Risk factors for patients with acute hospital-acquired symptomatic pulmonary thromboembolism.

This study aimed to identify independent risk factors for acute hospital-acquired symptomatic pulmonary embolism (HA-SPE) by comparing the clinical data of HA-SPE and acute nonhospital-acquired symptomatic pulmonary embolism (NHA-SPE). A total of 292 patients were included in the analysis and divided into two groups: 191 patients had acute NHA-SPE, and 101 patients had acute HA-SPE. The average age of these 292 patients was 63.2 years, and the sample included 145 males. Multivariate analysis showed that malignant tumour (OR, 3.811; 95% CI [1.914-7.586], P = 0.000), recent surgery (OR, 7.310; 95% CI 3.392-15.755], P = 0.000), previous VTE (OR, 5.973; 95% CI 2.194 16.262], P = 0. 000), and the length of stay (LOS) (OR, 1.075; 95% CI [1.040-1.111], P = 0.000) were independent risk factors for acute HA-AEP. The c-statistic for this model was 0.758 (95% CI [0.698-0.800], P < 0.0001). The K-M curve showed that the hazard ratio (HR) of the HA group to the NHA group in all-cause mortality was 3.807 (95% CI [1.987, 7.295], P = 0.0061). Strengthening the prevention and control of patients with these risk factors may reduce the incidence of acute HA-SPE.

Acute septic thrombophlebitis of the lower extremities due to foreign body injury and infection: a case report.

BACKGROUND: Septic thrombophlebitis (STP) of the lower extremities caused by foreign bodies is rare in the clinic, and the symptoms are serious. If the correct treatment is not implemented as soon as possible, the patient may progress to sepsis. CASE PRESENTATION: We report the case of a 51-year-old normally healthy male who developed fever 3 days after field work. When he was weeding with a lawn mower in the field, a metal foreign body from the grass flew into his left lower abdomen, resulting in an eschar on his left lower abdomen. He was diagnosed with scrub typhus but did not respond well to anti-infective treatment. After a detailed inquiry of his medical history and an auxiliary examination, the diagnosis was confirmed as STP of the left lower limb caused by a foreign body. After surgery, anticoagulation and anti-infection treatment, the infection and thrombosis were controlled, and the patient was cured and discharged. CONCLUSIONS: STP caused by foreign bodies is rare. Early detection of the aetiology of sepsis and early adoption of the correct measures can effectively block the progression of the disease and reduce the patient's pain. Clinicians should identify the source of sepsis through a medical history and clinical examination.

Human thermal sensation and its algorithmic modelization under dynamic environmental thermal characteristics of vehicle cabin.

Thermal conditions are strongly changeable in a vehicle cabin, where passengers could suffer consecutive self-thermoregulation to such dynamic changing thermal stresses, though its HVAC system works well. To observe human overall and local thermal sensations in dynamic thermal conditions, a series of experiments under various conditions were carried out in a cabin-like climate chamber. The results showed that the head, chest, back, and hands during hot exposure are warmer leading to the overall thermal sensation being hot. The thermal sensation of the head was warmer than the overall thermal sensation. During cold exposure, arms, hands, legs, and feet were the main areas causing coldness. In a dynamic thermal environment, the previous skin temperature state and thermal sensation form a thermal sensation overshoot, causing a shift in the body's neutral temperature point. This study proposes a thermal sensation model for the prediction of human thermal sensation local and overall based on skin temperature changes in a dynamic environment. Considering the airflow characteristics in the cabin, the human body is set into seven local parts in the local thermal sensation model. To compensate for sensation overshoot from this, defining recovery points rp for local parts differentiate temperature setpoints according to the experienced thermal state so that the effect resulting from the dynamic condition is integrated into the model algorithm. The model provides a scientific basis for guiding design optimization and intelligent regulation in the dynamic environment of the vehicle cabin, so as to achieve efficient energy utilization.

Analysis and evaluation of different sequencing depths from 5 to 20 million reads in shotgun metagenomic sequencing, with optimal minimum depth being recommended.

