BACKGROUND: The profile and clinical significance of the oral microbiome in patients with non-obstructive hypertrophic cardiomyopathy (noHCM) and obstructive hypertrophic cardiomyopathy (oHCM) remain unexplored. The objective of this study was to evaluate the difference of oral microbiome between noHCM and oHCM patients. METHODS: This cross-sectional study enrolled 18 noHCM patients and 26 oHCM patients from Fuwai Hospital, Chinese Academy of Medical Sciences between 2020 and 2021. Clinical and periodontal evaluations were conducted, and subgingival plaque samples were collected. Metagenomic sequencing and subsequent microbial composition and functional analyses were performed. RESULTS: Compared to oHCM patients, those with noHCM had higher systolic blood pressure (138.1 ± 18.8 mmHg vs . 124.2 ± 13.8 mmHg, P = 0.007), a larger body circumference (neck circumference: 39.2 ± 4.0 cm vs . 35.1 ± 3.7 cm, P = 0.001; waist circumference: 99.7 ± 10.5 cm vs . 92.2 ± 10.8 cm, P = 0.027; hip circumference: 102.5 ± 5.6 cm vs . 97.5 ± 9.1 cm, P = 0.030), a greater left ventricular end-diastolic diameter (46.6 ± 4.9 mm vs . 43.1 ± 4.9 mm, P = 0.026), and a lower left ventricular ejection fraction (64.1 ± 5.7 % vs . 68.5 ± 7.8%, P = 0.048). While overall biodiversity and general microbial composition were similar between the noHCM and oHCM groups, ten taxa displayed significant differences at the genus and species levels, with Porphyromonas gingivalis showing the highest abundance and greater enrichment in noHCM (relative abundance: 7.79535 vs . 4.87697, P = 0.043). Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis identified ten distinct pathways, with pathways related to energy and amino acid metabolism being enriched in oHCM patients, and those associated with genetic information processing less abundant in the oHCM group. Metabolic potential analysis revealed ten significantly altered metabolites primarily associated with amino sugar and nucleotide sugar metabolism, porphyrin metabolism, pentose and glucuronate interconversion, and lysine degradation. CONCLUSIONS The higher abundance of Porphyromonas gingivalis , which is known to impact cardiovascular health, in noHCM patients may partially account for clinical differences between the groups. Pathway enrichment and metabolic potential analyses suggest microbial functional shifts between noHCM and oHCM patients, potentially reflecting inherent metabolic changes in HCM.
Humans ; Cardiomyopathy, Hypertrophic/microbiology* ; Female ; Male ; Microbiota/genetics* ; Middle Aged ; Cross-Sectional Studies ; Adult ; Mouth/microbiology* ; Aged

Perilla frutescens (L.) Britt. is a characteristic oil crop rich in polyunsaturated fatty acids, particularly α-linolenic acid, which has important development and utilization value. The Dof transcription factor is one of the plant-specific transcription factor families, which is widely involved in important biological processes such as plant growth, development, and metabolic regulation. In order to explore the key Dof transcription factors involved in the oil biosynthesis and systematically analyze their regulatory mechanisms of P. frutescens seeds, a total of 56 PfDof gene family members were identified from the genome and transcriptome data of P. frutescens and classified into four subfamilies according to sequence characteristics. All PfDofs contained highly conserved C₂-C₂ zinc finger domains, with gene duplication being the primary mechanism driving their evolution and expansion. Genes within the same subgroup exhibited similar gene structures and conserved motifs. The 56 PfDofs were predicted as unstable hydrophilic proteins, with α-helixes and random coils as their predominant structural components. The RNA-seq results revealed that 11 PfDofs exhibited differential expression during different developmental stages of P. frutescens seeds. RT-qPCR was performed to further validate the expression patterns of these 11 members across various tissue samples (root, stem, leaf, and flower) of P. frutescens and at different developmental stages of its seeds. The results showed that PfDof29 exhibited the highest expression level in seeds, which was consistent with the transcriptome data. Subcellular localization studies demonstrated that PfDof29 was localized to the nucleus and had a transcriptional activation activity. Overexpression of PfDof29 in Nicotiana tabacum resulted in a significant increase in total oil content of tobacco leaves, accompanied by reductions in starch and soluble sugar content, while the protein content remained unchanged. Additionally, the metabolic balance between saturated and unsaturated fatty acids in the transgenic tobacco leaves was altered, with a significant increase in α-linolenic acid content. The expression levels of the fatty acid desaturase genes NtFAD2, NtFAD3, and NtFAD8 were significantly upregulated. A yeast one-hybrid assay revealed that PfDof29 could directly bind to the promoter region of PfFAD8, thereby regulating its expression. This study provides an initial understanding of the regulatory mechanisms of PfDof transcription factors in the synthesis and accumulation of oil in P. frutescens. These findings offer new insights into the enhancement of oil content and quality of P. frutescens seeds.
