Azacitidine combined with venetoclax alleviates AML-MR with TP53 mutation in SDS: a case report and literature review.

Shwachman-Diamond syndrome (SDS) is an autosomal recessive genetic disease, which is prone to transform into myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). TP53 mutation is a driving factor involved in the transformation of SDS into MDS/AML, and in the evolution of MDS to AML. Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) is the only curable approach, however, challenge remains regarding the balance between efficacy and the high risk from treatment-related toxicity and mortality to achieve temporary disease control before transplantation to gain time and opportunities for transplantation. At present, pre-transplant bridging therapy has emerged as one of the important options with improved efficacy, reduced tumor burden, and less treatment-related toxicity. Here we reported azacitidine combined with venetoclax was used as pre-transplant bridging regimen in a TP53-mutant AML-MR case developed from SDS. He achieved complete remission with incomplete recovery and proceeded to Allo-HSCT. We hope to provide some evidence and insight for in-depth research and clinical treatment by presenting this case.

The peanut root exudate increases the transport and metabolism of nutrients and enhances the plant growth-promoting effects of burkholderia pyrrocinia strain P10.

BACKGROUND: Burkholderia pyrrocinia strain P10 is a plant growth-promoting rhizobacterium (PGPR) that can substantially increase peanut growth. However, the mechanisms and pathways involved in the interaction between B. pyrrocinia P10 and peanut remain unclear. To clarify complex plant-PGPR interactions and the growth-promoting effects of PGPR strains, the B. pyrrocinia P10 transcriptome changes in response to the peanut root exudate (RE) were elucidated and the effects of RE components on biofilm formation and indole-3-acetic acid (IAA) secretion were analyzed. RESULTS: During the early interaction phase, the peanut RE enhanced the transport and metabolism of nutrients, including carbohydrates, amino acids, nitrogen, and sulfur. Although the expression of flagellar assembly-related genes was down-regulated, the expression levels of other genes involved in biofilm formation, quorum sensing, and Type II, III, and VI secretion systems were up-regulated, thereby enabling strain P10 to outcompete other microbes to colonize the peanut rhizosphere. The peanut RE also improved the plant growth-promoting effects of strain P10 by activating the expression of genes associated with siderophore biosynthesis, IAA production, and phosphorus solubilization. Additionally, organic acids and amino acids were identified as the dominant components in the peanut RE. Furthermore, strain P10 biofilm formation was induced by malic acid, oxalic acid, and citric acid, whereas IAA secretion was promoted by the alanine, glycine, and proline in the peanut RE. CONCLUSION: The peanut RE positively affects B. pyrrocinia P10 growth, while also enhancing colonization and growth-promoting effects during the early interaction period. These findings may help to elucidate the mechanisms underlying complex plant-PGPR interactions, with potential implications for improving the applicability of PGPR strains.

Molecular mechanism of Tsukamurella tyrosinosolvens strain P9 in response to root exudates of peanut.

Tsukamurella tyrosinosolvens strain P9 is a rare actinomycete with plant growth-promoting properties and can improve the growth of peanut. We analyzed the differentially expressed genes (DEGs) of P9 under the influence of peanut root exudates from RNA-sequencing data and analyzed the effects of root exudates and their organic acid and amino acid components on the growth and growth-promoting effects of this strain to explore the molecular mechanism of the P9 response. The results showed that peanut root exudates promoted the growth and growth-promoting activity of P9. Transcriptome analysis revealed 126 DEGs in P9, comprising 81 up-regulated and 45 down-regulated genes. The DEGs were significantly enriched in 17 KEGG metabolic pathways, including arginine biosynthesis, butyric acid metabolism, fatty acid degradation, and tryptophan metabolism. Peanut root exudates induced up-regulation of nutrient transport, carbohydrate metabolism and energy production, siderophore and IAA biosynthesis, adhesion, and biofilm formation, and down-regulation of arginine biosynthesis and the urea cycle in P9. Organic acids and amino acids are the major components of peanut root exudates. Glycine, proline, and alanine promoted the growth and IAA secretion of P9. Proline, alanine (40 mM), and oxalic acid significantly enhanced siderophore biosynthesis, whereas citric acid, oxalic acid, and malic acid significantly promoted biofilm formation of P9. This study clarifies the response of T. tyrosinosolvens P9 to peanut root exudates at the molecular level, examining the molecular basis of the relationship between P9 and peanut, and provides a theoretical foundation for improved exertion of the growth-promoting properties of P9.

