Influence of temperature on performance and mechanism of advanced synergistic nitrogen removal in lab-scale denitrifying filter with biogenic manganese oxides.

Temperature is a significant operational parameter of denitrifying filter (DF), which affects the microbial activity and the pollutants removal efficiency. This study investigated the influence of temperature on performance of advanced synergistic nitrogen removal (ASNR) of partial-denitrification anammox (PDA) and denitrification, consuming the hydrolytic and oxidation products of refractory organics in the actual secondary effluent (SE) as carbon source. When the test water temperature (TWT) was around 25, 20, 15 and 10 °C, the filtered effluent total nitrogen (TN) was 1.47, 1.70, 2.79 and 5.52 mg/L with the removal rate of 93.38%, 92.25%, 87.33% and 74.87%, and the effluent CODcr was 8.12, 8.45, 10.86 and 12.29 mg/L with the removal rate of 72.41%, 66.17%, 57.35% and 51.87%, respectively. The contribution rate of PDA to TN removal was 60.44%∼66.48%, and 0.77-0.96 mg chemical oxygen demand (CODcr) was actually consumed to remove 1 mg TN. The identified functional bacteria, such as anammox bacteria, manganese oxidizing bacteria (MnOB), hydrolytic bacteria and denitrifying bacteria, demonstrated that TN was removed by the ASNR, and the variation of the functional bacteria along the DF layer revealed the mechanism of the TWT affecting the efficiency of the ASNR. This technique presented a strong adaptability to the variation of the TWT, therefore, it has broad application prospect and superlative application value in advanced nitrogen removal of municipal wastewater.

Optimizing the aldosterone-to-renin ratio cut-off for screening primary aldosteronism based on cardiovascular risk: a collaborative study.

OBJECTIVES: Aldosterone-to-renin ratio (ARR) based screening is the first step in the diagnosis of primary aldosteronism (PA). However, the guideline-recommended ARR cutoff covers a wide range, from the equivalent of 1.3 to 4.9 ng·dl-1/mIU∙l-1. We aimed to optimize the ARR cutoff for PA screening based on the risk of cardiovascular diseases (CVD). METHODS: Longitudinally, we included hypertensive participants from the Framingham Offspring Study (FOS) who attended the sixth examination cycle and followed up until 2014. At baseline (1995-1998), we used circulating concentrations of aldosterone and renin to calculate ARR (unit: ng·dl-1/mIU∙l-1) among 1,433 subjects who were free of CVD. We used spline regression to calculate the ARR threshold based on the incident CVD. We used cross-sectional data from the Chongqing Primary Aldosteronism Study (CONPASS) to explore whether the ARR cutoff selected from FOS is applicable to PA screening. RESULTS: In FOS, CVD risk increased with an increasing ARR until a peak of ARR 1.0, followed by a plateau in CVD risk (hazard ratio 1.49, 95%CI 1.19-1.86). In CONPASS, when compared to essential hypertension with ARR < 1.0, PA with ARR ≥ 1.0 carried a higher CVD risk (odds ratio 2.24, 95%CI 1.41-3.55), while essential hypertension with ARR ≥ 1.0 had an unchanged CVD risk (1.02, 0.62-1.68). Setting ARR cutoff at 2.4 ~ 4.9, 10% ~30% of PA subjects would be unrecognized although they carried a 2.45 ~ 2.58-fold higher CVD risk than essential hypertension. CONCLUSIONS: The CVD risk-based optimal ARR cutoff is 1.0 ng·dl-1/mIU∙l-1 for PA screening. The current guideline-recommended ARR cutoff may miss patients with PA and high CVD risk. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT03224312).

Treatment decision based on unilateral index from nonadrenocorticotropic hormone-stimulated and adrenocorticotropic hormone-stimulated adrenal vein sampling in primary aldosteronism.