Our study was to analyze and evaluate the impact of different shotgun metagenomic sequencing depths from 5 to 20 million in metagenome-wide association studies (MWASs), and to determine the optimal minimum sequencing depth. We included a set of 200 previously published gut microbial shotgun metagenomic sequencing data on obesity (100 obese vs. 100 non-obese). The reads with original sequencing depths >20 million were downsized into seven experimental groups with depths from 5 to 20 million (interval 2.5 million). Using both integrated gene cluster (IGC) and metagenomic phylogenetic analysis 2 (MetaPhlAn2), we obtained and analyzed the read matching rates, gene count, species richness and abundance, diversity, and clinical biomarkers of the experimental groups with the original depth as the control group. An additional set of 100 published data from a colorectal cancer (CRC) study was included for validation (50 CRC vs. 50 CRC-free). Our results showed that more genes and species were identified following the increase in sequencing depths. When it reached 15 million or higher, the species richness became more stable with changing rate of 5% or lower, and the species composition more stable with ICC intraclass correlation coefficient (ICC) higher than 0.75. In terms of species abundance, 81% and 97% of species showed significant differences in IGC and MetaPhlAn2 among all groups with p < 0.05. Diversity showed significant differences across all groups, with decreasing differences of diversity between the experimental and the control groups following the increase in sequencing depth. The area under a receiver operating characteristic curve, AUC, of the obesity classifier for running the obesity testing samples showed an increasing trend following the increase in sequencing depth (τ = 0.29). The validation results were consistent with the above results. Our study found that the higher the sequencing depth is, the more the microbial information in structure and composition it provides. We also found that when sequencing depth was 15 million or higher, we obtained more stable species compositions and disease classifiers with good performance. Therefore, we recommend 15 million as the optimal minimum sequencing depth for an MWAS.

Study on the Mechanism of circRNA-0024103 Reducing Endothelial Cell Injury by Regulating miR-363/MMP-10.

Cardiovascular diseases could damage the heart and blood vessels, which cause mortality and morbidity. It is of great significance to explore targeted therapeutic approaches for atherosclerosis that is one of the most common vascular lesions and the main pathological basis of cardiovascular disease. However, the function of circRNA-0024103 in cardiovascular diseases is still not clear. Therefore, we aim to observe the effect of circRNA-0024103 modulation of miR-363/MMP-10 axis on biological behaviors such as proliferation and migration of endothelial cells after ox-LDL induction. The effects on the proliferation ability of endothelial cells were observed by CCK-8 assay and EdU assay based on overexpression of circRNA-0024103 in combination with miR-363 mimic or MMP-10 siRNA, and then, the effects on apoptosis were detected by flow cytometry analysis. The effects on cell migration, invasion, and angiogenesis were further examined by scratch assay, transwell assay, and tube formation assay. The results in CCK-8 and EdU assays showed that miR-363 mimic or MMP-10siRNA significantly attenuated the proliferation-promoting effect of overexpressed circRNA-0024103 on cell proliferation. In flow cytometry assays to detect apoptosis, overexpression of circRNA-0024103 inhibited apoptosis of endothelial cells, and the intervention of combined miR-363 mimic or MMP-10 siRNA counteracted the inhibitory effect of overexpression of circRNA-0024103 on apoptosis, resulting in a significant increase in the number of endothelial cells undergoing apoptosis. The migration, invasion, and tube-forming ability of endothelial cells were significantly enhanced when circRNA-0024103 was overexpressed, while the promotion of migration, invasion, and the tube-forming ability by overexpression of circRNA-0024103 alone was counteracted when combined with miR-363 mimic or MMP-10 siRNA. circRNA-0024103 regulates the biological behaviors of endothelial cells such as proliferation, apoptosis, migration, and invasion through the miR-363/MMP-10 axis. Our finding provides a new therapeutic target for the treatment of atherosclerosis.

Knockdown of hsa_circ_0005699 attenuates inflammation and apoptosis induced by ox-LDL in human umbilical vein endothelial cells through regulation of the miR-450b-5p/NFKB1 axis.

