Association between copy number variation of SERPINA3-1 gene and growth traits in Chinese cattle.

Serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 3 (SERPINA3) belongs to the serine protease inhibitor family A subtype, and contains 8 genes from SERPINA3-1 to SERPINA3-8. Although the regulatory effects of these 8 genes have been revealed one by one in recent years, the related effects of SERPINA3-1 gene on cattle growth is still unclear. This study used quantitative Real time PCR (qPCR) to detect the type of copy number variation (CNV) of SERPINA3-1 gene in a total of 542 Chinese cattle, and expression of SERPINA3-1 gene in different tissues of Qinchuan cattles (adult) on mRNA level. Then association analysis was conducted between the detection results and cattle growth traits. The results showed that the Duplication type in SERPINA3-1 gene performed better on the growth traits and the CNV was significantly correlated with multiple growth traits (p < 0.05). In addition, SERPINA3-1 gene has different expression conditions in different tissues, results showed that SERPINA3-1 gene has a low expression in muscle. In conclusion, we speculate that the SERPINA3-1 gene can be used as a molecular marker and the result of this study could be a basic material for candidate functional genes for beef cattle growth and development.

In order to detect the gene expression diversification of the SERPINA3-1 gene, blood samples were collected from five Chinese cattle breeds, we detected related signal and made an associated analyze with cattle growth traits. We determined the copy number variation distribution of the SERPINA3-1 gene in cattle populations and found that the SERPINA3-1 gene has a certain promoting effect on the growth and development of Chinese cattle. For example, Pinan cattle with Duplication type copy number have a better performance on growth traits. This study has enriched the candidate genes of Chinese cattle molecular breeding and provided basic data for Chinese cattle breeding.

Effects of oxycodone hydrochloride sustained-release tablets and morphine hydrochloride sustained-release tablets on peripheral blood T cell levels in advanced lung squamous cell carcinoma with moderate to severe cancer pain.

Objective: To investigate the effects of morphine hydrochloride sustained-release tablets and oxycodone hydrochloride sustained-release tablets on T-cell levels in advanced lung squamous cell carcinoma(LUSC) with moderate to severe cancer pain. Methods: A retrospective study was used, ninety-eight patients who were admitted to The First Affiliated Hospital of Hebei North University for treatment of advanced LUSC with moderate to severe cancer pain between January 2021 and December 2021 were randomized into two groups(n=49 each) using the sealed envelope system. The reference group was treated with morphine hydrochloride sustained-release tablets, while the experimental group received oxycodone hydrochloride sustained-release tablets to compare pain relief rates(PRRs), levels of T cells, pain intensity, et al. Blood samples were collected for lymphocyte levels by flow cytometry. Results: The experimental group had significantly higher level than the reference group(P<0.05). Before administration, the two groups did not differ greatly in levels of T-cell subsets or pain scores on the visual analog scale(P>0.05, respectively). At 15 days of administration, the Treg level in the experimental group was higher than in the reference group; T helper 17 and 22 cells were reduced in both groups, and the decrease was more pronounced in the experimental group. At seven and 15 days of administration, the experimental group had a VAS score significantly lower than the reference group(P<0.05). The total adverse reaction rate was significantly lower in the experimental group as compared with the reference group(P<0.05). Conclusions: Oxycodone hydrochloride sustained-release tablets demonstrate desirable efficacy and safety in advanced LUSC with moderate to severe cancer pain by modulating T-cells in the body and improving the PRR.

High-dose omega-3 polyunsaturated fatty acid supplementation might be more superior than low-dose for major depressive disorder in early therapy period: a network meta-analysis.

BACKGROUND: The application of n-3 Polyunsaturated Fatty Acids (n-3 PUFAs) supplementation for major depressive disorder (MDD) has been widely discussed in recent years, but its efficacy and application are still controversial. This network meta-analysis was conducted to compare the efficacy of different dosages of n-3 PUFAs on MDD patients in the early period of treatment. METHODS: Randomized controlled trials (RCTs) exploring the efficacy of n-3 PUFA supplementation for patients with MDD were retrieved from the databases of Pubmed, Embase and the Cochrane Library. RCTs comparing the efficacy of n-3 PUFA for adult (≥18 years) MDD patients without comorbidity were eligible for our study. The score of depressive symptoms in early therapy period of the treatment (≤9 weeks) was extracted. Standardized mean deviations (SMDs) of all the sores from the eligible RCTs were synthesized in a pairwise meta-analysis in frequentist framework and a random-effects network meta-analysis in Bayesian framework for the overall and subgroups (high- and low-dose) efficacy of n-3 PUFAs. RESULTS: A total of 910 MDD patients in 10 trials with 3 adjuvant therapy strategies (high-dose n-3 PUFAs, low-dose n-3 PUFAs and placebo) were included. Results of pairwise meta-analysis showed that n-3 PUFAs were superior to placebo (SMD: 1.243 ± 0.596; 95% CI: 0.060 ~ 2.414). Results of the network meta-analysis showed that both the high (SMD: 0.908 ± 0.331; 95% CI: 0.262 ~ 1.581) and the low-dose (SMD: 0.601 ± 0.286; 95% CI: 0.034 ~ 1.18) n-3 PUFAs were superior to placebo, and the efficacy of high-dose n-3 PUFAs is superior to that of low-dose. CONCLUSIONS: High-dose n-3 PUFAs supplementation might be more superior than low-dose in the early therapy period for MDD. More head-to-head clinical trials need to be carried out to provide more direct comparison and enhance the evidence of the efficacy of n-3PUFAs for MDD.

