Osteoporosis and coronary heart disease: a bi-directional Mendelian randomization study.

Background: Osteoporosis (OP) and cardiovascular disease (CVD) are major global public health issues, especially exacerbated by the challenges of an aging population. As these problems intensify, the associated burden on global health is expected to increase significantly. Despite extensive epidemiological investigations into the potential association between OP and CVD, establishing a clear causal relationship remains elusive. Methods: Instrumental variables were selected from summary statistics of the IEU GWAS database. Five different components of BMD (heel BMD, LS BMD, FA BMD, FN BMD, and TB BMD) were used as OP phenotypes. CHD, MI, and stroke were selected to represent CVD. Multiple analysis methods were used to evaluate the causal relationship between CVD and OP comprehensively. In addition, sensitivity analyses(Cochran's Q test, MR-Egger intercept test, and "leave one out" analysis) were performed to verify the reliability of the results. Results: The MR showed a significant causal relationship between CHD on heel BMD and TB BMD; in the reverse analysis, there was no evidence that OP has a significant causal effect on CVD. The reliability of the results was confirmed through sensitivity analysis. Conclusion: The study results revealed that CHD was causally associated with Heel BMD and TB BMD, while in the reverse MR analysis, the causal relationship between OP and CVD was not supported. This result posits CHD as a potential etiological factor for OP and prompts that routine bone density assessment at traditional sites (forearm, femoral neck, lumbar spine) using DAX may inadequately discern underlying osteoporosis issues in CHD patients. The recommendation is to synergistically incorporate heel ultrasound or DAX for total body bone density examinations, ensuring clinical diagnostics are both precise and reliable. Moreover, these findings provide valuable insights for public health, contributing to the development of pertinent prevention and treatment strategies.

An acquired BMF with FANCL gene heterozygous mutation: Case report.

RATIONALE: Bone marrow failure (BMF) includes inherited and acquired BMFs. Acquired BMF can be secondary to various factors, such as autoimmune dysfunction, benzene, drugs, radiation, viral infection and so on. Fanconi anemia (FA) complementation group L (FANCL) is an E3 ubiquitin ligase that participates in the repair of DNA damage. Homozygous or compound heterozygous mutations of FANCL can lead to the onset of FA, which is one of the most common inherited BMFs. PATIENT CONCERNS AND DIAGNOSES: Here, we report a case of acquired BMF. This patient had a history of benzene exposure for half a year before the onset of the disease, and presented with progressive pancytopenia, especially the reduction of erythrocytes and megakaryocyte, without malformation. Interestingly, this patient and his brother/father had a heterozygous (non-homozygous/compound heterozygous) mutation (Exon9, c.745C > T, p.H249Y) in the FANCL gene. INTERVENTIONS AND OUTCOMES: The patient successfully underwent unrelated and fully compatible umbilical cord blood hematopoietic stem cell transplantation. LESSONS SUBSECTIONS: We report for the first time an acquired BMF case with FANCL gene heterozygous mutation, and the mutation site (Exon9, c.745C > T, p.H249Y) has never been reported. This case suggests that heterozygous mutations in FANCL gene may be associated with increased susceptibility to acquired BMF. Based on current reports and this case, we speculate that heterozygous mutations in the FA complementation gene may exist in a certain proportion of tumor and acquired BMF patients, but have not been detected. We recommend routine screening for FA complementation gene mutations in tumor and acquired BMF patients in clinical practice. If positive results are found, further screening can be conducted on their families.

Osteoarthritis and cardiovascular disease: A Mendelian randomization study.

Objective: This Mendelian randomization (MR) study aimed to investigate the causal relationship between osteoarthritis (OA) and cardiovascular disease (CVD). Methods: From a genome-wide association study of European ancestry, we selected single nucleotide polymorphisms for two types of OA, knee osteoarthritis (KOA) and hip osteoarthritis (HOA), as instrumental variables. We evaluated three types of CVD: coronary heart disease (CHD), heart failure (HF), and stroke. We used the traditional inverse variance weighting (IVW) method and other methods to estimate causality. Heterogeneity and sensitivity tests were also applied. Finally, we conducted a MR analysis in the opposite direction to investigate reverse causality. Results: IVW analysis showed that HOA significantly affected the incidence of HF [odds ratio (OR): 1.0675; 95% confidence interval (CI): 0.0182-0.1125, P = 0.0066]. HOA significantly affected the incidence of stroke (OR: 1.1368; 95% CI: 1.0739-1.2033, P = 9.9488e-06). CHD could dramatically affect the incidence of KOA (OR: 0.9011; 95% CI: 0.8442-0.9619, P = 0.0018). The rest of the results were negative. Conclusions: Our results revealed a potential causal relationship between HOA and risk of HF, and a potential causal relationship between HOA and risk of stroke. Our findings also suggested that CHD has a significant causal relationship with the risk of KOA. This paper may provide new ideas for the treatment of OA and CVD.