Atherosclerosis (AS) remains the leading cause of mortality throughout the world, and vascular endothelial cell dysfunction is one of the key events leading to this pathology. In recent years, there has been an increased interest in the role of circulating RNAs in various diseases; these noncoding RNAs can regulate gene products by acting as microRNA (miR) sponges. Furthermore, it has been shown that foam cells exhibit high expression levels of hsa_circ_0005699 (circ_0005699); however, to the best of our knowledge, no previous study has investigated the role of circ_0005699 in the regulation of vascular endothelial function. The present study employed human umbilical vein endothelial cells (HUVECs), which have been widely used to study vascular endothelial cell function. In addition, apolipoprotein E (ApoE)-deficient mice were used, which have been shown to rapidly develop AS and are widely used as a model of this disease. Cellular and biochemical techniques were performed, including gene transfection and short hairpin RNA-mediated gene silencing for cell transfection, luciferase reporter gene assay to confirm predicted genes, Cell Counting Kit-8 assay and flow cytometry to assess cell viability and apoptosis, and reverse transcription-quantitative PCR and western blotting for detection of mRNA and protein expression. In the present study, the expression levels of circ_0005699 were increased by oxidized low-density lipoprotein in a time- and dose-dependent manner in HUVECs; this was also associated with increased apoptosis of these cells. In addition, the expression levels of circ_0005699 were elevated, along with increased levels of inflammatory cytokines, in ApoE-deficient mice. An RNA pull-down assay indicated that circ_0005699 can bind miR-450b-5p to decrease its expression, whereas silencing of circ_0005699 resulted in increased expression of miR-450b-5p. In addition, the online bioinformatics tool starBase predicted NFKB1 as a target gene of miR-450b-5p, which was further confirmed by the luciferase reporter gene assay. Notably, knockdown of circ_0005699 resulted in the increased survival of HUVECs, which was associated with decreased protein expression levels of NFKB1 and inflammatory cytokines. By contrast, the effects of circ-0005699 silencing on survival were reversed by miR-450b-5p inhibition or NFKB1 overexpression. In conclusion, knockdown of circ_0005699 may ameliorate endothelial cell injury through regulation of the miR-450b-5P/NFKB1 signaling axis.

A retrospective cohort study of disease-related risk factors for central venous catheter-related symptomatic thrombosis in intensive care unit inpatients.

ABSTRACT: Central venous catheters (CVC) are widely used in critically ill patients given their benefits in monitoring vital signs, treatment administration, and renal replacement therapy in intensive care unit (ICU) patients, but these catheters have the potential to induce symptomatic catheter-related venous thrombosis (CRVT). This study reported the rate of symptomatic CRVT in ICU patients receiving CVC and analyzed the disease-related risk factors for symptomatic CRVT in ICU patients.A retrospective analysis was performed on the consecutive ICU 1643 critically ill patients with CVCs inserted from January 2015 to December 2019. Symptomatic CRVT was confirmed by ultrasound. CVCs were divided into 2 groups based on the presence of symptomatic CRVT, and the variables were extracted from the electronic medical record system. Logistic univariate and multivariate regression analyses were used to determine the disease-related risk factors of symptomatic CRVT.A total of 209 symptomatic CRVT events occurred among 2114 catheters. The rate of CRVT was 9.5 per 1000 catheter days. Univariate analysis revealed that trauma, major surgery, heart failure, respiratory failure, and severe acute pancreatitis were risk factors for symptomatic CRVT in the ICU. Multivariate analysis showed that trauma (odds ratio [OR], 2.046; 95% confidence interval [CI] [1.325-3.160], P = .001), major surgery (OR, 2.457; 95% CI [1.641-3.679], P = .000), and heart failure (OR, 2.087; 95% CI [1.401-3.111], P = .000) were independent disease-related risk factors for symptomatic CRVT in ICU. The C-statistic for this model was 0.61 (95% CI [0.57-0.65], P = .000).The incidence rate of symptomatic CRVT in the ICU population was 9.5 per 1000 catheter days. Trauma, major surgery, and heart failure are independent disease-related risk factors of symptomatic CRVT.

The plasma D-dimer trends and their value in acute lower limb ischemia patients treated by catheter directed thrombolysis.

