Interleukin 25 promotes muscle regeneration in sarcopenia by regulating macrophage-mediated Sonic Hedgehog signaling.

OBJECTIVE: Sarcopenia manifests as a chronic, low-level inflammation along with multiple inflammatory cells infiltration. Interleukin (IL)-25 can regulate the function of macrophages. However, the specific role and mechanisms through which IL-25 functions in sarcopenia are still not fully understood and require further investigation. METHODS: Aged mice were utilized as sarcopenia models and examined the expression of inflammatory factors. To investigate the effects of IL-25 on sarcopenia, the model mice received IL-25 treatment and underwent in vivo adoptive transfer of IL-25-induced macrophages. Meanwhile, RAW264.7 cells, bone marrow-derived macrophages, satellite cells and C2C12 cells were used in vitro. Shh insufficiency was induced through intramuscular administration of SHH-shRNA adenoviruses. Then, various assays including scratch wound, cell counting kit-8 and Transwell assays, as well as histological staining and molecular biological methods, were conducted. RESULTS: Aged mice exhibited an accelerated decline in muscle strength and mass, along with an increased muscle lipid droplets and macrophage infiltration, and decreased IL-25 levels compared to the young group. IL-25 therapy and the transfer of IL-25-preconditioned macrophages could improve these conditions by promoting M2 macrophage polarization in vivo as well as in vitro. M2 macrophage conditioned medium enhanced satellite cell proliferation and migration, as well as the vitality, migration, and differentiation of C2C12 cells in vitro. Furthermore, IL-25 enhanced Shh expression in macrophages in vitro, and activated the Shh signaling pathway in muscle tissue of aged mice, which could be suppressed by either the inhibitor cyclopamine or Shh knockdown. Mechanistic studies showed that Shh insufficiency suppressed the activation of Akt/mTOR signaling pathway in muscle tissue of aged mice. CONCLUSION: IL-25 promotes the secretion of Shh by M2 macrophages and activates the Shh/Akt/mTOR signaling pathway, which improves symptoms and function in sarcopenia mice. This suggests that IL-25 has potential as a therapeutic agent for treating sarcopenia.

The diagnostic performance of Cr/CysC for sarcopenia and its predictive value on clinical outcomes in hospitalized older patients: a prospective cohort study.

PURPOSE: The utilization of the creatinine-to-cystatin C ratio (Cr/CysC) represents an innovative method for predicting sarcopenia. Our objectives encompassed the evaluation of sarcopenia diagnostic accuracy for Cr/CysC, SARC-F, SARC-CalF, the combination of Cr/CysC and SARC-CalF, and the Ishii score, as well as an exploration of the predictive value of Cr/CysC concerning clinical outcomes within hospitalized older individuals. METHODS: We employed receiver operating characteristic (ROC) curves and calculated areas under the curves (AUCs) to assess the diagnostic accuracy. Furthermore, we applied univariate and multivariate Cox proportional-hazard models to calculate the hazard ratio (HR) and 95% confidence interval (CI) of risk factors affecting prognosis. RESULTS: Our study included 312 participants, comprising 167 men and 145 women, with an average age of 71 years. Among males, the AUCs for Cr/CysC, SARC-F, SARC-CalF, the combination of Cr/CysC and SARC-CalF, and the Ishii score were 0.717 [95% CI 0.642-0.784], 0.669 (95% CI 0.592-0.739), 0.845 (95% CI 0.781-0.896), 0.882 (95% CI 0.823-0.926), and 0.938 (95% CI 0.890-0.969), respectively. In females, the AUCs for Cr/CysC, SARC-F, SARC-CalF, the combination of Cr/CysC and SARC-CalF, and the Ishii score were 0.706 (95% CI 0.625-0.779), 0.631 (95% CI 0.547-0.710), 0.763 (95% CI 0.686-0.830), 0.789 (95% CI 0.714-0.853), and 0.898 (95% CI 0.837-0.942), respectively. After adjusting for age, sex, physical exercise, smoking, drinking, hypertension, coronary heart disease (CHD), chronic obstructive pulmonary disease (COPD), chronic kidney disease (CKD), and cancer, sarcopenia identified by Cr/CysC (adjusted HR = 2.176, 95% CI 1.062-4.460, P = 0.034) was independently associated with poor overall survival in hospitalized older patients. CONCLUSIONS: Cr/CysC has satisfactory diagnostic accuracy for sarcopenia diagnosis and predictive value for poor outcomes in hospitalized older patients. The combination of Cr/CysC and SARC-CalF may provide a more accurate screening for sarcopenia and the Ishii score may be the most accurate clinical method for detecting sarcopenia.

