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OBJECTIVES: Relapsed/refractory acute B-cell lymphoblastic leukemia (R/R B-ALL) often responds poorly to induction chemotherapy. However, recent research has shown a novel and effective drug treatment for R/R B-ALL. METHODS: A total of eight patients with R/R B-ALL were enrolled in the study from November 2021 to August 2022. All patients received chemotherapy based on a combination regimen of venetoclax and azacitidine. The regimen was as follows venetoclax 100 mg d1, 200 mg d2, 400 mg d3-14, azacitidine 75 mg/m2 d1-7. RESULTS: Five of eight patients achieved very deep and complete remission (CR) with minimal residual disease (MRD) less than 0.1%. One patient achieved partial remission. Two patients did not achieve remission. There were no serious adverse events and all patients were well tolerated. Three patients were eligible for consolidation chemotherapy and were bridged to CAR-T therapy. CONCLUSIONS: The combined regimen of venetoclax and azacitidine may be beneficial for patients with R/R B-ALL.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Azacitidine , Bridged Bicyclo Compounds, Heterocyclic , Sulfonamides , Humans , Azacitidine/therapeutic use , Azacitidine/administration & dosage , Bridged Bicyclo Compounds, Heterocyclic/therapeutic use , Bridged Bicyclo Compounds, Heterocyclic/administration & dosage , Female , Male , Sulfonamides/therapeutic use , Sulfonamides/administration & dosage , Middle Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Adult , Aged , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/drug therapyABSTRACT
OBJECTIVE: To investigate the efficacy and safety of venetoclax (VEN) combined with demethylating agents (HMA) in the treatment of relapsed/refractory acute myeloid leukemia (R/R AML). METHODS: The clinical data of 26 adult R/R AML patients who received the combination of VEN with azacitidine (AZA) or decitabine (DAC) in Huai'an Second People's Hospital from February 2019 to November 2021 were retrospectively analyzed. The treatment response, adverse events as well as survival were observed, and the factors of influencing the efficacy and survival were explored. RESULTS: The overall response rate (ORR) of 26 patients was 57.7% (15 cases), including 13 cases of complete response (CR) and CR with incomplete count recovery (CRi) and 2 cases of partial response (PR). Among the 13 patients who got CR/CRi, 7 cases achieved CRm (minimal residual disease negative CR) and 6 cases did not, with statistically significant differences in overall survival (OS) and event-free survival (EFS) between the two groups (P=0.044, 0.036). The median OS of all the patients was 6.6 (0.5-15.6) months, and median EFS was 3.4 (0.5-9.9) months. There were 13 patients in the relapse group and refractory group, respectively, with response rate of 84.6% and 30.8% (P=0.015). The survival analysis showed that the relapse group had a better OS than the refractory group (P=0.026), but there was no significant difference in EFS (P=0.069). Sixteen patients who treated for 1-2 cycles and 10 patients who treated for more than 3 cycles achieved response rates of 37.5% and 90.0%, respectively (P=0.014), and patients treated for more cycles had superior OS and EFS (both P<0.01). Adverse effects were mainly bone marrow suppression, complicated by various degrees of infection, bleeding, and gastrointestinal discomfort was common, but these could be all tolerated by patients. CONCLUSION: VEN combined with HMA is an effective salvage therapy for patients with R/R AML and is well tolerated by patients. Achieving minimal residual disease negativity is able to improve long-term survival of patients.