Stress-Resistance and Growth-Promoting Characteristics and Effects on Vegetable Seed Germination of Streptomyces sp. Strains Isolated from Wetland Plant Rhizospheres.

Wetlands are the most biologically diverse ecosystems on Earth. The isolation of Streptomyces strains from wetlands is helpful to study their diversity and functions in such habitats. In this study, six strains of Streptomyces were isolated from the rhizosphere soil of three plant species in the Huaxi Wetland at Guiyang and were identified as Streptomyces galilaeus, S. avidinii, S. albogriseolus, S. albidoflavus, S. spororaveus, and S. cellulosae, respectively. The six strains all solubilized phosphate, fixed nitrogen, and produced ACC deaminase and siderophores, and four strains also secreted indole-3-acetic acid. The six strains had the ability to resist to certain degrees of salinity, drought, and acidic/alkaline pH stress. In addition, the S. avidinii WL3 and S. cellulosae WL9 strains significantly promoted seed germination of mung bean, pepper, and cucumber, especially the WL3 strain. A pot experiment further showed that WL3 significantly promoted the growth of cucumber seedlings. Thus, strains of six species of Streptomyces with multiple plant growth-promoting characteristics were isolated from the wetland. These results lay a foundation for their potential use as microbial agents for seed-coating treatments.

Appropriate dose of intravitreal ranibizumab for ROP: a retrospective study.

OBJECTIVE: To compare the recurrence rate of retinopathy of prematurity (ROP) after treatment with 0.3 mg vs. 0.25 mg ranibizumab. SUBJECTS: All patients with ROP who underwent intravitreal injection of ranibizumab in Hainan General Hospital between January 2014 and May 2020 were included in this retrospective study. METHODS: Eighty-two cases (146 eyes) who received intravitreal injection of 0.25 mg ranibizumab were included in the conventional-dose group, and 59 cases (108 eyes) who received intravitreal injection of 0.3 mg ranibizumab were included in the high-dose group. The two groups were further divided into the 25-28-week, 29-31-week, 32-34-week, and 35-36-week GA subgroups. The differences between the conventional-dose group and the high-dose group in gestational age (GA), birth weight (BW), age at initial injection (weeks), incidence of systemic diseases, the recurrence rate of ROP, and age at retinal vascularization completed (weeks) were analyzed. RESULTS: GA, BW, age at initial injection, and the incidence of systemic diseases were not significantly different between the conventional-dose group and the high-dose group (p > 0.05). The recurrence rates of ROP were significantly lower in the 25-28-week, 29-31-week, and 32-34-week subgroups of the high-dose group than in the same subgroups of the conventional-dose group (p < 0.05). Within the conventional-dose group, the recurrence rate of ROP was significantly lower in the 32-34-week and 35-36-week subgroups than in the 25-28-week and 29-31-week subgroups (p < 0.05). Within the high-dose group, the recurrence rate of ROP was not significantly different between the four subgroups (p > 0.05). Retinal vascularization was completed at a later age in the 32-34-week subgroup of the high-dose group than in the 32-34-week subgroup of the conventional-dose group (p < 0.05) but was not significantly different between the two groups at any other GA range (p > 0.05). No severe ocular or systemic complications occurred in any patient. CONCLUSION: Treatment with 0.3 mg ranibizumab can reduce the recurrence rate of ROP without prolonging retinal vascularization or causing serious systemic complications. Therefore, this dose may be an appropriate therapeutic dose for ROP.