OBJECTIVE: Adrenal venous sampling (AVS) is recommended for identifying the subtype of primary aldosteronism before making a surgical treatment decision, but failed cannulation of one adrenal vein is common. To evaluate whether using results of one adrenal vein during AVS could accurately predict unilateral primary aldosteronism. METHODS: A retrospective study was conducted in primary aldosteronism patients receiving bilaterally or unilaterally successful AVS. The aldosterone-cortisol ratio from the adrenal vein divided by the aldosterone-cortisol ratio from the inferior vena cava (IVC) was calculated as the AV/IVC index. RESULTS: The study examined 455 patients with primary aldosteronism, including 347 patients with unilateral primary aldosteronism. Among them, 250 and 125 patients received non- adrenocorticotropic hormone (ACTH) and ACTH-stimulated AVS, respectively, and 80 patients received both forms of AVS. Under non-ACTH-stimulated AVS, AUC of the AV/IVC index to diagnose ipsilateral and contralateral primary aldosteronism were 0.778 and 0.924, respectively. The specificity was 100% for both, with sensitivities of 5 and 26%, respectively, when using cutoffs of 17.05 to diagnose ipsilateral primary aldosteronism and 0.15 to diagnose contralateral primary aldosteronism. When using cutoffs of 3.60 and 0.70, the specificity decreased, but if combined with CT results (ipsilateral or contralateral adrenal nodules larger than 10 mm), the specificity could be maintained at 99%, with sensitivities of 33 and 45%, respectively. Under ACTH-stimulated AVS, the AV/IVC index showed similar accuracy to diagnose ipsilateral and contralateral primary aldosteronism. CONCLUSION: The unilateral AV/IVC index can be used to diagnose unilateral primary aldosteronism during AVS. Combining CT results can increase the accuracy further.

Primary aldosteronism and lower-extremity arterial disease: a two-sample Mendelian randomization study.

BACKGROUND AND AIMS: Primary aldosteronism (PA) is an adrenal disorder of autonomous aldosterone secretion which promotes arterial injury. We aimed to explore whether PA is causally associated with lower-extremity arterial disease (LEAD). METHODS: We included 39,713 patients with diabetes and 419,312 participants without diabetes from UK Biobank. We derived a polygenic risk score (PRS) for PA based on previous genome-wide association studies (GWAS). Outcomes included LEAD and LEAD related gangrene or amputation. We conducted a two-sample Mendelian randomization analysis for PA and outcomes to explore their potential causal relationship. RESULTS: In whole population, individuals with a higher PA PRS had an increased risk of LEAD. Among patients with diabetes, compared to the subjects in the first tertile of PA PRS, subjects in the third tertile showed a 1.24-fold higher risk of LEAD (OR 1.24, 95% CI 1.03-1.49) and a 2.09-fold higher risk of gangrene (OR 2.09, 95% CI 1.27-3.44), and 1.72-fold higher risk of amputation (OR 1.72, 95% CI 1.10-2.67). Among subjects without diabetes, there was no significant association between PA PRS and LEAD, gangrene or amputation. Two-sample Mendelian randomization analysis indicated that genetically predictors of PA was significantly associated with higher risks of LEAD and gangrene (inverse variance weighted OR 1.20 [95% CI 1.08-1.34]) for LEAD, 1.48 [95% CI 1.28-1.70] for gangrene), with no evidence of significant heterogeneity or directional pleiotropy. CONCLUSIONS: Primary aldosteronism is genetically and causally associated with higher risks of LEAD and gangrene, especially among patients with diabetes. Targeting on the autonomous aldosterone secretion may prevent LEAD progression.

Clinical efficacy of ultrasound-guided stellate ganglion block combined with extracorporeal shock wave therapy on limb spasticity in patients with ischemic stroke.

