Developmentally dependent reprogramming of the Arabidopsis floral transcriptome under sufficient and limited water availability.

BACKGROUND: Environmental stresses negatively impact reproductive development and yield. Drought stress, in particular, has been examined during Arabidopsis reproductive development at morphological and transcriptomic levels. However, drought-responsive transcriptomic changes at different points in reproductive development remain unclear. Additionally, an investigation of the entire transcriptome at various stages during flower development is of great interest. RESULTS: Here, we treat Arabidopsis plants with well-watered and moderately and severely limiting water amounts when the first flowers reach maturity and generate RNA-seq datasets for early, middle, and late phases during flower development at 5, 6, and 7 days following treatment. Under different drought conditions, flowers in different developmental phases display differential sets of drought-responsive genes (DTGs), including those that are enriched in different GO functional categories, such as transcriptional regulation and response to stresses (early phase), lipid storage (middle phase), and pollen and seed development and metabolic processes (late phase). Some gene families have different members induced at different floral phases, suggesting that similar biochemical functions are carried out by distinct members. Developmentally-regulated genes (DVGs) with differential expression among the three floral phases belong to GO terms that are similar between water conditions, such as development and reproduction, metabolism and transport, and signaling and stress response. However, for different water conditions, such similar GO terms correspond to either distinct gene families or different members of a gene family, suggesting that drought affects the expression of distinct families or family members during reproductive development. A further comparison among transcriptomes of tissues collected on different days after treatment identifies differential gene expression, suggesting age-related genes (ARGs) might reflect the changes in the overall plant physiology in addition to drought response and development. CONCLUSION: Together, our study provides new insights into global transcriptome reprogramming and candidate genes for drought response, flower development, aging and coordination among these complex biological processes.

Postbiotics: emerging therapeutic approach in diabetic retinopathy.

Diabetic retinopathy (DR) is a prevalent microvascular complication in diabetic patients that poses a serious risk as it can cause substantial visual impairment and even vision loss. Due to the prolonged onset of DR, lengthy treatment duration, and limited therapeutic effectiveness, it is extremely important to find a new strategy for the treatment of DR. Postbiotic is an emerging dietary supplement which consists of the inactivate microbiota and its metabolites. Numerous animal experiments have demonstrated that intervention with postbiotics reduces hyperglycemia, attenuates retinal peripapillary and endothelial cell damage, improves retinal microcirculatory dysfunction, and consequently delays the progression of DR. More strikingly, unlike conventional probiotics and prebiotics, postbiotics with small molecules can directly colonize the intestinal epithelial cells, and exert heat-resistant, acid-resistant, and durable for storage. Despite few clinical significance, oral administration with postbiotics might become the effective management for the prevention and treatment of DR. In this review, we summarized the basic conception, classification, molecular mechanisms, and the advances in the therapeutic implications of postbiotics in the pathogenesis of DR. Postbiotics present great potential as a viable adjunctive therapy for DR.

Prediction of the efficacy of group cognitive behavioral therapy using heart rate variability based smart wearable devices: a randomized controlled study.

BACKGROUND: Depression and anxiety are common and disabling mental health problems in children and young adults. Group cognitive behavioral therapy (GCBT) is considered that an efficient and effective treatment for these significant public health concerns, but not all participants respond equally well. The aim of this study was to examine the predictive ability of heart rate variability (HRV), based on sensor data from consumer-grade wearable devices to detect GCBT effectiveness in early intervention. METHODS: In a study of 33 college students with depression and anxiety, participants were randomly assigned to either GCBT group or a wait-list control (WLC) group. They wore smart wearable devices to measure their physiological activities and signals in daily life. The HRV parameters were calculated and compared between the groups. The study also assessed correlations between participants' symptoms, HRV, and GCBT outcomes. RESULTS: The study showed that participants in GCBT had significant improvement in depression and anxiety symptoms after four weeks. Higher HRV was associated with greater improvement in depressive and anxious symptoms following GCBT. Additionally, HRV played a noteworthy role in determining how effective GCBT was in improve anxiety(P = 0.002) and depression(P = 0.020), and its predictive power remained significant even when considering other factors. CONCLUSION: HRV may be a useful predictor of GCBT treatment efficacy. Identifying predictors of treatment response can help personalize treatment and improve outcomes for individuals with depression and anxiety. TRIAL REGISTRATION: The trial has been retrospectively registered on [22/06/2023] with the registration number [NCT05913349] in the ClinicalTrials.gov. Variations in heart rate variability (HRV) have been associated with depression and anxiety, but the relationship of baseline HRV to treatment outcome in depression and anxiety is unclear. This study predicted GCBT effectiveness using HRV measured by wearable devices. 33 students with depression and anxiety participated in a trial comparing GCBT and wait-list control. HRV parameters from wearables correlated with symptoms (PHQ, PSS) and GCBT effectiveness. Baseline HRV levels are strongly associated with GCBT treatment outcomes. HRV may serve as a useful predictor of efficacy of GCBT treatment,facilitating personalized treatment approaches for individuals with depression and anxiety.