Biological characteristics and salt-tolerant plant growth-promoting effects of an ACC deaminase-producing Burkholderia pyrrocinia strain isolated from the tea rhizosphere.

Plant growth-promoting rhizobacteria that produce 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase can promote plant growth and enhance abiotic stress tolerance. In this study, Burkholderia pyrrocinia strain P10, with an ACC deaminase activity of 33.01-µmol/h/mg protein, was isolated from the tea rhizosphere and identified based on morphological, biochemical, and molecular characteristics. In addition to its ACC deaminase activity at pH 5.0-9.0 and in response to 5% NaCl and 20% polyethylene glycol, strain P10 can also solubilize phosphorus compounds, produce indole-3-acetic acid, and secrete siderophores. Pot experiments revealed that strain P10 can significantly enhance peanut seedling growth under saline conditions (100- and 170-mmol/L NaCl). Specifically, it increased the fresh weight and root length of plants by 90.12% and 79.22%, respectively, compared with high-salt stress. These results provide new insights into the biological characteristics of Burkholderia pyrrocinia, which may be useful as a bio-fertilizer.

Progranulin and Activin A Concentrations are Elevated in Serum from Patients with Acute Exacerbations of Idiopathic Pulmonary Fibrosis.

PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrotic lung disease of unknown cause with a variable course. Acute exacerbations of IPF (AE-IPF) is sudden accelerations of the disease or a superimposed idiopathic acute injury significantly reducing lung function. To examine the serum concentrations of Progranulin (PGRN) and activin A in patients with AE-IPF in a pilot study. METHODS: Twenty-one patients with AE-IPF were compared with 23 patients with stable IPF as a control group. Serum PGRN and activin A levels, arterial blood gas measurements, and lung function were determined in these two groups. RESULTS: Peripheral blood PGRN and activin A levels in patients with AE-IPF were 83.7 + 10.0 and 14.2 ± 1.7 ng/ml (mean + SD), respectively; higher than those in the control group 61.0 + 5.8 and 5.8 + 1.0 (p < 0.001). PGRN and activin A levels were significantly negatively correlated with carbon monoxide diffusion capacity r = - 0.857 (p < 0.001) and r = - 0.757 (p < 0.001). CONCLUSION: Progranulin (PGRN) and activin A may be involved in the pathogenesis of AE-IPF. They may be possible markers of disease activity in AE-IPF.

Long-term effects of alcohol consumption on cognitive function in seniors: a cohort study in China.

BACKGROUND: In the context of increasing global aging, the long-term effects of alcohol consumption on cognitive function in older adults were analyzed in order to provide rationalized health recommendations to the elderly population. METHODS: The study used the Chinese Longitudinal Healthy Longevity Survey (CLHLS) dataset, from which 5354 Chinese seniors aged 65-112 years were selected as the subjects, spanning the years 1998-2018. Data on alcohol, diet, activity, and cognition were collected by questionnaire and cognitive levels were judged by the Mini-Mental State Examination scale (also referenced to the Functional Assessment Staging Test). Data cleaning and preprocessing was implemented by R software. The dynamic Cox model was applied for model construction and data analysis. RESULTS: The results of the dynamic Cox model suggested that seniors who drank alcohol were at higher risk of cognitive decline compared to those who never drank (HR = 1.291, 95%CI: 1.175-1.419). The risk was similarly exacerbated by perennial drinking habits (i.e., longer drinking years, HR = 1.008, 95%CI: 1.004-1.013). Compared to non-alcoholic beverages, liquor (≥ 38°), liquor (< 38°), wine and rice wine all showed negative effects. Whereas, the risk of cognitive decline was relatively lower in seniors who consumed liquors (< 38°) and rice wine compared to the high-level liquor (HR: 0.672 (0.508, 0.887) and 0.732 (0.559, 0.957), respectively). CONCLUSIONS: Alcohol consumption has a negative and long-term effects on cognitive function in seniors. For the elderly, we suggested that alcohol intake should be avoided as much as possible.

