Menopausal hormone therapy and women's health: An umbrella review.

BACKGROUND: There remains uncertainty about the impact of menopausal hormone therapy (MHT) on women's health. A systematic, comprehensive assessment of the effects on multiple outcomes is lacking. We conducted an umbrella review to comprehensively summarize evidence on the benefits and harms of MHT across diverse health outcomes. METHODS AND FINDINGS: We searched MEDLINE, EMBASE, and 10 other databases from inception to November 26, 2017, updated on December 17, 2020, to identify systematic reviews or meta-analyses of randomized controlled trials (RCTs) and observational studies investigating effects of MHT, including estrogen-alone therapy (ET) and estrogen plus progestin therapy (EPT), in perimenopausal or postmenopausal women in all countries and settings. All health outcomes in previous systematic reviews were included, including menopausal symptoms, surrogate endpoints, biomarkers, various morbidity outcomes, and mortality. Two investigators independently extracted data and assessed methodological quality of systematic reviews using the updated 16-item AMSTAR 2 instrument. Random-effects robust variance estimation was used to combine effect estimates, and 95% prediction intervals (PIs) were calculated whenever possible. We used the term MHT to encompass ET and EPT, and results are presented for MHT for each outcome, unless otherwise indicated. Sixty systematic reviews were included, involving 102 meta-analyses of RCTs and 38 of observational studies, with 102 unique outcomes. The overall quality of included systematic reviews was moderate to poor. In meta-analyses of RCTs, MHT was beneficial for vasomotor symptoms (frequency: 9 trials, 1,104 women, risk ratio [RR] 0.43, 95% CI 0.33 to 0.57, p < 0.001; severity: 7 trials, 503 women, RR 0.29, 95% CI 0.17 to 0.50, p = 0.002) and all fracture (30 trials, 43,188 women, RR 0.72, 95% CI 0.62 to 0.84, p = 0.002, 95% PI 0.58 to 0.87), as well as vaginal atrophy (intravaginal ET), sexual function, vertebral and nonvertebral fracture, diabetes mellitus, cardiovascular mortality (ET), and colorectal cancer (EPT), but harmful for stroke (17 trials, 37,272 women, RR 1.17, 95% CI 1.05 to 1.29, p = 0.027) and venous thromboembolism (23 trials, 42,292 women, RR 1.60, 95% CI 0.99 to 2.58, p = 0.052, 95% PI 1.03 to 2.99), as well as cardiovascular disease incidence and recurrence, cerebrovascular disease, nonfatal stroke, deep vein thrombosis, gallbladder disease requiring surgery, and lung cancer mortality (EPT). In meta-analyses of observational studies, MHT was associated with decreased risks of cataract, glioma, and esophageal, gastric, and colorectal cancer, but increased risks of pulmonary embolism, cholelithiasis, asthma, meningioma, and thyroid, breast, and ovarian cancer. ET and EPT had opposite effects for endometrial cancer, endometrial hyperplasia, and Alzheimer disease. The major limitations include the inability to address the varying effects of MHT by type, dose, formulation, duration of use, route of administration, and age of initiation and to take into account the quality of individual studies included in the systematic reviews. The study protocol is publicly available on PROSPERO (CRD42017083412). CONCLUSIONS: MHT has a complex balance of benefits and harms on multiple health outcomes. Some effects differ qualitatively between ET and EPT. The quality of available evidence is only moderate to poor.

Effect of sarcolipin-mediated cell transdifferentiation in sarcopenia-associated skeletal muscle fibrosis.

Fibrosis is a key pathological event during muscle aging that accelerates the development of sarcopenia. We show that sarcolipin (SLN) is highly expressed during aging, promotes intracellular calcium overload and participates in impaired myogenic differentiation. d-Galactose (D-gal) was used to induce senescence in C2C12 myoblasts. Conventional AAV-mediated SLN knockdown cells were used to study the role of SLN in muscle physiology and pathophysiology. C2C12 cells were treated with D-gal, which promoted fibrosis and SLN upregulation. The expression of TGF-ß1 and α-SMA, which participate in myogenic transdifferentiation, were also elevated. C2C12 cells with reduced sarcolipin expression produced decreased amounts of collagen. Our study identified an unrecognized role of SLN in regulating myogenic transdifferentiation during aging-associated skeletal muscle cell fibrosis. Targeting SLN may be a novel therapeutic strategy to relieve sarcopenia-associated muscle fibrosis.