Efficacy of single-pill combination in uncontrolled essential hypertension: A systematic review and network meta-analysis.

This study aimed to evaluate the efficacy of single-pill combination (SPC) antihypertensive drugs in patients with uncontrolled essential hypertension. Through Searching Pubmed, EMBASE, the Cochrane Library, and Web of Science collected only randomized controlled trials on the efficacy of single-pill combination antihypertensive drugs in people with uncontrolled essential hypertension. The search period is from the establishment of the database to July 2022. The methodological quality of the included studies was assessed using the Cochrane Risk of Bias Assessment, and statistical analyses were performed using Review Manage 5.3 and Stata 15.1 software. This review ultimately included 32 references involving 16 273 patients with uncontrolled essential hypertension. The results of the network meta-analysis showed that a total of 11 single-pill combination antihypertensive drugs were included, namely: Amlodipine/valsartan, Telmisartan/amlodipine, Losartan/HCTZ, Candesartan/HCTZ, Amlodipine/benazepril, Telmisartan/HCTZ, Valsartan/HCTZ, Irbesartan/amlodipine, Amlodipine/losartan, Irbesartan/HCTZ, and Perindopril/amlodipine. According to SUCRA, Irbesartan/amlodipine may rank first in reducing systolic blood pressure (SUCRA: 92.2%); Amlodipine/losartan may rank first in reducing diastolic blood pressure (SUCRA: 95.1%); Telmisartan/amlodipine may rank first in blood pressure control rates (SUCRA: 83.5%); Amlodipine/losartan probably ranks first in diastolic response rate (SUCRA: 84.5%). Based on Ranking Plot of the Network, we can conclude that single-pill combination antihypertensive drugs are superior to monotherapy, and ARB/CCB combination has better advantages than other SPC in terms of systolic blood pressure, diastolic blood pressure, blood pressure control rate, and diastolic response rate. However, due to the small number of some drug studies, the lack of relevant studies has led to not being included in this study, which may impact the results, and readers should interpret the results with caution.

Unilateral adrenal tuberculosis whose computed tomography imaging characteristics mimic a malignant tumor: A case report.

BACKGROUND: Adrenal tuberculosis usually presents with bilateral involvement. It has special characteristics in computed tomography (CT) images, such as small size, low attenuation in the center, and peripheral rim enhancement, which differ from those of primary tumors. CASE SUMMARY: A 42-year-old female presented to the hospital with low back pain. She had been diagnosed with hypertension as well as pulmonary and cerebral tuberculosis but denied having any fever, fatigue, anorexia, night sweats, cough, or weight loss. Abdominal CT revealed an irregular 6.0 cm × 4.5 cm mass with uneven density in the right adrenal gland, while the left adrenal gland was normal. No abnormalities were observed in plasma total cortisol (8 am), adrenocorticotropic hormone, aldosterone/renin ratio, blood catecholamines, or urine catecholamines. A fine-needle aspiration biopsy of the right adrenal gland provided evidence of tuberculosis. After three years of anti-tuberculosis treatments, the large mass in the right adrenal gland was reduced to a slight enlargement. CONCLUSION: This is a case of unilateral adrenal tuberculosis with CT imaging characteristics mimicking those of a malignant tumor. Extended anti-tuberculosis therapy is recommended in such cases.

Serum creatinine and cystatin C-based diagnostic indices for sarcopenia in advanced non-small cell lung cancer.