Subject(s)
Bridged Bicyclo Compounds, Heterocyclic , Leukemia, Myeloid, Acute , Adult , Humans , Retrospective Studies , Neoplasm, Residual/chemically induced , Neoplasm, Residual/drug therapy , Bridged Bicyclo Compounds, Heterocyclic/adverse effects , Recurrence , Leukemia, Myeloid, Acute/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic useABSTRACT
Atypical chronic myeloid leukemia (CML) is a rare BCR::ABL1-negative hematopoietic stem cell disease characterized by granulocytic proliferation and granulocytic dysplasia. Due to both the challenging diagnosis and the rarity of atypical CML, comprehensive molecular annotation-based analyses of this disease population have been scarce, and it is currently difficult to identify the optimal treatment for atypical CML. To explore atypical CML genomic landscape and treatment options, we performed a systematic retrospective of the clinical data and outcomes of 31 atypical CML patients. We observed that the molecular landscape of atypical CML was highly heterogeneous, with multiple molecular events driving its pathogenesis. Patients with atypical CML had a low response to current therapies, with an overall response rate (ORR) of 33.3% to hypomethylating agent (HMA)-based therapy. The current treatment strategies, including hematopoietic stem cell transplantation (HSCT), did not improve overall survival (OS) in atypical CML patients, with a median survival of 20 months. Thus, the benefits from HSCT and candidates for HSCT remain to be further evaluated. Acute myeloid leukemia (AML)-like chemotherapy followed by bridging allogeneic HSCT may be an ideal regimen for suitable individuals. The large-scale and prospective clinical studies will help to address the dilemma.
Subject(s)
Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative , Humans , Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative/therapy , Retrospective Studies , Prospective Studies , World Health Organization , Molecular BiologyABSTRACT
The associations of red/processed meat consumption and cancer-related health outcomes have been well discussed. The umbrella review aimed to summarise the associations of red/processed meat consumption and various non-cancer-related outcomes in humans. We systematically searched the systematic reviews and meta-analyses of associations between red/processed meat intake and health outcomes from PubMed, Embase, Web of Science and the Cochrane Library databases. The umbrella review has been registered in PROSPERO (CRD 42021218568). A total of 40 meta-analyses were included. High consumption of red meat, particularly processed meat, was associated with a higher risk of all-cause mortality, CVD and metabolic outcomes. Dose-response analysis revealed that an additional 100 g/d red meat intake was positively associated with a 17 % increased risk of type 2 diabetes mellitus (T2DM), 15 % increased risk of CHD, 14 % of hypertension and 12 % of stroke. The highest dose-response/50 g increase in processed meat consumption at 95 % confident levels was 1·37, 95 % CI (1·22, 1·55) for T2DM, 1·27, 95 % CI (1·09, 1·49) for CHD, 1·17, 95 % CI (1·02, 1·34) for stroke, 1·15, 95 % CI (1·11, 1·19) for all-cause mortality and 1·08, 95 % CI (1·02, 1·14) for heart failure. In addition, red/processed meat intake was associated with several other health-related outcomes. Red and processed meat consumption seems to be more harmful than beneficial to human health in this umbrella review. It is necessary to take the impacts of red/processed meat consumption on non-cancer-related outcomes into consideration when developing new dietary guidelines, which will be of great public health importance. However, more additional randomised controlled trials are warranted to clarify the causality.
Subject(s)
Diabetes Mellitus, Type 2 , Meat Products , Red Meat , Stroke , Humans , Diet/adverse effects , Meat/adverse effects , Meat Products/adverse effects , Red Meat/adverse effects , Risk Factors , Systematic Reviews as Topic , Meta-Analysis as TopicABSTRACT
Current studies on teachers' wellbeing are mainly on lowering stress or burnout. Few studies have noted that faculty wellbeing is related to teaching activities. Teaching engagement and teaching experience are important predictor variables of teachers' wellbeing, but the internal and external influencing mechanisms of teachers' wellbeing have not been clearly revealed. Based on the survey data of 7,408 teachers from 271 undergraduate colleges and universities across China, the internal and external influencing mechanisms of teaching engagement and teaching experience on teachers' wellbeing were investigated through multicluster structural equation modeling. The results were that teachers' wellbeing was influenced by both teaching engagement and teaching experience. Among teaching engagement, teachers' pre-class preparation and post-class communication positively influenced teaching experience, but in-class delivery negatively influenced teaching experience. Teaching experience partially mediates the relationship between engagement and wellbeing. At the level of internal influence, the more teachers identify with and feel accomplished by teaching, the more they invest time and energy in teaching; at the level of external influence, the school environment, leadership, and colleague support affect teachers' wellbeing through the teaching experience. Universities should offer good teaching hardware and software for teachers, provide adequate teaching support, especially encourage teacher-student communication after class, weaken the rigid constraints and controls on teachers' teaching in class, give teachers enough teaching autonomy, and reduce their teaching burden to inspire teachers to be more actively involved in teaching, improve their teaching experience, and thus enhance their sense of wellbeing.