Fish intake during pregnancy or infancy and allergic outcomes in children: A systematic review and meta-analysis.

It has been suggested that n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs) have anti-inflammatory properties and may reduce the risk of allergic disease. Fish is a great source of n-3 LC-PUFAs. However, the effect of fish on allergic disease remains controversial. PubMed, EMBASE, and Cochrane Central Register of Controlled Trials were searched for randomized controlled trials (RCTs) and prospective cohort studies regarding the effect of fish intake during pregnancy or infancy on allergic outcomes in children. The outcomes of interest were atopy, eczema, allergic rhinitis, wheeze, asthma, and food allergy. One RCT and 17 publications from 13 prospective cohort studies were included for maternal fish intake during pregnancy, and eight publications from five prospective cohort studies for fish intake in infancy. Pooled analysis suggested that maternal fish intake during pregnancy was not associated with lower risk of any allergic outcome, both in RCT and observational studies. Consumption of fish during the first year of life reduced the risk of eczema (RR 0.61; 95% CI 0.47, 0.80; p = 0.0003; I2  = 68%) and allergic rhinitis (RR 0.54; 95% CI 0.36, 0.81; p = 0.003; I2  = 74%). Current evidence indicates that fish intake in infancy could reduce the risk of eczema and allergic rhinitis in children, whereas maternal fish intake during pregnancy does not affect any atopic outcome. The intake of fish per se in infancy, not specially n-3 LC-PUFAs, may have an allergy protective effect. High-quality and adequately powered RCTs are warranted to confirm this.

Value of Endobronchial Ultrasound Elastography in Diagnosis of Central Lung Lesions.

BACKGROUND Ultrasound elastography is an imaging modality used to show tissue stiffness in tumor pathophysiological processes that promote the formation of stiffer tissues. Endobronchial ultrasound (EBUS) elastography is an ultrasound elastography-based technique for measuring tissue stiffness during EBUS-guided transbronchial needle aspiration (EBUS-TBNA). The diagnostic value of EBUS elastography in central lung lesions remains largely unknown. MATERIAL AND METHODS A total of 57 patients with central lung lesions underwent ultrasonic bronchoscope examination. EBUS with standard B mode evaluation and elastography with grading score measurement were performed before EBUS-guided transbronchial needle aspiration (EBUS-TBNA). Comparison of the diagnosis accuracy in malignant lung lesions between elastography and standard EBUS was made. RESULTS Our data showed that the hypoechoic lesions, uneven echo, distinct boundary, and no air bronchogram were significant indicators of standard EBUS in diagnosis of malignant lung lesions (P<0.01). The differences in elastosonography grading scores between the benign and malignant lung lesions were statistically significance (P<0.01), and the elastography grading score was more sensitive and specific than the standard EBUS criteria in diagnosing malignant lung lesions. The area under the receiver operating characteristic curve (ROC) for the elastography grading score was 0.793. The best cut-off point of the elastography grading score for distinguishing malignant from benign lung lesions was 2.5. The elastography grading score had a sensitivity of 72.2%, specificity of 76.2%, positive predictive value of 83.4%, and negative predictive value of 61.5% for distinguishing malignant from benign lung lesions. The overall accuracy of elastography grading score was 73.7%. CONCLUSIONS BUS elastography can effectively diagnose central lung lesions. The diagnostic accuracy of elastography in malignant lung lesions is higher than that of standard EBUS criteria.

The effect of vitamin A on renal damage following acute pyelonephritis in children: a meta-analysis of randomized controlled trials.

BACKGROUND: Renal scarring after acute pyelonephritis (APN) in children is of concern and in the worst cases leads to long-term cardiovascular morbidity. There are reports that vitamin A may alleviate renal damage following APN. We conducted a meta-analysis to investigate the role of vitamin A in the alleviation of renal damage. METHODS: We searched PubMed, EMBASE, the Cochrane Central Register of Controlled trials (CENTRAL, the Cochrane Library) and the Wang Fang database (Chinese) from their inception to February 3, 2015 for randomized controlled trials (RCTs) investigating vitamin A and renal damage. Primary outcome was number of patients/kidneys with renal damage, defined as persistence of photopenic lesions based on technetium-99m dimercaptosuccinic acid renal scintigraphy. We calculated pooled relative risks for renal damage in the vitamin A group. RESULTS: Four RCTs, involving a total of 248 patients aged 1-144 months (120 in experimental group, 128 in control group), were included in the meta-analysis. Vitamin A was inversely associated with renal damage (relative risk 0.53, 95 % confidence interval 0.43, 0.67) when compared with placebo group after an average follow-up of 5 months. CONCLUSIONS: Current evidence indicates that vitamin A may exert a preventive effect on renal damage in children with APN. However, this finding largely relies on a few studies of low methodological quality, i.e., high risk of selection bias, performance bias and attrition bias. Hence, high-quality and adequately powered RCTs are warranted.

