Homozygous mutations in C14orf39/SIX6OS1 cause non-obstructive azoospermia and premature ovarian insufficiency in humans.

Human infertility is a multifactorial disease that affects 8%-12% of reproductive-aged couples worldwide. However, the genetic causes of human infertility are still poorly understood. Synaptonemal complex (SC) is a conserved tripartite structure that holds homologous chromosomes together and plays an indispensable role in the meiotic progression. Here, we identified three homozygous mutations in the SC coding gene C14orf39/SIX6OS1 in infertile individuals from different ethnic populations by whole-exome sequencing (WES). These mutations include a frameshift mutation (c.204_205del [p.His68Glnfs∗2]) from a consanguineous Pakistani family with two males suffering from non-obstructive azoospermia (NOA) and one female diagnosed with premature ovarian insufficiency (POI) as well as a nonsense mutation (c.958G>T [p.Glu320∗]) and a splicing mutation (c.1180-3C>G) in two unrelated Chinese men (individual P3907 and individual P6032, respectively) with meiotic arrest. Mutations in C14orf39 resulted in truncated proteins that retained SYCE1 binding but exhibited impaired polycomplex formation between C14ORF39 and SYCE1. Further cytological analyses of meiosis in germ cells revealed that the affected familial males with the C14orf39 frameshift mutation displayed complete asynapsis between homologous chromosomes, while the affected Chinese men carrying the nonsense or splicing mutation showed incomplete synapsis. The phenotypes of NOA and POI in affected individuals were well recapitulated by Six6os1 mutant mice carrying an analogous mutation. Collectively, our findings in humans and mice highlight the conserved role of C14ORF39/SIX6OS1 in SC assembly and indicate that the homozygous mutations in C14orf39/SIX6OS1 described here are responsible for infertility of these affected individuals, thus expanding our understanding of the genetic basis of human infertility.

Nuclear translocation of MTL5 from cytoplasm requires its direct interaction with LIN9 and is essential for male meiosis and fertility.

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.

Molecular genetics and management of world health organization defined atypical chronic myeloid leukemia.

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.

Red/processed meat consumption and non-cancer-related outcomes in humans: umbrella review.

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.

Meta-analysis of alcohol consumption and venous thromboembolism.

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.

HLA-mismatched stem cell microtransplantation compared to matched-sibling donor transplantation for intermediate/high-risk acute myeloid leukemia.

HLA-mismatched stem cell microtransplantation is a new form of transplantation reported in recent years. We compared 59 patients undergoing microtransplantation to 66 patients undergoing HLA-matched sibling donor (MSD) transplantation at the same period from April 2012 to December 2016, who all suffered from intermediate/high-risk acute myelogenous leukemia (AML) in first complete remission (CR1). The estimated overall survival (OS) at 2 years was 74.1% ± 6.2% and 34.3% ± 7.9% in MSD and microtransplantation group, respectively (P = 0.001). The estimated leukemia-free survival (LFS) at 2 years was 73.3% ± 6.1% in the MSD group and 31.6% ± 7.6% in the microtransplantation group (P = 0.000). The 2-year cumulative incidence of relapse was 17.6% and 62.3% in the MSD and microtransplantation groups, respectively (P < 0.0001). The 2-year cumulative incidence of nonrelapse mortality was 10.9% in MSD group and 4.2% in the microtransplantation group (P = 0.251). Hematopoietic recovery time was shorter in the microtransplantation group than in the MSD group (P < 0.05). The infection rate was higher in the MSD group than in the microtransplantation group (P = 0.012). The preliminary results suggested that OS and LFS of microtransplantation were inferior to MSD transplantation for intermediate/high-risk AML in CR1.

Efficacy of porcine antihuman lymphocyte immunoglobulin compared to rabbit antithymocyte immunoglobulin as a first-line treatment against acquired severe aplastic anemia.

Immunosuppressive therapy (IST) with antithymocyte immunoglobulin (ATG) or antilymphocyte immunoglobulin (ALG) and cyclosporine A (CsA) is the treatment of choice against severe aplastic anemia (SAA) worldwide. However, a comparison of the efficacy of porcine ALG (pALG) and rabbit ATG (rATG) as a first-line treatment for acquired SAA has not been reported. In the present study, we retrospectively analyzed SAA patients treated with either pALG (n = 43) or rATG (n = 32) and compared their hematologic responses and survivals. There were no significant differences in overall response (OR) rates between pALG and rATG groups at 3 months (OR 41.86 versus 40.62% (P = 0.914), 6 months (OR 66.67 versus 61.29% (P = 0.635), 9 months (OR 69.05 versus 61.29% (P = 0.490), or 12 months (OR 69.05 versus 64.51% (P = 0.684), respectively. The OR rates in patients with SAA or very severe aplastic anemia (vSAA) in both groups were similar after a 12-month treatment (pALG 74.07 versus 60.00%, P = 0.550; rATG 70.00 versus 54.55%, P = 0.640). Patients who experienced <30-day interval between diagnosis and treatment displayed higher OR rates (at 12 months) than those with intervals ≥30 days (pALG 83.33 versus 50.00%, P = 0.021; rATG 87.50 versus 40.00%, P = 0.006). There were no significant differences in 2-year overall survival (OS) between pALG (87.4 ± 6.2%) and rATG (83.2 ± 7.8%) (P = 0.493). Infection was the major cause of death in both groups. In summary, pALG + CsA showed similar efficacy as rATG + CsA, as a first-line treatment for acquired SAA.

The ability of decline in intrinsic capacity to indicate the risk of mortality in older adults: A meta-analysis.