INTRODUCTION: To observe the clinical efficacy of ultrasound-guided stellate ganglion block (SGB) + extracorporeal shock wave therapy (ESWT) for limb spasticity in patients with ischemic stroke. METHODS: A total of 60 patients with post-stroke limb spasticity in our hospital were selected and randomly divided into four groups (n = 15). In the control group, patients received routine rehabilitation training. Based on routine rehabilitation training, SGB group patients underwent ultrasound-guided SGB, ESWT group patients received ESWT, and SGB + ESWT group patients received ultrasound-guided SGB combined with ESWT. The total treatment course was one month. The Modified Barthel Index (MBI) score, Fugl-Meyer Assessment and upper limb rehabilitation training system were applied to evaluate the activities of daily living, upper limb motor function and upper limb performance before and after treatment. Finally, the improvement after treatment was compared among different groups. RESULTS: After treatment, compared with the control group, the MBI score and the upper limb score based on Fugl-Meyer Assessment in the SGB, ESWT, and SGB + ESWT groups were significantly increased (P < 0.05). Furthermore, compared with the SGB and ESWT groups, SGB + ESWT exhibited a higher upper limb function score (P < 0.05), while the MBI score was not significantly different (P > 0.05). In terms of upper limb performance ability, patients in the SGB, ESWT and SGB + ESWT groups had better fitting degree, participation and exertion of exercise than those in the control group, and the SGB + ESWT group patients had the same movement trajectory as robots. CONCLUSION: Ultrasound-guided SGB and ESWT can reduce the muscle tension of patients, alleviate spasticity, promote the motor function of the upper limb, and improve the working performance of patients. However, the effect of SGB combined with ESWT is better.

Correlation analysis between foot deformity and diabetic foot with radiographic measurement.

Background: Foot deformity is a risk factor for diabetic foot ulcer. This study was aimed to investigate the relationship between hallux valgus (HV) and diabetic foot through the radiographic measurement. Methods: The patients with diabetic foot hospitalizing in the Department of Endocrinology, the First Affiliated Hospital of Chongqing Medical University from September 2016 to June 2020 were selected. Then the foot plain X-ray radiographs were completed, and the size of HV angle (HVA) was measured. Their clinical data were collected, and the ulcer recurrence rate, amputation rate and mortality rate of the patients were followed up. Results: A total of 370 patients were included. According to HVA, patients were divided into non-HV group (HVA<15°), and mild (15°≤HVA ≤ 20°), moderate (20°40°) HV groups. The age, height, BMI, smoking history and glycosylated hemoglobin level among the non-HVA, mild, moderate, and severe HV group (P<0.05), while smoking history, HbA1c, eGFR and autonomic neuropathy were significantly lower in HV group than those in non-HV group (P<0.05). The ulcer area in patients with moderate HV was larger than that in non-HV patients, and the severity of infection in patients with severe HV was significantly higher than that the other three groups (P<0.05). Conclusion: The occurrence of HV is not only related to age and BMI, but also to the creatinine and eGFR level, autonomic neuropathy, lower limb arteriosclerosis occlusion, coronary heart disease and hypertension. Therefore, more attention should be paid to renal function screening, neuropathy screening and evaluation of lower extremity vascular lesions in patients with diabetes, especially those with moderate or higher HV.

Advanced synergetic nitrogen removal of municipal wastewater using oxidation products of refractory organic matters in secondary effluent by biogenic manganese oxides as carbon source.

Due to the high operational cost and secondary pollution of the conventional advanced nitrogen removal of municipal wastewater, a novel concept and technique of advanced synergetic nitrogen removal of partial-denitrification anammox and denitrification was proposed, which used the oxidation products of refractory organic matters in the secondary effluent of municipal wastewater treatment plant (MWWTP) by biogenic manganese oxides (BMOs) as carbon source. When the influent NH4+-N in the denitrifying filter was about 1.0, 2.0, 3.0, 4.0, 5.0 and 7.0 mg/L, total nitrogen (TN) in the effluent decreased from about 22 mg/L to 11.00, 7.85, 6.85, 5.20, 4.15 and 2.09 mg/L, and the corresponding removal rate was 49.15, 64.82, 69.40, 76.70, 81.36 and 90.58%, respectively. The proportional contribution of the partial-denitrification anammox pathway to the TN removal was 12.00, 26.45, 39.70, 46.04, 54.97 and 64.01%, and the actual CODcr consumption of removing 1 mg TN was 0.75, 1.43, 1.26, 1.17, 1.08 and 0.99 mg, respectively, which was much lower than the theoretical CODcr consumption of denitrification. Furthermore, CODcr in the effluent decreased to 8.12 mg/L with a removal rate of 72.40%, and the removed organic matters were mainly non-fluorescent organic matters. Kinds of denitrifying bacteria, anammox bacteria, hydrolytic bacteria and manganese oxidizing bacteria (MnOB) were identified in the denitrifying filter, which demonstrated that the advanced synergetic nitrogen removal was achieved. This novel technology presented the advantages of high efficiency of TN and CODcr removal, low operational cost and no secondary pollution.