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In recent years, there has been growing concern about the impact of the gastrointestinal microbiome on human health outcomes. To clarify the evidence for a link between the gastrointestinal microbiome and a variety of health outcomes in humans, we conducted an all-encompassing review of meta-analyses and systematic reviews that included 195 meta-analyses containing 950 unique health outcomes. The gastrointestinal microbiome is related to mortality, gastrointestinal disease, immune and metabolic outcomes, neurological and psychiatric outcomes, maternal and infant outcomes, and other outcomes. Existing interventions for intestinal microbiota (such as probiotics, fecal microbiota transplant, etc.) are generally safe and beneficial to a variety of human health outcomes, but the quality of evidence is not high, and more detailed and well-designed randomized controlled trials are necessary.
Subject(s)
Gastrointestinal Microbiome , Probiotics , Synbiotics , Fecal Microbiota Transplantation , Humans , PrebioticsABSTRACT
OBJECTIVE: The study of artificial intelligence needs tracing back to the working mechanism of the human brain, and based on simulating brain cognition activity, information technology is the most widely influential technology. METHOD: Language cognition is the core and foundation of human cognition. Biolinguistics' core problem about brain mechanisms (a psychological mechanism) is related to the development of human language cognition in that the cognitive process of humans is from the construction of mediation and language is the very cognitive mediation. The logical law of human language cognition algorithm is about the process of human cognitive psychology that is from the neurological stage, the psychological perception stage, and to the cognitive stage of symbols, which makes psychological certainty account for the connection from mental content to language meaning. Language cognition is where the "awakening" of artificial intelligence begins. First of all, humans produce mental images based on sensory perception and categories. The referential functions of mental images extend the human cognitive scope. Then, categorization is realized through the mediation of mental images. At the time the category is formed, the symbol is required. Language is involved in the thinking process in the cognitive stage of symbols to realize the construction of the mediation to represent the category abstracted from the concrete things. RESULTS: Above all, human language metacognition is realized from the subject-predicate structure that is the grammatical structure on the surface but is throughout the whole process of human rational knowledge and configures the content of rational knowledge, which is the developmental goal of "awakening" artificial intelligence. CONCLUSIONS: The demonstration of this proposition is conducive to providing a theoretical basis for the research of the working mechanism of the human brain stimulated by artificial intelligence. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
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Irregular hemorrhagic traumas always threaten the health of patients due to uncontrollable bleeding and wound infections. The traditional hemostatic materials show dissatisfactory hemostatic efficiency and antibacterial activity in solving these potential bleeding dangers. Herein, we proposed a kind of composites based on flexible wood membrane (FWM) loaded with chitosan/alginate derivative for accelerating rapid hemostasis and preventing infection. FWM was removed part of hemicellulose and lignin by using NaOH/Na2SO3 mixture to obtain excellent flexibility while retaining the original porous structure, followed by loading silver nanoparticles on the FWM surface to prepare AgNPs-FWM as an antibacterial bio-carrier. Then, AgNPs-FWM was coated with polyoxyethylene stearate-modified chitosan and multi-aldehyde sodium alginate to fabricate the composites of chitosan/alginate/AgNPs-FWM (CSA/AgNPs-FWM) using in-situ Schiff base reaction. Furthermore, in vitro and in vivo experiments showed that the CSA/AgNPs-FWM composites exhibited lower BCI value (2.6 ± 1.3 %), more rapid hemostasis (26 s) and lower blood loss (67.8 mg) than that of the traditional materials. The possible mechanism for the hemostasis process was not only the high blood absorption capacity, but also the synergistic interaction between hydrophobic alkane chains, amino groups, aldehydes, hydroxyl groups and blood cells. Moreover, CSA/AgNPs-FWM showed exceptional superiorities in mechanical properties and antibacterial activity, which endowed composites high potential in hemostasis application for irregular external wound.
