Treatment of a femoral neck fracture combined with ipsilateral femoral head and intertrochanteric fractures: A case report.

BACKGROUND: This article presents a rare case of a complex hip fracture involving the ipsilateral femoral neck, trochanter, and femoral head, that was accompanied by hip dislocation. Currently, there is no established standard treatment method for this specific type of fracture. Therefore, it is crucial to comprehensively consider factors such as patient age, fracture type, and degree of displacement to achieve a successful outcome. CASE SUMMARY: A 38-year-old man sustained a comminuted fracture of his right hip as a result of a car accident. The injuries included a fracture of the femoral head, a fracture of the femoral neck, an intertrochanteric fracture of the femur, and a posterior dislocation of the hip on the same side. We opted for a treatment approach combining the use of a proximal femoral locking plate, cannulated screws, and Kirschner wires. Following the surgery, we developed an individualized rehabilitation program to restore patient limb function. CONCLUSION: For this complex fracture, we selected appropriate internal fixation and formulated individualized rehabilitation, which ultimately achieved good results.

Altered activation patterns of the sensory-motor cortex in patients with knee osteoarthritis during knee isokinetic movement at different speeds.

Background: Abnormal brain activation patterns in patients with knee osteoarthritis (KOA) at rest have been revealed, but it is unclear how brain activation patterns change during movement. This study aimed to investigate the alterations in brain activation patterns in KOA patients during knee isokinetic movement, and the correlation between cortical activity changes and pain severity and dysfunction. Methods: Eighteen patients with KOA and 18 healthy controls (HC) were recruited, and to performed the knee isokinetic test with three speeds. Functional near-infrared spectroscopy (fNIRS) was used to detect the cerebral cortex hemodynamics changes of primary somatosensory (S1), primary motor (M1) and somatosensory association cortex (SAC) in the region of interest (ROI) during movement. Then, we evaluated potential correlations between M1, S1 and SAC values and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and visual analog scale (VAS) scores. Results: The results showed that peak torque of knee extension in KOA patients was significantly smaller than that in HC. For HC, unilateral knee movement activated bilateral ROIs. The contralateral activation was dominant, showing the phenomenon of high contralateral activation. For KOA patients, there were no statistical difference in the activation level between the left and right of the cerebral cortex, with both sides showing lower activation levels compared to HC. Further analysis found that the contralateral M1, S1, and SAC of the affected knee in KOA patients were significantly lower than those in HC, while no difference was found on the ipsilateral side. Moreover, during isokinetic movement at 180°/s, VAS score in KOA patients was negatively correlated with the activation level of the contralateral S1 and M1 values, and WOMAC was negatively correlated with the activation level of the contralateral M1 value. Conclusion: Contralateral activation of the sensorimotor cortex exists during unilateral knee movement, but in KOA patients, this contralateral cortical activation is suppressed. Furthermore, the clinical pain and dysfunction in KOA patients are associated with activation levels of specific brain regions. These findings can provide a better understanding of KOA brain science and are expected to contribute to the development of central intervention for the disease.

Application of multidisciplinary team-based integrated traditional Chinese medicine and Western medicine in rotator cuff injury patients undergoing arthroscopic surgery.

BACKGROUND: Arthroscopic rotator cuff repair is a common surgical treatment for rotator cuff injuries (RCIs). Although this procedure has certain clinical advantages, it requires rehabilitation management interventions to ensure therapeutic efficacy. AIM: To investigate the effect of integrated traditional Chinese medicine and Western medicine (TCM-WM) under the multidisciplinary team (MDT) model on the postoperative recovery of patients undergoing arthroscopic surgery for RCIs. METHODS: This study enrolled 100 patients who underwent arthroscopic rotator cuff repair for RCIs at the Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine between June 2021 and May 2024. They were divided into a control group (n = 48) that received routine rehabilitation treatment and an experimental group (n = 52) that received TCM-WM under the MDT model (e.g., acupuncture, TCM traumatology and orthopedics, and rehabilitation). The results of the Constant-Murley Shoulder Score (CMS), Visual Analogue Scale (VAS), Shoulder Pain and Disability Index (SPADI), muscular strength evaluation, and shoulder range of motion (ROM) assessments were analyzed. RESULTS: After treatment, the experimental group showed significantly higher CMS scores in terms of pain, functional activity, shoulder joint mobility, and muscular strength than the baseline and those of the control group. The experimental group also exhibited significantly lower VAS and SPADI scores than the baseline and those of the control group. In addition, the experimental group showed significantly enhanced muscular strength (forward flexor and external and internal rotator muscles) and shoulder ROM (forward flexion, abduction, and lateral abduction) after treatment compared with the control group. CONCLUSION: TCM-WM under the MDT model improved shoulder joint function, relieved postoperative pain, promoted postoperative functional recovery, and facilitated the recovery of muscular strength and shoulder ROM in patients with RCIs who underwent arthroscopic rotator cuff repair.