Transcription Factors/physiology* ; Perilla frutescens/metabolism* ; Plant Proteins/metabolism* ; Gene Expression Regulation, Plant ; alpha-Linolenic Acid/biosynthesis* ; Lipids/biosynthesis* ; Seeds/genetics*

Objective:To evaluate the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with myelodysplastic syndrome accompanied by myelodysplasia (MDS-EB) and to compare the prognosis of different subtypes of patients classified by World Health Organization (WHO) 2022.Methods:A total of 282 patients with MDS-EB who underwent allo-HSCT at the Hematology Hospital of the Chinese Academy of Medical Sciences from October 2006 to December 2022 were included in the study. The WHO 2022 diagnostic criteria reclassified MDS into three groups: myelodysplastic tumors with type 1/2 of primitive cell proliferation (MDS-IB1/IB2, 222 cases), MDS with fibrosis (MDS-f, 41 cases), and MDS with biallelic TP53 mutation (MDS-biTP53, 19 cases). Their clinical data were retrospectively analyzed.Results:① The median age of 282 patients was 46 (15-66) years, with 191 males and 91 females. Among them, 118 (42% ) and 164 (58% ) had MDS-EB1 and MDS-EB2, respectively. ②Among the 282 patients, 256 (90.8% ) achieved hematopoietic reconstruction after transplantation, with 11 (3.9% ) and 15 (5.3% ) having primary and secondary implantation dysfunctions, respectively. The cumulative incidence of acute graft-versus-host disease (GVHD) 100 days post-transplantation was (42.6±3.0) %, and the cumulative incidence of grade Ⅱ-Ⅳ acute GVHD was (33.0±2.8) %. The cumulative incidence of chronic GVHD 1 year post-transplantation was (31.0±2.9) %. Post-transplantation, 128 (45.4% ), 63 (22.3% ), 35 (12.4% ), and 17 patients (6.0% ) developed cytomegalovirus infection, bacteremia, pulmonary fungal infection, and Epstein-Barr virus infection. ③The median follow-up time post-transplantation was 22.1 (19.2-24.7) months, and the 3-year overall survival (OS) and disease-free survival (DFS) rates were 71.9% (95% CI 65.7% -78.6% ) and 63.6% (95% CI 57.2% -70.7% ), respectively. The 3-year non-recurrent mortality rate (NRM) is 17.9% (95% CI 13.9% -22.9% ), and the 3-year cumulative recurrence rate (CIR) is 9.8% (95% CI 6.7% -13.7% ). The independent risk factors affecting OS post-transplantation include monocyte karyotype ( P=0.004, HR=3.26, 95% CI 1.46-7.29), hematopoietic stem cell transplantation complication index (HCI-CI) of ≥3 points ( P<0.001, HR=2.86, 95% CI 1.72-4.75), and the occurrence of acute gastrointestinal GVHD of grade Ⅱ-Ⅳ ( P<0.001, HR=5.94, 95% CI 3.50-10.10). ④The 3-year OS and DFS rates in the MDS-IB1/IB2 group post-transplantation were better than those in the MDS-biTP53 group [OS: 72.0% (95% CI 63.4% -80.7% ) vs 46.4% (95% CI 26.9% –80.1% ), P=0.020; DFS: 67.4% (95% CI 60.3% -75.3% ) vs 39.7% (95% CI 22.3% -70.8% ), P=0.015]. The 3-year CIR was lower than that of the MDS-biTP53 group [7.3% (95% CI 4.3% -11.4% ) vs 26.9% (95% CI 9.2% -48.5% ), P=0.004]. The NRM at 3 years post-transplantation in the MDS-IB1/IB2, MDS-f, and MDS-biTP53 groups were 16.7% (95% CI 12.1% -22.1% ), 20.5% (95% CI 9.4% -34.6% ), and 26.3% (95% CI 9.1% -47.5% ), respectively ( P=0.690) . Conclusion:Allo-HSCT is an effective treatment for MDS-EB, with monomeric karyotype, HCI-CI, and grade Ⅱ-Ⅳ acute gastrointestinal GVHD as independent risk factors affecting the patient’s OS. The WHO 2022 classification helps distinguish the efficacy of allo-HSCT in different subgroups of patients. Allo-HSCT can improve the poor prognosis of patients with MDS-f, but those with MDS-biTP53 have a higher risk of recurrence post-transplantation.