MIL-101(Fe)-derived magnetic porous carbon as sorbent for stir bar sorptive-dispersive microextraction of sulfonamides.

Using MIL-101(Fe) as the source of carbon and Fe, a magnetic porous carbon (MPC) material with Fe3C nanoparticles encapsulated in porous carbon was prepared through one-pot pyrolysis under N2 atmosphere. With MPC as adsorption material, a stir bar sorptive-dispersive microextraction (SBSDME) method was proposed to extract and preconcentrate sulfonamides (SAs) prior to HPLC-DAD determination. To investigate their extraction ability, different MPC materials were prepared under different carbonization temperatures (600, 700, 800, 900, and 1000 °C). The material prepared under 900 °C (MPC-900) exhibited the highest extraction ability for SAs. The as-prepared MPC materials were also characterized by Raman spectroscopy, scanning electron microscopy, X-ray photoelectron spectroscopy, zeta potential, and other techniques. The main parameters that affect extraction were systematically studied. Under optimal conditions, favorable linearity (R2 ≥ 0.9938) and detection limits (0.02-0.04 ng mL-1) of sulfonamides were obtained. The average recoveries for spiked milk and lake water samples ranged from 76.9 to 109% and from 75.4 to 118% with RSDs of 3.10-9.63% and 1.71-11.3%, respectively. Sulfameter and sulfisoxazole were detected in milk sample. Sulfisoxazole was detected in the lake water sample. The MPC-900 material demonstrated excellent reusability. It can be reused 24 times with peak areas having no obvious decline. The method can be applied to extract ultra-trace compounds in complex sample matrices. Schematic presentation of a stir bar sorptive-dispersive microextraction (SBSDME) by using magnetic porous carbon (MPC) composites as sorbent combined with high-performance liquid chromatography for sensitive analysis of sulfonamides in milk and lake water samples.

Identification of a phosphorus-solubilizing Tsukamurella tyrosinosolvens strain and its effect on the bacterial diversity of the rhizosphere soil of peanuts growth-promoting.

Phosphate solubilizing microorganisms widely exist in plant rhizosphere soil, but report about the P solubilization and multiple growth-promoting properties of rare actinomycetes are scarce. In this paper, a phosphate solubilizing Tsukamurella tyrosinosolvens P9 strain was isolated from the rhizosphere soil of tea plants. Phosphorus-dissolving abilities of this strain were different under different carbon and nitrogen sources, the soluble phosphorus content was 442.41 mg/L with glucose and potassium nitrate as nutrient sources. The secretion of various organic acids, such as lactic acid, maleic acid, oxalic acid, etc., was the main mechanism for P solubilization and pH value in culture was very significant negative correlation with soluble P content. In addition, this strain had multiple growth-promoting characteristics with 37.26 µg/mL of IAA and 72.01% of siderophore relative content. Under pot experiments, P9 strain improved obviously the growth of peanut seedlings. The bacterial communities of peanut rhizoshpere soil were assessed after inoculated with P9 strain. It showed that there was no significant difference in alpha-diversity indices between the inoculation and control groups, but the P9 treatment group changed the composition of bacterial communities, which increased the relative abundance of beneficial and functional microbes, which relative abundances of Chitinophagaceae at the family level, and of Flavihumibacter, Ramlibacter and Microvirga at the genus level, were all siginificant increased. Specially, Tsukamurella tyrosinosolvens were only detected in the rhizosphere of the inoculated group. This study not only founded growth-promoting properties of T. tyrosinosolvens P9 strain and its possible phosphate solublizing mechanism, but also expected to afford an excellent strain resource in biological fertilizers.