Single-Cell RNA Sequencing Analysis of Steroidogenesis and Spermatogenesis Impairment in the Testis of db/db Mice.

Objective: The mechanism of steroidogenesis and spermatogenesis impairment in men with type 2 diabetes remains unclear. We aimed to explore the local changes of steroidogenesis and spermatogenesis in the testis of db/db mice. Research Design and Methods. We performed single-cell RNA sequencing analysis in the testis of db/db and C57BL/6J mice. The differentially expressed genes were then confirmed by real-time PCR. The histopathological characteristics of testis in db/db mice and C57BL/6J control were also performed. Results: The 20-week-old db/db mice had significantly higher blood glucose and body weight (both p < 0.001). The serum testosterone levels (4.4 ± 0.8 vs. 9.8 ± 0.7 ng/ml, p=0.001) and weight of the testis (0.16 ± 0.01 vs. 0.24 ± 0.01 g, p < 0.001) were significantly lower in db/db mice than that in C57BL/6J controls. db/db mice had a lower cross-sectional area of seminiferous tubules and thickness of the cell layer (both p < 0.05). The numbers of Sertoli cells and Leydig cells decreased in db/db mice (both p < 0.01). Single-cell RNA sequencing analysis showed that compared with the control group, the percentage of spermatogonia was significantly higher in the db/db mouse (p < 0.001), while the proportions of spermatocytes, round and elongating spermatids, and sperms were all lower in the db/db mouse (p all < 0.001). The most differentially expressed genes were found in round spermatids (n = 86), which were not found in spermatogonia, spermatocyte, and sperm. Igfbp5 was the most significantly decreased gene in Leydig cells of the db/db mouse, while the expression of Cd74, H2-Aa, and H2-Eb1 was elevated. Ccl7 and Ptgds were the most significantly increased and decreased genes in Sertoli cells of the db/db mouse. Conclusions: The present study indicates spermiogenesis and steroidogenesis defects in db/db mice. The mechanism of steroidogenesis impairment in the testis of db/db mice deserves further investigation.

Matrix metallopeptidase 9 contributes to the beginning of plaque and is a potential biomarker for the early identification of atherosclerosis in asymptomatic patients with diabetes.

Aims: To determine the roles of matrix metallopeptidase-9 (MMP9) on human coronary artery smooth muscle cells (HCASMCs) in vitro, early beginning of atherosclerosis in vivo in diabetic mice, and drug naïve patients with diabetes. Methods: Active human MMP9 (act-hMMP9) was added to HCASMCs and the expressions of MCP-1, ICAM-1, and VCAM-1 were measured. Act-hMMP9 (n=16) or placebo (n=15) was administered to diabetic KK.Cg-Ay/J (KK) mice. Carotid artery inflammation and atherosclerosis measurements were made at 2 and 10 weeks after treatment. An observational study of newly diagnosed drug naïve patients with type 2 diabetes mellitus (T2DM n=234) and healthy matched controls (n=41) was performed and patients had ultrasound of carotid arteries and some had coronary computed tomography angiogram for the assessment of atherosclerosis. Serum MMP9 was measured and its correlation with carotid artery or coronary artery plaques was determined. Results: In vitro, act-hMMP9 increased gene and protein expressions of MCP-1, ICAM-1, VCAM-1, and enhanced macrophage adhesion. Exogenous act-hMMP9 increased inflammation and initiated atherosclerosis in KK mice at 2 and 10 weeks: increased vessel wall thickness, lipid accumulation, and Galectin-3+ macrophage infiltration into the carotid arteries. In newly diagnosed T2DM patients, serum MMP9 correlated with carotid artery plaque size with a possible threshold cutoff point. In addition, serum MMP9 correlated with number of mixed plaques and grade of lumen stenosis in coronary arteries of patients with drug naïve T2DM. Conclusion: MMP9 may contribute to the initiation of atherosclerosis and may be a potential biomarker for the early identification of atherosclerosis in patients with diabetes. Clinical trial registration: https://clinicaltrials.gov, identifier NCT04424706.