Quantitative evaluation method of smoke exhaust performance and application on exhaust volume optimization in tunnel fires under lateral centralized mode.

This study investigated the indicators in the quantitative method of evaluating the smoke exhaust performance, which provided a theoretical basis for the optimization of the smoke extraction system under the lateral centralized mode in tunnel fires. The criterion was proposed for plug-holing, and the theoretical models of smoke exhaust efficiency were established to distinguish whether the plug-holing occurs or not. The relationship between efficiency, effectiveness, and efficacy was analyzed from the perspective of smoke and heat exhaust. Meanwhile, this evaluation method was applied to the optimization of exhaust volume in a practical engineering through FDS numerical simulation. The results show that Ri is a vital basis for reflecting the movement form of smoke and the exhaust effect. The critical value of Ri is 1.09 when plug-holing occurs in a standard three-lane immersed tunnel, resulting in a significant reduction in the efficiency of smoke exhaust. The greater the exhaust volume of the exhaust fan, the greater the Ri value, the higher the total smoke and heat exhaust efficiency, and the better the exhaust effectiveness of smoke inlets without plug-holing. Under longitudinal ventilation, the optimal exhaust volume is 180 m3/s at 20 MW and 360 m3/s at 50 MW in the application case.

Causal association between celiac disease and inflammatory bowel disease: A two-sample bidirectional Mendelian randomization study.

Background: An epidemiological link between celiac disease (CeD) and inflammatory bowel disease (IBD) has been well established recently. In this study, Mendelian randomization (MR) analysis was performed employing pooled data of publicly available genome-wide association studies (GWAS) to determine the causal relationship between CeD and IBD, encompassing ulcerative colitis (UC) and Crohn's disease (CD). Methods: Dataset of CeD was acquired from GWAS for 12,041 cases and 12,228 controls. A GWAS of more than 86,000 patients and controls was used to identify genetic variations underlying IBD. MR analyses were performed with an inverse-variance-weighted approach, an MR-Egger regression, a weighted-mode approach, a weighted-median method, and sensitivity analyses of MR pleiotropy residual sum and outlie (MR-PRESSO). Results: MR demonstrated that genetic predisposition to CeD was linked to a augmented risk of IBD (OR: 1.1408; 95% CI: 1.0614-1.2261; P = 0.0003). In the analysis of the two IBD subtypes, genetic predisposition to CeD was also linked to increased risks of UC (OR: 1.1646; 95% CI: 1.0614-1.2779; P = 0.0012) and CD (OR: 1.1865; 95% CI: 1.0948-1.2859; P = 3.07E-05). Reverse MR analysis results revealed that genetic susceptibility to IBD and CD was correlated with an augmented risk of CeD. However, there was no genetic correlation between UC and CeD. All of the above results were validated with other GWAS databases. Conclusion: There is a bidirectional causal relationship of CeD with IBD and CD. However, UC only augments the risk of developing CeD.

Assessment of different ventilation strategies on ventilation performance in immersed tunnels.

Investigations of ventilation in an immersed tunnel have recently drawn greater research attentions; however, analyses on the influence of vent design and tunnel width on ventilation performance have rarely been addressed. For the sake of the security of evacuees in an immersed tunnel fire, the influence of three vent designs and two immersed tunnel widths on mechanical ventilation performance during tunnel fires were numerically investigated using large eddy simulation. The pollutant gas flow characteristics in the tunnel after a fire were analyzed, and the pollutant gas exhaust efficiency based on the mass conservation of carbon monoxide in the smoke was proposed in this study. By comparing the smoke propagation, smoke distribution, and exhaust efficiency between three different vent designs, it was determined that the Top Vent Design has the best smoke exhaust effect, and the Sidewall Vent Design (with an activated vertical smoke screen) has a better smoke exhaust effect than the Sidewall Vent Design. The influences of the tunnel width and heat release rate of the fire on the ventilation effect were also investigated.