Development and validation of a rapid LC-MS/MS method to quantify letrozole in human plasma and its application to therapeutic drug monitoring.

A selective, rapid, and sensitive liquid chromatography-tandem mass spectrometry(LC-MS/MS) method was developed and validated for the determination of letrozole (LTZ) in human plasma, using anastrozole as internal standard (IS). Sample preparation was performed by one-step protein precipitation with methanol. The analyte and IS were chromatographed on a reversed-phase YMC-ODS-C18 column (2.0 × 100 mm i.d., 3 µm) with a flow rate of 0.3 mL/min. The mobile phase consisted of water containing 0.1% formic acid (v/v) and methanol containing 0.1% formic acid (v/v). The mass spectrometer was operated in selected reaction monitoring mode through electrospray ionization ion mode using the transitions of m/z 286.2 → 217.1 for LTZ and m/z 294.1 → 225.1 for IS, respectively. The method was validated for selectivity, linearity, lower limit of quantitation, precision, accuracy, matrix effects and stability in accordance with the US Food and Drug Administration guidelines. Linear calibration curves were 1.0-60.0 ng/mL. Intra- and inter-batch precision (CV) for LTZ were <9.34%, and the accuracy ranged from 97.43 to 105.17%. This method was successfully used for the analysis of samples from patients treated with LTZ in the dose of 2.5 mg/day. It might be suitable for therapeutic drug monitoring of these patients and contribute to predict the risk of adverse reactions.

Simultaneous quantification of olanzapine and its metabolite N-desmethylolanzapine in human plasma by liquid chromatography tandem mass spectrometry for therapeutic drug monitoring.

A simple, sensitive, and selective liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous quantification of olanzapine (OLZ) and its metabolite N-desmethylolanzapine (DMO) in human plasma for therapeutic drug monitoring. Sample preparation was performed by one-step protein precipitation with methanol. The analytes were chromatographed on a reversed-phase YMC-ODS-AQ C18 Column (2.0 × 100 mm,3 µm) by a gradient program at a flow rate of 0.30 mL/min. Quantification was performed on a triple quadrupole tandem mass spectrometer via electrospray ionization in positive ion mode. The method was validated for selectivity, linearity, accuracy, precision, matrix effect, recovery and stability. The calibration curve was linear over the concentration range 0.2-120 ng/mL for OLZ and 0.5-50 ng/mL for DMO. Intra- and interday precisions for OLZ and DMO were <11.29%, and the accuracy ranged from 95.23 to 113.16%. The developed method was subsequently applied to therapeutic drug monitoring for psychiatric patients receiving therapy of OLZ tablets. The method seems to be suitable for therapeutic drug monitoring of patients undergoing therapy with OLZ and might contribute to prediction of the risk of adverse reactions.

Antioxidative responses of Pseudomonas fluorescens YZ2 to simultaneous exposure of Zn and Cefradine.