Metformin induces pyroptosis in leptin receptor-defective hepatocytes via overactivation of the AMPK axis.

Metformin is the biguanide of hepatic insulin sensitizer for patients with non-alcohol fatty liver disease (NAFLD). Findings regarding its efficacy in restoring blood lipids and liver histology have been contradictory. In this study, we explore metformin's preventive effects on NAFLD in leptin-insensitive individuals. We used liver tissue, serum exosomes and isolated hepatocytes from high-fat diet (HFD)-induced Zucker diabetic fatty (ZDF) rats and leptin receptor (Lepr) knockout rats to investigate the correlation between hepatic Lepr defective and liver damage caused by metformin. Through immunostaining, RT-PCR and glucose uptake monitoring, we showed that metformin treatment activates adenosine monophosphate (AMP)-activated protein kinase (AMPK) and its downstream cytochrome C oxidase (CCO). This leads to overactivation of glucose catabolism-related genes, excessive energy repertoire consumption, and subsequent hepatocyte pyroptosis. Single-cell RNA sequencing further confirmed the hyper-activation of glucose catabolism after metformin treatment. Altogether, we showed that functional Lepr is necessary for metformin treatment to be effective, and that long-term metformin treatment might promote NAFLD progression in leptin-insensitive individuals. This provides important insight into the clinical application of metformin.

Insights into Circulating Tumor Cell Clusters: A Barometer for Treatment Effects and Prognosis for Prostate Cancer Patients.

Prostate cancer (PCa) exhibits high cellular heterogeneity across patients. Therefore, there is an urgent need for more real-time and accurate detection methods, in both prognosis and treatment in clinical settings. Circulating tumor cell (CTC) clusters, a population of tumor cells and non-malignant cells in the blood of patients with tumors, are a promising non-invasive tool for screening PCa progression and identifying potential benefit groups. CTC clusters are associated with tumor metastasis and possess stem-like characteristics, which are likely attributable to epithelial-mesenchymal transition (EMT). Additionally, these biological properties of CTC clusters, particularly androgen receptor V7, have indicated the potential to reflect curative effects, guide treatment modalities, and predict prognosis in PCa patients. Here, we discuss the role of CTC clusters in the mechanisms underlying PCa metastasis and clinical applications, with the aim of informing more appropriate clinical decisions, and ultimately, improving the overall survival of PCa patients.

Circ_SNX27 regulates hepatocellular carcinoma development via miR-637/FGFR1 axis.

BACKGROUND: Circular RNAs (circRNAs) serve as critical regulatory factors in cancer development. Nonetheless, the potential regulatory mechanism of circRNA sorting nexin 27 (circ_SNX27) in hepatocellular carcinoma (HCC) is still unknown. METHODS: The circ_SNX27, microRNA-637 (miR-637), and fibroblast growth factor receptor 1 (FGFR1) levels were quantified by quantitative real-time polymerase chain reaction and western blot analysis. Next, function experiments were conducted using in vitro assays and in vivo senograft study. The relationship between miR-637 with circ_SNX27 or FGFR1 was uncovered by dual-luciferase reporter and RNA pull-down assays. RESULTS: The circ_SNX27 and FGFR1 levels were up-regulated, but miR-637 content was reduced in HCC. Circ_SNX27 down-regulation inhibited HCC cell proliferation, motility, and invasion and promoted apoptosis in vitro, as well as weakened tumor growth in vivo. Circ_SNX27 served as a sponge of miR-637 to promote FGFR1 expression. MiR-637 reduction abolished the restrained effect of circ_SNX27 absence on HCC cell development. Moreover, miR-637 curbed HCC cell malignant phenotype by regulating FGFR1. CONCLUSION: Circ_SNX27 contributed to HCC development via miR-637/FGFR1 axis, offering a new idea for the treatment of HCC.