Subject(s)
Chitosan , Hemostatics , Metal Nanoparticles , Alginates/chemistry , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Chitosan/chemistry , Chitosan/pharmacology , Hemostasis , Hemostatics/pharmacology , Humans , Metal Nanoparticles/chemistry , Silver/chemistry , Silver/pharmacology , WoodABSTRACT
As one of 21st century key skills, self-leadership is not only the internal factor of private college undergraduates' independent development, but also related to the quality improvement of talent cultivation of private undergraduate colleges. It is proved that mindfulness or metacognition separately has the predictive effect on self-leadership, but their structural relationships has not been revealed. The present study explored the interrelations between mindful agency, metacognitive ability, and self-leadership through the mediation analysis with structural equation modeling, and bootstrapping was conducted to test the mediating effect. The sample comprised 1,244 private undergraduate sophomore (38.4% male and 61.6% female), and they completed online questionnaires of mindful agency, metacognitive ability, and self-leadership. The results revealed that mindful agency of private undergraduate students not only directly and positively predicted self-leadership, but also indirectly and positively predicted self-leadership through the mediating effect of metacognitive ability. Metacognitive ability partially mediated the relationship between mindful agency and self-leadership. The direct effect of mindful agency and the mediating effect of metacognitive ability, respectively, account for 86.9% and 13.1% of the total effect. The results suggest that the more mindful private college undergraduates are, the more willing they are to practise their metacognitive skills in their learning, and the more progress in self-leadership they make. Educational implications for mindfulness training and metacognition practice to foster their self-leadership are discussed.
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BACKGROUND & AIMS: Patients who undergo gastrectomy often have a high risk of postoperative complications. This study aimed to investigate the effects of n-3 polyunsaturated fatty acids (PUFAs) on immune function, the inflammatory response, nutritional status, and rehabilitation of patients with gastric cancer. METHODS: A total of 120 patients with gastric cancer who underwent elective radical gastrectomy in the Department of Gastrointestinal Surgery, West China Hospital, Sichuan University from September 2019 to December 2020 were randomly divided into the n-3 PUFAs group (n = 60) and control group (n = 60). Patients in N-3 PUFAs group were treated with enteral nutrition (EN) combined with parenteral nutrition (PN) enriched with n-3 PUFAs from postoperative Day 1 to Day 5, whereas patients in the control group were administered EN combined with PN without n-3 PUFAs. Immune parameters (lymphocyte count [LYM], CD3+, CD4+, CD8+, CD4+/CD8+), inflammatory indicators (white blood cell [WBC], C-reactive protein [CRP], interleukin 6 [IL-6], tumor necrosis factor α [TNF-α]), nutrition parameters (hemoglobin [Hb], total protein [TP], albumin [Alb], prealbumin [PAB], transferrin [TRF]), the incidence of postoperative complications and rehabilitation parameters were compared between the two groups. RESULTS: The immune parameters (LYM, CD3+, CD4+, CD4+/CD8+) and nutritional parameters (TP, Alb, PAB) of the n-3 PUFAs group were significantly increased compared with the control group, and inflammatory indicators (CRP, IL-6, TNF-α) were lower compared with the control group. The rate of postoperative complications in the n-3 PUFAs group (7%) was significantly lower than that in the control group (20%), and the time to first aerofluxus and defecation were earlier in the n-3 PUFAs group. No differences in postoperative length of stay, unplanned 30-day readmission or reoperation after surgery were noted. CONCLUSION: The study shows that n-3 PUFAs contribute to the recovery of immune function, inflammatory response, and early rehabilitations of patients with gastric cancer undergoing gastrectomy. N-3 PUFAs were safe and effective in promoting the rehabilitation of patients with gastrectomy in our study. More high-quality and large sample studies are needed. Registration number of Clinical Trial: ChiCTR1900028381.