Monodispersed mesoporous SiO2@metal-organic framework (MSN@MIL-101(Fe)) composites as sorbent for extraction and preconcentration of phytohormones prior to HPLC-DAD analysis.

The monodispersed mesoporous SiO2@metal-organic framework (MSN@MIL-101(Fe)) composites were prepared by grafting MSN-NH2 onto MIL-101(Fe) particles with a solvothermal method. The adsorption ability of the composites was greatly improved compared to that of pristine MSNs or MIL-101(Fe) for phytohormones (Phys). The MSN@MIL-101(Fe) composites were characterized by scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, energy dispersive spectrometer, and mapping analysis. Using MSN@MIL-101(Fe) composites as sorbent, a dispersive solid-phase extraction procedure (dSPE) was developed to extract three endogenous Phys (abscisic acid (ABA), indole-3-aceticacid (IAA), and indole-3-butyric acid (IBA)) and two exogenous Phys (1-naphthylacetic acid (1-NAA) and 2-naphthylacetic acid (2-NAA)) prior to HPLC-DAD analysis. The experimental parameters including sample volume, sorbent amount, adsorption time, adsorption pH, desorption time, and desorption solvent on extraction efficiency were optimized and evaluated. Under optimized conditions, the working range of 0.08 to 0.45 ng mL-1 with enrichment factors from 144 to 207 were achieved. The linear range is 0.75-200 ng mL-1 for IAA, 0.20-200 ng mL-1 for ABA, and 1.0-200 ng mL-1 for IBA, 1-NAA, and 2-NAA. With MSN@MIL-101(Fe) as sorbent for extraction of Phys and determination by HPLC-DAD, two endogenous Phys (IAA and ABA) were detected from mung bean sprouts which were made in a laboratory, and the results were further confirmed by high-resolution mass spectrometry. The composites can be applied to extract other small molecules, which have similar chemical structures with Phys in biological, environmental, and food samples. Graphical abstract Schematic presentation of a dispersive solid-phase extraction using monodispersed mesoporous SiO2@metal-organic framework composites (MSNs@MIL-101(Fe)) as the sorbent for extraction, clean-up, and preconcentration of phytohormones in mung bean sprouts prior to HPLC-DAD analysis.

Expression and cloning of catA encoding a catechol 1,2-dioxygenase from the 2,4-D-degrading strain Cupriavidus campinensis BJ71.

Catechol 1,2-dioxygenases catalyze catechol ring-opening, a critical step in the degradation of aromatic compounds. Cupriavidus campinensis BJ71, an efficient 2,4-dichlorophenoxyacetic acid (2,4-D)-degrading bacterial strain, was previously isolated from an environment contaminated with 2,4-D. In this study, catA encoding a catechol 1,2-dioxygenase was cloned from the BJ71 strain. The gene was 939 bp long and encoded a polypeptide of 312 amino acids with a molecular weight of 34 kDa. To investigate its enzymatic characteristics, CatA was heterologously expressed in Escherichia coli. Optimal reaction conditions for the pure enzyme were 35 °C and pH 8.0. The enzyme remained stable within a range of 25 °C-45 °C and pH 6.0-9.0, thus indicating that CatA has wide temperature and pH adaptability. After incubation at 45 °C, the enzyme activity of CatA decreased to 37.12%, but its activity was not affected by incubation at pH 9.0. The pure enzyme was able to use catechol, 4-methyl-catechol and 4-chlorocatechol as substrates. Enzyme kinetic parameters Km and Vmax were 39.97 µM and 10.68 U/mg, respectively. This is the first report of the cloning of a gene encoding a catechol 1,2-dioxygenase from a 2,4-D-degrading bacterial strain.

Utility of colon leakage score in left-sided colorectal surgery.