[Electroacupuncture at "Zusanli"(ST36) promotes gastrointestinal motility possibly by suppres-sing excessive autophagy via AMPK/ULK1 signaling in rats with functional dyspepsia].

OBJECTIVE: To explore the effect of electroacupuncture (EA) at "Zusanli" (ST36) on gastrointestinal motility and expression of autophagy marker LC3 and autophagy signaling pathway molecule AMP-activated protein kinase (AMPK) in rats with functional dyspepsia (FD), so as to explore its mechanisms underlying improvement of FD. METHODS: A total of 40 male SD rats were randomly divided into blank control, model, EA, AMPK inhibitor and EA＋AMPK inhibitor groups, with 8 rats in each group. The FD model was established by tail-clip (30 min/time, twice daily) ＋ single day feeding, and gavage of normal saline (2 mL/time, twice a day) for 2 successive weeks. For rats of EA and EA＋AMPK inhibitor groups, EA (4 Hz, 1.0 mA) was applied to bilateral ST36 for 20 min, once daily for 7 successive days. For rats of the AMPK-inhibitor and EA＋AMPK inhibitor groups, Compound C (20 mg/kg) solution was administered by intraperitoneal injection before every EA administration. The gastric residual rate and small intestinal transit rate were calculated based on the weight of stomach and length of ink propelling and total small intestine, respectively. The expression levels of c-kit, microtubule-associated protein 1 light chain 3, Beclin 1, phosphorylated (p)-AMPK and p-unc-51 like autophagy activating kinase 1(ULK1) in the gastric antrum tissue were detected by using Western blot. RESULTS: Compared with the blank control group, the gastric residual rate and the expression levels of LC3-Ⅱ/LC3Ⅰ， Beclin 1, p-AMPK and p-ULK1 proteins were significantly increased, and the small intestinal transit rate and the expression of c-kit protein obviously decreased in the model group (P<0.01). After EA intervention, modeling-induced increase of gastric residual rate and the expression of LC3-Ⅱ/LC3Ⅰ， Beclin 1, p-AMPK and p-ULK1 proteins, and decrease of small intestinal transit rate and expression of c-kit protein were reversed in the EA, AMPK inhibitor and EA＋AMPK inhibitor groups (P<0.05, P<0.01). The therapeutic effect of EA and EA＋AMPK was significantly superior to that of AMPK inhibitor in down-regulating the expression of LC3Ⅱ/LC3Ⅰ， Beclin 1, p-AMPK and p-ULK1 proteins and in up-regulating the expression of c-kit protein (P<0.05, P<0.01). No significant differences were found among the EA, AMPK inhibitor and EA＋AMPK inhibitor groups in lowering gastric residual rate and elevating the small intestinal transit rate (P>0.05). CONCLUSION: EA at ST36 can promote gastrointestinal motility in FD rats, which is possibly mediated by inhibiting excessive autophagy of interstitial cells of Cajal via down-regulating AMPK/ULK1 signaling.

[Expression and Function of miR-99a-5p in Bone Marrow of Patients with MDS].