OBJECTIVE: To evaluate the ability of decline in intrinsic capacity to indicate the risk of mortality in older adults. DESIGN: Meta-analysis. METHODS: PubMed, EMBASE, Web of Science, the Cochrane Library, Wanfang Database, CNKI, VIP, and CBM were searched for relevant studies published from inception to October 31, 2023. Stata17.0 software was used to perform the meta-analysis. A random effects model was used to pool the results of the risk of mortality (as hazard ratios, HRs) in older adults and decline in intrinsic capacity. The Newcastle Ottawa Scale was used to evaluate the quality of studies. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system was used to determine the confidence in the estimated effect of pooled outcomes. RESULTS: Twelve studies, with a total of 38,531 participants, were included in this meta-analysis. The findings show that older adults with intrinsic capacity decline have a higher risk of mortality (HR = 1.11, 95 % CI 1.08-1.14, I2 = 95.9 %, P<0.001) than older adults with normal intrinsic capacity. The pooled HR estimates for the locomotion, vitality, and cognitive dimensions of intrinsic capacity in the prediction of mortality were 0.89 (HR = 0.89, 95%CI 0.83-0.96, I2 = 41.3 %, P = 0.146), 0.76 (HR = 0.98, 95 % CI 0.59-0.97, I2 = 60.8 %, P = 0.078), and 0.99 (HR = 0.99, 95 % CI 0.98-1.00, I2 = 0.0 %, P = 0.664), respectively. The pooled HR estimates of the psychological dimension to predict mortality were not statistically significant (P > 0.05). GRADE evaluations of outcome indicators were of moderate confidence. CONCLUSIONS: Decline in intrinsic capacity is a significant predictor of mortality. Locomotion, vitality, and cognition dimensions can all predict mortality. Clinical personnel should early assess the intrinsic capacity of older adults, focusing on changes in the dimensions of locomotion and vitality, to identify the risk of mortality, avoid adverse health outcomes, and improve the quality of life of older adults. Review protocol registered in PROSPERO: CRD42023481246.

Combination of venetoclax and azacitidine in relapsed/refractory acute B-cell lymphoblastic leukemia: a case series from a single center.

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.

[Change and significance of Th22 cells in patients with aplastic anemia].

OBJECTIVE: To explore the proportion of Th22 cells in peripheral blood of patients with aplastic anemia (AA) and evaluate its significance. METHODS: From January 2011 to June 2012, a total of 47 AA patients were recruited and divided into 4 groups: severe aplastic anemia (SAA) pre-therapy (group A, n = 11), non-severe aplastic anemia (NSAA) pre-therapy (group B, n = 12), SAA post-therapy (group C, n = 12), NSAA post-therapy (group D, n = 12) and healthy donor controls (n = 12). The proportion of Th22 cells in peripheral blood of each group was evaluated by flow cytometry. The cytokines interleukin-22 (IL-22), transforming growth factor-ß (TGF-ß), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were measured by ELISA. And the level of IL-22 mRNA was examined by reverse transcription-PCR (RT-PCR). RESULTS: The percentage of Th22 cells and the level of IL-22, TNF-α, IL-6 and IL-22 mRNA in group A (4.3% ± 1.4%, (57 ± 17) ng/L, (497 ± 123) ng/L, (323 ± 88) ng/L, 1.65 ± 0.51) and group C (2.6% ± 0.6%, (34 ± 10) ng/L, (314 ± 79) ng/L, (187 ± 45) ng/L, 0.92 ± 0.28) were significantly higher than that in control group (1.2% ± 0.3%, (19 ± 6) ng/L, (228 ± 50) ng/L, (134 ± 26) ng/L, 0.47 ± 0.09,all P < 0.05). The percentage of Th22 cells and the level of IL-22, TNF-α , IL-6 and IL-22 mRNA in group A were higher than those in group C (all P < 0.05). NSAA patients had similar results. The percentage of Th22 cells and the level of IL-22, TNF-α , IL-6 and IL-22 mRNA in group A were higher than those in group B (all P < 0.05). But the level of TGF-ß in groups A and C were significantly lower than that in control group ((3.4 ± 1.1) and (5.8 ± 1.7) vs (9.7 ± 2.8) ng/L, P < 0.05). And the level of TGF-ß in group A was lower than that of group B (P < 0.05). CONCLUSIONS: The number of Th22 cells is elevated in AA patients. Th22 cells may be positively correlated with the development of AA. And a higher level of TNF-α, IL-6 and a lower level of TGF-ß promote the differentiation of Th22 cells.

[Clinical Observation of Venetoclax Combined with Demethylating Agents on the Treatment of Relapsed/Refractory Acute Myeloid Leukemia].

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.

The Relationship Between Mindful Agency and Self-Leadership of Chinese Private College Undergraduates: Mediating Effect of Metacognitive Ability.

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.

An empirical study on the influencing mechanism of Chinese university teachers' wellbeing.

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.

Psychological mechanism of language cognition to "awaken" artificial intelligence.

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).

Efficacy of early enteral nutrition versus total parenteral nutrition for patients with gastric cancer complicated with diabetes mellitus: A systematic review and meta-analysis.

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.

Gastrointestinal Microbiome and Multiple Health Outcomes: Umbrella Review.

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.

Effects of EN combined with PN enriched with n-3 polyunsaturated fatty acids on immune related indicators and early rehabilitation of patients with gastric cancer: A randomized controlled trial.

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.

Chitosan-based composites reinforced with antibacterial flexible wood membrane for rapid hemostasis.

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.

ZFP541 maintains the repression of pre-pachytene transcriptional programs and promotes male meiosis progression.

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.