Renin-independent aldosteronism and chronic kidney disease in diabetes: Observational and Mendelian randomization analyses.

BACKGROUND: Renin-independent aldosteronism (RIA) describes the spectrum of autonomous aldosterone secretion from mild to overt. We aimed to explore whether RIA is causally associated with chronic kidney disease (CKD) in patients with diabetes. METHODS: We cross-sectionally included 1027, 402 and 39,709 patients with any type of diabetes from cohorts of EIMDS, CONPASS and UK Biobank, respectively. In EIMDS, we defined RIA and renin-dependent aldosteronism based on plasma aldosterone and renin concentrations. We performed captopril challenge test to confirm renin-dependent or independent aldosteronism in CONPASS. In UK Biobank, we generated genetic instruments for RIA based on the genome-wide association studies (GWAS). We extracted the corresponding single nucleotide polymorphisms (SNPs) information from the GWAS data of CKD in diabetes. We harmonized the SNP-RIA and SNP-CKD data to conduct the two-sample Mendelian randomization analyses. FINDINGS: In EIMDS and CONPASS, when compared to subjects with normal aldosterone concentration or renin-dependent aldosteronism, participants with RIA had a lower estimated glomerular filtration rate, a higher prevalence of CKD, and a higher multivariate-adjusted odds ratio (OR) of CKD (OR 2.62 [95%CI 1.09-6.32] in EIMDS, and 4.31 [1.39-13.35] in CONPASS). The two-sample Mendelian randomization analysis indicated that RIA was significantly associated with a higher risk of CKD (inverse variance weighted OR 1.10 [95 % CI 1.05-1.14]), with no evidence of significant heterogeneity or substantial directional pleiotropy. INTERPRETATION: Among patients with diabetes, renin-independent aldosteronism is causally associated with a higher risk of CKD. Targeted treatment of autonomous aldosterone secretion may benefit renal function in diabetes.

Sarcopenia is an independent risk factor for all-cause mortality rate in patients with diabetic foot ulcers.

Objective: This study aimed to determine whether sarcopenia affects the all-cause mortality rate of patients with diabetic foot ulcers (DFUs). Research design and methods: The clinic-based observational study included 217 patients treated at the Department of Endocrinology, the First Affiliated Hospital of Chongqing Medical University during a 4-year period. All subjects underwent dual-energy X-ray absorptiometry to determine their body composition during hospitalization. Diagnosis of sarcopenia was based on the Baumgartner diagnostic criteria. Patients were followed up regularly by phone calls until April 1, 2019, and their survival status was recorded.Univariate and multivariate Cox risk ratio regression models were used to analyze factors influencing the all-cause mortality rate of patients with DFUs. Results: Of the 217 patients, 158 people survived (82.7%), 33 died (17.3%), and 26 were lost to follow-up. The median follow-up time was 23 (Range 11-34) months. The majority of patients were male (68.6%), with a mean age of 67.29 ± 11.14 years. The 5-year survival rate was 68.3% and 45.9% for all study patients (n = 217) and sarcopenia patients (n = 81), respectively. Multivariate Cox risk regression model showed that age (HR 1.042[95%CI:1.006, 1.078], P = 0.021), sarcopenia (HR 5.051[95%CI:1.968, 12.961], P = 0.001), and serum creatinine (HR 1.007[95%CI: 1.003, 1.010], P < 0.001) were independent risk factors for all-cause mortality rate of patients with DFUs. Kaplan-Meier survival curve indicated that the survival rate of patients with sarcopenia was significantly lower than non-sarcopenia patients (P < 0.001). Conclusions: Sarcopenia is an independent risk factor for all-cause mortality of patients with DFUs and hence an important prognostic factor for patients with DFUs. Active prevention and improvement of sarcopenia can potentially improve the survival outcomes of this patient population.

Self-Assembling Peptide SCIBIOIII Hydrogel for Three-Dimensional Cell Culture That Promotes Wound Healing in Diabetic Mice.