OBJECTIVE: To detect the expression of miR-99a-5p in myelodysplastic syndrome (MDS), to predict the target genes and to analyze its function by using bioinformatics. METHODS: The expression levels of bone marrow miR-99a-5p in MDS patients were detected by qRT-PCR, and the correlation of miR-99a-5p expression with clinical pathological characteristics, percentage of marrow blasts , chromosome karyotype and peripheral blood hemogram were analyzed. The target genes of miR-99a-5p were predicted by Targetscan, Miranda and Microcosm, and the intersection of the predicted results of 3 softwares was used as a potential target gene for miR-99a-5p. RESULTS: The expression level of bone marrow miR-99a-5p in MDS patients was significantly higher than that of healthy controls (P<0.01); According to the prognostic score of IPSS, MDS patients were divided into relatively low risk group (including low risk group and intermediate risk group 1) and relatively high risk group (including intermediate risk group 2 and high risk group). Analysis showed that the expression level of bone marrow miR-99a-5p in relatively low risk group was 2.40 times higher than that in healthy control group (P<0.01), the expression level of bone marrow miR-99a-5p in relatively high risk group was 6.66 times higher than that in healthy control group (P<0.01), the expression level of miR-99a-5p in relatively high risk group was 2.80 times higher than that in the relatively low risk group ( P<0.01) ; the expression level of bone marrow miR-99a-5p in t-MDS group was 6.35 times higher than that in healthy control group (P<0.001). There was a significant positive correlation between the expression level of miR-99a-5p and the percentage of marrow blasts (P<0.01), but the expression of miR-99a-5p did not correlate with chromosome karyotype and peripheral blood hemogram; In this study it was obtained that ST5 might participate in pathological mechanism of MDS by bioinformatic analyses and references. CONCLUSION: The expression levels of miR-99a-5p is up-regulated in MDS patients, and its expression showed a rising tendency which may be involved in the pathogenesis of MDS by regulating target gene ST5.

Expression and Function of miR-99a-5p in Bone Marrow of Patients with MDS / 中国实验血液学杂志

OBJECTIVE@#To detect the expression of miR-99a-5p in myelodysplastic syndrome (MDS), to predict the target genes and to analyze its function by using bioinformatics.@*METHODS@#The expression levels of bone marrow miR-99a-5p in MDS patients were detected by qRT-PCR, and the correlation of miR-99a-5p expression with clinical pathological characteristics, percentage of marrow blasts , chromosome karyotype and peripheral blood hemogram were analyzed. The target genes of miR-99a-5p were predicted by Targetscan, Miranda and Microcosm, and the intersection of the predicted results of 3 softwares was used as a potential target gene for miR-99a-5p.@*RESULTS@#The expression level of bone marrow miR-99a-5p in MDS patients was significantly higher than that of healthy controls (P<0.01); According to the prognostic score of IPSS, MDS patients were divided into relatively low risk group (including low risk group and intermediate risk group 1) and relatively high risk group (including intermediate risk group 2 and high risk group). Analysis showed that the expression level of bone marrow miR-99a-5p in relatively low risk group was 2.40 times higher than that in healthy control group (P<0.01), the expression level of bone marrow miR-99a-5p in relatively high risk group was 6.66 times higher than that in healthy control group (P<0.01), the expression level of miR-99a-5p in relatively high risk group was 2.80 times higher than that in the relatively low risk group ( P<0.01) ; the expression level of bone marrow miR-99a-5p in t-MDS group was 6.35 times higher than that in healthy control group (P<0.001). There was a significant positive correlation between the expression level of miR-99a-5p and the percentage of marrow blasts (P<0.01), but the expression of miR-99a-5p did not correlate with chromosome karyotype and peripheral blood hemogram; In this study it was obtained that ST5 might participate in pathological mechanism of MDS by bioinformatic analyses and references.@*CONCLUSION@#The expression levels of miR-99a-5p is up-regulated in MDS patients, and its expression showed a rising tendency which may be involved in the pathogenesis of MDS by regulating target gene ST5.

[Effects of Electroacupuncture on Gastrointestinal Motility and Expressions of VIP and CGRP in Functional Dyspepsia Model Rats].

Objective To observe the effects of electroacupuncture (EA) on vasoactive intesti- nal peptide (VIP) , calcitonin gene-related peptide (CGRP) expression, gastric emptying, and small in- testine advance rate in functional dyspepsia (FD) rats. Methods Totally 48 SD rats were randomly di- vided into three groups, the blank group, the model group, and the EA group, 16 in each group. Except rats in the blank group, FD model was established by tail clamped stimulation plus irregular diet, and ice physiological saline gastrogavage for 14 successive days. After successful modeling EA at Zusanli (ST36) and Taichong (LR3) were performed, once per day for 28 days. Rats were intervened by gastro- gavage at the end of the treatment. Gastric tissue and small intestinal tissue were sampled after anatomy. The rates of gastric emptying and small intestinal transit were determined. Pathological changes of gastric antrum and jejunum tissue were observed by HE staining. mRNA expression levels of VIP and CGRP in gastric antrum and jejunum tissue were determined by Real-time PCR. Results No organic change oc- curred in tissues of the 3 groups. No gastric or intestinal ulcers , inflammatory infiltration, or glandular ep- ithelial lesion occurred in the 3 groups. Compared with the blank group, gastric residual rate obviously in- creased, small intestinal transit rate was lowered, mRNA expression levels of VIP and CGRP in gastric antrum and jejunum tissue were obviously elevated in the model group (P <0. 01, P <0. 05). Compared with the model group, gastric residual rate was obviously reduced, small intestinal transit was obviously elevated, mRNA expression levels of VIP and CGRP in gastric antrum and jejunum tissue were obviously decreased (P <0. 05, P <0. 01). Conclusions EA could significantly decrease mRNA expressions of VIP and CGRP in gastrointestinal tract, accelerate gastric emptying rate and small intestinal transit rate. EA's improving the gastrointestinal motility might be related to decreasing mRNA expressions of VIP and CGRP in gastrointestinal tract, indicating that abnormal secretion braingut peptide might be one of important mechanisms for FD.