Binary pollution of both heavy metals and antibiotics has received increasing attentions for their joint effects of eco-toxicity and health hazards. To reveal the effects of mixtures of different pollutants on bacterial antioxidant response system, Pseudomonas fluorescens ZY2, a new strain isolated from swine wastewater, was chosen to determinate growth (bacterial density OD600), reactive oxygen species (ROS) concentration, protein concentration and superoxide dismutase (SOD) activity under exposure treatments of Zn, Cefradine or Zn + Cefradine. Bacterial densities of all the treatment groups increased significantly over the incubation time, but those containing pollutant addition were slightly lower than the control at different times of incubation. Both ROS concentration and SOD activity increased first and then decreased (p < 0.01) over time, which was opposite to the protein concentrations (p < 0.01), showing a much significant increase by Cefradine alone. With Zn concentration increasing from 40 to 160 mg/L, the intracellular SOD activity increased as a response to the improvement of ROS (p < 0.05), while the balance between ROS and SOD was broken down due to the disproportionate change of total SOD activity and ROS concentration, the bacterial densities therefore decreased for the weak resistance. With the combined treatment of Zn (200 mg/L) and Cefradine (1 mg/L), though the toxicity of Zn caused a much significant increase of ROS, the bacterial resistance was further improved showing a more significant increase of total SOD activity and the bacterial densities therefore increased bacterial growth. Zn concentration also affected the protein synthesis. Either single or binary stress induced the bacterial resistance by regulating SOD activity to eliminate ROS. All results of the bacterial oxidant stress, SOD response and protein synthesis in the combined treatment groups were more complicated than those in single treatment groups, which depended on the properties of the single treatment as well as the interaction between the two treatments upon bacterial activity. For P. fluorescens ZY2, the mediation of SOD activity to eliminate ROS in response to the combined exposure to Zn and Cefradine was first revealed as one of the co-resistance mechanisms, which is informative to further understanding the risk of antibiotics resistant bacteria to human and environmental health more accurately.

Pharmacokinetics and bioequivalence study of three oral formulations of ambroxol 30 mg: a randomized, three-period crossover comparison in healthy volunteers.

OBJECTIVE: To compare the pharmacokinetic properties of two newly developed generic ambroxol formulations with a branded innovator product in healthy Chinese male volunteers. METHODS: This was a single-dose, randomized, open-label, three-period crossover study in healthy volunteers aged 18 - 45 years under fasting conditions. Subjects were assigned to receive 1 of 2 test formulations or a reference tablet of ambroxol 30 mg. Each study period was separated by a 1-week washout phase. Blood samples were collected at pre-specified times. A non-compartmental method was employed to determine pharmacokinetic properties (C(max), t(max), AUC(0-tlast), AUC(0-∞)) to test for bioequivalence. The predetermined regulatory range of 90% CI for bioequivalence was 80 - 125%. RESULTS: 24 subjects were enrolled in and completed the study. The geometric mean C(max) values for the test tablet, test capsule, and reference product were 82.73, 85.36, 84.56 ng/mL, and their geometric mean AUC(0-tlast) (AUC(0-∞)) were 660.87 (753.49), 678.98 (756.79), and 639.41 (712.14) ng x h/mL, respectively. For test tablet vs. reference, the 90% CIs of the least squares mean test/reference ratios of C(max), AUC(0-tlast), and AUC(0-∞) were 91.2% to 104.9%, 96.5% to 110.7%, and 98.8% to 113.4%, respectively. For test capsule, the corresponding values were 94.1% to 108.3%, 99.2% to 113.7%, and 99.2% to 113.9%, respectively. No adverse events occurred during the study. CONCLUSIONS: The ambroxol 30 mg tablets and capsules were considered bioequivalent to the reference formulation in accordance with predetermined regulatory criteria.

[Effects of xuebijing on nitric oxide and VEGF-A in exhaled breath condensate of patients with ALI/ARDS].

OBJECTIVE: To observe the clinical significance of changes of nitric oxide (NO) and vascular endothelial growth factor A (VEGF-A) in exhaled breath condensate (EBC) of patients with acute lung injury/acute respiratory distress syndrome (ALI/ARDS) after they were treated by Xuebijing (XBJ), and to evaluate the effect of the EBC detection technology. METHODS: Totally 32 ALI/ARDS patients receiving mechanical ventilation at intensive care unit (ICU) were randomly assigned to the treatment group and the control group, 16 cases in each group. Patients in the control group were treated by routine therapy, while those in the treatment group were treated by routine therapy + XBJ. The therapeutic course for all was 5 days. The EBC sample was collected by improved EcoScreen condenser within 24 h after confirmed diagnosis of ALI/ARDS and on the fifth day of medication. The levels of NO and VEGF-A were measured by EIA in EBC and serum. The changes of NO and VEGF-A in EBC were observed before and after treatment. RESULTS: Compared with before treatment, the level of NO in EBC and serum decreased and VEGF-A increased after treatment, showing statistical difference (P < 0.05, P < 0.01). After treatment the level of NO in EBC and serum was lower in the treatment group than in the control group (P < 0.05). The VEGF-A in EBC was higher in the treatment group than in the control group (P < 0.05). There was no statistical difference in the serum VEGF-A level between the two groups (P > 0.05). CONCLUSIONS: XBJ was an effective therapeutic drug capable to control the in vivo inflammation reaction in patients with ALI/ARDS. The detection of changes of VEGF-A and NO levels by EBC could judge the inflammatory reaction degree in ALI/ARDS patients, and help evaluating the therapeutic effect.

