Hepatic Klf10-Fh1 axis promotes exercise-mediated amelioration of NASH in mice.

Exercise is an effective non-pharmacological strategy for the treatment of nonalcoholic steatohepatitis (NASH), but the underlying mechanism needs further investigation. Kruppel-like factor 10 (Klf10) is a transcriptional factor that is expressed in multiple tissues including liver, whose role in NASH is not well defined. In our study, exercise induces hepatic Klf10 expression through the cAMP/PKA/CREB pathway. Hepatocyte-specific knockout of Klf10 (Klf10LKO) increases lipid accumulation, cell death, inflammation and fibrosis in NASH diet-fed mice and reduces the protective effects of treadmill exercise against NASH, while hepatocyte-specific overexpression of Klf10 (Klf10LTG) works in concert with exercise to reduce NASH in mice. Mechanistically, Klf10 promotes the expression of fumarate hydratase 1 (Fh1), thereby reducing fumarate accumulation in hepatocytes. This decreases the trimethyl (me3) levels of histone 3 lysine 4 (H3K4me3) on lipogenic genes promoters to attenuate lipogenesis, thus ameliorating free fatty acids (FFAs)-induced hepatocytes steatosis, apoptosis, insulin resistance and blunting dysfunctional hepatocytes-mediated activation of macrophages and hepatic stellate cells. Therefore, by regulating the Fh1/fumarate/H3K4me3 pathway, Klf10 acts as a downstream effector of exercise to combat NASH.

Comorbidities of Chronic Prurigo: A Systematic Review and Meta-Analysis.

BACKGROUND: Chronic prurigo (CPG) is an inflammatory skin disease. Comorbidities including dermatological, cardiovascular, and psychiatric diseases have been reported in patients with CPG; however, the evidence has not been systematically evaluated. We aim to summarize the comorbidities, discuss underlying pathogenesis, and highlight the evaluation of CPG patients. METHODS: We performed a systematic search using PubMed, Embase, and Web of Science databases for all articles reporting possible associated diseases with CPG. Pooled random-effects odds ratios (ORs) with 95% CI were calculated. RESULTS: A total of 17 studies were included in this systematic review. Statistically significant association (p <0.05) with CPG has been demonstrated with atopic diseases: atopic dermatitis (pooled OR, 10.91; 95% CI, 3.65-32.67), allergic rhinitis (2.66; 1.12-6.27), asthma (3.23; 1.55-6.74); infectious diseases: hepatitis B (pooled OR, 2.15; 95% CI, 1.11-4.14); endocrine diseases: diabetes (pooled OR, 4.93; 95% CI, 1.13-21.56), type 1 diabetes (2.46; 2.16-2.81), type 2 diabetes (1.89; 1.34-2.68), hyperlipoproteinemia (2.90; 1.61-5.22); cardiovascular diseases: heart failure (pooled OR, 4.13; 95% CI, 1.15-14.91), hypertension (3.17; 1.56-6.45); respiratory system diseases: chronic obstructive pulmonary disease (pooled OR, 3.19; 95% CI, 1.42-7.16); urinary system diseases: chronic kidney disease (pooled OR, 4.16; 95% CI, 1.79-9.66); digestive system disease: inflammatory bowel disease (pooled OR, 2.06; 95% CI, 1.26-3.36); and others: osteoporosis (pooled OR, 3.08; 95% CI, 1.70-5.59), thyroid disease (1.70; 1.17-2.47). CONCLUSION: CPG is associated with various systemic disorders. Recognition of comorbidities is critical to the appropriate management of affected patients.

Effectiveness of Dupilumab for Chronic Prurigo in Chinese Patients: A Real-World Case Series Study.