Subject(s)
Fatty Acids, Omega-3 , Stomach Neoplasms , C-Reactive Protein , Enteral Nutrition , Humans , Interleukin-6 , Parenteral Nutrition , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/prevention & control , Stomach Neoplasms/complications , Stomach Neoplasms/surgery , Tumor Necrosis Factor-alphaABSTRACT
AIM: This study aimed to synthesise available data and evaluate the clinical evidence regarding the effect of early enteral nutrition versus total parenteral nutrition on nutritional status and blood glucose in patients with gastric cancer complicated with diabetes mellitus after gastrectomy. METHODS: This systematic review and meta-analysis was designed, conducted and reported following the PRISMA guideline. We performed searches in PubMed, Embase, Medline, Web of Science, Cochrane Library, Chinese Biomedicine Literature Database, Chinese Scientific Journal Database, Chinese National Knowledge Infrastructure and Wanfang Database. The study designs were randomised controlled trials, quasi-randomised controlled trials, and controlled clinical trials. The trials compared early enteral nutrition (experimental group) with total parenteral nutrition (control group) in patients with gastric cancer complicated with diabetes mellitus after gastrectomy. The risk of bias was assessed using the Cochrane risk of bias tool. RESULTS: A total of 19 trials (1255 patients) were included. Meta-analysis showed a significantly shorter length of hospital stay (days; mean difference -5.07, 95% confidence interval [CI] [-6.28, -3.86], p < 0.00001) and a lower post-operative complications rate (%; odds ratio 0.29, 95% CI [0.16, 0.50], p < 0.0001) in the early enteral nutrition group than in the total parenteral nutrition group. Compared with the total parenteral nutrition group, the early enteral nutrition group had lower blood glucose fluctuation values (mmol/L; mean difference -2.03, 95% CI [-2.44, -1.61], p < 0.00001), lower levels of glycosylated haemoglobin (%; mean difference -0.62, 95% CI [-1.22, -0.03], p = 0.04), higher levels of prealbumin (g/L; p = 0.002), transferrin (g/L; p = 0.002), total protein (g/L; p = 0.001) and haemoglobin (g/L; p = 0.005). CONCLUSIONS: Early enteral nutrition may maintain stable blood glucose levels and improve nutritional status, leading to better therapeutic effectiveness in gastric cancer complicated with diabetes mellitus patients.
Subject(s)
Diabetes Mellitus , Stomach Neoplasms , Enteral Nutrition , Humans , Length of Stay , Parenteral Nutrition, Total , Stomach Neoplasms/therapyABSTRACT
The DSB machinery, which induces the programmed DNA double-strand breaks (DSBs) in the leptotene and zygotene stages during meiosis, is suppressed before the onset of the pachytene stage. However, the biological significance and underlying mechanisms remain largely unclear. Here, we report that ZFP541 is indispensable for the suppression of DSB formation after mid-pachytene. The deletion of Zfp541 in mice causes the aberrant recruitment of DSB machinery to chromosome axes and generation of massive DSBs in late pachytene and diplotene spermatocytes, leading to meiotic arrest at the diplotene stage. Integrated analysis of single-cell RNA sequencing (scRNA-seq) and chromatin immunoprecipitation (ChIP) sequencing data indicate that ZFP541 predominantly binds to promoters of pre-pachytene genes, including meiotic DSB formation-related genes (e.g., Prdm9 and Mei1) and their upstream activators (e.g., Meiosin and Rxra), and maintains their repression in pachytene spermatocytes. Our results reveal that ZFP541 functions as a transcriptional regulator in pachytene spermatocytes, orchestrating the transcriptome to ensure meiosis progression.