Pharmacokinetic and Bioequivalence Evaluation of 2 Tadalafil Tablets in Healthy Male Chinese Subjects Under Fasting and Fed Conditions.

Tadalafil is an effective, reversible, and competitive phosphodiesterase 5 inhibitor mainly used to treat erectile dysfunction. This study investigated the bioequivalence of generic and marketed formulations of 10-mg tadalafil tablets under fasted and fed conditions. This open-label, randomized, single-dose, 2-period crossover study included 53 healthy Chinese men (aged 20-43 years). Plasma samples were collected from 0.5 hours before treatment to 72 hours after each dose and analyzed using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry. Pharmacokinetic parameters were calculated using noncompartmental analysis. Safety assessments were performed throughout the study. For the fasted state, the 90% confidence intervals of the geometric mean ratios between the generic and marketed formulations were 86.1% to 99.1% for the maximum plasma concentration and 88.4% to 100.3% for the area under the plasma concentration-time curve from time 0 to infinity, and the corresponding values under the fed state were and 99.9% to 108.4% and 95.7% to 104.3%, respectively. All data were within the accepted bioequivalence range of 80% to 125%. After consuming high-fat, high-calorie meals in the fed condition, the time to the maximum plasma concentration was similar between the formulations, and area under the plasma concentration-time curve from time 0 to infinity and maximum plasma concentration were 10.2% and 6.55% higher, respectively, for the marketed formulation. Thus, food had no clinically relevant effect on tadalafil exposure following a single oral dose in healthy Chinese men. No serious adverse reactions were reported. These results indicated that the analyzed generic and marketed tadalafil tablets were bioequivalent with similar safety profiles.

The Whole-transcriptome Landscape of Diabetes-related Sarcopenia Reveals the Specific Function of Novel lncRNA Gm20743.

While the exact mechanism remains unclear, type 2 diabetes mellitus increases the risk of sarcopenia which is characterized by decreased muscle mass, strength, and function. Whole-transcriptome RNA sequencing and informatics were performed on the diabetes-induced sarcopenia model of db/db mice. To determine the specific function of lncRNA Gm20743, the detection of Mito-Sox, reactive oxygen species, Ethynyl-2'-deoxyuridine, and myosin heavy chain was performed in overexpressed and knockdown-Gm20743 C2C12 cells. RNA-seq data and informatics revealed the key lncRNA-mRNA interactions and indicated a potential regulatory role of lncRNAs. We characterized three core candidate lncRNAs Gm20743, Gm35438, 1700047G03Rik, and their potential function. Furthermore, the results suggested lncRNA Gm20743 may be involved in regulating mitochondrial function, oxidative stress, cell proliferation, and myotube differentiation in skeletal muscle cells. These findings significantly improve our understanding of lncRNAs that may mediate muscle mass, strength, and function in diabetes and represent potential therapeutic targets for diabetes-induced sarcopenia.

Decomposition of organic matter by the ericoid mycorrhizal endophytes of Formosan rhododendron (Rhododendron formosanum Hemsl.).

Ericoid mycorrhizas are associated with a number of host plants in the Ericaceae in high-elevation regions of Taiwan. The ability of these microorganisms to thrive in harsh environmental conditions in the regions implies their capability of decomposing plant organic matter (raw humus). The objective of this study was to investigate the decomposition characteristics of three ericoid mycorrhizal endophytes isolated from the roots of Formosan rhododendron (Rhododendron formosanum Hemsl.). Molecular analysis indicated that strains Rf9 and Rf32 belong to the genus Cryptosporiopsis while strain Rf28 is a member of the genus Phialocephala. Mycorrhizal synthesis experiment showed that the roots of synthesized seedlings produced hyphal coils, a characteristic of ericoid mycorrhiza. Decomposition ability analysis revealed that strains Rf28 and Rf32 had the highest rates of decomposition of organic matter (up to 10.4% after 70 days) while the value for strain Rf9 was about 6.8%. Consistently, these strains secreted extracellular oxidases when cultured on tannic acid medium. Enzyme assay revealed that strains Rf28 and Rf32 secreted peroxidase, laccase, tyrosinase, and cellulase, but strain Rf9 secreted mainly peroxidase and tyrosinase. Apparently, the differences in secreted hydrolytic enzymes among the three endophytes are related to their ability to decompose organic matter. In the mycorrhizal synthesis experiment, all inoculated seedlings survived in the organic matter substrate for 70 days and exhibited a stronger vigor than the control. This study demonstrated that these three isolated endophytes, Rf9, Rf28, and Rf32, are ericoid mycorrhizal fungi, capable of forming ericoid mycorrhiza with Formosan rhododendron. Meanwhile, all three endophytes can secrete hydrolytic enzymes to decompose organic matter for growth, presumably a prerequisite for the adaptation of Formosan rhododendron to the harsh environments of high elevation.