Objective:To analyze the correlation between related indexes of serum lipid and insulin resistance and cognitive impairment in middle-aged and elderly people with mild cognitive impairment (MCI).Methods:In this cross-sectional study, 262 middle-aged and elderly patients with a Montreal Cognitive Function Scale (MoCA) cognitive score greater than or equal to 18 points who underwent physical examination in the Health Management Center of Beijing Tiantan Hospital Affiliated to Capital Medical University from January 1 to July 31, 2021 were selected as subjects. According to the cognitive function and MoCA score, the patients were divided into MCI group (143 cases) and normal cognition group (119 cases). Basic data, fasting blood glucose, triglyceride (TG), total cholesterol, apolipoprotein E(ApoE) genotype and other clinical indicators were collected. Hypothesis test was used to compare the differences in basic data, related indicators of blood lipid and insulin resistance between the two groups. Spearman correlation analysis was used to analyze the correlation between related indicators of blood lipid and insulin resistance and MoCA score in the two groups.Results:The age and the proportion of patients with hypertension, coronary heart disease and diabetes in the MCI group were all significantly higher than those in normal cognition group [(54.83±8.29) vs (50.76±6.34) years, 37.76% vs 31.93%, 4.20% vs 0.84%, 16.08% vs 8.40%] (all P<0.05). The elevation of serum TG ( r=-0.50, 95% CI:-0.88--0.12), TG glucose product index (TyG) ( r=-0.75, 95% CI:-1.29--0.20) and TG to high-density lipoprotein cholesterol ratio (TG/HDL-C) ( r=-0.52, 95% CI:-0.91--0.13) were all negatively correlated with MoCA score (all P<0.05). After adjusting for age and gender, the elevation of TG ( r=-0.39, 95% CI:-0.75--0.31) and TG/HDL-C ( r=-0.43, 95% CI:-0.80--0.05) were both still negatively correlated with MoCA score (both P<0.05). There was no significant correlation between all indexes and MoCA scores in the normal cognition group (all P>0.05). The elevated TG was negatively correlated with MoCA score in the MCI group ( r=-0.70, 95% CI:-1.23-0.16, P=0.017). There was no significant correlation between elevated TG and MoCA score in patients carrying ApoE ε2 and ApoE ε3 genotypes in MCI group (all P>0.05). Conclusion:Elevated related indexes of blood lipids and insulin resistance are negatively correlated with cognitive scores in middle-aged and elderly people with MCI, and it′s more obvious in patients with ApoE ε4 genotype.