An important clinical challenge is improving the healing rate of diabetic chronic wounds, and developing new approaches that can promote chronic wound healing is essential. A new biomaterial that has demonstrated great potential for tissue regeneration and repair is self-assembling peptides (SAPs); however, they have been less studied for the treatment of diabetic wounds. Here, we explored the role of an SAP, SCIBIOIII, with a special nanofibrous structure mimicking the natural extracellular matrix for chronic diabetic wound repair. The results showed that the SCIBIOIII hydrogel in vitro has good biocompatibility and can create a three-dimensional (3D) culture microenvironment for the continuous growth of skin cells in a spherical state. The SCIBIOIII hydrogel in diabetic mice (in vivo) significantly improved wound closure, collagen deposition, and tissue remodeling and enhanced chronic wound angiogenesis. Thus, the SCIBIOIII hydrogel is a promising advanced biomaterial for 3D cell culture and diabetic wound tissue repair.

Phosphoproteomics Reveals the Wolframin-Calcium Axis as an Important Pathogenic Signaling Node in Primary Aldosteronism.

BACKGROUND: Aldosterone-producing adenoma (APA) is a benign adrenal tumor with autonomous aldosterone production which causes hypertension and excess cardiovascular risk. Protein phosphorylation regulates aldosterone secretion from adrenal cortical cells, but how signaling networks are remodeled in APA remains unknown. METHODS: We performed an integrated proteomic and phosphoproteomic profiling of 15 APA and 10 matched nonfunctioning adrenocortical tumors (NFAT) based on the 4-dimensional label-free technique. We further validated our main findings in enlarged APA samples, mice, and adrenocortical cell line. RESULTS: The proteomic and phosphoproteomic profiling of APA and NFAT quantified 5989 proteins and 9011 phosphopeptides. We highlighted differentially expressed and phosphorylated proteins which modulated aldosterone synthesis and secretion from APA. As intracellular calcium is the central signal for aldosterone synthesis, our integrated calcium signaling network implicated wolframin in the control of calcium influx and CYP11B2 (aldosterone synthase) activation in APA (ratio of wolframin expression in APA to NFAT: 6.411, P<0.001). Among 97 APA cases for validation, a higher expression level of wolframin was associated with a higher plasma aldosterone concentration postcaptopril challenge test and a higher systolic blood pressure. In vitro, the secretion of aldosterone was enhanced by wolframin overexpression, while aldosterone secretion in response to potassium or angiotensin II was inhibited by the knockdown of wolframin. Further in vivo and in vitro data demonstrated the wolframin-calcium axis as an important regulator of CYP11B2 expression and aldosterone production. CONCLUSIONS: Wolframin is a regulatory protein in aldosterone hypersecretion. Remodeled calcium transportation and mitochondrial function are involved in wolframin-related aldosterone secretion.

Advanced nitrogen removal performance and microbial community structure of a lab-scale denitrifying filter with in-situ formation of biogenic manganese oxides.

Advanced nitrogen removal faces the challenges of high operational cost resulted from the additional carbon source and secondary pollution caused by inaccurate carbon source dosage in municipal wastewater. To address these problems, a novel carbon source was developed, which was the oxidation products of refractory organic matters in the secondary effluent of municipal wastewater treatment plant (MWWTP) by in-situ generated biogenic manganese oxides (BMOs) in the denitrifying filter. In the steady phase, the effluent chemical oxygen demand (CODcr), NO3--N and total nitrogen (TN) in the denitrifying filter 2# with BMOs was 11.27, 9.03 and 10.36 mg/L, and the corresponding removal efficiency was 54.79%, 51.85% and 48.03%, respectively, which was significantly higher than those in the control denitrifying filter 1# that the removal efficiency of CODcr, NO3--N and TN was only 32.30%, 28.58% and 29.36%, respectively. Kinds of denitrifying bacteria (Candidatus Competibacter, Defluviicoccus, Dechloromonas, Candidatus Competibacter, Dechloromonas, Pseudomonas, Thauera, Acinetobacter, Denitratisoma, Anaerolineae and Denitratisoma) and anammox bacteria (Pirellula, Gemmata, Anammoximicrobium and Brocadia) were identified in the denitrifying filters 1# and 2#, which explained why the actual CODcr consumption (1.55 and 1.44 mg) of reducing 1 mg NO3--N was much lower than the theoretical CODcr consumption. While manganese oxidizing bacteria (MnOB, Bacillus, Crenothrix and Pedomicrobium) was only identified in the denitrifying filter 2#. This novel technology presented the advantages of no additional carbon source, low operational cost and no secondary pollution. Therefore, the novel technology has superlative application value and broad application prospect.