High triiodothyronine levels induce myocardial hypertrophy via BAFF overexpression.

Activated B cells contribute to heart diseases, and inhibition of B-cell activating factor (BAFF) expression is an effective therapeutic target for heart diseases. Whether activated B cells participate in the development and progression of hyperthyroid heart disease, and what induces B cells activation in hyperthyroidism are unknown. The present study aimed to determine the roles of BAFF overexpression induced by high concentrations of triiodothyronine (T3) in the pathogenesis of hyperthyroid heart disease. Female C57BL/6J mice were subcutaneously injected with T3 for 6 weeks, and BAFF expression was inhibited using shRNA. Protein and mRNA expression of BAFF in mouse heart tissues evaluated via immunohistochemistry, western blotting and polymerase chain reaction (PCR). Proportions of B cells in mouse cardiac tissue lymphocytes were quantified via flow cytometry. Morphology and left ventricle function were assessed using pathological sections and echocardiography, respectively. Here, we demonstrate that compared with the control group, the proportion of myocardial B cells was larger in the T3 group; immunohistochemistry, western blotting and PCR analyses revealed increased protein and mRNA expression levels of TNF-α and BAFF in heart tissues of the T3 group. Compared with the normal controls group, in the T3 group, the diameter of myocardial cells and some echocardiographic values significantly increased and hypertrophy and structural disorder were noticeable. Our results revealed that elevated levels of circulating T3 can promote the expression of BAFF in myocardial cells and can lead to B-cell activation, an elevated inflammatory response and ventricular remodelling.

Perilipin 2 Protects against Lipotoxicity-Induced Islet Fibrosis by Inducing Islet Stellate Cell Activation Phenotype Changes.

Aims: We explored whether and how perilipin 2 (Plin2) protected islets against lipotoxicity-induced islet dysfunction by regulating islet stellate cells (ISCs) activation. Methods: Six-week-old male rats were given a high-fat diet or a control diet for 28 weeks. Glucose metabolic phenotypes were assessed using glucose/insulin tolerance tests, masson, and immunohistochemical staining. ISCs activation levels were assessed from rats and palmitic acid- (PA-) treated cultured ISCs by immunofluorescence, Oil red O staining, electron microscopy, quantitative PCR, and western blotting. Changes in ISCs phenotype of activation degree and its underlying mechanisms were assessed by target gene lentiviral infection, high-performance liquid chromatography (HPLC), and western blotting. Results: Obese rats showed glucose intolerance, decreased endocrine hormone profiles, and elevated expression of α-smooth muscle actin (α-SMA), a polygonal appearance without cytoplasmic lipid droplets of ISCs in rats and isolated islets. PA-treated cultured ISCs exhibited faster proliferation and migration abilities with the induction of mRNA levels of lipid metabolism proteins, especially Plin2. The overexpression of Plin2 resulted in ISCs "re-quiescent" phenotypes associated with inhibition of the Smad3-TGF-ß signaling pathways. Conclusions: Our observations suggest a protective role of Plin2 in weakening ISCs activation. It may serve as a novel therapeutic target for preventing islet fibrosis for T2DM.

Spatio-temporal trajectory evolution and cause analysis of air pollution in Chengdu, China.