Research status of correlation between myopia and accommodative function / 国际眼科杂志(Guoji Yanke Zazhi)

Ocular accommodation refers to the process by which the ciliary muscle creates a clear image of the object in the retina by changing the refractive power of the lens. When the accommodation ability of the eye is insufficient, the imaging focus falls on the region behind the retina and hyperopic defocus is easily formed, resulting in axial growth and leading to the development of myopia, and it is found that most myopic patients usually have some accommodation dysfunction. Myopia has become a public health problem in China, and the prevalence of adolescents has increased dramatically. How to prevent and stop the occurrence and development of myopia is a major challenge. Previous studies have found that ocular accommodation dysfunction is associated with the occurrence and development of myopia, and the measurement of parameters related to accommodation function has certain guiding significance for the prevention and control of myopia. The purpose of this paper is to review the correlation between myopia and ocular accommodation function, with a view to providing new ideas for the prevention, control and treatment of myopia.

School-based Evaluation Advancing Response for Child Health (SEARCH): a mixed longitudinal cohort study from multifaceted perspectives in Jiangsu, China.

BACKGROUND: Schools play a crucial role in providing mental health services to children and adolescents. However, the vastness of the student population and mental health workforce shortage in China severely limit the capacity for adequate care access and delivery. OBJECTIVE: We propose a large, mixed longitudinal cohort study, 'School-based Evaluation Advancing Response for Child Health (SEARCH)', aimed at addressing the increasing demand from individuals seeking access to mental healthcare services. METHODS: SEARCH uses a digital platform and school-based protocol for comprehensive assessment of the mental well-being of Chinese students in grades 4-12 incorporating individual, caregiver and teacher input, including capture of facial and acoustic features and response times, as well as mental well-being assessments. FINDINGS: We completed first wave data collection from nearly 20 000 participants (students, caregivers and teachers) at 11 schools, grades 4-12, in 3 cities in Jiangsu province in Southeast China from September 2022 to February 2023. We intend to conduct follow-up assessments for grades 4 through 12 at the 11 school sites every 6 months for 5 years. CONCLUSIONS: SEARCH will provide important insight into the developmental trajectory of mental well-being in Chinese children and adolescents. The study protocol does not simply focus on student self-report and incorporates caregiver and teacher viewpoints as well. It also collects objective indicators that may facilitate development of screening tools. CLINICAL IMPLICATIONS: We believe future study findings will guide the development and implementation of school-based mental healthcare initiatives to improve the well-being of children and adolescents.

Paeoniflorin inhibits colorectal cancer cell stemness through the miR-3194-5p/catenin beta-interacting protein 1 axis.

Paeoniflorin (PF) is a natural plant ingredient with remarkable antitumor effects. Herein, we investigated the biological effects and mechanism of PF in colorectal cancer (CRC) cell stemness. The messenger RNA (mRNA) and protein expressions were assessed using quantitative real-time polymerase chain reaction and western blot. The viability, proliferation, and migration and invasion of CRC cells were evaluated using cell counting kit-8, clone-formation, and transwell migration and invasion assays, respectively. The sphere-formation capacity was determined using the sphere-formation assay. A dual-luciferase reporter gene assay was employed to analyze the interaction between miR-3194-5p and catenin beta-interacting protein 1 (CTNNBIP1). The viability, migration, invasion, epithelial-mesenchymal transition, and stemness of CRC cells were repressed by PF. MiR-3194-5p was upregulated in CRC tissues and cells. MiR-3194-5p knockdown suppressed CRC cell stemness, while miR-3194-5p overexpression had the opposite effect. In addition, the inhibition of CRC cell stemness caused by PF was eliminated by miR-3194-5p overexpression. CTNNBIP1 functioned as the target of miR-3194-5p, whose knockdown abrogated the repression of CRC cell stemness and Wnt/ß-catenin signaling activation by PF.PF regulated the miR-3194-5p/CTNNBIP1/Wnt/ß-catenin axis to repress CRC cell stemness.