Subject(s)
Meiotic Prophase I , Spermatocytes , Animals , Chromosomal Proteins, Non-Histone/metabolism , DNA Breaks, Double-Stranded , Histone-Lysine N-Methyltransferase/metabolism , Male , Meiosis , Mice , Pachytene Stage , Spermatocytes/metabolism , Transcription Factors/genetics , Transcription Factors/metabolismABSTRACT
Faithful segregation of X and Y chromosomes requires meiotic recombination to form a crossover between them in the pseudoautosomal region (PAR). Unlike autosomes that have approximately 10-fold more double-strand breaks (DSBs) than crossovers, one crossover must be formed from the one or two DSBs in PARs, implying the existence of a sex chromosomespecific recombination mechanism. Here, we found that RAD51AP2, a meiosis-specific partner of RAD51, is specifically required for the crossover formation on the XY chromosomes, but not autosomes. The decreased crossover formation between X and Y chromosomes in Rad51ap2 mutant mice results from compromised DSB repair in PARs due to destabilization of recombination intermediates rather than defects in DSB generation or synapsis. Our findings provide direct experimental evidence that XY recombination may use a PAR-specific DSB repair mechanism mediated by factors that are not essential for recombination on autosomes.
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BACKGROUND: The associations of alcohol consumption and venous thromboembolism (VTE) have been investigated widely, but the conclusions were inconsistent. OBJECTIVE: To summarize the relationship of alcohol consumption and VTE. METHODS: This study has been registered in PROSPERO (ID: CRD42020164567). We searched the PubMed, Embase, Web of Science and the Cochrane Library databases from inception to September 2019 and reviewed the reference list of relevant articles to identify studies assessing the association between alcohol consumption and risk of VTE. RESULTS: Fourteen cohorts and four case-control studies were included in the meta-analysis. Compared with non-drinkers, the risk of VTE was decreased (RR: 0.93; 95% confidence interval [CI] 0.88-0.99) for alcohol drinkers. The pooled RRs of VTE were 0.91 (95% CI 0.84-0.99) for low to moderate alcohol intake (0.1-14.0 drinks/week) and 0.91 (95% CI 0.78-1.06) for high alcohol intake (>14.0 drinks/week) compared with non-drinker. Subgroup analysis showed liquor intake might slightly increase the risk of VTE (1.01; 95% CI 0.85-1.21) although the difference was not significant. CONCLUSIONS: Alcohol consumption in low to moderate was associated with a lower risk of VTE. However, precautions are needed when providing personal drinking advice considering the potential harm of alcohol. Further studies are warranted to determine whether moderate alcohol consumption has a causal role in VTE.
Subject(s)
Venous Thromboembolism , Alcohol Drinking/adverse effects , Alcohol Drinking/epidemiology , Case-Control Studies , Humans , Venous Thromboembolism/epidemiology , Venous Thromboembolism/etiologyABSTRACT
OBJECTIVE: To evaluate the incidence and clinical characteristics of metabolic syndrome (MS) within one year after hematopoietic stem cell transplantation (HSCT) in order to screen the risk factors for HSCT-MS, provide early intervention and improve the long-term quality of survival of patients. METHODS: The clinical follow-up data of 64 HSCT patients (survival time > 1 year) who received HSCT in our center from January 2007 to August 2018 were collected. Among them, 50 cases were allogeneic hematopoietic stem cell transplantation (allo-HSCT) and 14 cases were autologous hematopoietic stem cell transplantation (auto-HSCT). The changes of MS-related indexes and clinical characteristics before and 1, 3, 6 and 12 months after HSCT were analyzed retrospectively. RESULTS: In allo-HSCT group, 14 cases were diagnosed as MS before operation, including high-density lipoprotein cholesterol (hypo-HDL-C)> hyper triglyceridesï¼hyper-TGï¼> hyper fasting glucoseï¼hyper-FBGï¼> abdominal obesity (AO) > hypertension. The preoperative diagnosis of MS in the auto-HSCT group was 5 cases, in the order of hyper-FBG> hyper-TG> AO> hypo-HDL-C> hypertension. Incidence of MS at 1, 3, 6 and 12 months after transplantation: 19, 26, 24 and 20 cases in the allo-HSCT group, respectively; auto-HSCT group were 7, 7, 6 and 6 cases, respectively. Hyper-TG and hypo-HDL-C were prominent in both groups. CONCLUSION: The incidence of HSCT-MS is significantly higher within 1 year after HSCT. Regardless of allo-HSCT and auto-HSCT, the prevention and control of HSCT-MS is emphasized as an important guarantee to improve the long-term survival quality of HSCT patients.