Fibrinogen, fibrin degradation products and risk of sarcopenia.

BACKGROUND & AIMS: Increasing data suggests that chronic low-grade inflammation plays an important role on development of sarcopenia. The present study was designed to identify the association between fibrinogen, fibrin degradation products (FDP) and sarcopenia risk in hospitalized old patients. METHODS: A total of 437 patients were enrolled in this cross-sectional study (148 with sarcopenia and 289 without sarcopenia). Sarcopenia was diagnosed according to the Asian Working Group for Sarcopenia (AWGS) 2019 criteria. Body composition, grip strength and gait speed were performed to participants. Fibrinogen, FDP levels were measured. Logistic regression analyses were carried out to assess the association between fibrinogen and sarcopenia, between FDP and sarcopenia, respectively. RESULTS: Compared to non-sarcopenic patients, fibrinogen and FDP levels were found to be higher in the sarcopenic group (3.07 g/L vs 2.79 g/L, 1.75 µg/mL vs 1.00 µg/mL, respectively, p < 0.05). Multiple linear regression analysis showed a significant negative association between fibrinogen and gait speed (ß: -0.164, p = 0.008), and muscle strength (ß: -0.231, p < 0.001). Multivariable logistic regression analysis showed that fibrinogen and FDP were independently associated with sarcopenia (odds ratio 1.32 [95% confidence interval 1.03, 1.70], p = 0.009; odds ratio 1.07 [95% confidence interval 1.01, 1.19], p = 0.049, respectively). ROC curve revealed that the cutoff values of fibrinogen and FDP to predict sarcopenia risk were 2.54 g/L and 1.15 µg/mL, respectively. CONCLUSIONS: In hospitalized old patients, serum fibrinogen and FDP levels are elevated in sarcopenia patients than those without sarcopenia. Fibrinogen and FDP are associated with sarcopenia in a concentration-dependent manner.

Role of Farnesoid X Receptor in the Pathogenesis of Respiratory Diseases.

Farnesoid X receptor (FXR) is a bile acid receptor encoded by the Nr1h4 gene. FXR plays an important role in maintaining the stability of the internal environment and the integrity of many organs, including the liver and intestines. The expression of FXR in nondigestible tissues other than in the liver and small intestine is known as the expression of "nonclassical" bile acid target organs, such as blood vessels and lungs. In recent years, several studies have shown that FXR is widely involved in the pathogenesis of various respiratory diseases, such as chronic obstructive pulmonary disease, bronchial asthma, and idiopathic pulmonary fibrosis. Moreover, a number of works have confirmed that FXR can regulate the bile acid metabolism in the body and exert its anti-inflammatory and antifibrotic effects in the airways and lungs. In addition, FXR may be used as a potential therapeutic target for some respiratory diseases. For example, FXR can regulate the tumor microenvironment by regulating the balance of inflammatory and immune responses in the body to promote the occurrence and development of non-small-cell lung cancer (NSCLC), thereby being considered a potential target for immunotherapy of NSCLC. In this article, we provide an overview of the internal relationship between FXR and respiratory diseases to track the progress that has been achieved thus far in this direction and suggest potential therapeutic prospects of FXR in respiratory diseases.

The value of red blood cell distribution width, neutrophil-to-lymphocyte ratio, and hemoglobin-to-red blood cell distribution width ratio in the progression of non-small cell lung cancer.