ILC2 influence the differentiation of alveolar type II epithelial cells in bronchopulmonary dysplasia mice.

Bronchopulmonary dysplasia, a common complication of premature infants, is mainly characterized by blocked alveolarization. Proverbially, the injury of alveolar type II epithelial cells is regarded as the pathologic basis of occurrence and development of bronchopulmonary dysplasia. In the case of alveolar epithelial damage, alveolar type II epithelial cells can also differentiate to alveolar type I epithelial cells as progenitor cells. During bronchopulmonary dysplasia, the differentiation of alveolar type II epithelial cells becomes abnormal. Group 2 innate lymphoid cells can produce type 2 cytokines in response to a variety of stimuli, including the epithelial cytokines IL-25, IL-33, and thymic stromal lymphopoietin. Previous studies have shown that group 2 innate lymphoid cells can inhibit the alveolarization process of bronchopulmonary dysplasia by secreting IL-13. However, whether group 2 innate lymphoid cells can affect the differentiation of alveolar type II epithelial cells in the pathologic process of bronchopulmonary dysplasia remains unclear. In this study, we have shown that IL-13 secreted by group 2 innate lymphoid cells increased during bronchopulmonary dysplasia, which was related to the release of large amounts of IL-33 by impaired alveolar type II epithelial cells. This led to abnormal differentiation of alveolar type II epithelial cells, reduced differentiation to alveolar type I epithelial cells, and increased transdifferentiation to mesenchymal cells through the epithelial-mesenchymal transition. Taken together, our study provides a complementary understanding of the development of bronchopulmonary dysplasia and highlights a novel immune mechanism in the pathogenesis of bronchopulmonary dysplasia.

A {Cu6}-added polyoxometalate cluster-organic framework: synthesis, structure and application as a solid support for enzyme immobilization.

A new two-dimensional {Cu6}-added polyoxometalate cluster-organic framework (Cu-POMCOF) was prepared by a hydrothermal method from lacunary polyoxoanions and was applied as a solid support for immobilizing MP-11 and Cyt c. The biocomposite complex exhibits higher stability and catalytic activity than the original free enzyme.

NetMoST: A network-based machine learning approach for subtyping schizophrenia using polygenic SNP allele biomarkers.

Subtyping neuropsychiatric disorders like schizophrenia is essential for improving the diagnosis and treatment of complex diseases. Subtyping schizophrenia is challenging because it is polygenic and genetically heterogeneous, rendering the standard symptom-based diagnosis often unreliable and unrepeatable. We developed a novel network-based machine-learning approach, netMoST, to subtyping psychiatric disorders. NetMoST identifies polygenic risk SNP-allele modules from genome-wide genotyping data as polygenic haplotype biomarkers (PHBs) for disease subtyping. We applied netMoST to subtype a cohort of schizophrenia subjects into three distinct biotypes with differentiable genetic, neuroimaging and functional characteristics. The PHBs of the first biotype (36.9% of all patients) were related to neurodevelopment and cognition, the PHBs of the second biotype (28.4%) were enriched for neuroimmune functions, and the PHBs of the third biotype (34.7%) were associated with the transport of calcium ions and neurotransmitters. Neuroimaging patterns provided additional support to the new biotypes, with unique regional homogeneity (ReHo) patterns observed in the brains of each biotype compared with healthy controls. Our findings demonstrated netMoST's capability for uncovering novel biotypes of complex diseases such as schizophrenia. The results also showed the power of exploring polygenic allelic patterns that transcend the conventional GWAS approaches.

Sustained over-expression of calpain-2 induces age-dependent dilated cardiomyopathy in mice through aberrant autophagy.