BACKGROUND: Treatment of chronic prurigo (CPG) is challenging. As an antagonist of IL-4R, dupilumab has shown effectiveness in treating CPG in several clinical studies. Recently, the US Food and Drug Administration (FDA) approved dupilumab for the treatment of prurigo nodularis (PN). OBJECTIVES: The purpose of this study was to examine the efficacy of dupilumab in Chinese patients with CPG, and to analyze the difference in response between subtypes of CPG. METHODS: This retrospective study included 18 patients with CPG who were treated with dupilumab for at least 16 weeks from March 2022 to October 2022. Disease severity and patient self-assessment questionnaires were assessed at baseline and each visit, including the peak Pruritus Visual Analogue Scale (PP-VAS), Prurigo Activity and Severity Score (PAS), Investigator Global Assessment (IGA), Dermatology Life Quality Index (DLQI), Hospital Anxiety and Depression Scale (HADS) and Itchy-specific Quality of Life questionnaire (ItchyQoL). RESULTS: After 2 weeks of dupilumab treatment, pruritus scores were significantly reduced as measured by PP-VAS scores. Prurigo Activity and Severity scores decreased significantly at Week 2, whereas IGA improved significantly at Week 8. The DLQI, HADS, and ItchyQoL scores at Week 16 also showed significant improvement from baseline. Patients in all subtypes showed improvement in pruritus and lesion severity. CONCLUSIONS: Dupilumab was effective in improving pruritus and lesions in patients with various subtypes of CPG.

Machine and deep learning-based clinical characteristics and laboratory markers for the prediction of sarcopenia.

BACKGROUND: Sarcopenia is an age-related progressive skeletal muscle disorder involving the loss of muscle mass or strength and physiological function. Efficient and precise AI algorithms may play a significant role in the diagnosis of sarcopenia. In this study, we aimed to develop a machine learning model for sarcopenia diagnosis using clinical characteristics and laboratory indicators of aging cohorts. METHODS: We developed models of sarcopenia using the baseline data from the West China Health and Aging Trend (WCHAT) study. For external validation, we used the Xiamen Aging Trend (XMAT) cohort. We compared the support vector machine (SVM), random forest (RF), eXtreme Gradient Boosting (XGB), and Wide and Deep (W&D) models. The area under the receiver operating curve (AUC) and accuracy (ACC) were used to evaluate the diagnostic efficiency of the models. RESULTS: The WCHAT cohort, which included a total of 4057 participants for the training and testing datasets, and the XMAT cohort, which consisted of 553 participants for the external validation dataset, were enrolled in this study. Among the four models, W&D had the best performance (AUC = 0.916 ± 0.006, ACC = 0.882 ± 0.006), followed by SVM (AUC =0.907 ± 0.004, ACC = 0.877 ± 0.006), XGB (AUC = 0.877 ± 0.005, ACC = 0.868 ± 0.005), and RF (AUC = 0.843 ± 0.031, ACC = 0.836 ± 0.024) in the training dataset. Meanwhile, in the testing dataset, the diagnostic efficiency of the models from large to small was W&D (AUC = 0.881, ACC = 0.862), XGB (AUC = 0.858, ACC = 0.861), RF (AUC = 0.843, ACC = 0.836), and SVM (AUC = 0.829, ACC = 0.857). In the external validation dataset, the performance of W&D (AUC = 0.970, ACC = 0.911) was the best among the four models, followed by RF (AUC = 0.830, ACC = 0.769), SVM (AUC = 0.766, ACC = 0.738), and XGB (AUC = 0.722, ACC = 0.749). CONCLUSIONS: The W&D model not only had excellent diagnostic performance for sarcopenia but also showed good economic efficiency and timeliness. It could be widely used in primary health care institutions or developing areas with an aging population. TRIAL REGISTRATION: Chictr.org, ChiCTR 1800018895.

[Value of Baseline Calcitonin for Differential Diagnosis of Medullary Thyroid Cancer].