Association Between the Polymorphism of Aldehyde Dehydrogenase 2 Gene and Cerebral Infarction in a Hakka Population in Southern China.

Genetic factors play an important role in determining the susceptibility to ischemic stroke. Herein, we examined the association of an aldehyde dehydrogenase 2 (ALDH2) gene polymorphism with cerebral infarction. Patients with cerebral infarction (n = 963) and healthy controls (n = 921) were included. Genotyping was performed using gene chip platform analysis, and Sanger sequencing was used to confirm ALDH2 genotypes. The risk prediction of ALDH2 polymorphisms for cerebral infarction was examined under three genetic modes of inheritance. For males, ALDH2*2/*2 genotype was a significant risk factor for cerebral infarction in the co-dominant model (age-, smoking-, and drinking-adjusted OR 1.514, 95% CI 1.005-2.282, p = 0.047) and the recessive model (age-, smoking-, and drinking-adjusted OR 1.601, 95% CI 1.078-2.379, p = 0.020). However, for females, ALDH2*2/*2 genotype was a protective factor for cerebral infarction in the co-dominant model (age-, smoking-, and drinking-adjusted OR 0.450 95% CI 0.215-0.941, p = 0.034) and the recessive model (age-, smoking-, and drinking-adjusted OR 0.440, 95% CI 0.214-0.903, p = 0.025). Further, logistic regression analysis revealed that age, smoking, hypertension, hyperlipidemia, and hypercholesterolemia were significant risks for the presence of cerebral infarction. In conclusion, these findings support an association of ALDH2 gene polymorphisms with ischemic stroke in a Chinese Hakka population. In particular, homozygote ALDH2*2/*2 may be a risk factor for cerebral infarction in males, but contribute to reduced risk for cerebral infarction in females.

A simple approach to prepare a sulfone-embedded stationary phase for HPLC.

In the present study, a polar-embedded reversed-phase liquid chromatographic stationary phase that contained internal sulfone groups was prepared. The synthesis involved the "thiol-ene" click chemistry between the vinyl functionalized silica and 1-octadecanethiol, followed by the oxidization of sulfide to sulfone groups. The resulting material simultaneously possessed the alkyl chain, i.e. C18, and the internal sulfone groups. Elemental analysis demonstrates that the element contents of the C18/sulfone silica were C 8.94%, H 1.87% and S 0.66%. Chromatographic evaluations indicate that the C18/sulfone stationary phase exhibited a little less retention than the C18/sulfide one. A comparable chromatographic performance of neutral analytes was obtained on these two columns, but much better chromatographic performance in the case of basic and acid analytes was obtained on C18/sulfone stationary phase with additional features such as lower silanol activity, better stability (stable working conditions of pH 1.0-10.0), and better compatibility with 100% aqueous mobile phases. The batch-to-batch reproducibility was acceptable (the RSDs of retention times for the probes were no higher than 1.73%), demonstrating the suitability of the applied synthetic strategy for the new stationary phase. The C18/sulfone is a promising polar-embedded RPLC stationary phase.

A narrative review of mentoring programmes in general practice.

Mentoring in general practice nurtures personal and professional development among mentees and mentors and enhances organisational productivity. Yet, failure to define it leads to variations in understanding and practice and conflation with other educational approaches. As a result, mentoring in general practice is underutilised and poorly overseen. This review seeks to identify elements among successful mentoring relationships to aid the design of local mentoring programmes. Reports of undergraduate and postgraduate mentoring programmes in general practice were analysed thematically. A literature search of mentoring of junior postgraduates or undergraduates by experienced mentors in general practice between 1 January 2000 and 31 December 2015 was done using PubMed, ERIC, ScienceDirect, Cochrane Database of Systematic Reviews and OVID. A total of 1973 abstracts were retrieved and 9 full-text articles were included and analysed. Three themes were identified, including the initiation of mentoring relationships, the mentoring relationship and the mentoring environment. Successful mentoring programmes pivot upon effective mentoring relationships. Based on the themes identified, a framework to guide practice, structure and oversight of the mentoring process is forwarded. Further context-specific study is needed to ensure the viability of the Mentoring Framework to better employ mentoring in general practice.

Psychometric properties of the Chinese version of the Reproductive Concerns After Cancer Scale (RCAC) for young female cancer survivors.