Calpains have been implicated in heart diseases. While calpain-1 has been detrimental to the heart, the role of calpain-2 in cardiac pathology remains controversial. In this study we investigated whether sustained over-expression of calpain-2 had any adverse effects on the heart and the underlying mechanisms. Double transgenic mice (Tg-Capn2/tTA) were generated, which express human CAPN2 restricted to cardiomyocytes. The mice were subjected to echocardiography at age 3, 6, 8 and 12 months, and their heart tissues and sera were collected for analyses. We showed that transgenic mice over-expressing calpain-2 restricted to cardiomyocytes had normal heart function with no evidence of cardiac pathological remodeling at age 3 months. However, they exhibited features of dilated cardiomyopathy including increased heart size, enlarged heart chambers and heart dysfunction from age 8 months; histological analysis revealed loss of cardiomyocytes replaced by myocardial fibrosis and cardiomyocyte hypertrophy in transgenic mice from age 8 months. These cardiac alterations closely correlated with aberrant autophagy evidenced by significantly increased LC3BII and p62 protein levels and accumulation of autophagosomes in the hearts of transgenic mice. Notably, injection of 3-methyladenine, a well-established inhibitor of autophagy (30 mg/kg, i.p. once every 3 days starting from age 6 months for 2 months) prevented aberrant autophagy, attenuated myocardial injury and improved heart function in the transgenic mice. In cultured cardiomyocytes, over-expression of calpain-2 blocked autophagic flux by impairing lysosomal function. Furthermore, over-expression of calpain-2 resulted in lower levels of junctophilin-2 protein in the heart of transgenic mice and in cultured cardiomyocytes, which was attenuated by 3-methyladenine. In addition, blockade of autophagic flux by bafilomycin A (100 nM) induced a reduction of junctophilin-2 protein in cardiomyocytes. In summary, transgenic over-expression of calpain-2 induces age-dependent dilated cardiomyopathy in mice, which may be mediated through aberrant autophagy and a reduction of junctophilin-2. Thus, a sustained increase in calpain-2 may be detrimental to the heart.

Diamond Model of Green Commitment and Low-Carbon Travel Motivation, Constraint, and Intention.

Although consumers generally accept and care about environmental issues, consumers have not adjusted their behavior accordingly. Based on the diamond model theory, this study proposes and tests the direct impact of personal green commitments on low-carbon travel motivation and constraint, and the possibility of subsequent low-carbon travel intention. According to the results of 358 valid questionnaire surveys, this study shows that green commitments positively affect the low-carbon travel motivation and intention, while negatively affecting the low-carbon travel constraint. The low-carbon travel motivation has some mediating effects. The research results can be used as a reference by relevant managers of the tourism industry to make changes in the content of travel services that are more suitable for specific populations.

Schizophrenia and Inflammation Research: A Bibliometric Analysis.

Background: Schizophrenia (SCZ) is a severe psychiatric disorder that involves inflammatory processes. The aim of this study was to explore the field of inflammation-related research in SCZ from a bibliometric perspective. Methods: Regular and review articles on SCZ- and inflammation-related research were obtained from the Web of Science Core Collection (WOSCC) database from its inception to February 19, 2022. R package "bibliometrix" was used to summarize the main findings, count the occurrences of the top keywords, visualize the collaboration network between countries, and generate a three-field plot. VOSviewer software was applied to conduct both co-authorship and co-occurrence analyses. CiteSpace was used to identify the top references and keywords with the strongest citation burst. Results: A total of 3,596 publications on SCZ and inflammation were included. Publications were mainly from the USA, China, and Germany. The highest number of publications was found in a list of relevant journals. Apart from "schizophrenia" and "inflammatory", the terms "bipolar disorder," "brain," and "meta-analysis" were also the most frequently used keywords. Conclusions: This bibliometric study mapped out a fundamental knowledge structure consisting of countries, institutions, authors, journals, and articles in the research field of SCZ and inflammation over the past 30 years. The results provide a comprehensive perspective about the wider landscape of this research area.

Exploring the Relationship Between Hospital Service Quality, Patient Trust, and Loyalty From a Service Encounter Perspective in Elderly With Chronic Diseases.

Based on the service encounter perspective, this study combines theoretical foundations for such factors as service quality and the characteristics of the hospital service industry to develop a research model scale to investigate whether the quality of hospital services affects patients' perceptions of health service encounters, trust, and loyalty. Nowadays, with the advancement of medical technology, patients pay more attention to the quality of medical services and good service encounters provided by healthcare professionals in order to establish positive patient relationships; hospitals need to improve their own service quality and establish good patient trust relationships so that doctor-patient satisfaction and loyalty can be improved. In a review of related literature, this study found that most past studies focused on issues related of quality of medical services and patient satisfaction, but ignored those related to the relationship between medical service encounters and patient trust and loyalty, as well as the lack of scientific measurement markers for service encounters in the Chinese medical service industry. Therefore, this study uses the Service Encounter Perspective and Service Quality Theory Development Research Scale to collect and analyze data for a typical case of a Chinese tertiary hospital. Finally, this study explores the relationship between the four variables of service quality, service encounter, trust, and loyalty by means of a questionnaire and statistical analysis of the data. Finally, it is concluded that the higher the service quality of the hospital, the higher the customer trust, the higher the service encounter, and in the greater the doctor-patient loyalty.