Objective: To analyze the efficacy of using baseline calcitonin (bCtn) for auxiliary diagnosis of medullary thyroid cancer (MTC) in the hypercalcitoninemic population with thyroid nodules and to explore the relationship between preoperative levels of bCtn and carcinoembryonic antigen (CEA) and MTC staging. Methods: The clinical, pathological, imaging, and lab test data of 58 MTC patients and 84 non-MTC patients were retrospectively reviewed in the study. The patients were hospitalized at West China Hosptal, Sichuan University between 2011 and 2020. Receiver operating characteristic (ROC) curves were constructed to calculate the MTC diagnostic efficacy of bCtn and CEA. The differences in the preoperative bCtn and CEA levels of MTC patients with different primary tumor sites and regional lymph node involvement were compared. Results: The bCtn cutoff values were 31.54 pg/mL for men and 22.60 pg/mL for women for diagnosing MTC in the hypercalcitoninemic population with thyroid nodules. There were statistical differences in preoperative bCtn levels ( H=16.166, P=0.001) and in preoperative CEA levels ( H=9.447, P=0.024) in MTC patients of different T stages. There were statistical differences in preoperative bCtn levels ( H=7.919, P=0.019) and in preoperative CEA levels ( H=7.934, P=0.019) in MTC patients of different N stages. Conclusion: The best bCtn cutoff values for the diagnosis of MTC in the hypercalcitoninemic population with thyroid nodules and are 31.54 pg/mL for men and 22.60 pg/mL for women.

Determination of skeletal muscle mass by aspartate aminotransferase / alanine aminotransferase ratio, insulin and FSH in Chinese women with sarcopenia.

BACKGROUND: Sarcopenia is an age-related skeletal muscle disorder that involves a loss of muscle mass or strength and physiological function. Skeletal muscle deteriorates in both quantity and quality. The endocrine system is an important regulator of muscle metabolism. Therefore, we aimed to explore the relationship between biochemical markers and muscle mass in sarcopenia. METHODS: We used the AWGS 2014 as the diagnostic criteria for sarcopenia, considering both the loss in muscle mass, muscle strength and physical performance. A total of 2837 elderly female participants over 50 years of age from the West China Health and Aging Trend (WCHAT) study were included. Insulin, glucose, 25(OH)VD, procalcitonin, alanine aminotransferase, aspartate aminotransferase, total protein, prealbumin, albumin, thyroid-stimulating hormone, free triiodothyronine, free tetraiodothyronine, triglycerides, cholesterol, high-density lipoprotein, very low-density lipoprotein, cortisol, and follicle-stimulating hormone were measured. Based on the findings of univariate analysis, multivariate regression and receiver operating characteristic (ROC) curves were established. RESULTS: Participants with sarcopenia had significantly lower free triiodothyronine, insulin, total protein, albumin, prealbumin, albumin/prealbumin ratio (A/G), alanine aminotransferase, triglycerides, and very low-density lipoprotein concentrations (P < 0.05). Compared with those without sarcopenia, those with sarcopenia had significantly higher free tetraiodothyronine, cortisol, follicle-stimulating hormone (FSH), aspartate aminotransferase/alanine aminotransferase ratio (AST/ALT), and high-density lipoprotein concentrations (P < 0.05). Insulin (OR = 0.854), FSH (OR = 1.016), and the AST/ALT ratio (OR = 1.819) were independent risk factors for low muscle mass (P < 0.001). The AUC of insulin was the highest, followed by the AST/ALT ratio and FSH (0.691, 0.671, and 0.634, respectively), and the AUC of the mixture of the above three reached 0.736. CONCLUSION: In this cross-sectional study of elderly Chinese females aged over 50 years from the WCHAT, FSH, insulin, and AST/ALT ratio were associated with sarcopenia and risk factors for low muscle mass.

Corrigendum: Antithyroglobulin Antibody Variation During Follow-Up Has a Good Prognostic Value for Preoperative Antithyroglobulin Antibody-Positive Differentiated Thyroid Cancer Patients: A Retrospective Study in Southwest China.

[This corrects the article DOI: 10.3389/fendo.2021.774275.].

High Serum AST/ALT Ratio and Low Serum INS*PA Product Are Risk Factors and Can Diagnose Sarcopenia in Middle-Aged and Older Adults.