BACKGROUND: Lung cancer is the leading cause of cancer-related deaths worldwide, with non-small cell lung cancer (NSCLC) accounting for 85% of all lung cancer cases. Inflammation has been proven to be one of the characteristics of malignant tumors. Chronic inflammatory response mediated by cytokines in the tumor microenvironment is an important factor in tumorigenesis. The purpose of this study was to observe and evaluate the value of red blood cell distribution width (RDW), neutrophil-to-lymphocyte ratio (NLR), and hemoglobin-to-red blood cell distribution width ratio (HRR) in the progression of NSCLC. METHODS: A total of 245 patients with NSCLC, 97 patients with benign pulmonary nodules, and 94 healthy volunteers were included in this study. Factors, such as age, gender, smoking history, histological type, lymph node metastasis, distant metastasis, TNM stage, and differentiation degree were statistically analyzed. The correlation of RDW, NLR, and HRR of patients with NSCLC with other clinical experimental parameters were also analyzed. Then, the diagnostic value of RDW, NLR, and HRR in the progression of NSCLC was evaluated. RESULTS: RDW, NLR, and HRR could be used to distinguish patients with NSCLC from healthy controls (p < 0.05). In addition, only the RDW in the NSCLC group with III-IV stage was significantly different from that in the benign pulmonary nodules group (p = 0.033), while NLR and HRR could significantly distinguish patients with NSCLC and benign pulmonary nodules (p < 0.001). RDW and NLR were positively correlated with NSCLC stage, whereas HRR was negatively correlated with NSCLC stage. RDW, NLR, and HRR were also significantly associated with the differentiation degree of NSCLC (p < 0.05). The ROC curve analysis showed that the combination of RDW with NLR, HRR, and CEA could show significantly higher diagnostic value than any one marker alone (AUC = 0.925, 95% CI: 0.897-0.954, and sensitivity and specificity of 79.60% and 93.60%, respectively). CONCLUSION: RDW, NLR, and HRR can be utilized as simple and effective biomarkers for the diagnosis and evaluation of NSCLC progression.

Clinical value of exhaled breath condensate let-7 in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is one of the most common causes of tumor-associated mortality worldwide. Early diagnosis is the key focus for improving prognosis. In the present study, the association between exhaled breath condensate (EBC) let-7 and NSCLC diagnosis and clinicopathologic characteristics was investigated in order to explore non-invasive simple technological therapeutic methods. The expression levels of let-7 from 180 samples were analyzed using the reverse transcription-quantitative polymerase chain reaction (RT-qPCR), consisting of 30 patients with NSCLC (lung cancer and para-carcinoma tissues, serum and EBC) and 30 healthy volunteers (serum and EBC). The results revealed that the let-7 levels in tumor tissues, serum, and EBC in NSCLC were significantly decreased compared with the control group (all, P<0.001). The let-7 expression in lung cancer tissue, serum, and EBC in NSCLC decreased alongside the progression of disease (tumor-node-metastasis stage and lymph node metastasis; all P<0.05). No significant association between let-7 expression and other clinicopathologic characteristics (age, sex, smoking status and histopathologic classification) was identified. A receiver operating characteristic curve (ROC) was used to present data and the area under the curve (AUC) of lung cancer tissue let-7 was 0.894, and the specificity and sensitivity were 90% and 93.3%, respectively. The AUC of serum let-7 in NSCLC diagnosis was 0.771, and the specificity and sensitivity were 86.7% and 60%, respectively. The AUC of let-7 in EBC was 0.750, and the specificity and sensitivity were 76.7% and 66.7%, respectively. In addition, the let-7 expression in EBC was positively correlated with that in lung cancer tissue (r=0.6048, P<0.001) and positively correlated with that in serum (r=0.6454, P<0.001). Taken together, the results of the present study indicated that detection of let-7 was feasible in EBC and with the advantages associated with EBC, and let-7 in EBC may be a promising biomarker for the diagnosis and evaluation of NSCLC.

Type 2 diabetes-induced overactivation of P300 contributes to skeletal muscle atrophy by inhibiting autophagic flux.