Icariin Treatment Rescues Diabetes Induced Bone Loss via Scavenging ROS and Activating Primary Cilia/Gli2/Osteocalcin Signaling Pathway.

Diabetes-associated bone complications lead to fragile bone mechanical strength and osteoporosis, aggravating the disease burden of patients. Advanced evidence shows that chronic hyperglycemia and metabolic intermediates, such as inflammatory factor, reactive oxygen species (ROS), and advanced glycation end products (AGEs), are regarded as dominant hazardous factors of bone complications, whereas the pathophysiological mechanisms are complex and controversial. By establishing a diabetic Sprague-Dawley (SD) rat model and diabetic bone loss cell model in vitro, we confirmed that diabetes impaired primary cilia and led to bone loss, while adding Icariin (ICA) could relieve the inhibitions. Mechanistically, ICA could scavenge ROS to maintain the mitochondrial and primary cilia homeostasis of osteoblasts. Intact primary cilia acted as anchoring and modifying sites of Gli2, thereby activating the primary cilia/Gli2/osteocalcin signaling pathway to promote osteoblast differentiation. All results suggest that ICA has potential as a therapeutic drug targeting bone loss induced by diabetes.

SIRT1/Notch1 signal axis involves in the promoting effect of Segetalin B on bone formation.

Phytoestrogens are a class of potential natural medicines for treating postmenopausal osteoporosis (PMOP). Segetalin B (SB) is a cyclic peptide compound showing estrogenic activity. This study reports the effect of SB on bone formation among ovariectomized (OVX) rats. The bone marrow mesenchymal stem cells (BMSCs) from OVX rats were cultured in vitro. Alizarin Red staining was utilized to observe the effect of SB on the mineralization of BMSCs. The levels of alkaline phosphatase (ALP), osteocalcin, bone morphogenetic protein (BMP-2), and Sirtuin 1 (SIRT1) activities were detected. The OVX rats were treated with SB in vivo. Micro-CT was utilized for imaging analysis. Urine calcium and phosphorus, and ALP activity in bone marrow were assayed. Western blot analysis and immunofluorescence were incorporated to detect protein expressions in vitro and in vivo. The results showed that SB dose-dependently promoted mineralization of OVX rat-derived BMSCs in vitro increased the level of Osteocalcin, BMP-2, ALP, and SIRT1 activity. Moreover, it upregulated expressions of Runx2, Osterix, and SIRT1, downregulated expressions of Notch intracellular domain (NICD), acetyl-NICD, and hairy and enhancer of split 1 (Hes1). In addition, SB treatment significantly decreased bone loss, inhibited calcium and phosphorus loss, elevated ALP activity, upregulated Runx2, Osterix, and SIRT1, and downregulated NICD and Hes1 in OVX rats in vivo. However, EX527, a SIRT1-selective inhibitor, could reverse the above effects of SB in vitro or in vivo. These results indicate that SB is a potential natural medicine to improve PMOP. Thus, its mechanism of promoting bone formation involves the SIRT1/Notch1 signaling axis.

Prevalence and Characteristics of Adrenal Tumors in an Unselected Screening Population : A Cross-Sectional Study.