HOXC6 Regulates the Epithelial-Mesenchymal Transition through the TGF-ß/Smad Signaling Pathway and Predicts a Poor Prognosis in Glioblastoma.

Background: The HOX gene family of transcription factors, characterized by conserved homeodomains, is positively correlated with the resistance to chemotherapy drugs and poor prognosis, as well as the initiating potential of gliomas. However, there are few studies regarding the HOXC6 gene in glioma cells. Therefore, in the present study, we explored the regulatory roles and detailed mechanisms underlying the relationship between HOXC6 and the progression of GBM. Methods: The expression levels and prognostic value of HOXC6 in GBM were evaluated using the data obtained from the GCCA, GEPIA, and ONCOMINE databases. The relationship between GBM prognosis and levels of HOXC6 was identified using Kaplan-Meier curves. The protein levels of HOXC6 in GBM and adjacent normal tissues were identified via Western blot and immunohistochemistry (IHC) staining methods. Lentiviruses containing full-length HOXC6 and HOXC6 specific siRNA sequences were used to overexpress and knock down, respectively, the expression of HOXC6 in U87 and U251 cells. The role of HOXC6 in the regulation of migration and proliferation of GBM cells was accessed using Transwell, wound healing, CCK-8, and colony formation assays. The activation of the TGF-ß/Smad signaling pathway was detected via Western blotting. Results: Compared to normal tissues and control cells, GBM tissues and cell lines showed higher expressions of HOXC6. The expression of HOXC6 was associated with disease-free and the overall survival of GBM patients. Additionally, positive correlations between the expression of HOXC6 and the migration and proliferation of GBM cells were observed in vitro. The mechanistic analyses indicated that HOXC6 exerts its promotive effect on the progression and invasion of glioma cells by promoting the activation of the EMT and TGF-ß/Smad signaling pathways. Conclusions: HOXC6 enhances the migration and proliferation of GBM by activating the EMT signaling pathway.

Efficacy and safety of sirolimus early conversion protocol in liver transplant patients with hepatocellular carcinoma: A single-arm, multicenter, prospective study.

Mammalian target of rapamycin (mTOR) inhibitor as an attractive drug target with promising antitumor effects has been widely investigated. High quality clinical trial has been conducted in liver transplant (LT) recipients in Western countries. However, the pertinent studies in Eastern world are paucity. Therefore, we designed a clinical trial to test whether sirolimus can improve recurrence-free survival (RFS) in hepatocellular carcinoma (HCC) patients beyond the Milan criteria after LT. This is an open-labeled, single-arm, prospective, multicenter, and real-world study aiming to evaluate the clinical outcomes of early switch to sirolimus-based regimens in HCC patients after LT. Patients with a histologically proven HCC and beyond the Milan criteria will be enrolled. The initial immunosuppressant regimens are center-specific for the first 4-6 weeks. The following regimens integrated sirolimus into the regimens as a combination therapy with reduced calcineurin inhibitors based on the condition of patients and centers. The study is planned for 4 years in total with a 2-year enrollment period and a 2-year follow-up. We predict that sirolimus conversion regimen will provide survival benefits for patients particular in the key indicator RFS as well as better quality of life. If the trial is conducted successfully, we will have a continued monitoring over a longer follow-up time to estimate indicator of overall survival. We hope that the outcome will provide better evidence for clinical decision-making and revising treatment guidelines based on Chinese population data. Trial register: Trial registered at http://www.chictr.org.cn: ChiCTR2100042869.