This study comprehensively analyzed air pollution in Chengdu (CD), a megacity in southwest China, evaluated the Variation Characteristics of air quality during 2015-2018, and conducted Random Forest classification of air pollution data of 2017. The classification results showed three pollution periods: severe (December, January and February), ozone (May‒August), and slight (March and November). These features were combined with potential source contribution function (PSCF), concentration weighted trajectory (CWT) and backward trajectory model (HYSPLIT) for simulating spatio-temporal trajectory of air polluted during each pollution periods. The results show that PM2.5 mainly comes from CD and surrounding cities, and some may be from India, Myanmar and Chongqing; PM10 mainly comes from CD and surrounding cities and some may be from India and Myanmar; NO2 mainly comes from CD and surrounding cities and cities and Some of the pollution may come from the input of India, Myanmar, Chongqing and Inner Mongolia; O3 mainly comes from the urban agglomeration of Sichuan Basin and some areas from Chongqing, Sichuan Liangshan and Yunnan Guizhou. Combined with the meteorological data of temperature, relative humidity and wind speed, aerosol optical depth, planetary boundary layer height and thermal anomaly data, the Monthly, daily and hourly spatio-temporal characteristics and the possible occurred cause of the main air pollution during each pollution period in CD were revealed detail. The research in this paper is critical for pollution control and prevention and provides a scientific basis for studying the spatio-temporal characteristics and sources of pollution in megacities in terrain such as basins and mountains.Implications: Air pollution has a significant impact on human and ecological health. In 2013, Chengdu was one of the five cities with the most serious PM2.5 pollution in the world. In the previous study of air pollution in Chengdu, it was only for a short period of pollution. It is impossible to fully understand the spatio-temporal trajectory and cause of air pollution. Chengdu is surrounded by mountains, and the meteorological conditions have been stagnant for a long time. The research on the spatio-temporal evolution of the main air pollution trajectories in each pollution period in Chengdu is particularly important. Quantifying the pollution trajectory and air pollution concentration is helpful to fully understand the air quality in Chengdu. The comprehensive analysis of multi-source data such as air pollution and meteorology has focused on strengthening the in-depth research on the transmission law of air pollution, the spatio-temporal change trend of air pollution, the sources of air pollution and the causes of air pollution, so as to help people fully understand the sources and causes of pollution in Chengdu. Aiming at the trajectory law, causes and occurrence time of air pollution, it is conducive for the government to formulate corresponding policies, carry out regional emission reduction and joint prevention and control, improve air quality and minimize the harm of air pollution to the public.

Real-Time Flash Glucose Monitoring Had Better Effects on Daily Glycemic Control Compared With Retrospective Flash Glucose Monitoring in Patients With Type 2 Diabetes on Premix Insulin Therapy.

Background and Aims: To compare the effects of real-time and retrospective flash glucose monitoring (FGM) on daily glycemic control and lifestyle in patients with type 2 diabetes on premix insulin therapy. Methods and Results: A total of 172 patients using premix insulin, with HbA1c ≥ 7.0% (56 mmol/mol), or the time below the target (TBR) ≥ 4%, or the coefficient of variation (CV) ≥36% during the screening period, were randomly assigned to retrospective FGM (n = 89) or real-time FGM group (n = 83). Another two retrospective or real-time 14-day FGMs were performed respectively, 1 month apart. Both groups received educations and medication adjustment after each FGM. Time in range (3.9~10.0 mmol/l, TIR) increased significantly after 3 months in the real-time FGM group (6.5%) compared with the retrospective FGM group (-1.1%) (p = 0.014). HbA1c decreased in both groups (both p < 0.01). Real-time FGMs increased daily exercise time compared with the retrospective group (p = 0.002). Conclusions: Real-time FGM with visible blood glucose improves daily glycemic control and diabetes self-care behaviors better than retrospective FGM in patients with type 2 diabetes on premix insulin therapy. Clinical Trial Registration: https://clinicaltrials.gov/NCT04847219.

Thymosin beta-4 improves endothelial function and reparative potency of diabetic endothelial cells differentiated from patient induced pluripotent stem cells.

BACKGROUND: Prior studies show that signature phenotypes of diabetic human induced pluripotent stem cells derived endothelial cells (dia-hiPSC-ECs) are disrupted glycine homeostasis, increased senescence, impaired mitochondrial function and angiogenic potential as compared with healthy hiPSC-ECs. In the current study, we aimed to assess the role of thymosin ß-4 (Tb-4) on endothelial function using dia-hiPSC-ECs as disease model of endothelial dysfunction. METHODS AND RESULTS: Using dia-hiPSC-ECs as models of endothelial dysfunction, we determined the effect of Tb-4 on cell proliferation, senescence, cyto-protection, protein expression of intercellular adhesion molecule-1 (ICAM-1), secretion of endothelin-1 and MMP-1, mitochondrial membrane potential, and cyto-protection in vitro and angiogenic potential for treatment of ischemic limb disease in a mouse model of type 2 diabetes mellitus (T2DM) in vivo. We found that 600 ng/mL Tb4 significantly up-regulated AKT activity and Bcl-XL protein expression, enhanced dia-hiPSC-EC viability and proliferation, limited senescence, reduced endothelin-1 and MMP-1 secretion, and improved reparative potency of dia-hiPSC-ECs for treatment of ischemic limb disease in mice with T2DM. However, Tb4 had no effect on improving mitochondrial membrane potential and glycine homeostasis and reducing intercellular adhesion molecule-1 protein expression in dia-hiPSC-ECs. CONCLUSIONS: Tb-4 improves endothelial dysfunction through enhancing hiPSC-EC viability, reducing senescence and endothelin-1 production, and improves angiogenic potency in diabetes.