Subject(s)
Hematopoietic Stem Cell Transplantation , Metabolic Syndrome , Hematopoietic Stem Cells , Humans , Retrospective Studies , Transplantation, HomologousABSTRACT
To the best of our knowledge, the effect of miR-212-3p on sex-determining region Y-box 11 (SOX11) expression has not been previously investigated and how this effect affects cell proliferation and migration in lymphoma remains unclear. The present study aimed to assess the association between microRNA-212-3p (miR-212-3p) and SOX11, and the effects of miR-212-3p on cell proliferation and migration in mantle cell lymphoma. Cancer tissue and corresponding paracancerous tissue samples were collected from 65 patients with mantle cell lymphoma. The mRNA expression levels of miR-212-3p and SOX11 were analyzed using quantitative PCR, and SOX11 protein expression was determined using western blotting. Following transfection, the miR-212-3p mimic group exhibited a significantly lower SOX11 mRNA and protein expression than the miR-NC group. After 48-72 h of transfection, cell proliferation in the miR-212-3p mimic group was significantly lower than that in the miR-NC group. Furthermore, the miR-212-3p mimic group exhibited significantly lower cell invasion and significantly higher apoptosis than the miR-NC group. The current results suggested that miR-212-3p inhibited lymphoma cell proliferation and migration, and promoted their apoptosis by specifically regulating SOX11. Therefore, miR-212-3p may serve as a novel therapeutic target and marker for lymphoma.
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Meiosis is essential for the generation of gametes and sexual reproduction, yet the factors and underlying mechanisms regulating meiotic progression remain largely unknown. Here, we showed that MTL5 translocates into nuclei of spermatocytes during zygotene-pachytene transition and ensures meiosis advances beyond pachytene stage. MTL5 shows strong interactions with MuvB core complex components, a well-known transcriptional complex regulating mitotic progression, and the zygotene-pachytene transition of MTL5 is mediated by its direct interaction with the component LIN9, through MTL5 C-terminal 443-475 residues. Male Mtl5c-mu/c-mu mice expressing the truncated MTL5 (p.Ser445Arg fs*3) that lacks the interaction with LIN9 and is detained in cytoplasm showed male infertility and spermatogenic arrest at pachytene stage, same as that of Mtl5 knockout mice, indicating that the interaction with LIN9 is essential for the nuclear translocation and function of MTL5 during meiosis. Our data demonstrated MTL5 translocates into nuclei during the zygotene-pachytene transition to initiate its function along with the MuvB core complex in pachytene spermatocytes, highlighting a new mechanism regulating the progression of male meiosis.
Subject(s)
Meiosis/physiology , Metallothionein/metabolism , Tumor Suppressor Proteins/metabolism , Active Transport, Cell Nucleus/physiology , Animals , Cell Cycle Proteins/metabolism , Chromosome Pairing/genetics , Cytoplasm , DNA-Binding Proteins , Fertility/genetics , Fertility/physiology , Infertility, Male/genetics , Infertility, Male/metabolism , Male , Meiotic Prophase I/physiology , Metallothionein/genetics , Mice , Mice, Inbred C57BL , Pachytene Stage/genetics , Spermatocytes/physiology , Spermatogenesis/physiology , Testis , Tumor Suppressor Proteins/physiologyABSTRACT
BACKGROUND: Postoperative pneumonia is the third most common complication after surgery, and its occurrence is associated with a poor prognosis in patients. Perioperative chlorhexidine oral care has been reported to reduce the incidence of postoperative pneumonia in patients undergoing cardiac surgery. However, whether perioperative chlorhexidine oral care can reduce the incidence of postoperative pneumonia in noncardiac surgical patients is still unknown. The aim of this systematic review and meta-analysis was to determine the association between perioperative chlorhexidine oral care and postoperative pneumonia in noncardiac surgical patients. METHODS: A comprehensive systematic search of PubMed, Ovid Embase, Web of Science, the Cochrane Library, Wanfang Database, and the China National Knowledge Infrastructure was conducted to include studies from the inception of each database through March 2021. The reference lists of all included studies were also searched by hand. Eligible studies were published and unpublished randomized controlled trials and observational studies evaluating the effect of perioperative chlorhexidine oral care on the reported incidence of postoperative pneumonia. Relative risks or odds ratio with their 95% confidence intervals were calculated and risk of bias was assessed for eligible studies. RESULTS: Seven randomized controlled trials with a total of 1,773 patients and 3 observational studies with a total of 12,528 noncardiac surgical patients were included. A total of 621 and 5,904 patients received perioperative chlorhexidine oral care in randomized controlled trials and observational studies, respectively. Six (85%) randomized controlled trials had a high risk of bias, and 2 (67%) observational studies had a high quality. Perioperative chlorhexidine oral care significantly reduced the incidence of postoperative pneumonia in randomized controlled trials (relative risk, 0.60; 95% confidence interval, 0.44-0.80; P < .001) and observational studies (odds ratio, 0.26; 95% confidence interval, 0.08-0.90; P = .03). CONCLUSION: Perioperative chlorhexidine oral care led by a nurse significantly decreases the incidence of postoperative pneumonia in noncardiac surgical patients and may be more convenient and economical compared with dental professional-led perioperative oral care.