BACKGROUND: The aim of the study was to evaluate the clinical utility of the colon leakage score (CLS) in predicting the risk of anastomotic leakage (AL) after left-sided colorectal surgery. MATERIALS AND METHODS: This investigation was designed as a retrospective study of 304 patients who underwent left-sided colorectal surgery. The patients were classified into two groups as those who developed AL and those who did not develop AL, and the CLSs of the two groups were compared. The predictive value and the cutoff value of the CLS were assessed by receiver operating characteristic and logistic regression analysis. RESULTS: A significant difference was noted in the mean CLSs of the groups with and without AL (P < 0.001). The values of the area under the receiver operating characteristic curve (0.965; confidence interval, 0.913-1.00) and the odds ratio (2.9; confidence interval, 1.59-4.83; P < 0.001) indicated that CLS was a good predictor of AL. A CLS of 11 was found to be the best cutoff value, with a sensitivity and specificity of 84.6% and 87.2%, respectively. CONCLUSIONS: Our findings indicate that CLS can effectively predict the risk of AL after left-sided colorectal surgery and that a CLS of 11 can be used as a cutoff value for the risk level.

Cloning, expression, characterization and mutational analysis of the tfdA gene from Cupriavidus campinensis BJ71.

2,4-Dichlorophenoxyacetic acid (2,4-D)/α-ketoglutarate (α-KG) dioxygenase (TfdA) is an Fe(II)-dependent enzyme that catalyzes the first step in degradation of the herbicide 2,4-D. Previous studies focused on the tfdA gene in Ralstonia eutropha JMP134 isolated in Australia. In this study, a new tfdA gene was cloned from Cupriavidus campinensis BJ71, an effective degrading bacteria from China, based on the iCOnsensus-DEgenerate Hybrid Oligonucleotide Primers (iCODEHOPs) protocol, combined with high-efficiency Thermal Asymmetric Interlaced PCR (hiTAIL-PCR). The open reading frame of 861 bp encoded a putative 287 amino acid protein with a theoretical molecular mass of 32.32 kDa. The gene was overexpressed in Escherichia coli BL21 (DE3) and the purified TfdA showed optimal activity at pH 6.75 and 30 °C. This enzyme was more thermostable and it could use 3-hydrocinnamic acid as substrate, with a similar enzyme activity compared with 2,4-D. TfdA and its variants were created as maltose-binding protein (MBP) tagged fusion proteins to examine the roles of putative substrate-binding residues. The MBP-N110A, MBP-V198A and MBP-R207K proteins showed decreased k cat and increased Km, and MBP-R278A was inactive, suggesting these residues may affect 2,4-D binding or catalysis.

16S rRNA gene phylogeny and tfdA gene analysis of 2,4-D-degrading bacteria isolated in China.

Twenty-two 2,4-dichlorophenoxyacetic acid (2,4-D)-degrading bacterial isolates were collected from agricultural soils at three sites in China. Sequence analysis of the 16S rRNA genes indicated that the isolates were phylogenetically grouped into four categories: Ochrobactrum anthropi, in the Alpha- class of the phylum Proteobacteria (3 out of 22 isolates), Cupriavidus sp., of the Betaproteobacteria (3 out of 22), Pseudomonas sp. and Stenotrophomonas sp., which are Gammaproteobacteria (7 out of 22), and Bacillus sp., of the phylum Firmicutes (9 out of 22). Primers were designed to amplify the conserved domain of tfdA, which is known to be involved in the degradation of 2,4-D. Results showed that the tfdA genes of all 22 strains were most similar to that of Cupriavidus necator JMP134, which belongs to the 2,4-D/α-ketoglutarate dioxygenase TfdA protein family, indicating that the JMP134-type tfdA gene is likely to be almost universal among the 2,4-D-degrading bacteria isolated from China. Degradation abilities of these 22 strains were investigated in assays using 2,4-D as the sole source of carbon and energy. Thirteen strains degraded >60 % of the available 2,4-D (500 mg l(-1)) over a 1-week incubation period, while a further nine Bacillus sp. strains degraded 50-81 % of the available 2,4-D. None of these nine strains degraded other selected herbicides, such as mecoprop, 2-methyl-4-chlorophenoxyacetic acid, quizalofop, and fluroxypyr. This is the first report of 2,4-D-degradation by Bacilli.