AIMS: Although autophagy impairment is a well-established cause of muscle atrophy and P300 has recently been identified as an important regulator of autophagy, the effects of P300 on autophagy and muscle atrophy in type 2 diabetes (T2D) remain unexplored. We aimed at characterizing the role of P300 in diabetic muscle and its underlying mechanism. MAIN METHODS: Protein levels of phosphorylated P300, total P300, acetylated histone H3, LC3, p62 and myosin heavy chain, and mRNA levels of Atrogin-1 and MuRF1 were analyzed in palmitic acid (PA)-treated myotubes and db/db mice. Autophagic flux was assessed using transmission electron microscopy, immunofluorescence and mRFP-GFP-LC3 lentivirus transfection in cells. Muscle weight, blood glucose and grip strength were measured in mice. Hematoxylin and eosin (H&E) staining was performed to determine changes in muscle fiber size. To investigate the effects of P300 on autophagy and myofiber remodeling, a P300 specific inhibitor, c646, was utilized. 3-Methyladenine (3-MA) was utilized to inhibit autophagosomes formation, and chloroquine (CQ) was used to block autophagic flux. KEY FINDINGS: Phosphorylation of P300 in response to PA enhanced its activity and subsequently suppressed autophagic flux, leading to atrophy-related morphological and molecular changes in myotubes. Inhibition of P300 reestablished autophagic flux and ameliorated PA-induced myotubes atrophy. However, this effect was largely abolished by co-treatment with the autophagy inhibitor CQ. In vivo results demonstrated that inhibition of P300 partially rescued muscle wasting in db/db mice, accompanied with autophagy reactivation. SIGNIFICANCE: The findings revealed that T2D-induced overactivation of P300 contributes to muscle atrophy by blocking autophagic flux.

[Clinical observation on treatment of 10 patients with chronic inflammatory demyelinating polyneuropathy by gullong tongluo capsule combined with prednisone].

OBJECTIVE: To observe and evaluate objectively the clinical effect of Guilong Tongluo Capsule (GTC) in treating chronic inflammatory demyelinating polyneuropathy (CIDP). METHODS: Sixty CIDP patients were equally randomized into two groups. The treated group was administered with GTC and prednisone, while the control group with prednisone alone. Changes before and after 3-month treatment in terms of muscle force, functional and sensory disturbance of extremities, as well as scoring by Activity of Daily Living Scale (ADL) and electromyogram (EMG) for nerve conduction velocity were observed and compared. RESULTS: The total effective rate gained in the treated group and the control group was 90.0% (27/30) and 70.0% (21/30) respectively, showing significant difference between them (chi2 = 14.82, P < 0.01). The improvement in the treated group was superior to the control group in muscle force of lower limb, motive and sensory function of extremities, ADL scores and motive function of ulnar nerve (P < 0.05, P < 0.01). CONCLUSION: The curative effect of GTC combined with prednisone in treating CIDP was better than that of prednisone alone.

The effects of resveratrol feeding and exercise training on the skeletal muscle function and transcriptome of aged rats.

This study investigated the effects of resveratrol feeding and exercise training on the skeletal muscle function and transcriptome of aged rats. Male SD rats (25 months old) were divided into the control group (Old), the daily exercise training group (Trained), and the resveratrol feeding group (Resveratrol). After 6 weeks of intervention, the body mass, grip strength, and gastrocnemius muscle mass were determined, and the muscle samples were analyzed by transcriptome sequencing. The differentially expressed genes were analyzed followed by GO enrichment analysis and KEGG analysis. The Old group showed positive increases in body mass, while both the Trained and Resveratrol groups showed negative growth. No significant differences in the gastrocnemius muscle index and absolute grip strength were found among the three groups. However, the relative grip strength was higher in the Trained group than in the Old group. Only 21 differentially expressed genes were identified in the Trained group vs. the Old group, and 12 differentially expressed genes were identified in the Resveratrol group vs. the Old group. The most enriched GO terms in the Trained group vs. the Old group were mainly associated with RNA metabolic processes and transmembrane transporters, and the significantly upregulated KEGG pathways included mucin-type O-glycan biosynthesis, drug metabolism, and pyrimidine metabolism. The most enriched GO terms in the Resveratrol group vs. the Old group were primarily associated with neurotransmitter transport and synaptic vesicle, and the upregulated KEGG pathways included synaptic vesicle cycle, nicotine addiction, retinol metabolism, insulin secretion, retrograde endocannabinoid signaling, and glutamatergic synapse. Neither exercise training nor resveratrol feeding has a notable effect on skeletal muscle function and related gene expression in aged rats. However, both exercise training and resveratrol feeding have strong effects on weight loss, which is beneficial for reducing the exercise loads of the elderly.