To investigate the change trends of plasma D-dimer during catheter-directed thrombolysis (CDT) in acute lower limb ischemia (ALI) patients and their clinical value. A retrospective review of patients with ALI who received CDT was carried out. The repeated measurements of plasma D-dimer were analyzed by generalized estimating equations (GEEs) and the change trends of D-dimer were analyzed by spline regression approach. A total of 150 patients were included. Among them, 3 days of CDT was ineffective in 41 cases, effective in 33 cases and markedly effective in 76 cases. The results of GEEs analysis showed that serum D-dimer changed significantly with time (time effect, P < 0.001). Serum D-dimer levels of patients with different treatment outcomes were different after treatment (group effect, P < 0.001), and serum D-dimer levels in these three groups showed different trends over time (group*time effect, P < 0.001). The different trends in serum D-dimer level with time after treatment in the three groups could be directly seen in the spline regression curve (P < 0.001). The plasma D-dimer changes regularly during CDT for ALI. We can predict the efficacy of CDT and guide adjustments of the therapeutic regimen according to the trend of D-dimer changes during thrombolysis.

A retrospective cohort study of open preperitoneal repair versus open suture repair for the treatment of emergency femoral hernia.

To compare the outcomes of open preperitoneal repair (OPR) with the use of mesh and open suture repair (OSR) without mesh via inguinal approach for the treatment of emergency femoral hernia (FH). The primary outcome was the postoperative complication and the secondary outcomes were the recurrence rate of FH and the postoperative comfort level at the surgical site. 104 patients with emergency FHs were included, of whom 51 patients were treated with OPR, 53 patients were treated with OSR. Between the two groups, no significant difference was found in surgical site infection (SSI) (P = 0.801) or seroma (P = 0.843), while there was significant difference in the improvement of comfort at the surgical site (P = 0.013). The results of the 2-year follow-up demonstrated 1 and 8 cases of recurrence in the OPR and OSR group respectively, which was statistically significant (HR, 8.193 [95% CI, 1.024 to 65.547], P = 0.047). Compared with OSR, OPR with the use of mesh did not increase the risk of SSI and was safe to apply even under the condition of an emergency FH operation with intestine resection; OPR could reduce the recurrence rate of FH and improve the comfort at the surgical site.

A retrospective cohort study comparing two treatments for active venous leg ulcers.

Endovenous laser ablation (EVLA) and ultrasound-guided foam sclerotherapy (UGFS) have largely replaced traditional surgery for treatment of varicose veins (VVs) with active venous leg ulcers (VLUs), and multiple combined modes have emerged. A retrospective cohort study was performed to compare the effect of traditional surgery (high ligation and stripping followed with compression [compression plus HL-S]) to high ligation-endovenous laser ablation-foam sclerotherapy followed with compression (compression plus HL-EVLA-FS) on the treatment of active VLUs.Data of active VLUs treated in our center from 2008 to 2017 and followed up for 1 year were analyzed. The intervention measures in the first 5 years were compression plus HL-S, and in the following 5 years were compression plus HL-EVLA-FS. The primary outcome was ulcer healing time. The secondary outcomes were the VVs occlusion and clinical success as assessed by a change in venous clinical severity score (VCSS) and complications.The study included 120 patients and 200 patients treated with HL-S and HL-EVLA-FS, respectively, during 2008 to 2017. The average ulcer healing time were 2.3 ±â€Š2.4 and 1.7 ±â€Š1.7 months, respectively. Significant difference was found in the cumulative ulcers healing rate between the two groups (Hazard ratio [HR] and 95% confidence interval [CI] was respectively 1.458 and 1.140-1.865, P = .0002), but no difference was found in the VVs occlusion (HR and 95% CI was respectively 1.005 and 0.774-1.3071, P = .967). Significant difference occurred in 6 months and 12 months post-operatively in the VCSS change and in the procedure data and some complications between the 2 groups.In conclusion, the treatment of HL-EVLA-FS can accelerate the healing of VLUs, improve the VCSS and present superior procedure data. However, no advantage could be found in the VVs occlusion compared with control group.

Chronic mesh infection complicated by an enterocutaneous fistula successfully treated by infected mesh removal and negative pressure wound therapy: A case report.