Phenotypic Heterogeneity and Fertility Potential of Patients With 17-Hydroxylase/17,20-lyase Deficiency.

CONTEXT: 17α-Hydroxylase/17,20-lyase deficiency (17OHD) is caused by a human CYP17A1 gene mutation and has the classical phenotype of hypertension, hypokalemia, sexual infantilism, and primary amenorrhea in females (46,XX) and disorders of sexual development in males (46,XY). To date, few cases of 17OHD have been reported, and the likelihood of pregnancy has rarely been explored. OBJECTIVE: To study the clinical characteristics, phenotype heterogeneity, genotyping, and the likelihood of pregnancy of patients with 17OHD. DESIGN: Genotype analysis was performed by direct sequencing of the CYP17A1 gene and next-generation sequencing in nonclassical patients. In vitro enzyme activity assays and 3-dimensional structure observations were used to assess the function of 3 missense mutations of the CYP17A1 gene. Progestin-primed ovarian stimulation (PPOS) was chosen for ovulation induction in 2 patients. RESULTS: Eight mutations were identified from 13 patients, including the homozygous mutations p. N395D and p. R496C and compound heterozygous mutations p. Y329fs/p. A421A and p. I332T/p. D487_F489del in 4 nonclassical patients. For the 3 missense mutations, an in vitro functional study showed mild impairment of 17α-hydroxylase activities 15.3-25.0% but residual 17,20-lyase activities 6.6%-9.4%. Two 46,XX females succeeded in pregnancy and delivery by combined PPOS, in vitro fertilization embryo transfer (IVF-ET), and the use of low-dose glucocorticoids. CONCLUSIONS: Partial 17OHD present nonclassical clinical features, without hypertension and hypokalemia. Successful pregnancy in such 46,XX patients could be attained by the appropriate choice of ovulation induction regimen, precise dose of glucocorticoid to reduce progesterone levels, and the use of IVF-ET.

Effects of Dapagliflozin Adjunct to Insulin on Glycemic Variations in Patients with Newly Diagnosed Type 2 Diabetes: A Randomized, Controlled, Open-Labeled Trial.

BACKGROUND: This study is aimed at investigating whether dapagliflozin adjunct to insulin therapy further improves glycemic control compared to insulin therapy alone in patients with newly diagnosed type 2 diabetes (T2D). METHODS: This single-centre, randomized, controlled, open-labeled trial recruited newly diagnosed T2D patients. Subjects were randomized 1 : 1 to the dapagliflozin add-on to continuous subcutaneous insulin infusion (CSII) group (DAPA) or the CSII therapy group for 5 weeks. Standard meal tests were performed 3 times at days -3, 7, and 35 for glucose, C-peptide, and insulin level determination. Two-time continuous glucose monitoring (CGM) was performed at baseline and at the end of the study. The primary endpoint was the difference in the mean amplitude of glycemic excursions (MAGEs) between the groups. RESULTS: A total of 66 subjects completed the study, with 34 and 32 patients in the DAPA and CSII groups, respectively. Patients in the DAPA group exhibited significant decreases in MAGE levels at the endpoint. We also observed that patients in the DAPA group had a lower homoeostasis model assessment insulin resistance (HOMA-IR) and a higher homoeostasis model assessment B (HOMA-B) value at 1 week and 5 weeks compared to those with insulin therapy, respectively. In addition, our data showed that patients in the DAPA group showed a significantly lower insulin dose (0.07 U/kg) and weighed less than those in the CSII group. CONCLUSION: Our data indicate that dapagliflozin adjunct to insulin is a safe and effective therapy for improving glycemic variations, insulin sensitivity, and weight loss in newly diagnosed T2D patients.