Perilla (Perilla frutescens L.) is an important edible-medicinal oil crop, with its seed containing 46%-58% oil. Of perilla seed oil, α-linolenic acid (C18:3) accounts for more than 60%. Lysophosphatidic acid acyltransferase (LPAT) is one of the key enzymes responsible for triacylglycerol assembly in plant seeds, controlling the metabolic flow from lysophosphatidic acid to phosphatidic acid. In this study, the LPAT2 gene from the developing seeds of perilla was cloned and designated as PfLPAT2. The expression profile of PfLPAT2 gene was examined in various tissues and different seed development stages of perilla (10, 20, 30, and 40 days after flowering, DAF) by quantitative real-time PCR (qRT-PCR). In order to detect the subcellular localization of PfLPAT2 protein, a fusion expression vector containing PfLPAT2 and GFP was constructed and transformed into Nicotiana benthamiana leaves by Agrobacterium-mediated infiltration. In order to explore the enzymatic activity and biological function of PfLPAT2 protein, an E. coli expression vector, a yeast expression vector and a constitutive plant overexpression vector were constructed and transformed into an E. coli mutant SM2-1, a wild-type Saccharomyces cerevisiae strain INVSc1, and a common tobacco (Nicotiana tabacum, variety: Sumsun NN, SNN), respectively. The results showed that the PfLPAT2 open reading frame (ORF) sequence was 1 155 bp in length, encoding 384 amino acid residues. Functional structure domain prediction showed that PfLPAT2 protein has a typical conserved domain of lysophosphatidic acid acyltransferase. qRT-PCR analysis indicated that PfLPAT2 gene was expressed in all tissues tested, with the peak level in seed of 20 DAF of perilla. Subcellular localization prediction showed that PfLPAT2 protein is localized in cytoplasm. Functional complementation assay of PfLPAT2 in E. coli LPAAT mutant (SM2-1) showed that PfLPAT2 could restore the lipid biosynthesis of SM2-1 cell membrane and possess LPAT enzyme activity. The total oil content in the PfLPAT2 transgenic yeast was significantly increased, and the content of each fatty acid component changed compared with that of the non-transgenic control strain. Particularly, oleic acid (C18:1) in the transgenic yeast significantly increased, indicating that PfLPAT2 has a higher substrate preference for C18:1. Importantly, total fatty acid content in the transgenic tobacco leaves increased by about 0.42 times compared to that of the controls, with the C18:1 content doubled. The increased total oil content and the altered fatty acid composition in transgenic tobacco lines demonstrated that the heterologous expression of PfLPAT2 could promote host oil biosynthesis and the accumulation of health-promoting fatty acids (C18:1 and C18:3). This study will provide a theoretical basis and genetic elements for in-depth analysis of the molecular regulation mechanism of perilla oil, especially the synthesis of unsaturated fatty acids, which is beneficial to the genetic improvement of oil quality of oil crops.
Acyltransferases ; Cloning, Molecular ; Escherichia coli/metabolism* ; Fatty Acids ; Perilla frutescens/metabolism* ; Plant Oils ; Plant Proteins/metabolism* ; Saccharomyces cerevisiae/metabolism* ; Seeds/chemistry* ; Tobacco/genetics*

Objective:To investigate the long term efficacy and side effects of a donor-derived CD19 chimeric antigen receptor (CAR) T-cell (HI19α-4-1BB-ζ CAR-T) therapy in the treatment of patients with relapsed B-cell acute lymphoblastic leukemia (B-ALL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) .Methods:A total of 9 subjects with relapsed B-ALL post allo-HSCT received donor-derived CD19 CAR-T therapy from July 2017 to May 2020. All subjects were infused with donor CD3-positive T cells after lymphodepletion chemotherapy, and a median dose of CAR-T cells was 1.79 (range, 0.86-3.53) ×10 6/kg. Results:①All subjects achieved complete remission and MRD-negative at 28-42 d post CAR-T cells infusion. ②Cytokine releasing syndrome (CRS) occurrd in all subjects and was grade 3 in 2, grade 2 in 4, grade 1 in 3 cases respectively. Four subjects developed immune effector cell-associated neurotoxicity syndrome (ICANS) , which was grade 2 in 1, grade 1 in 3. One subject developed grade IV acute graft-versus-host disease (GVHD) , and side effects were all controllable. ③Four subjects relapsed at a median period of 8.6 (4.6-19.3) months, 2 subjects died of disease progression after receiving chemotherapy and another one also died of disease progression 14 months after a second transplant, only 1 subject achieved complete remission after CD22 CAR-T cell therapy. Until last follow-up date, 6 subjects were leukemia-free and achieved complete donor chimerism. The estimated 1-year and 2-year leukemia-free survival (LFS) rate was 63.5% and 50.8%, with a median LFS of 18.1 months. ④After a median follow-up of 25.1 (range, 6.9-36.7) months, the estimated 2-year and 2.5-year OS rate were 87.5% and 52.5%, respectively.Conclusion:The donor-derived CD19 CAR-T cell therapy obtain a high remission rate in relapsed B-ALL patients post allo-HSCT with tolerable side effects, half subjects survived more than 2 years without disease recurrence, though long-term efficacy requires further observation. Chinese Clinical Trial Registry: ChiCTR1900025419