RATIONALE: Tension-free repair of inguinal hernia with prosthetic materials in adults has become a routine surgical procedure. However, serious complications may arise such as mesh displacement, infection, and even enterocutaneous fistula (EF). The management of chronic mesh infection (CMI) complicated by an EF is very challenging. A simple treatment of infected mesh removal and negative pressure wound therapy (NPWT) may cure the patients with EF with CMI. PATIENT CONCERNS: A 75-year-old male patient underwent tension-free treatment for a bilateral inguinal hernia at a county hospital 10 years ago. Three months before admission, the right groin gradually formed a skin sinus with outflow of fetid thin pus, and it could not heal. DIAGNOSES: The patient was diagnosed preoperatively with mesh plug adhesion to the intestine, which resulted in low-flow EF combined with CMI. INTERVENTIONS: The patient received a simple treatment mode consisting of an incision made from the original incision, but the new incision did not penetrate the abdominal cavity; treatment included resection of the fistula, removal of the mesh, repair of the intestine and local tissue, and continuous irrigation of vacuum sealing drainage (VSD) devices for NPWT. OUTCOMES: The infected mesh was completely removed. Five VSD devices were utilized to treat the EF and wound. The time from intervention to wound healing was 35 days, and follow-up for 6 months revealed no infection and no hernia recurrence in the right groin. LESSONS: The NPWT is effective in treating CMI concomitant with EF and does not increase the risk of hernia recurrence.

Comparison of combined compression and surgery with high ligation-endovenous laser ablation-foam sclerotherapy with compression alone for active venous leg ulcers.

We aimed to assess the ulcer healing time and recurrence rates after treatment with compression therapy (CT) with or without high ligation-endovenous laser ablation-foam sclerotherapy (HL-EVLA-FS) in people with active venous leg ulcers (VLUs). A retrospective cohort study was conducted with 350 patients with active VLUs treated by compression with or without HL-EVLA-FS in our hospital from 2013 to 2017. The primary outcome was the ulcer healing time; secondary outcomes were the 12-month recurrence rates, the relationship between recurrence and venous reflux, and the complications of the two treatments. In total, 193 patients (200 limbs) underwent compression plus HL-EVLA-FS, and 157 patients (177 limbs) underwent CT alone. The ulcer healing time was shorter in the compression plus HL-EVLA-FS group than in the CT alone group (Hazard Ratio [HR] for ulcer healing, 1.845 [95% CI, 1.474-2.309], P = 0.0001). The 12-month ulcer recurrence rates were significantly reduced in the compression plus HL-EVLA-FS group (HR for ulcer recurrence, 0.418 [95% CI, 0.258-0.677], P = 0.0001). Calf perforator vein reflux (CPVR) and isolated superficial venous reflux (ISVR) were risk factors for ulcer recurrence. The combined operation with CT resulted in faster healing of VLUs, a lower ulcer recurrence rate and lower VCSS values after intervention than CT alone.

Factors related to the size of venous leg ulcers: A cross-sectional study.

Venous leg ulcers (VLUs) are an important health problem, and the size of ulcers often affects patient care, healing time, and quality of life. However, the risk factors associated with ulcer size have been rarely reported. The aim of this study was to establish the risk factors for the size of venous ulceration by analyzing the patient demographics and the results of duplex ultrasonography.This study was an in-patient population-based cross-sectional study conducted at a single center during the period from 2013 to 2017. Men and women aged >18 years, who consecutively presented to our hospital with VLU, were included. According to the size of the ulcer, patients were divided into two groups, those with ulcers≤2 cm and those with ulcers >2 cm. Demographic, anthropometric, and clinical data were collected. For the analysis, univariate and multivariate logistic regressions were used.A total of 232 patients with VLUs were admitted to our hospital from 2013 to 2017, including 117 patients (50.4%) with ulcer diameters ≤2 cm and 115 patients (49.6%) with ulcer diameters >2 cm. According to the results of the multivariate analysis, the ulcer duration (P = .001), the diameter of perforating veins (PVs) around the ulcers (P = .025), the reflux time of common femoral veins (CFVs) (P = .013), the reflux time of great saphenous veins (GSVs) (P = .021), and the reflux time of PVs around the ulcers (P = .001) were independent risk factors for VLUs.These findings provide evidence that the size of VLU was significantly related to the ulcer duration, the diameter of PV around the ulcers, the CFV reflux time, the GSV reflux time, and the PV reflux time.