BACKGROUND: With the widespread use of advanced imaging technology, adrenal tumors are increasingly being identified. OBJECTIVE: To investigate the prevalence and characteristics of adrenal tumors in an unselected screening population in China. DESIGN: Cross-sectional study. (ClinicalTrials.gov: NCT04682938). SETTING: A health examination center in China. PATIENTS: Adults having an annual checkup were invited to be screened for adrenal tumors by adrenal computed tomography. MEASUREMENTS: The participants with adrenal tumors had further evaluation for malignancy risk and adrenal function. RESULTS: A total of 25 356 participants were screened, 351 of whom were found to have adrenal tumors, for a prevalence of 1.4%. The prevalence increased with age, from 0.2% in participants aged 18 to 25 years to 3.2% in those older than 65 years. Among 351 participants with adrenal tumors, 337 were diagnosed with an adrenocortical adenoma, 14 with another benign nodule, and none with a malignant mass. In 212 participants with an adenoma who completed endocrine testing, 69.3% were diagnosed with a nonfunctioning adenoma, 18.9% with cortisol autonomy, 11.8% with primary aldosteronism, and none with pheochromocytoma. Proportions of nonfunctioning adenomas were similarly high in various age groups (72.2%, 67.8%, and 72.2% in those aged <46, 46 to 65, and ≥66 years, respectively). LIMITATION: Only 212 of 337 participants with an adrenocortical adenoma had endocrine testing. CONCLUSION: The prevalence of adrenal tumors in the general adult screening population is 1.4%, and most of these tumors are nonfunctioning regardless of patient age. Cortisol and aldosterone secretion are the main causes of functional adenomas. PRIMARY FUNDING SOURCE: National Key Research and Development Program of China and National Natural Science Foundation of China.

Association between fat mass and mortality: analysis of Mendelian randomization and lifestyle modification.

BACKGROUND: The association between fat mass and mortality has been equivocally shown to be linear, J-shaped, and U-shaped. We aimed to clarify this relationship based on Mendelian randomization (MR) analysis and lifestyle modification. METHODS: This prospective analysis included 449,831 participants from UK Biobank. Linear MR analysis was used to estimate the linear relationship between fat mass and mortality. We assessed whole body fat mass by bioimpedance analysis at baseline and categorized subjects into five equal groups based on fat mass index (FMI). The association between FMI and mortality were investigated among whole population and in subgroups stratified by individual lifestyle factors, including diet, physical activity, smoking, alcohol, sleep and psychological health. FINDINGS: Linear MR analyses indicated a positive association between genetically predicted fat mass and all-cause mortality (HR 1.10, 95 % CI 1.08-1.12, P < 0.001). The association between FMI and all-cause mortality was manifested as J-shaped (HRs across FMI categories: 1.04, 1.00, 1.07, 1.21, 1.54), which was significantly modified by the number of low-risk lifestyle factors (P for interaction<0.001). When evaluating individual lifestyle factors, we observed a nonlinear relationship between FMI and all-cause mortality among participants who had high-risk lifestyle factors, while a linear relationship was observed among participants who had low-risk lifestyle factors, especially for those with adequate physical activity (HRs across FMI categories: 0.95, 1.00, 1.05, 1.17, 1.44) and who never smoked (0.96, 1.00, 1.03, 1.14, 1.51). INTERPRETATION: Genetically determined fat mass is causally and linearly associated with mortality. The J-shape association between anthropometric FMI and mortality is caused by high-risk lifestyle factors.

Distribution and drug sensitivity of pathogenic bacteria in diabetic foot ulcer patients with necrotizing fasciitis at a diabetic foot center in China.

BACKGROUND: Diabetic foot ulcer is one of the major complications for patients with diabetes, and has become an important cause of non-traumatic amputation. Necrotizing fasciitis is a life-threatening soft-tissue infection involving the fascia and subcutaneous tissue. When diabetic foot ulcers are complicated by necrotizing fasciitis (DNF), this increases the risk for amputation and mortality, making DNF treatment more complicated, and eventually leading to amputation and mortality. However, studies on pathogenic bacteria's distribution and drug sensitivity in DNF patients remain lacking. This study investigated the distribution and susceptibility of pathogenic bacteria in DNF patients, and provided empirical antibacterial guidance for the clinic. METHODS: In a single diabetic foot center, the results from microbial cultures and drug susceptibility tests of patients with DNF from October 2013 to December 2020 were collected and analyzed. RESULTS: A total of 101 DNF patients were included in this study, of whom 94 had positive culture test results. A total of 124 pathogens were cultured, including 76 Gram-positive bacterial strains, 42 Gram-negative bacterial strains, and six fungal strains. Polymicrobial infections accounted for 26.7% and monomicrobial infections accounted for 66.3%. Staphylococcus aureus was the most common bacterium isolated, followed by Enterococcus faecalis and Streptococcus agalactiae. Pseudomonas aeruginosa, Klebsiella pneumoniae, and Proteus mirabilis were the most common Gram-negative bacteria. Thirty-five strains of multi-drug resistant bacteria were isolated, representing 28.2% of the total isolates. Gram-positive bacteria were more sensitive to levofloxacin, moxifloxacin, vancomycin, teicoplanin, tigecycline, and linezolid, while Gram-negative bacteria were more sensitive to amikacin, piperacillin/tazobactam, cefoperazone/sulbactam, ceftazidime, cefepime, imipenem, and meropenem. CONCLUSIONS: Gram-positive bacteria were the main bacteria isolated from DNF patients. The bacterial composition, the proportion of multi-drug resistant bacteria among the pathogens, and the high risk for amputation should be fully considered in the initial empirical medication, and broad-spectrum antibacterials are recommended.

