastroesophageal junction (GEJ) adenocarcinoma. Patients diagnosed as locally advanced GC or Siewert II/III GEJ adenocarcinoma with clinical stage T3-4 and/or N positive were prospectively enrolled. Patients underwent NCRT (45 Gy/25 fractions) with concurrent S-1, followed by NCCT (4 to 6 cycles of the SOX regimen) 2 to 4 weeks after NCRT. Gastric cancer radical resection with D2 lymph node dissection was performed 4 to 6 weeks after the total neoadjuvant therapy. The study was conducted from November 2019 to January 2023, enrolling a total of 46 patients. During the NCRT, all patients completed the treatment without dose reduction or delay. During the NCCT, 32 patients (69.6%) completed at least 4 cycles of chemotherapy. Grade 3 or higher adverse events in NCRT (5 cases) were non-hematological. During the course of NCCT, a notable occurrence of hematological toxicities was observed, with grade 3 or higher leukopenia (9.7%) and thrombocytopenia (12.2%) being experienced. A total of 28 patients (60.9%) underwent surgery, achieving R0 resection in all cases. A significant proportion of cases (71.4%) exhibited pathological downstaging to ypT0-2, while 10 patients (35.7%) demonstrated a pathologic complete response (pCR). The total neoadjuvant therapy comprising NCRT followed by NCCT and surgery demonstrates a low severe adverse reactions and promising efficacy, which could be considered as a viable treatment for locally advanced GC or GEJ adenocarcinoma.Trial registration: Clinicaltrials.gov (registration number: NCT04062058); the full date of first trial registration was 20/08/2019.


Assuntos
Adenocarcinoma , Neoplasias Esofágicas , Neoplasias Gástricas , Humanos , Terapia Neoadjuvante , Neoplasias Gástricas/terapia , Neoplasias Gástricas/patologia , Estudos Prospectivos , Quimiorradioterapia , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/patologia , Adenocarcinoma/terapia , Adenocarcinoma/patologia , Junção Esofagogástrica/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Resultado do Tratamento
14.
Trends Cancer ; 10(5): 389-392, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38494372

RESUMO

The cancer mycobiome has recently become a research hotspot. While the intratumor mycobiota is implicated in cancer initiation and progression, the gut mycobiota functions as biomarkers for cancer diagnosis and treatment. In this forum article we highlight the involvement of the mycobiome in correlation-, causation-, and prediction-oriented cancer research and discuss the potential of this burgeoning field.


Assuntos
Microbioma Gastrointestinal , Micobioma , Neoplasias , Humanos , Neoplasias/microbiologia , Biomarcadores Tumorais/metabolismo , Pesquisa Biomédica
16.
Anal Chem ; 96(13): 5323-5330, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38501982

RESUMO

Oxidative DNA damage is closely associated with the occurrence of numerous human diseases and cancers. 8-Oxo-7,8-dihydroguanine (8-oxoG) is the most prevalent form of DNA damage, and it has become not only an oxidative stress biomarker but also a new epigenetic-like biomarker. However, few approaches are available for the locus-specific detection of 8-oxoG because of the low abundance of 8-oxoG damage in DNA and the limited sensitivity of existing assays. Herein, we demonstrate the elongation and ligation-mediated differential coding for label-free and locus-specific analysis of 8-oxoG in DNA. This assay is very simple without the involvement of any specific labeled probes, complicated steps, and large sample consumption. The utilization of Bsu DNA polymerase can specifically initiate a single-base extension reaction to incorporate dATP into the opposite position of 8-oxoG, endowing this assay with excellent selectivity. The introduction of cascade amplification reaction significantly enhances the sensitivity. The proposed method can monitor 8-oxoG with a limit of detection of 8.21 × 10-19 M (0.82 aM), and it can identify as low as 0.001% 8-oxoG damage from a complex mixture with excessive undamaged DNAs. This method can be further applied to measure 8-oxoG levels in the genomic DNA of human cells under diverse oxidative stress, holding prospect potential in the dynamic monitoring of critical 8-oxoG sites, early clinical diagnosis, and gene damage-related biomedical research.


Assuntos
DNA Polimerase Dirigida por DNA , DNA , Guanina/análogos & derivados , Humanos , DNA/genética , DNA Polimerase Dirigida por DNA/metabolismo , Dano ao DNA , Biomarcadores , Reparo do DNA
17.
Environ Sci Pollut Res Int ; 31(18): 27240-27258, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38509309