Background: Sarcopenia is an age-related clinical condition and associated with an increased risk of adverse outcomes. However, to date, there is no global standard for the diagnosis of sarcopenia, and fewer serum biomarkers have been suggested for the diagnosis of sarcopenia. It is, thus, important that sarcopenia-related serological diagnostic markers be explored. The present study was based on the Asian Working Group on Sarcopenia 2019 (AWGS 2019) criteria to assess whether aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio and fasting insulin*prealbumin (INS*PA) product are diagnostic markers associated with sarcopenia in various ethnic groups in western China. Methods: This cross-sectional study included 4,099 adults (1,471 men and 2,628 women) from the West China Health and Aging Trend (WCHAT) study. The value of serum biomarkers was based on laboratory data. The accompanying metabolic disorders and the associated parameters were evaluated. Logistic regression analysis was used to explore the association between markers and sarcopenia. Receiver operating characteristic curve (ROC) analysis was used to evaluate the diagnostic efficacy of the test in differentiating sarcopenia. Results: Binary regression analysis showed that high serum AST/ALT (OR = 2.247) and adrenal cortisol (PTC, OR = 1.511), low serum INS*PA (OR = 2.970), free triiodothyronine (FT3, OR = 1.313), 25-OH-VitD (VitD, in male participants, OR = 1.817), and diastolic blood pressure (DBP, in female subjects, OR = 1.250) were independent risk factors for sarcopenia (P < 0.05). AST/ALT and INS*PA were not affected by metabolic factors and had better diagnostic efficacy for sarcopenia. The AUC of the INS*PA was the highest (0.705, 0.706, and 0.701, respectively, P < 0.05), followed by that of the AST/ALT (0.680, 0.675, and 0.695, respectively, P < 0.05). The AUC of the AST/ALT/(INS*PA)*10,000 used to diagnose sarcopenia was 0.727. Conclusion: Among middle-aged and older adults of multiple ethnicities in western China, we found that higher AST/ALT and lower INS*PA levels are associated with an increased prevalence of sarcopenia. Since these serum biomarkers are inexpensive and can be obtained easily from biochemical routine, regular follow-up of AST/ALT and INS*PA may be an effective strategy in sarcopenia screening and management.

Carboxymethyl chitosan-grafted polyvinylpyrrolidone-iodine microspheres for promoting the healing of chronic wounds.

Chronic wounds that fail to heal are the most common complications experienced by diabetic patients, and current treatment remains unsatisfactory, mainly due to the vulnerability of diabetic wounds to bacterial infections. Chitosan derivatives are widely used to treat chronic wounds due to their excellent hydrophilicity, biodegradability, and antimicrobial activity and substantial contribution to tissue regeneration. However, the antimicrobial effect of chitosan is not sufficient due to the complicated pathological mechanism of diabetes mellitus. Here, we prepared carboxymethyl chitosan-grafted polyvinylpyrrolidone-iodine (CMC-g-PVPI) microspheres and used them to treat chronic wounds. Carboxymethyl chitosan (CMC) was used as the skeleton and was grafted with polyvinylpyrrolidone-iodine (PVPI) to form a CMC-g-PVPI complex hydrogel and CMC-g-PVPI microspheres, which formed as a result of the high shearing dispersion of the complex hydrogel. In vivo experiments on diabetic wounds revealed significantly accelerated wound closure in the presence of the microspheres, demonstrating the excellent potential of CMC-g-PVPI to promote skin wound regeneration under diabetic conditions.

Corrigendum: Diagnostic Performance of Clinical Laboratory Indicators With Sarcopenia: Results From the West China Health and Aging Trend Study.

[This corrects the article DOI: 10.3389/fendo.2021.785045.].

Diagnostic Performance of Clinical Laboratory Indicators With Sarcopenia: Results From the West China Health and Aging Trend Study.