Stearoyl-ACP Δ⁹ desaturase (SAD) catalyzes the synthesis of monounsaturated oleic acid or palmitoleic acid in plastids. SAD is the key enzyme to control the ratio of saturated fatty acids to unsaturated fatty acids in plant cells. In order to analyze the regulation mechanism of soybean oleic acid synthesis, soybean (Glycine max) GmSAD family members were genome-wide identified, and their conserved functional domains and physicochemical properties were also analyzed by bioinformatics tools. The spatiotemporal expression profile of each member of GmSADs was detected by qRT-PCR. The expression vectors of GmSAD5 were constructed. The enzyme activity and biological function of GmSAD5 were examined by Agrobacterium-mediated transient expression in Nicotiana tabacum leaves and genetic transformation of oleic acid-deficient yeast (Saccharomyces cerevisiae) mutant BY4389. Results show that the soybean genome contains five GmSAD family members, all encoding an enzyme protein with diiron center and two conservative histidine enrichment motifs (EENRHG and DEKRHE) specific to SAD enzymes. The active enzyme protein was predicted as a homodimer. Phylogenetic analysis indicated that five GmSADs were divided into two subgroups, which were closely related to AtSSI2 and AtSAD6, respectively. The expression profiles of GmSAD members were significantly different in soybean roots, stems, leaves, flowers, and seeds at different developmental stages. Among them, GmSAD5 expressed highly in the middle and late stages of developmental seeds, which coincided with the oil accumulation period. Transient expression of GmSAD5 in tobacco leaves increased the oleic acid and total oil content in leaf tissue by 5.56% and 2.73%, respectively, while stearic acid content was reduced by 2.46%. Functional complementation assay in defective yeast strain BY4389 demonstrated that overexpression of GmSAD5 was able to restore the synthesis of monounsaturated oleic acid, resulting in high oil accumulation. Taken together, soybean GmSAD5 has strong selectivity to stearic acid substrates and can efficiently catalyze the biosynthesis of monounsaturated oleic acid. It lays the foundation for the study of soybean seed oleic acid and total oil accumulation mechanism, providing an excellent target for genetic improvement of oil quality in soybean.
Fatty Acid Desaturases ; genetics ; metabolism ; Gene Expression Profiling ; Oleic Acid ; biosynthesis ; Phylogeny ; Plant Proteins ; genetics ; Seeds ; chemistry ; Soybeans ; classification ; enzymology ; genetics

Objective The bispectral index (BIS) was introduced into the sedation strategy of critical patients in intensive care unit (ICU) and replaced the Richmond agitation sedation scale (RASS).The ventilation time,ICU length of stay,and 90-day mortality were compared between the two groups of patients who performed early goal-directed sedation (EGDS) or standard traditional directed sedation (STDS) strategies.Methods A prospective controlled study of severe patients with mechanical ventilation ≥48 h in ICU (20 cases from April 2016 to May 2017,46 cases from June 2017 to April 2018) were randomly divided into EGDS or STDS group.There were no significant differences in age,gender,and acute physiology and chronic health evaluation score Ⅱ (APACHE Ⅱ) score between the two groups in the two periods.The correlation between RASS and BIS was analyzed in the first period.The BIS of the patients in a RASS range of (-2-1) was 73.65 ± 7.87 in the EGDS group,and that of RASS range of (-3--1) was 64.14 ± 7.25 in the STDS group.The above BIS was applied to the two sedation strategies in the second period respectively.The ventilation time,ICU length of stay,and 90-day mortality were recorded.Results There was no significant difference in the ventilation time between the two groups [(164.12 ± 137.96) h and (155.33 ±64.86)h,P =0.08].ICU length of stay of the EGDS group was longer than that of the STDS group.The 90-day mortality of the EGDS group was higher than that of the STDS group.Conclusions Correlations between RASS and BIS were found in this study,and BIS can be used for sedation assessment in ICU patients.Large sample study is still needed to compare EGDS and STDS with BIS.