Transcriptional alterations of peanut root during interaction with growth-promoting Tsukamurella tyrosinosolvens strain P9.

The plant growth-promoting rhizobacterium Tsukamurella tyrosinosolvens P9 can improve peanut growth. In this study, a co-culture system of strain P9 and peanut was established to analyze the transcriptome of peanut roots interacting with P9 for 24 and 72 h. During the early stage of co-culturing, genes related to mitogen-activated protein kinase (MAPK) and Ca2+ signal transduction, ethylene synthesis, and cell wall pectin degradation were induced, and the up-regulation of phenylpropanoid derivative, flavonoid, and isoflavone synthesis enhanced the defense response of peanut. The enhanced expression of genes associated with photosynthesis and carbon fixation, circadian rhythm regulation, indoleacetic acid (IAA) synthesis, and cytokinin decomposition promoted root growth and development. At the late stage of co-culturing, ethylene synthesis was reduced, whereas Ca2+ signal transduction, isoquinoline alkaloid synthesis, and ascorbate and aldarate metabolism were up-regulated, thereby maintaining root ROS homeostasis. Sugar decomposition and oxidative phosphorylation and nitrogen and fatty acid metabolism were induced, and peanut growth was significantly promoted. Finally, the gene expression of seedlings inoculated with strain P9 exhibited temporal differences. The results of our study, which explored transcriptional alterations of peanut root during interacting with P9, provide a basis for elucidating the growth-promoting mechanism of this bacterial strain in peanut.

Exercise may delay cognitive decline in Chinese older adults: a causal inference for ordered multi-categorical exposures with a Mendelian randomization approach.

The cognitive problems are prominent in the context of global aging, and the traditional Mendelian randomization method is not applicable to ordered multi-categorical exposures. Therefore, we aimed to address this issue through the development of a method and to investigate the causal inference of cognitive-related lifestyle factors. The study sample was derived from the Chinese Longitudinal Healthy Longevity Survey, which included 897 older adults aged 65 + . This study used genome-wide association analysis to screen genetic loci as instrumental variables and innovatively combined maximum likelihood estimation to infer causal associations between ordered multi-categorical exposures (diet, exercise, etc.) and continuous outcomes (cognitive level). The causal inference method for ordered multi-categorical exposures developed in this study was simple, easy to implement, and able to effectively and reliably discover the potential causal associations between variables. Through this method, we found a potential positive causal association between exercise status and cognitive level in Chinese older adults ( ß ^ = 1.883, 95%CI 0.182-3.512), in which there was no horizontal pleiotropy (p = 0.370). The study provided a causal inference method applicable to ordered multi-categorical exposures, that addressed the limitations of the traditional Mendelian randomization method.

Association of cardiometabolic multimorbidity with all-cause and cardiovascular disease mortality among Chinese hypertensive patients.