Background: Sarcopenia is an age-related and skeletal muscle disorder involving the loss of muscle mass or strength, and physiological function. Although the diagnostic indicators used in the different guidelines are for muscle mass, strength and physical performance, there are currently no uniform diagnostic criteria. Therefore, we aimed to explore the relationship between a series of biomarkers with sarcopenia in southwest China. Methods: We included 4302 patients from West China Health and Aging Trend (WCHAT) study. Sarcopenia was defined according to the Asian Working Group for Sarcopenia: 2019 Consensus Update on Sarcopenia Diagnosis and Treatment. Thyroxine、albumin、total protein、prealbumin、albumin to globulin ratio (A/G)、25(OH)VD、fasting insulin、adrenal cortisol、triglyceride、high-density lipoprotein、hemoglobin and aspartate aminotransferase to alanine aminotransferase ratio (AST/ALT) were measured. The receiver operating characteristic curves (ROC) were established to describe the predictive value for sarcopenia and we also used multivariate logistic regression analysis to identify risk factors of the disease. Results: In terms of protein state, patients with sarcopenia had lower value in total protein, albumin, prealbumin, A/G than the control (P<0.001). Patients had lower value in triglyceride but higher value in high-density lipoprotein compared with the healthy in the indicators of lipid metabolism (P<0.001). In the aspect of hormone state, patients had lower free triiodothyronine, fasting insulin but higher free tetraiodothyronine and adrenal cortisol than the healthy (P<0.001). The fasting insulin level (AUC=0.686) and the AST/ALT ratio (AUC=0.682) were the best predictors of sarcopenia among biomarkers. The diagnostic performance of fasting insulin combined with the AST/ALT ratio (AUC=0.720) is equal to multiple indicators (AUC=0.742). Conclusion: The fasting insulin combined with the AST/ALT ratio exhibits good diagnostic performance for sarcopenia.

Multifunctional Magnesium Organic Framework-Based Microneedle Patch for Accelerating Diabetic Wound Healing.

Diabetic wound healing is one of the major challenges in the biomedical fields. The conventional single drug treatments have unsatisfactory efficacy, and the drug delivery effectiveness is restricted by the penetration depth. Herein, we develop a magnesium organic framework-based microneedle patch (denoted as MN-MOF-GO-Ag) that can realize transdermal delivery and combination therapy for diabetic wound healing. Multifunctional magnesium organic frameworks (Mg-MOFs) are mixed with poly(γ-glutamic acid) (γ-PGA) hydrogel and loaded into the tips of MN-MOF-GO-Ag, which slowly releases Mg2+ and gallic acid in the deep layer of the dermis. The released Mg2+ induces cell migration and endothelial tubulogenesis, while gallic acid, a reactive oxygen species-scavenger, promotes antioxidation. Besides, the backing layer of MN-MOF-GO-Ag is made of γ-PGA hydrogel and graphene oxide-silver nanocomposites (GO-Ag) which further enables excellent antibacterial effects for accelerating wound healing. The therapeutic effects of MN-MOF-GO-Ag on wound healing are demonstrated with the full-thickness cutaneous wounds of a diabetic mouse model. The significant improvement of wound healing is achieved for mice treated with MN-MOF-GO-Ag.

Diagnostic performance of the calcium/phosphate ratio for primary hyperparathyroidism in southwest China.

BACKGROUND: The diagnosis of primary hyperparathyroidism (PHPT) remains a challenge because of increased asymptomatic PHPT or patients with normocalcaemic PHPT (NPHPT). In addition, some primary hospitals in China have no equipment to measure parathyroid hormone (PTH) levels. Therefore, an additional, simple, and inexpensive laboratory biochemical marker is urgently needed. The calcium/phosphate (Ca/P) ratio and chloride/phosphate (Cl/P) ratio have been proposed as suitable tools to diagnose PHPT in Europe; however, the Ca/P ratio has never been tested in China. We aimed to conduct a confirmatory study to explore the diagnostic performance of the Ca/P ratio for PHPT in China. METHODS: From January 2015 to December 2020, a total of 155 patients who underwent parathyroidectomy (143 PHPT patients and 12 NPHPT patients) and 153 controls were enrolled in this single-center , retrospective study. Serum calcium, phosphate, parathyroid hormone, 25-hydroxyvitamin vitamin D (25(OH) vitamin D), chloride, alanine transaminase (ALT), aspartate aminotransaminase (AST), estimated glomerular filtration rate (eGFR), and creatinine levels were recorded for all the study participants. Pairwise comparisons were made between groups, and the diagnostic performance of the Ca/P ratio was determined using receiver-operating characteristic (ROC) analysis. RESULTS: Patients with PHPT had a higher Ca/P ratio than controls (P < 0.001). A Ca/P ratio above 2.94 with a sensitivity of 95.5% and specificity of 98.7% can distinguish PHPT patients from healthy individuals. This index was positively correlated with the PTH level (r = 0.875, P < 0.001). CONCLUSION: The Ca/P ratio is an ideal and inexpensive indicator for diagnosing PHPT in China when using a cut-off value of 2.94.