[Expression of miR-550a-5p in Myelodysplastic Syndrome and Its Prediction of Target Genes].

OBJECTIVE: To investigate the expression of miR-550a-5p in bone marrow of patients with myelodysplastic syndrome (MDS), and to predict its target genes and function by bioinformatics analyses, so as to provide the evidence to furthre explore the role of miR-550a-5p and its target genes in pathogenesis of MDS. METHODS: Real-time PCR was used to detect the expression of miR-550a-5p in 54 MDS patients, 16 acute myeloid leukemia transformed from MDS (sfAML) and 19 healthy controls, and the correlation between the expression of miR-550a-5p and clinical pathologic characteristics of MDS, including chromosome, percentage of marrow blasts, absolute neutrophil count, platelet count and hemoglobin levels were analyzed. The sequence of miR-550 was searched in miRBase database. Target genes of miR-550a-5p were predicted by Microcosm,Miranda and Targetscan, and the predective results were collected, then the enrichment analyses of target gene function(GO) and signalling pathway(pathway of miR-550a-5p) were carried out by using gene ontology darabase and KEGG database. RESULTS: The expression of miR-550a-5p in bone marrow of all MDS patients was higher than that in controls: the expression level of miR-550a-5p in low risk MDS and middl risk 1 MDS was 1.7 times of controls (P=1.23×10-10); the expression of miR-550a-5p in midde risk 2 MDS and high risk MDS was 1.9 times of controls (P=1.20×10-10); the expression of miR-550a-5p in tAML was 2.0 times of controls (P=5.61×10-10). The miR-550a-5p expression level was up-regulated gradually with the enhancement of disease risk of MDS, but there was no correlation between the expression level of miR-550a-5p and clinical pathologic characteristics of MDS(chromosome: Normal: 1.11±0.19, Abnormal:1.26±0.15, P>0.05; Percentage of Marrow Blasts: r=0.29,P=0.07; absolute neutrophil count: r=-0.02,P=0.89; hemoglobin level: r=0.09,P=0.57; platelet count: r=0.25,P=0.08). The sequence of miR-550 was conservative among different species, and the prediced results indicated that there were 19 target genes in intersection. The functions of target genes were enriched in regulation of stress-activated cascade, MAPK pathway, regulation of muscle organ development, regulation of protein homodimerization activity and other biological processes; they participated in some molecular functions including enzyme activity, combination processes of some molecules as protein, cAMP and domain existed in cell junction, synapse, coated vesicle, dendrite and other cellular components. Two of them-PDLIM2 and PSME1 were selected which might play a role in pathologic mechanism of MDS regulated by miR-550a-5p. CONCLUSION: The expression of miR-550a-5p in bone marrow of MDS patients increases specifically, and miR-550a-5p may play a role in the pathogenesis of MDS through regulation of target genes, PDLIM2 and PSME1.

[Involvement of Neurotensin-mediated Brain-gut Axis in Electroacupuncture Intervention Induced Improvement of Functional Dyspepsia in Rats].