BACKGROUND: Sarcopenia is an important prognostic factor of lung cancer. The serum creatinine/cystatin C ratio (CCR) and the sarcopenia index (SI, serum creatinine × cystatin C-based glomerular filtration rate) are novel screening tools for sarcopenia; however, the diagnostic accuracy of the CCR and SI for detecting sarcopenia remains unknown. We aimed to explore and validate the diagnostic values of the CCR and SI for determining sarcopenia in non-small cell lung cancer (NSCLC) and to explore their prognostic values for overall survival. METHODS: We conducted a prospective cohort study of adult patients with stage IIIB or IV NSCLC. Levels of serum creatinine and cystatin C were measured to calculate the CCR and SI. Sarcopenia was defined separately using CCR, SI, and the Asian Working Group for Sarcopenia (AWGS) 2019 criteria. Participants were randomly sampled into derivation and validation sets (6:4 ratio). The cutoff values for diagnosing sarcopenia were determined based on the derivation set. Diagnostic accuracy was analysed in the validation set through receiver operating characteristic (ROC) curves. Cox regression models and survival curves were applied to evaluate the impact of different sarcopenia definitions on survival. RESULTS: We included 579 participants (women, 35.4%; mean age, 58.4 ± 8.9 years); AWGS-defined sarcopenia was found in 19.5% of men and 10.7% of women. Both CCR and SI positively correlated with computed tomography-derived and bioimpedance-derived muscle mass and handgrip strength. The optimal cutoff values for CCR and SI were 0.623 and 54.335 in men and 0.600 and 51.742 in women, with areas under the ROC curves of 0.837 [95% confidence interval (CI): 0.770-0.904] and 0.833 (95% CI: 0.765-0.901) in men (P = 0.25), and 0.808 (95% CI: 0.682-0.935) and 0.796 (95% CI: 0.668-0.924) in women (P = 0.11), respectively. The CCR achieved sensitivities and specificities of 73.0% and 93.7% in men and 85.7% and 65.7% in women, respectively; the SI achieved sensitivities and specificities of 75.7% and 86.5% in men and 92.9% and 62.9% in women, respectively. CCR-defined, SI-defined, and AWGS-defined sarcopenia were independently associated with a high mortality risk [hazard ratio (HR) = 1.75, 95% CI: 1.25-2.44; HR = 1.55, 95% CI: 1.11-2.17; and HR = 1.76, 95% CI: 1.22-2.53, respectively]. CONCLUSIONS: CCR and SI have satisfactory and comparable diagnostic accuracy and prognostic values for sarcopenia in patients with advanced NSCLC. Both may serve as surrogate biomarkers for evaluating sarcopenia in these patients. However, further external validations are required.

IQGAP2 acts as an independent prognostic factor and is related to immunosuppression in DLBCL.

BACKGROUND: Almost one-third of patients with diffuse large B-cell lymphoma (DLBCL) cannot be cured with initial therapy and will eventually succumb to the disease. Further elaboration of prognostic markers of DLBCL will provide therapeutic targets. IQ motif-containing GTPase activating protein 2 (IQGAP2) acts as a tumour suppressor in hepatocellular, prostate, and gastric cancers. However, the role of IQGAP2 in DLBCL remains unclear. METHODS: We collected mRNA expression data from 614 samples and the corresponding clinical information. The survival time of patients was compared between groups according to the mRNA expression level of IQGAP2. Survival analyses were performed in different subgroups when considering the effect of age, tumour stage, serum lactate dehydrogenase (LDH) concentration, performance status, and the number of extra nodal disease sites. The biological processes associated with IQGAP2-associated mRNAs were analysed to predict the function of IQGAP2. The correlation of IQGAP2 mRNA with immunosuppressive genes and leukocyte infiltration were analysed. RESULTS: The overall survival of patients with increased IQGAP2 mRNA levels was reduced even after aggressive treatment independent of age, tumour stage, serum LDH concentration, performance status, and the number of extra nodal disease sites. Furthermore, the biological processes of IQGAP2-associated mRNAs were mainly immune processes. IQGAP2 mRNA expression was correlated with the expression of immunosuppressive genes and leukocyte infiltration. CONCLUSION: IQGAP2 mRNA is an independent prognostic factor and is related to immunosuppression in DLBCL. This discovery may provide a promising target for further development of therapy.

Inflammatory indexes are not associated with sarcopenia in Chinese community-dwelling older people: a cross-sectional study.