Bacterial diversity in ballast water and sediments revealed by 2b-RAD sequencing.

Despite that the ballast water management (BWM) convention has come into force to prevent the spread of harmful aquatic organisms, to date, very few bacteria can be identified through microbial culture method. In this study, we explored a reduced-representation sequencing of 2b-RAD approach to investigate the bacterial diversity in ballast water and sediments (BWS). Our results indicated a large amount of bacteria species (1496) detected in BWS up to now, including 13 pathogens that are seriously concerning in marine environment and aquaculture like the most harmful Vibrio harveyi and Aurantimonas coralicida. We showed that the ballast water had relative lower species, which was dominated by Proteobacteria. In contrast, the sediments had richer species, which was dominated by Bacteroidetes. Although BWS differed significantly in species composition, sediments shared most of the concerned pathogens with ballast water, highlighting the importance of sediment management. In conclusion, 2b-RAD sequencing shows promise in future BWM.

High Levels of Thyroid Hormone Impair Regulatory T Cell Function Via Reduced PD-1 Expression.

CONTEXT: Regulatory T cell (Treg) dysfunction plays an important role in the development and progression of Graves' disease (GD). Programmed cell death 1 (PD-1) prompts FoxP3 in Treg expression and enhances the suppressive activity of Tregs. Whether abnormal expression of PD-1 contributes to the breakdown of Tregs and the role of thyroid hormone in the PD-1 expression of Tregs in GD remain substantially undefined. OBJECTIVE: To evaluate the role of PD-1 in Treg function and triiodothyronine (T3) in PD-1 expression in patients with GD and mice treated with T3. METHODS: We recruited 30 patients with GD and 30 healthy donors. PD-1 expression in Tregs and Treg function were determined. To evaluate the effects of thyroid hormone on PD-1 expression in Tregs, we used T3 for the treatment of human peripheral blood mononuclear cells (PBMCs). We then treated mice with T3 to confirm the effect of thyroid hormone on PD-1 expression in Tregs and Tregs function in vivo. RESULTS: PD-1 expression in Tregs and the suppressive function of Tregs significantly decreased in patients with GD. T3 reduced PD-1 expression in human Tregs in a concentration- and time-dependent manner in vitro. High levels of circulating T3 reduced PD-1 expression in Tregs, impaired Treg function, and disrupted T-helper cell (Th1 and Th2) balance in mice treated with T3. CONCLUSION: Treg dysfunction in GD patients might be due to downregulation of PD-1 expression in Tregs induced by high levels of serum T3.

Effect of Metformin on Testosterone Levels in Male Patients With Type 2 Diabetes Mellitus Treated With Insulin.

Aim: To explore the chronic effects of metformin on testosterone levels in men with type 2 diabetes mellitus (T2DM). Methods: This is a secondary analysis of a real-world study evaluating the efficacy and safety of premixed insulin treatment in patients with T2DM via 3-month intermittent flash glucose monitoring. Male patients aged 18-60 who were using metformin during the 3-month study period were included as the metformin group. The control group included males without metformin therapy by propensity score matching analysis with age as a covariate. Testosterone levels were measured at baseline and after 3-month treatment. Results: After 3-month treatment, the control group had higher levels of total testosterone, free and bioavailable testosterone than those at baseline (P<0.05). Compared with the control group, the change of total (-0.82 ± 0.59 vs. 0.99 ± 0.59 nmol/L) and bioavailable (-0.13 ± 0.16 vs. 0.36 ± 0.16 nmol/L) testosterone levels in the metformin group significantly decreased (P=0.036 and 0.029, respectively). In Glycated Albumin (GA) improved subgroup, the TT, FT, and Bio-T levels in the control subgroup were higher than their baseline levels (P < 0.05). Compared with the metformin subgroup, TT level in the control subgroup also increased significantly (P=0.044). In GA unimproved subgroup, the change of TT level in the metformin subgroup was significantly lower than that in the control subgroup (P=0.040). Conclusion: In men with T2DM, 3-month metformin therapy can reduce testosterone levels, and counteract the testosterone elevation that accompanied with the improvement of blood glucose. Clinical Trial Registration: https://www.clinicaltrials.gov/ct2/show/NCT04847219?term=04847219&draw=2&rank=1.