Antithyroglobulin Antibody Variation During Follow-Up Has a Good Prognostic Value for Preoperative Antithyroglobulin Antibody-Positive Differentiated Thyroid Cancer Patients: A Retrospective Study in Southwest China.

Objective: Antithyroglobulin antibody (TgAb) is a potential tumour marker for detecting differentiated thyroid cancer (DTC) recurrence, but insufficient data have supported its clinical applications. Our study aimed to describe the changing trend of TgAb after surgery and identify the relationship between this trend and clinical outcomes. Patients and Methods: We reviewed the electronic records of 1,686 DTC patients who had undergone total thyroidectomy (TT) and radioactive iodine (131I) therapy at West China Hospital of Sichuan University from January 2015 to December 2017. Finally, 289 preoperative TgAb-positive DTC patients were included and divided into four subgroups depending on the clinical outcome: Group A (tumour free), Group B (uncertain), Group C (incomplete biochemical response), and Group D (structural disease). The patient demographics, tumour characteristics, operations, pathology reports, and all serological biomarkers were reviewed and compared, and the prognostic efficacy of TgAb was evaluated. Results: Among all 1,686 patients, 393 (23.65%) were TgAb positive (>40 IU/ml) preoperatively. The TgAb level in Group A decreased significantly after surgery and 131I therapy and stabilised at a low level after 1-2 years of 131I therapy. However, in the other three groups, the decrease in TgAb was not significant after treatment. Conversely, TgAb declined slowly and remained stable or increased. The variations in TgAb relative to the preoperative level of Group A were significantly larger than those of Groups B, C, and D at most time points of follow-up (p < 0.001). By receiver operating characteristic (ROC) analyses, the variations of TgAb > -77.9% at 6 months after 131I therapy (area under the curve (AUC) = 0.862; p < 0.001) and TgAb > -88.6% at 2 years after 131I therapy (AUC = 0.901; p < 0.001) had good prognostic efficacy in tumour-free survival. When the variation in TgAb > -88.6% at 2 years after 131I therapy was incorporated as a variable in the American Thyroid Association (ATA) categories, both intermediate- and high-risk patients also had a significantly increased chance of being tumour free (from 75.68% to 93.88% and 42.0% to 82.61%, respectively). Conclusions: For preoperative TgAb-positive DTC patients, variations in TgAb > -77.9% at 6 months after 131I therapy and TgAb > -88.6% at 2 years after 131I therapy had good prognostic efficacy. Their incorporation as variables in the ATA risk stratification system could more accurately predict disease-free survival.

Molecularly imprinted photoelectrochemical sensing based on ZnO/polypyrrole nanocomposites for acrylamide detection.

A highly sensitive quenching molecular imprinting (MIP) photoelectrochemical (PEC) sensor was proposed to detect acrylamide (AM) by using the photoactive composite of ZnO and polypyrrole (PPy) as the PEC signal probe. ZnO, with high electron mobility, excellent chemical and thermal stability as well as good biocompatibility, was selected as the photoelectrically active material. A polypyrrole film was formed on the nanodisk ZnO by electrochemical polymerization, and the recognition site of AM was left on the surface of the PPy film by elution, enabling the specific detection of AM. The transfer of electrons will be hindered when AM is adsorbed on the ZnO/PPy nanocomposites surface, which results in the decrease of photocurrent signal. The proposed molecularly imprinted PEC sensor exhibits significant detection performance of AM in the range of 10-1 M-2.5 × 10-9 M with a LOD of 2.147 × 10-9 M (S/N = 3). The use of photoelectrochemical technology combined with molecular imprinting technology enables the PEC sensor to have excellent selectivity, superior repeatability, preferable stability, low cost, and easy construction, providing a new method for the detection of AM. The high recovery rate in the detection of real samples of potato chips and biscuits indicates that the proposed PEC sensor has potential in monitoring the emerging food safety risks.