BACKGROUND: Inflammatory indexes (platelet-to-lymphocyte ratio [PLR], neutrophil-to-lymphocyte ratio [NLR], and lymphocyte-to-monocyte ratio [LMR]) are recently supposed to be the biomarkers of sarcopenia. We aimed to validate the association between these inflammatory indexes and sarcopenia in Chinese community-dwelling older people. METHODS: We consecutively recruited community-dwelling older adults aged 60 years or older. The neutrophil, lymphocyte, monocyte, and platelet counts, and C-reactive protein (CRP) were tested using standard methods. Sarcopenia was defined according to different criteria: the Asian Working Group for Sarcopenia (AWGS), the updated version of AWGS (AWGS 2019), the European Working Group on Sarcopenia in Older People (EWGSOP), the updated version of EWGSOP (EWGSOP2), the International Working Group on Sarcopenia (IWGS), and the Foundation for the National Institutes of Health Sarcopenia Project (FNIH). Multiple logistic regression analysis was performed. RESULTS: We included 384 participants. A total of 61 participants (15.9%) were diagnosed with sarcopenia according to the AWGS criteria. There was no significant difference in PLR, NLR, LMR, and CRP between the sarcopenia group and the non-sarcopenia group regardless of the diagnostic criteria. No significant association between PLR, NLR, LMR, and AWGS-defined sarcopenia was found (PLR per 1- standard deviation [SD]: adjusted odds ratio [OR] 1.09, 95% confidence interval [CI] 0.82 to 1.45; NLR per 1-SD: adjusted OR 0.96, 95% CI 0.71 to 1.30; LMR per 1-SD: adjusted OR 1.01, 95% CI 0.74 to 1.38). Similar results were found when sarcopenia was defined by different criteria and when PLR, NLR, LMR were treated as categorical variables. CONCLUSIONS: Our study did not support the utility of the inflammatory indexes (NLR, PLR, and LMR) as the biomarkers of sarcopenia in Chinese community-dwelling older people. However, considering the inflammatory indexes can be simply calculated from a routine blood test, further studies in different populations remain warranted.

Integrated Transcriptional and Proteomic Profiling Reveals Potential Amino Acid Transporters Targeted by Nitrogen Limitation Adaptation.

Nitrogen (N) is essential for plant growth and crop productivity. Organic N is a major form of remobilized N in plants' response to N limitation. It is necessary to understand the regulatory role of N limitation adaption (NLA) in organic N remobilization for this adaptive response. Transcriptional and proteomic analyses were integrated to investigate differential responses of wild-type (WT) and nla mutant plants to N limitation and to identify the core organic N transporters targeted by NLA. Under N limitation, the nla mutant presented an early senescence with faster chlorophyll loss and less anthocyanin accumulation than the WT, and more N was transported out of the aging leaves in the form of amino acids. High-throughput transcriptomic and proteomic analyses revealed that N limitation repressed genes involved in photosynthesis and protein synthesis, and promoted proteolysis; these changes were higher in the nla mutant than in the WT. Both transcriptional and proteomic profiling demonstrated that LHT1, responsible for amino acid remobilization, were only significantly upregulated in the nla mutant under N limitation. These findings indicate that NLA might target LHT1 and regulate organic N remobilization, thereby improving our understanding of the regulatory role of NLA on N remobilization under N limitation.

Sarcopenia index based on serum creatinine and cystatin C is associated with 3-year mortality in hospitalized older patients.

To investigate the association of the sarcopenia index (SI, serum creatinine value/cystatin C value × 100) with 3-year mortality and readmission among older inpatients, we reanalyzed a prospective study in the geriatric ward of a teaching hospital in western China. Older inpatients aged ≥ 60 years with normal kidney function were included. Survival status and readmission information were assessed annually during the 3-year follow-up. We applied Cox regression models to calculate the hazard ratio (HR) and 95% confidence intervals (CIs) of sarcopenia for predicting mortality and readmission. We included 248 participants (mean age: 81.2 ± 6.6 years). During the follow-up, 57 participants (23.9%) died, whereas 179 participants (75.2%) were readmitted at least one time. The SI was positively correlated with body mass index (BMI) (r = 0.214, p = 0.001), calf circumference (CC) (r = 0.253, p < 0.001), handgrip strength (r = 0.244, p < 0.001), and gait speed (r = 0.221, p < 0.001). A higher SI was independently associated with a lower risk of 3-year all-cause mortality after adjusting for potential confounders (HR per 1-SD = 0.80, 95% CI: 0.63-0.97). The SI was not significantly associated with readmission (HR per 1-SD = 0.97, 95% CI: 0.77-1.25). In conclusion, the SI is associated with 3-year all-cause mortality but not readmission in a study population of hospitalized older patients.

A multiomics approach reveals the pivotal role of subcellular reallocation in determining rapeseed resistance to cadmium toxicity.