A metagenome-wide association study of gut microbiota in asthma in UK adults.

BACKGROUND: Asthma, one of the most common chronic respiratory disorders, is associated with the hyper-activation of the T-cell subset of adaptive immunity. The gut microbiota may be involved in the development of asthma through the production of short-chain fatty acids (SCFAs), exhibiting modulatory effects on Th. So, we performed a metagenome-wide association study (MWAS) of the fecal microbiota from individuals with asthma and healthy controls. And that was the first case to resolve the relationship between asthma and microbiome among UK adults. RESULTS: The microbiota of the individuals with asthma consisted of fewer microbial entities than the microbiota of healthy individuals. Faecalibacterium prausnitzii, Sutterella wadsworthensis and Bacteroides stercoris were depleted in cases, whereas Clostridiums with Eggerthella lenta were over-represented in individuals with asthma. Functional analysis shows that the SCFAs might be altered in the microbiota of asthma patients. CONCLUSION: In all, the adult human gut microbiome of asthma patients is clearly different from healthy controls. The functional and taxa results showed that the change of asthma patients might related to SCFAs.

Risk factors for surgical opportunity in patients with femoral hernia: A retrospective cohort study.

Femoral hernias are extremely easily incarcerated and are recommended for early surgery. In the past, there were a number of definitely diagnosed femoral hernia patients who were not able to undergo elective surgery in a timely fashion, and then, they were obliged to undergo emergency surgery or even to lose the opportunity for surgery. The relevant epidemic factors of femoral hernia were thoroughly investigated in the clinic; however, the impact of these factors on surgical opportunity has not been widely reported. The purpose of this study is to preliminarily evaluate the risk factors affecting the femoral hernia patients' surgical opportunities.One hundred forty-two consecutive patients who were treated for femoral hernia with COD (course of disease) >1 month were analyzed. Depending on the surgical opportunity, the patients were divided into 2 groups: elective surgery and emergency surgery. A retrospective cohort study was performed in the 2 groups. Univariate and multivariate logistic regression analysis was used to assess the risk factors influencing the timing of femoral hernia surgery.Of the 163 patients with femoral hernia in our center between 2013 and 2017, 142 had COD > 1 month, including 66 elective and 76 emergency surgeries. Univariate logistic analyses revealed that age, COD, COPD (chronic obstructive pulmonary disease), cirrhosis, and hypertension were risk factors associated with surgical opportunity for femoral hernia; their corresponding odds ratios (ORs) and P values were (OR 9.931; P = .003), (OR 1.024; P = .000), (OR 14.769; P = .000), (OR 1.093; P = .000), and (OR 3.346; P = .007), respectively. On multivariate logistic regression analysis, age, COD, COPD, and cirrhosis were independent risk factors associated with the surgical opportunity of patients with femoral hernia; the corresponding ORs and P values were (OR 1.055; P = .026), (OR 1.022; P = .002), (OR 8.688; P = .009), and (OR 11.761; P = .005), respectively.The independent risk factors of patients with femoral hernia surgical opportunity were age, COD, and the comorbidities COPD and cirrhosis. Active treatment of comorbidities in elderly patients with femoral hernia, as well as timely hospitalization, may reduce the frequency of emergency surgery for femoral hernia.

The microbiota continuum along the female reproductive tract and its relation to uterine-related diseases.