Objective? To explore the value of individualized health education in early rehabilitation therapy after surgery in patients with intracranial tumor and its effects on patients＇ limb function recovery. Methods? Totally 88 patients with intracranial tumor treated in the First Affiliated Hospital of Hainan Medical University from June 2015 to November 2017 were selected by cross-sectional sampling and divided into the treatment group (n=44) and the control group (n=44) according to the random number table. All the patients received surgery. Patients in the control group received conventional nursing intervention, while patients in the treatment group received individualized health education. Short Form 36 Questionnaire (SF-36) and Simplified Fugl-Meyer Assessment of Motor Recovery (SFMA) were used to evaluate the quality of life and limb function recovery of the two groups after nursing care. Results? The quality of life score of the treatment group was (90.47±5.67), better than that of the control group, which was (79.84±4.77), and there was statistically significant difference between the two groups (P＜0.05) after nursing care. The limb function score of the treatment group was (89.68±5.77), better than that of the control group, which was (80.10±4.02), and there was statistically significant difference between the two groups (P＜ 0.05) after nursing care. Conclusions? Individualized health education provided as early as possible for patients with intracranial tumor is of great significance in improving patients＇ quality of life and limb function recovery, which is worth promoting in clinical practice.

Objective To understand the prevalence,treatment and influence factors of hypertension in maintenance hemodialysis (MHD) patients in Anhui Province.Methods A total of 2724 adult patients on MHD from January 1st 2014 to March 31st 2014 in 26 hospitals of southern,northern and central Anhui Province were investigated.Their demographic characteristics,primary disease,complications,medications,dialysis and laboratory examination were explored.The prevalence treatment rate and control rate of hypertension were analyzed.Associated factors for controlling hypertension [systolic blood pressure (SBP) ＜ 140 mmHg and diastolic blood pressure (DBP) ＜ 90 mmHg] were assessed by logistic regression analysis.Results (1) The prevalence of hypertension in the hemodialysis patients was 87.0％.Their treatment rate and control rate were 93.2％ and 23.9％ respectively.The average of SBP was (145.90±21.18) mmHg,and the DBP on average was (83.60± 12.21) mmHg.The most commonly used anti-hypertensive drug is calcium channel blocker (88.2％).Over one third (45.7％) of patients were treated with two kinds of anti-hypertensive drug,26.2％ with 1 kind,21.7％ with 3 kinds,and 6.4％ with 4 kinds or more.(2) Compared with non-hypertension patients,patients with hypertension have older age,higher body mass index (BMI),phosphorus,SBP and DBP,as well as lower hemoglobin and Kt/V (all P ＜ 0.05).(3) The multivariate logistic regression analysis showed that Ca ＞ 2.50 mmol/L (OR=2.084,95％CI 1.008-4.307,P=0.047) positively correlated with controlling hypertension,while smoke (OR=0.594,95％CI 0.356-0.911,P=0.046) and BMI 18.5 ～ 23.9 kg/m2 (OR=0.516,95％CI 0.293-0.907,P=0.022) negatively correlated with it.Conclusions High prevalence yet low control rate of hypertension in MHD patients in Anhui Province were observed.Hypocalcemia may be a protective factor for hypertension control,while smoke and BMI may be risk factors for it.