Oilseed rape (Brassica napus) has great potential for phytoremediation of cadmium (Cd)-polluted soils due to its large plant biomass production and strong metal accumulation. Enhanced plant Cd resistance (PCR) is a crucial prerequisite for phytoremediation through hyper-accumulation of excess Cd. However, the complexity of the allotetraploid genome of rapeseed hinders our understanding of PCR. To explore rapeseed Cd-resistance mechanisms, we examined two genotypes, 'ZS11' (Cd-resistant) and 'W10' (Cd-sensitive), that exhibit contrasting PCR while having similar tissue Cd concentrations, and characterized their different fingerprints in terms of plant morphophysiology (electron microscopy), ion abundance (inductively coupled plasma mass spectrometry), DNA variation (whole-genome resequencing), transcriptomics (high-throughput mRNA sequencing), and metabolomics (ultra-high performance liquid chromatography-mass spectrometry). Fine isolation of cell components combined with ionomics revealed that more Cd accumulated in the shoot vacuoles and root pectins of the resistant genotype than in the sensitive one. Genome and transcriptome sequencing identified numerous DNA variants and differentially expressed genes involved in pectin modification, ion binding, and compartmentalization. Transcriptomics-assisted gene co-expression networks characterized BnaCn.ABCC3 and BnaA8.PME3 as the central members involved in the determination of rapeseed PCR. High-resolution metabolic profiles revealed greater accumulation of shoot Cd chelates, and stronger biosynthesis and higher demethylation of root pectins in the resistant genotype than in the sensitive one. Our comprehensive examination using a multiomics approach has greatly improved our understanding of the role of subcellular reallocation of Cd in the determination of PCR.

A sarcopenia screening test predicts mortality in hospitalized older adults.

The aim of this study is to investigate the validation of a sarcopenia screening test (Ishii's formula) for predicting long-term mortality among older adult inpatients. A prospective, observational study was conducted in acute geriatric wards at three hospitals in western China. Sarcopenia was estimated using Ishii's formula. Survival status was assessed at 12, 24, and 36 months after the baseline investigation. Cox proportional-hazard models were applied to calculate the hazard ratio for mortality associated with sarcopenia. Three hundred and eighty participants (100 women) with a mean age of 80.2 ± 7.1 years were included. According to Ishii's formula, 264 participants (69.5%) were sarcopenic. The prevalence of sarcopenia was similar in men and women (71.1% vs. 65.0%, respectively, P = 0.258). Sixty-seven participants (17.6%) died during the 3-year follow-up period. The all-cause mortality was significantly higher in the sarcopenia group than in the non-sarcopenia group (20.1% vs. 12.1%, respectively, P < 0.05). Multivariate Cox proportional hazards analysis identified sarcopenia as a significant predictor of 3-year all-cause mortality (adjusted hazard ratio [HR]: 2.06; 95% confidence interval [CI]: 1.02-4.15). In conclusion, sarcopenia, estimated by Ishii's formula, can predict 3-year all-cause mortality in a study population of hospitalized older adults.

[Comparing overnight dexamethasone suppression test, urine free cortisol, and midnight serum cortisol for the initial diagnosis of Cushing' s syndrome].

OBJECTIVE: To identify retrospectively the optimal cut-off points and the values of overnight dexamethasone suppression test, urine free cortisol, and midnight serum cortisol in the initial diagnosis of Cushing's syndrome in Chinese people. METHODS: The results of overnight low-dose dexamethasone suppression test (PTC-DST), urine free cortisol (UFC) and late-night plasma total cortisol (PTC-24 h) of 102 patients who had clinically confirmed Cushing's syndrome and 102 patients without Cushing's syndrome were extracted from West China Hospital. Receiver operating characteristic (ROC) curves were drawn to identify optimal cut-off points of the three assays and their values in diagnosing Cushing' s syndrome. RESULTS: The optimal cut-off point (the point on the ROC curve closest to 1) for PTC-DST was set at 86 nmol/L, with 98. 7% sensitivity and 97. 2% specificity (100% sensitivity and 94. 4% specificity was achieved at 50 nmol/L 100%o sensitivity and 95. 8% specificity was achieved at 60 nmol/L). The optimal cut-off point for PTC-24 h was set at 347 nmol/L, with 93. 4% sensitivity and 98. 4% specificity (98. 9% sensitivity and 85. 2% specificity was achieved at 207 nmol/L). The optimal cut-off point for UFC was set at 230. 15 icrog/24 h, with 92. 2 sensitivity and 95. 7% specificity (96. 1% sensitivity and 85. 1% specificity was achieved at 127. 55 microg/24 h). There was no significant difference between PTC-DST and PTC-24 h in the areas under the ROC curves, whereas both had a greater area under the ROC curve than that of UFC (P< 0. 05). CONCLUSION: Compared with the recommended 50 nmol/L cut-off point for PTC-DST in the USA and the European countries, the same sensitivity and a higher specificity can be achieved at a cut-off at 60 nmol/L for the Chinese people. PTC-DST and PTC-24 h have similar values in the initial diagnosis of Cushing's syndrome, but PTC-DST is more convenient to be used in outpatient environment.