Comparison of Bolus and Continuous Infusion of Adrenocorticotropic Hormone During Adrenal Vein Sampling.

Background: Adrenocorticotropic hormone (ACTH) is widely used in adrenal vein sampling (AVS) and can be administered as a bolus injection or continuous infusion. The optimal administration method has not been determined. We aimed to compare the effects of ACTH bolus with infusion on cannulation success, lateralization assessment and adverse events (AEs). Methods: Retrospectively collected data from patients with primary aldosteronism who underwent AVS with ACTH at a tertiary hospital in China. Rate of successful cannulation, lateralization index (LI), complete biochemical remission and AEs related to AVS were analyzed. Results: The study included 80 patients receiving ACTH bolus and 94 receiving infusions. The rate of successful cannulation was comparable between bolus and infusion groups (75/80, 93.4% vs 88/94, 93.6%). In those with successful cannulation, the bolus group had a higher selectivity index than the infusion group, while LI [6.4(1.8-17.5) vs. 7.6(2.0-27.8), P=0.48] and rate of complete biochemical remission (43/44, 97.7% vs 53/53, 100%, P=0.45) did not significantly differ between the two groups. One in the bolus and one patient in the infusion group had adrenal vein rupture but they recovered with conservative treatment. The bolus group reported more transient AEs such as palpitation (52.9% vs 2.2%) and abdominal discomfort (40.0% vs 2.2%) than the infusion group. Conclusions: Due to their similar effects on cannulation success and lateralization, but a lower rate of transient AEs in the infusion group, the continuous infusion method should be recommended for ACTH stimulation in AVS.

Heightened Cardiovascular Risk in Hypertension Associated With Renin-Independent Aldosteronism Versus Renin-Dependent Aldosteronism: A Collaborative Study.

Background While both renin-dependent and renin-independent aldosterone secretion contribute to aldosteronism, their relative associations with cardiovascular disease (CVD) risk has not been investigated. Methods and Results A total of 2909 participants from the FOS (Framingham Offspring Study) with baseline, serum aldosterone concentration, and plasma renin concentration who attended the sixth examination cycle and were followed up until 2014 and who were free of CVD were included. We further recruited 2612 hypertensive participants from the CONPASS (Chongqing Primary Aldosteronism Study). Captopril challenge test was performed to confirm renin-dependent or -independent aldosteronism in CONPASS. Among 1433 hypertensive subjects of FOS, when compared with those with serum aldosterone concentration <10 ng dL-1 (normal aldosterone), participants who had serum aldosterone concentration ≥10 ng dL-1 and plasma renin concentration ≤15 mIU L-1 (identified as renin-independent aldosteronism) showed a higher risk of CVD (hazard ratio, 1.40 [95% CI, 1.08-1.82]), while those who had serum aldosterone concentration ≥10 ng dL-1 and plasma renin concentration >15 mIU L-1 (identified as renin-dependent aldosteronism) showed an unchanged CVD risk. In CONPASS, renin-independent aldosteronism carried a significantly higher risk of CVD than normal aldosterone (odds ratio, 2.57 [95% CI, 1.13-5.86]), while the CVD risk remained unchanged in renin-dependent aldosteronism. Elevation of the urinary potassium-to-sodium excretion ratio, reflective of mineralocorticoid receptor activity, was only observed in participants with renin-independent aldosteronism. Conclusions Among patients with hypertension, renin-independent aldosteronism is more closely associated with CVD risk than renin-dependent aldosteronism.