A retrospective comparative study of haplotype hematopoietic stem cell transplantation and human leukocyte antigen-matched sibling donor hematopoietic stem cell transplantation in the treatment of acute B-lymphocyte leukemia / 中华血液学杂志

Objective: To investigate whether haplotype hematopoietic stem cell transplantation (haplo-HSCT) is effective in the treatment of pre transplant minimal residual disease (Pre-MRD) positive acute B lymphoblastic leukemia (B-ALL) compared with HLA- matched sibling donor transplantation (MSDT) . Methods: A total of 998 patients with B-ALL in complete remission pre-HSCT who either received haplo-HSCT (n=788) or underwent MSDT (n=210) were retrospectively analyzed. The pre-transplantation leukemia burden was evaluated according to Pre-MRD determinedusing multiparameter flow cytometry (MFC) . Results: Of these patients, 997 (99.9% ) achieved sustained, full donor chimerism. The 100-day cumulative incidences of neutrophil engraftment, platelet engraftment, and grades Ⅱ-Ⅳ acute graft-versus-host disease (GVHD) were 99.9% (997/998) , 95.3% (951/998) , and 26.6% (95% CI 23.8% -29.4% ) , respectively. The 3-year cumulative incidence of total chronic GVHD was 49.1% (95% CI 45.7% -52.4% ) . The 3-year cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) of the 998 cases were 17.3% (95% CI 15.0% -19.7% ) and 13.8% (95% CI 11.6% -16.0% ) , respectively. The 3-year probabilities of leukemia-free survival (LFS) and overall survival (OS) were 69.1% (95% CI 66.1% -72.1% ) and 73.0% (95% CI 70.2% -75.8% ) , respectively. In the total patient group, cases with positive Pre-MRD (n=282) experienced significantly higher CIR than that of subjects with negative Pre-MRD [n=716, 31.6% (95% CI 25.8% -37.5% ) vs 14.3% (95% CI 11.4% -17.2% ) , P<0.001]. For patients in the positive Pre-MRD subgroup, cases treated with haplo-HSCT (n=219) had a lower 3-year CIR than that of cases who underwent MSDT [n=63, 27.2% (95% CI 21.0% -33.4% ) vs 47.0% (95% CI 33.8% -60.2% ) , P=0.002]. The total 998 cases were classified as five subgroups, including cases with negative Pre-MRD group (n=716) , cases with Pre-MRD<0.01% group (n=46) , cases with Pre-MRD 0.01% -<0.1% group (n=117) , cases with Pre-MRD 0.1% -<1% group (n=87) , and cases with Pre-MRD≥1% group (n=32) . For subjects in the Pre-MRD<0.01% group, haplo-HSCT (n=40) had a lower CIR than that of MSDT [n=6, 10.0% (95% CI 0.4% -19.6% ) vs 32.3% (95% CI 0% -69.9% ) , P=0.017]. For patients in the Pre-MRD 0.01% -<0.1% group, haplo-HSCT (n=81) also had a lower 3-year CIR than that of MSDT [n=36, 20.4% (95% CI 10.4% -30.4% ) vs 47.0% (95% CI 29.2% -64.8% ) , P=0.004]. In the other three subgroups, the 3-year CIR was comparable between patients who underwent haplo-HSCT and those received MSDT. A subgroup analysis of patients with Pre-MRD<0.1% (n=163) was performed, the results showed that cases received haplo-HSCT (n=121) experienced lower 3-year CIR [16.0% (95% CI 9.4% -22.7% ) vs 40.5% (95% CI 25.2% -55.8% ) , P<0.001], better 3-year LFS [78.2% (95% CI 70.6% -85.8% ) vs 47.6% (95% CI 32.2% -63.0% ) , P<0.001] and OS [80.5% (95% CI 73.1% -87.9% ) vs 54.6% (95% CI 39.2% -70.0% ) , P<0.001] than those of MSDT (n=42) , but comparable in 3-year NRM [5.8% (95% CI 1.6% -10.0% ) vs 11.9% (95% CI 2.0% -21.8% ) , P=0.188]. Multivariate analysis showed that haplo-HSCT was associated with lower CIR (HR=0.248, 95% CI 0.131-0.472, P<0.001) , and superior LFS (HR=0.275, 95% CI 0.157-0.483, P<0.001) and OS (HR=0.286, 95% CI 0.159-0.513, P<0.001) . Conclusion: Haplo HSCT has a survival advantage over MSDT in the treatment of B-ALL patients with pre MRD<0.1% .