OBJECTIVE: To observe The effect of electroacupuncture (EA) stimulation of "Zusanli" (ST 36) and "Taichong" (LR 3) on intestinal motor and neurotensin (NT) levels in the plasma, hypothalamus, and gastro-antrum tissues in functional dyspepsia (FD) rats so as to reveal its mechanisms underlying improvement of FD. METHODS: Forty-eight SD rats were randomly divided into control, model and EA groups, with 16 rats in each group. The FD model was established by clamping the rats' tails and alternate day's feeding according to the related references. EA (2 Hz/100 Hz, 2 mA) was applied to unilateral ST 36 and LR 3 for 30 min, once daily for 14 days. Rats of the control group were only restricted. The gastric emptying rate and propulsive rate of the small intestine were detected. The content of NT in the plasma was assayed using ELISA, and the immunoactivity levels of NT in the hypothalamus, gastric antrum mucous membrane and ileum tissues were detected using immunohistochemistry. RESULTS: Compared with the control group, the gastric emptying rate and propulsive rate of the small intestine were considerably lowered in the model group (P < 0.01), and the content and immunoactivity levels of NT in the plasma, hypothalamus, mucous membrane of the gastric antrum and ileum tissues were significantly increased (P < 0.05). After EA intervention, the decreased gastric emptying rate and intestinal propulsive rate, as well as the increased NT content and immunoactivity levels of plasma, hypothalamus, gastric antrum and ileum were reversed (P < 0.05). CONCLUSION: EA intervention can obviously promote gastrointestinal motor in FD rats, which may be related to its function in down-regulating NT levels in the plasma, hypothalamus, gastric antrum and ileum. It suggests an involvement of NT in the brain-gut axis in EA-induced improvement of FD.

Expression of miR-550a-5p in Myelodysplastic Syndrome and Its Prediction of Target Genes / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the expression of miR-550a-5p in bone marrow of patients with myelodysplastic syndrome (MDS), and to predict its target genes and function by bioinformatics analyses, so as to provide the evidence to furthre explore the role of miR-550a-5p and its target genes in pathogenesis of MDS.</p><p><b>METHODS</b>Real-time PCR was used to detect the expression of miR-550a-5p in 54 MDS patients, 16 acute myeloid leukemia transformed from MDS (sfAML) and 19 healthy controls, and the correlation between the expression of miR-550a-5p and clinical pathologic characteristics of MDS, including chromosome, percentage of marrow blasts, absolute neutrophil count, platelet count and hemoglobin levels were analyzed. The sequence of miR-550 was searched in miRBase database. Target genes of miR-550a-5p were predicted by Microcosm,Miranda and Targetscan, and the predective results were collected, then the enrichment analyses of target gene function(GO) and signalling pathway(pathway of miR-550a-5p) were carried out by using gene ontology darabase and KEGG database.</p><p><b>RESULTS</b>The expression of miR-550a-5p in bone marrow of all MDS patients was higher than that in controls: the expression level of miR-550a-5p in low risk MDS and middl risk 1 MDS was 1.7 times of controls (P=1.23×10); the expression of miR-550a-5p in midde risk 2 MDS and high risk MDS was 1.9 times of controls (P=1.20×10); the expression of miR-550a-5p in tAML was 2.0 times of controls (P=5.61×10). The miR-550a-5p expression level was up-regulated gradually with the enhancement of disease risk of MDS, but there was no correlation between the expression level of miR-550a-5p and clinical pathologic characteristics of MDS(chromosome: Normal: 1.11±0.19, Abnormal:1.26±0.15, P>0.05; Percentage of Marrow Blasts: r=0.29,P=0.07; absolute neutrophil count: r=-0.02,P=0.89; hemoglobin level: r=0.09,P=0.57; platelet count: r=0.25,P=0.08). The sequence of miR-550 was conservative among different species, and the prediced results indicated that there were 19 target genes in intersection. The functions of target genes were enriched in regulation of stress-activated cascade, MAPK pathway, regulation of muscle organ development, regulation of protein homodimerization activity and other biological processes; they participated in some molecular functions including enzyme activity, combination processes of some molecules as protein, cAMP and domain existed in cell junction, synapse, coated vesicle, dendrite and other cellular components. Two of them-PDLIM2 and PSME1 were selected which might play a role in pathologic mechanism of MDS regulated by miR-550a-5p.</p><p><b>CONCLUSION</b>The expression of miR-550a-5p in bone marrow of MDS patients increases specifically, and miR-550a-5p may play a role in the pathogenesis of MDS through regulation of target genes, PDLIM2 and PSME1.</p>