RESUMO

Growing evidence has found the health protective effects of greenness exposure on tuberculosis (TB) and the impact of ambient air pollutants on TB drug-resistance. However, it remains unclear whether residential greenness is also beneficial to reduce TB drug-resistance, and whether air pollution modify the greenness-TB resistance relationship. We enrolled 5006 newly-diagnosed TB patients from Shandong, China, during 2014 to 2021. Normalized Difference Vegetation Index (NDVI) in 250 m and 500 m buffer around individuals' residential zone was used to assess greenness exposure. All patients were divided by quartiles of NDVI250-m and NDVI500-m (from low to high: Q1, Q2, Q3, Q4) respectively. Six logistic regression models (NDVI, NDVI + PM2.5/PM10/SO2/NO2/O3) were used to estimate the association of NDVI and TB drug-resistance when adjusting different air pollutants or not. All models were adjusted for age, gender, body mass index, complications, smoking, drinking, population density, nighttime light index, road density. Compared with participants in NDVI250-m Q1 and NDVI500-m Q1, other groups had lower rates of MDR-TB, PDR-TB, RFP-resistance, SM-resistance, RFP + SM resistance, INH + RFP + EMB + SM resistance. NDVI500-m reduced the risk of multidrug resistant tuberculosis (MDR-TB) and the adjusted odds ratio (aOR, 95% confidence interval, CI) compared with NDVI500-m Q1 were 0.736 (0.547-0.991) in NDVI + PM10 model, 0.733 (0.544-0.986) in NDVI + PM2.5 model, 0.735(0.546-0.99) in NDVI + SO2 model, 0.736 (0.546-0.991) in NDVI + NO2 model, respectively, P < 0.05. NDVI500-m contributed to a decreased risk of streptomycin (SM)-resistance. The aOR of rifampicin (RFP) + SM resistance were 0.132 (NDVI250-m, Q4 vs Q1, 95% CI: 0.03-0.578), 0.199 (NDVI500-m, Q3 vs. Q1, 95% CI: 0.057-0.688) and 0.264 (NDVI500-m, Q4 vs. Q1, 95% CI: 0.087-0.799). The adjusted ORs (Q2 vs. Q1, 95% CI) of isoniazid (INH) + RFP + ethambutol (EMB) + SM resistance in 500 m buffer were 0.276 (0.119-0.639) in NDVI model, 0.279 (0.11-0.705) in NDVI + PM10 model, 0.281 (0.111-0.713) in NDVI + PM2.5 model, 0.279 (0.11-0.709) in NDVI + SO2 model, 0.296 (0.117-0.754) in NDVI + NO2 model, 0.294 (0.116-0.748) in NDVI + O3 model, respectively. The study showed, for the first time, that residential greenness exposure in 500 m buffer is beneficial for reducing newly-diagnosed DR-TB (including PDR-RB, MDR-TB, MR-TB), and ambient air pollutants may partially mediate this association.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Exposição Ambiental , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , China , Masculino , Feminino , Adulto , Pessoa de Meia-Idade
18.
Cancer Lett ; : 216793, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38513800

RESUMO

This study was to report proxy measures for mortality risk in patients with hematological malignancies across 185 countries globally and explore its association with their socioeconomic status and treatment. The incidence, mortality, and 5-year prevalence data were extracted from the GLOBOCAN database. The data regarding the human development index (HDI), gross national income (GNI), vulnerability index, and concordance with cancer Essential Medicines List (EML) were obtained from open-source reports. The ratio of mortality to 5-year-prevalence (MPR) and that of mortality to incidence (MIR) were calculated and age-standardized using Segi's world standard population. Finally, the possible associations were assessed using Pearson correlation analyses. In 2020, the global incidence, mortality, and 5-year prevalence of HMs were 1,278,362, 711,840, and 3,616,685, respectively. Global age-standardized MPR and MIR were 0.15 and 0.44, respectively; they varied significantly among 6 regions, 185 countries, 4 HM types, and 4 HDI groups worldwide. Older populations always had higher ratios. The correlation of MPRs and MIRs with HDI, GNI, and concordance with cancer EML was negative, whereas it was positive with the vulnerability index (lower was better). Increasing access to cancer drugs in resource-limited regions with a focus on vulnerable children may aid in reducing HM-related mortality risk.

19.
Leuk Lymphoma ; : 1-12, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38506231

RESUMO

The disease failure patterns and optimal treatment of bronchus-associated lymphoid tissue (BALT) lymphoma are unknown. This retrospective study involved 71 patients with primary BALT lymphoma who had received radiotherapy (RT), surgery, immunochemotherapy (IC), or observation. The median follow-up time was 66 months. The 5-year overall survival and lymphoma-specific survival were 91.2% and 96.1%, respectively, and were not significantly different among treatments. The 5-year cumulative incidence of overall failure for RT, surgery, IC, and observation was 0%, 9.7% (p = .160), 30.8% (p = .017), and 31.3% (p = .039). There was no grade ≥3 toxicity in RT group according to the CTCAE 5.0 reporting system. Quality of life (QoL) was at similarly good levels among the treatment groups. BALT lymphoma had a favorable prognosis but persistent risk of relapse after IC or observation. Given the very low disease failure risk and good QoL, RT remains an effective initial treatment for BALT lymphoma.Key PointsBALT lymphoma has a favorable prognosis but a persistent progression and relapse risk.Radiotherapy is associated with lower failure of disease progression and relapse, low toxicity and good quality of life.

20.
BMC Med Educ ; 24(1): 290, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38491487

RESUMO

BACKGROUND: To compare the value and efficiency of the three-dimensional (3D) heads-up surgical system and traditional microscopic (TM) system in teaching and learning vitreoretinal surgeries. METHODS: Twenty ophthalmologists and scrub nurses were recruited as teachers, and 45 junior ophthalmology residents and trainee doctors, trainee nurses, and medical students were recruited as observers. Each teacher and observer were assigned to both a 3D-assisted and TM-assisted vitreoretinal surgery and then asked to complete satisfaction questionnaires for both surgical systems at the end of each surgery. RESULTS: The 3D heads-up surgical system was rated significantly higher in most of the subscales and overall satisfaction score by both teachers and observers (P < 0.05). However, ratings for instrument adjustment were significantly higher in the TM group compared to the 3D group for junior ophthalmology residents and trainee doctors (6.1 ± 1.7 vs. 8.8 ± 1.1, P < 0.001). CONCLUSIONS: The 3D heads-up surgical system has great didactical value in the medical education of vitreoretinal surgeries, but it is important to consider the specific needs of different learners when choosing between the two systems. TRIAL REGISTRATION: Not applicable.


Assuntos
Educação Médica , Cirurgia Vitreorretiniana , Humanos , Cirurgia Vitreorretiniana/métodos , Estudos Prospectivos , Aprendizagem , Inquéritos e Questionários
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