Flash Glucose Monitoring Improves Glucose Control in People with Type 2 Diabetes Mellitus Receiving Anti-diabetic Drug Medication.

OBJECTIVE: To investigate the effects of Flash Glucose Monitoring (FGM) on glucose profile in people with Type 2 Diabetes Mellitus (T2DM) receiving anti-diabetic drug medication. METHODS: This is a prospective non-randomized uncontrolled study. 111 people with T2DM were enrolled and received FGM for 14 days. There was no change of anti-diabetic medication during the 14 days. The plasma glucose concentration on day 2 was used as baseline and the day 13 was considered as study end point. The parameters to compare were mean plasma glucose (MPG), glucose variations, and incidence of hypoglycemia during the FGM period. The multivariate linear stepwise regression analysis was applied to determine the independent factors that affect MPG difference. RESULTS: This study analyzed the data of a total of 111 people with T2DM (male 60 and female 51). The general clinical data of these patients were as follows: age: 65.0±6.7 years old; duration of diabetes: 11.6±6.8 years; HbA1c: 61.2±13.3 mmol/mol; body mass index (BMI): 25.2±3.2 kg/m². Using FGM, people with T2DM were able to change daily diet and exercise through which significant reductions in MPG on days 12 or 13 were achieved as compared with that of day 2 (P=0.04 or P=0.003, respectively). The glucose variations, such as standard deviation (SD) of plasma glucose, coefficient of variation (CV), and mean amplitude of glycemic excursion (MAGE), progressively declined starting from day 6 as compared with baseline (P=0.016, P=0.003, or P=0.012, respectively). The incremental area over the curve (AOC) of the hypoglycemia (<3.9 mmol/L) had a significant reduction starting from the day 3 (P=0.001). When people with T2DM were divided into 3 groups based on the tertile of HbA1c (high, middle, and low concentrations), the reduction of MPG in patients with high concentration of HbA1c were much larger than that in middle and low concentration group patients (P=0.001 for both). The incidence of hypoglycemia was improved in the low concentration group (P=0.017). The optimal frequency of scanning time required to maintain euglycemia was 11.7 times/day as calculated by the receiver operating characteristic (ROC) analysis. CONCLUSION: Using FGM to monitor glucose concentration at 11.7 times/day, people with T2DM can achieve a better glucose control in addition to anti-diabetic drug medication through changing daily diet and exercise, especially in patients with high concentration of HbA1c (>66.1 mmol/mol).

Paternal origin of Tungusic-speaking populations: Insights from the updated phylogenetic tree of Y-chromosome haplogroup C2a-M86.

OBJECTIVES: Haplogroup C2a-M48 is the predominant paternal lineage of Tungusic-speaking populations, one of the largest population groups in Siberia. Up until now, the origins and dispersal of Tungusic-speaking populations have remained unclear. In this study, the demographic history of Tungusic-speaking populations was explored using the phylogenetic analysis of haplogroup C2a-M86, the major subbranch of C2a-M48. MATERIALS AND METHODS: In total, 18 newly generated Y chromosome sequences from C2a-M48 males and 20 previously available Y-chromosome sequences from this haplogroup were analyzed. A highly revised phylogenetic tree of haplogroup C2a-M86 with age estimates was reconstructed. Frequencies of this lineage in the literature were collected and a comprehensive analysis of this lineage in 13 022 individuals from 245 populations in Eurasia was performed. RESULTS: The distribution map of C2a-M48 indicated the most probable area of origin and diffusion route of this paternal lineage in North Eurasia. Most C2a-M86 samples from Tungusic-speaking populations belonged to the sublineage C2a-F5484, which emerged about 3300 years ago. We identified six unique sublineages corresponding to the Manchu, Evenks, Evens, Oroqen, and Daurpopulations; these sublineages diverged gradually over the past 1900 years. Notably, we observed a clear north-south dichotomous structure for sublineages derived from C2a-F5484, consistent with the internal north-south divergence of Tungusic languages and ethnic groups. CONCLUSIONS: We identified the important founding paternal haplogroup, C2a-F5484, for Tungusic-speaking populations as well as numerous unique subgroups of this haplogroup. We propose that the timeframe for the divergence of C2a-F5484 corresponds with the early differentiation of ancestral Tungusic-speaking populations.