Reports on bacteria detected in maternal fluids during pregnancy are typically associated with adverse consequences, and whether the female reproductive tract harbours distinct microbial communities beyond the vagina has been a matter of debate. Here we systematically sample the microbiota within the female reproductive tract in 110 women of reproductive age, and examine the nature of colonisation by 16S rRNA gene amplicon sequencing and cultivation. We find distinct microbial communities in cervical canal, uterus, fallopian tubes and peritoneal fluid, differing from that of the vagina. The results reflect a microbiota continuum along the female reproductive tract, indicative of a non-sterile environment. We also identify microbial taxa and potential functions that correlate with the menstrual cycle or are over-represented in subjects with adenomyosis or infertility due to endometriosis. The study provides insight into the nature of the vagino-uterine microbiome, and suggests that surveying the vaginal or cervical microbiota might be useful for detection of common diseases in the upper reproductive tract.Whether the female reproductive tract harbours distinct microbiomes beyond the vagina has been a matter of debate. Here, the authors show a subject-specific continuity in microbial communities at six sites along the female reproductive tract, indicative of a non-sterile environment.

Gut microbiome and serum metabolome alterations in obesity and after weight-loss intervention.

Emerging evidence has linked the gut microbiome to human obesity. We performed a metagenome-wide association study and serum metabolomics profiling in a cohort of lean and obese, young, Chinese individuals. We identified obesity-associated gut microbial species linked to changes in circulating metabolites. The abundance of Bacteroides thetaiotaomicron, a glutamate-fermenting commensal, was markedly decreased in obese individuals and was inversely correlated with serum glutamate concentration. Consistently, gavage with B. thetaiotaomicron reduced plasma glutamate concentration and alleviated diet-induced body-weight gain and adiposity in mice. Furthermore, weight-loss intervention by bariatric surgery partially reversed obesity-associated microbial and metabolic alterations in obese individuals, including the decreased abundance of B. thetaiotaomicron and the elevated serum glutamate concentration. Our findings identify previously unknown links between intestinal microbiota alterations, circulating amino acids and obesity, suggesting that it may be possible to intervene in obesity by targeting the gut microbiota.

Lipidomic profiling reveals distinct differences in plasma lipid composition in healthy, prediabetic, and type 2 diabetic individuals.

The relationship between dyslipidemia and type 2 diabetes mellitus (T2D) has been extensively reported, but the global lipid profiles, especially in the East Asia population, associated with the development of T2D remain to be characterized. Liquid chromatography coupled to tandem mass spectrometry was applied to detect the global lipidome in the fasting plasma of 293 Chinese individuals, including 114 T2D patients, 81 prediabetic subjects, and 98 individuals with normal glucose tolerance (NGT). Both qualitative and quantitative analyses revealed a gradual change in plasma lipid features with T2D patients exhibiting characteristics close to those of prediabetic individuals, whereas they differed significantly from individuals with NGT. We constructed and validated a random forest classifier with 28 lipidomic features that effectively discriminated T2D from NGT or prediabetes. Most of the selected features significantly correlated with diabetic clinical indices. Hydroxybutyrylcarnitine was positively correlated with fasting plasma glucose, 2-hour postprandial glucose, glycated hemoglobin, and insulin resistance index (HOMA-IR). Lysophosphatidylcholines such as lysophosphatidylcholine (18:0), lysophosphatidylcholine (18:1), and lysophosphatidylcholine (18:2) were all negatively correlated with HOMA-IR. The altered plasma lipidome in Chinese T2D and prediabetic subjects suggests that lipid features may play a role in the pathogenesis of T2D and that such features may provide a basis for evaluating risk and monitoring disease development.

Shotgun Metagenomics of 250 Adult Twins Reveals Genetic and Environmental Impacts on the Gut Microbiome.

The gut microbiota has been typically viewed as an environmental factor for human health. Twins are well suited for investigating the concordance of their gut microbiomes and decomposing genetic and environmental influences. However, existing twin studies utilizing metagenomic shotgun sequencing have included only a few samples. Here, we sequenced fecal samples from 250 adult twins in the TwinsUK registry and constructed a comprehensive gut microbial reference gene catalog. We demonstrate heritability of many microbial taxa and functional modules in the gut microbiome, including those associated with diseases. Moreover, we identified 8 million SNPs in the gut microbiome and observe a high similarity in microbiome SNPs between twins that slowly decreases after decades of living apart. The results shed new light on the genetic and environmental influences on the composition and function of the gut microbiome that could relate to risk of complex diseases.