Short-term efficacy of venetoclax combined with azacitidine in acute myeloid leukemia: a single-institution experience / 中华血液学杂志

Objective: To explore the safety and short-term efficacy of venetoclax combined with azacitidine (Ven+AZA) in previously untreated patients unfit for standard chemotherapy and patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) in China. Methods: A retrospective study was conducted in 60 previously untreated patients unfit for standard chemotherapy and patients with R/R AML who received Ven+ AZA (venetoclax, 100 mg D1, 200 mg D2, 400 mg D3-28; azacitidine, 75 mg/m(2) D1- 7) at the Peking University Institute of Hematology from June 1, 2019 to May 31, 2021. The incidence of adverse events, complete remission (CR) /CR with incomplete hematological recovery (CRi) rate, objective remission rate (ORR) , and minimal residual disease (MRD) status in patients with different risk stratification and gene subtypes were analyzed. Results: The median age of the patients was 54 (18-77) years, 33 (55.0%) were males, and the median follow-up time was 4.8 (1.4-26.3) months. Among the 60 patients, 24 (40.0%) were previously untreated patients unfit for standard chemotherapy, and 36 (60.0%) were R/R patients. The median mumber cycles of Ven+AZA in the two groups were both 1 (1-5) . According to the prognostic risk stratification of the National Comprehensive Cancer Network, it was divided into 8 cases of favorable-risk, 2 cases of intermediate risk, and 14 cases of poor-risk. In previously untreated patients unfit for standard chemotherapy, after the first cycle of Ven+AZA, 17/24 (70.8%) cases achieved CR/CRi, 3/24 (12.5%) achieved partial remission (PR) , and the ORR was 83.3%. Among them, nine patients received a second cycle chemotherapy and two received a third cycle. Among CR/CRi patients, 8/17 (47.1%) achieved MRD negativity after two cycles of therapy. In the R/R group, after the first cycle of Ven+AZA, 21/36 (58.3%) cases achieved CR/CRi (7/21 achieved MRD negativity) , 3 achieved PR, and the ORR was 66.7%. Among R/R patients, 12 were treated for more than two cycles. There were no new CR/CRi patients after the second treatment cycle, and 14 cases (66.7%) achieved MRD negativity. According to the time from CR to hematological recurrence, the R/R group was divided into 12 cases in the favorable-risk group (CR to hematological recurrence ≥18 months) and 24 in the poor-risk group (CR to hematological recurrence<18 months, no remission after one cycle of therapy, and no remission after two or more cycles of therapy) . Eleven of 24 (45.8%) cases achieved CR/CRi after one cycle of Ven+AZA in the poor-risk R/R group, and 10 of 12 (83.3%) achieved CR/CRi in the favorable-risk R/R group, which was significantly superior to the poor-risk group (P=0.031) . After one cycle of treatment, 13 patients with IDH1/2 mutations and 4 that were TP53-positive all achieved CR/CRi. The CR/CRi rate of 18 patients with NPM1 mutations was 77.8%. Five patients with RUNX1-RUNX1T1 combined with KIT D816 mutation (two initial diagnoses and three recurrences) had no remission. Ven+ AZA was tolerable for AML patients. Conclusion: Ven+AZA has acceptable safety in previously untreated patients unfit for standard chemotherapy, patients with R/R AML can achieve a high response rate, and some patients can achieve MRD negativity. It is also effective in NPM1-, IDH1/IDH2-, and TP53-positive patients. The long-term efficacy remains to be observed.

Risk factors for lymph node metastasis and surgical scope in patients with cN0 non-small cell lung cancer: a single-center study in China.

BACKGROUND: It is difficult to determine the lymph node metastasis of patients with clinically negative lymph nodes (cN0) non-small cell lung cancer (NSCLC) before surgery. The purpose of this study is to investigate risk factors of lymph node metastasis in cN0 NSCLC, thereby to identify the surgical indications for lymph node dissection in cN0 NSCLC. METHODS: We conducted a retrospective study of patients with tumor size ≤ 30 mm who underwent radical resection of NSCLC. Binary logistic regression analysis was applied to predict risk factors for lymph node metastasis, and subject operating characteristics (ROC) curve was used to evaluate the independent risk factors. RESULTS: Overall, 44 patients (6.8%) with cN0 NSCLC had lymph node metastasis. Factors of tumor consolidation diameter (p < 0.001) and preoperative serum carcinoembryonic antigen (CEA) level (p = 0.017) are independent risk factors lymph node metastasis in cN0 NSCLC. The ROC curve showed that the cut-off value of consolidation diameter was 16.5 mm, and the area under the curve (AUC) was 0.825 (p < 0.001, 95% CI 0.780-0.870); the cut-off value of serum CEA level was 1.765 µg/L, and the AUC was 0.661 (p < 0.001, 95% CI: 0.568-0.754). Moreover, 8 of 461 patients with tumor parenchyma ≤ 16.5 mm had lymph node metastasis, and 36 of 189 patients with tumor parenchyma > 16.5 mm had lymph node metastasis. CONCLUSION: Tumor consolidation diameter and preoperative serum CEA are independent factors to predict cN0 NSCLC with tumor size ≤ 30 mm. For patients with tumor parenchyma > 16.5 mm, the probability of lymph node metastasis is higher and lymph node dissection is recommended. For patients with tumor parenchyma ≤ 16.5 mm, the probability of lymph node metastasis is lower and lymph node sampling is feasible.