Subject(s)
Chlorhexidine/adverse effects , Intensive Care Units , Oral Hygiene/methods , Perioperative Care/methods , Pneumonia, Ventilator-Associated/prevention & control , Postoperative Complications/prevention & control , Surgical Procedures, Operative/adverse effects , Global Health , Humans , Incidence , Pneumonia, Ventilator-Associated/epidemiology , Pneumonia, Ventilator-Associated/etiology , Postoperative Complications/epidemiology , Postoperative Complications/etiologyABSTRACT
BACKGROUND & AIMS: Preoperative oral carbohydrates are strongly recommended for routine use before various elective procedures. The regimen mainly includes preoperative oral single-dose carbohydrate (2-3 h before surgery) and preoperative oral double-dose carbohydrates (10 h before surgery and 2-3 h before surgery). The choice between the two options is still controversial. METHODS: A total of 139 patients with gastric cancer who underwent radical gastrectomy were recruited from a hospital in Sichuan Province, China. The patients were randomly assigned to a single-dose group (n = 70) or a double-dose group (n = 69). Insulin resistance indicators, subjective comfort indicators, inflammatory mediators, immunological indicators, postoperative recovery indexes, and complications were compared between the two groups. RESULTS: There were no differences in insulin resistance indicators (fasting plasma glucose, fasting insulin, and homeostasis model assessment indexes), inflammatory mediators (C-reactive protein, interleukin-6, and tumor necrosis factor-α), immunological indicators (CD3+, CD4+, CD8+, and CD4+/CD8+) between the single-dose group and double-dose group (all P > 0.05) at preoperative day 1, preoperative 3 h, and postoperative day 1. There were no differences in subjective comfort indicators (thirst, hunger, anxiety, nausea, fatigue, and weakness) between the two groups (all P > 0.05) at preoperative day 1, preoperative 3 h, preoperative 1 h, and postoperative day 1. The postoperative recovery indexes and complications (exhaust time, liquid intake time, postoperative hospital stay, complication incidence, unplanned readmission rate, and unplanned reoperation rate 30 days after operation) did not significantly differ between the two groups (all P > 0.05). The number of preoperative nighttime urinations in the double-dose group was higher than that in the single-dose group (88.3% VS 48.5%, P < 0.001), and the number of hours of preoperative sleep in the double-dose group was lower than that in the single-dose group (4.56 ± 0.68 VS 5.71 ± 0.57, P < 0.001). CONCLUSION: Oral carbohydrates administered the night before surgery did not enhance the effects of oral carbohydrates administered 2-3 h before surgery on insulin resistance, subjective comfort, inflammation, and immunity and might affect the patients' night rest. In making a decision between oral carbohydrate regimes, evening carbohydrates could be omitted. TRIAL REGISTRATION: ChiCTR, ChiCTR1900020608. Registered January 10, 2019, http://www.chictr.org.cn: ChiCTR1900020608.