BACKGROUND: Hypertension usually clusters with multiple comorbidities. However, the association between cardiometabolic multimorbidity (CMM) and mortality in hypertensive patients is unclear. This study aimed to investigate the association between CMM and all-cause and cardiovascular disease (CVD) mortality in Chinese patients with hypertension. METHODS: The data used in this study were from the China National Survey for Determinants of Detection and Treatment Status of Hypertensive Patients with Multiple Risk Factors (CONSIDER), which comprised 5006 participants aged 19-91 years. CMM was defined as the presence of one or more of the following morbidities: diabetes mellitus, dyslipidemia, chronic kidney disease, coronary heart disease, and stroke. Cox proportional hazard models were used to calculate the hazard ratios (HR) with 95% CI to determine the association between the number of CMMs and both all-cause and CVD mortality. RESULTS: Among 5006 participants [mean age: 58.6 ± 10.4 years, 50% women (2509 participants)], 76.4% of participants had at least one comorbidity. The mortality rate was 4.57, 4.76, 8.48, and 16.04 deaths per 1000 person-years in hypertensive patients without any comorbidity and with one, two, and three or more morbidities, respectively. In the fully adjusted model, hypertensive participants with two cardiometabolic diseases (HR = 1.52, 95% CI: 1.09-2.13) and those with three or more cardiometabolic diseases (HR = 2.44, 95% CI: 1.71-3.48) had a significantly elevated risk of all-cause mortality. The findings were similar for CVD mortality but with a greater increase in risk magnitude. CONCLUSIONS: In this study, three-fourths of hypertensive patients had CMM. Clustering with two or more comorbidities was associated with a significant increase in the risk of all-cause and cardiovascular mortality among hypertensive patients, suggesting more intensive treatment and control in this high-risk patient group.

Alcohol consumption, poor lifestyle choices, and air pollution worsen cognitive function in seniors: a cohort study in China.

Based on the complexity of cognitive-related influences and the specificity of Chinese liquor culture, this study aimed to explore the associations and potential interactions between demographic characteristics, alcohol consumption, life and atmospheric environment, and cognitive function in seniors through a comprehensive analysis, in order to provide evidence support and feasible recommendations. The study sample was selected from the Chinese Longitudinal Healthy Longevity Survey, which included 40,583 seniors aged 65-115 years. Data analysis and processing were performed by R 4.0.4. The relationship between the factors and cognition was modeled and analyzed by generalized additive model, and the interaction was explored by combining the ANOVA. The generalized additive model confirmed that alcohol consumption was detrimental to the cognitive status of older adults, especially for liquor (≥ 38°) and beer. The higher the average daily alcohol consumption, the greater the impairment. SO2 and PM2.5 showed the same negative effects. In contrast, life environment factors such as good education, balanced diet, and positive activity participation had a positive effect on cognition in seniors. In addition, interactions between alcohol consumption and average daily alcohol consumption, frequency of vegetable and meat intake, and between open-air activities, and air pollution were also confirmed. Poor lifestyle choices such as alcohol consumption, unbalanced diet, lower activity participation, and air pollution deteriorate cognitive function in seniors. It is recommended that the elderly population should avoid alcohol consumption, maintain a balanced diet, and be physically active. Attention should also be paid to the effects of air quality.

Network-based pharmacological study of the mechanism of kaiyuzhongyutang in the treatment of tubal fimbria obstruction.

To apply a network pharmacological approach to explore the targets and possible mechanisms of Kai Yu Zhong Yu Tang (KYZYT) in the treatment of tubal fimbria obstruction. The target information of KYZYT was extracted from TCMSP and HERB database. Genes related to tubal fimbria obstruction were searched using the GENECARD database. Target protein network maps (PPI) were drawn using string database analysis and Cytoscape 3.7.1 software. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and gene function analysis (GO) enrichment analysis were performed with the help of Perl language and biological program package in R language. To explore the multiple pharmacological mechanisms of action of KYZYT in the interventional treatment of tubal fimbria obstruction and to lay the foundation for further experimental validation. Through the collection and analysis of multiple databases, 355 biological targets of KYZYT were identified. 168 targets of tubal fimbria obstruction were obtained from disease database. The "drug-component" and "drug-target" networks of KYZYT were constructed, and the protein interaction network (PPI) of overlapping targets was analyzed to identify the key targets of the drug affecting the disease. In addition, KEGG pathway analysis and GO enrichment analysis were performed on the overlapping targets to explore the mechanism of KYZYT in the treatment of tubal fimbria obstruction. KYZYT has the characteristics of multi-component, multi-target and multi-pathway in the treatment of tubal fimbria obstruction, which provides new ideas and scientific basis for further clarification of the molecular mechanism.