Total Infectomes Characterization of Respiratory Infections in pre-COVID-19 Wuhan, China

At the end of 2019 Wuhan witnessed an outbreak of "atypical pneumonia" that later developed into a global pandemic. Metagenomic sequencing rapidly revealed the causative agent of this outbreak to be a novel coronavirus - SARS-CoV-2. Herein, to provide a snapshot of the pathogens in pneumonia-associated respiratory samples from Wuhan prior to the emergence of SARS-CoV-2, we collected bronchoalveolar lavage fluid samples from 408 patients presenting with pneumonia and acute respiratory infections at the Central Hospital of Wuhan between 2016 and 2017. Unbiased total RNA sequencing was performed to reveal their "total infectome", including viruses, bacteria and fungi. Consequently, we identified 37 pathogen species, comprising 15 RNA viruses, 3 DNA viruses, 16 bacteria and 3 fungi, often at high abundance and including multiple co-infections (12.8%). However, SARS-CoV-2 was not present. These data depict a stable core infectome comprising common respiratory pathogens such as rhinoviruses and influenza viruses, an atypical respiratory virus (EV-D68), and a single case of a sporadic zoonotic pathogen - Chlamydia psittaci. Samples from patients experiencing respiratory disease on average had higher pathogen abundance than healthy controls. Phylogenetic analyses of individual pathogens revealed multiple origins and global transmission histories, highlighting the connectedness of the Wuhan population. This study provides a comprehensive overview of the pathogens associated with acute respiratory infections and pneumonia, which were more diverse and complex than obtained using targeted PCR or qPCR approaches. These data also suggest that SARS-CoV-2 or closely related viruses were absent from Wuhan in 2016-2017.

Evolution of Anti-SARS-CoV-2 IgG Antibody and IgG Avidity Post Pfizer and Moderna mRNA Vaccinations

Messenger RNA (mRNA) based vaccines (Pfizer/BioNTech and Moderna) are highly effective at providing immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there is uncertainty about the duration of immunity, evolution of IgG antibody levels and IgG avidity (an index of antibody-antigen binding strength), and differences in the immune responses between vaccines. Here we performed a prospective pilot study of 71 previously COVID-19 free subjects upon receiving both doses of either the Pfizer (n = 54) or Moderna (n = 17) mRNA vaccine. Anti-spike protein receptor binding domain (RBD) IgG antibodies were measured longitudinally using a qualitative finger stick MidaSpot rapid test at the point-of-care for initial screening and a quantitative dry blood spot-based pGOLD laboratory test over [~] four months post-vaccination. The average anti-RBD IgG antibody levels peaked at [~] two weeks after the second dose of the vaccine and declined thereafter, while antibody avidity increased, suggesting antibody maturation. Moderna vaccine recipients compared to Pfizer vaccine recipients exhibited higher side effect severity, higher peak anti-RBD IgG antibody levels, and higher avidity up to the 90 days period. Differences in antibody levels diminished at [~] 120 days post-vaccination, in line with the similar efficacy observed in the two vaccines. The MidaSpot rapid test detected 100% anti-SARS-CoV-2 RBD positivity for fully vaccinated subjects in both Pfizer and Moderna cohorts post full vaccination but turned negative greater than 90 days post-vaccination for 5.4% of subjects in the Pfizer cohort, whose quantitative anti-IgG were near the minimum levels of the group. Immune responses were found to vary greatly among vaccinees. Personalized longitudinal monitoring of antibodies could be necessary to assess the immunity duration of vaccinated individuals.