PURPOSE: This study aimed to translate, culturally adapt, and test the psychometric properties of the Reproductive Concerns After Cancer scale (RCAC) in young Chinese female cancer survivors. METHODS: The Chinese version of the RCAC was developed using the standard Functional Assessment of Chronic Illness Therapy (FACIT) translation methodology, and then 800 young Chinese female cancer survivors were recruited to complete the scale. The validation of the RCAC is as follows: (1) content validity was evaluated by a group of experts; (2) factor structure was assessed using confirmatory factor analysis and factorial invariance analysis; (3) convergent validity was determined by correlations with the Patient Health Questionnaire 9 (PHQ-9) and Functional Assessment of Cancer Therapy-General (FACT-G) scale; (4) internal consistency reliability was assessed using Cronbach's α coefficient; and (5) test-retest reliability was assessed using intra-class correlations. RESULTS: Internal consistency (Cronbach's alpha coefficients ranged from 0.71 to 0.81) and test-retest reliability (intra-class correlation coefficients ranged from 0.82 to 0.95) of the Chinese version of the RCAC were satisfactory. Results also indicated that the content validity index of the RCAC (Chinese version) was good. The Chinese version of the RCAC score was correlated with the PHQ-9 (r = 0.568, p < 0.01) and FACT-G (r = -0.524, p < 0.01) scores, which indicated acceptable convergent validity. Confirmatory factor analysis supported a six-factor structure of the Chinese version of the RCAC with a good model fit. Moreover, multi-group confirmatory factor analysis indicated factorial invariance (configural, metric, scalar, and strict invariance) of the RCAC across cancer types. CONCLUSIONS: The translation and cross-cultural adaption of the RCAC into Chinese was successful. The Chinese version of the RCAC has suitable factor structure and psychometric properties for reproductive concerns evaluation in young female cancer patients and is appropriate to use in clinical trials of Chinese patients.

[Analyses of exercise-induced muscle damage-specific microRNA expression and molecular target of sarcolemmal damage in rats].

In the present study, we were to screen the specific microRNA (miRNA) of exercise-induced muscle damage (EIMD) and assess the EIMD-specific miRNAs-regulated target of sarcolemmal damage in rats. Twenty-four male Sprague-Dawley (SD) rats were randomly divided into 3 groups, which included sedentary (C), 24 h post-exercise (E24) and 48 h post-exercise (E48) groups. Rat EIMD model was established by an acute eccentric exercise, i.e., a downhill running treatment at -16º gradient. EIMD characteristics were verified by Evans blue dye staining, differentially expressed miRNAs were detected by microarray assay, EIMD-specific miRNAs expressions were further validated by real-time quantitative RT-PCR (RT-qPCR), and targets of the miRNAs were predicted based on mRNA expressions of associated proteins and related pathway core molecules of sarcolemmal damage. Two EIMD-specific expressed miRNAs, including miR-206-3p and miR-139-3p, were found in the study. There was a significantly negative correlation (P < 0.05) between miR-206-3p expression and dystrophin (r = -0.68), utrophin (r = -0.64), JNK (r = -0.62) or ERK1 (r = -0.68) respectively, but no correlation was found between miR-139-3p and these biomolecules. The results suggest that: i) the expression profile of miRNAs in rat is significantly affected by EIMD, ii) miR-206-3p and miR-139-3p are the EIMD-specific miRNAs, and iii) miR-206-3p may control sarcolemmal damage by regulating dystrophin, utrophin, JNK and ERK1.

[Effects of triterpenoid from Psidium guajava leaves ursolic acid on proliferation, differentiation of 3T3-L1 preadipocyte and insulin resistance].

OBJECTIVE: To investigate the influences of triterpenoid from Psidium guajava Leaves (ursolic acid) on the proliferation, differentiation of 3T3-L1 preadipocyte, and its possible mechanism treat for insulin resistance. METHODS: 3T3-L1 preadipocyte was cultured in vitro. After adding ursolic acid to the culture medium for 48h, the cell viability was tested by MTT assay. Induced for 6 days, the lipid accumulation of adipocyte was measured by Oil Red O staining. The insulin resistant cell model was established with Dexamethasone. Cellular glucose uptake was determined with GOD-POD assays and FFA concentration was determined at the time of 48h. Secreted adiponectin were measured by ELISA. The protein levels of PPARgamma and PTP1B in insulin resistant adipocyte were measured by Western Blotting. RESULTS: Compared with medium control group, 30, 100 micromol/L ursolic acid could increase its proliferation and differentiation significantly (P < 0.05 or P < 0.01). Compared with the model group, ursolic acid at 100 micromol/L could enhance cellular glucose uptake of insulin resistant adipocyte significantly both in basic and insulin stimulation state (P < 0.01), while ursolic acid at 30 micromol/L could already enhance its glucose uptake significantly (P < 0.05), and could already decrease its FFA production significantly (P < 0.05). Ursolic acid at 30 micromol/L could increase the secretion of adiponectin on insulin resistant adipocyte significantly (P < 0.05), up-regulate the expression of PPARgamma protein (P < 0.05), but showed no effect on the PTP1B protein expression (P > 0.05). CONCLUSION: Ursolic acid can improve the proliferation and differentiation of 3T3-L1 preadipocyte, enhance cellular glucose uptake, inhibit the production of FFA, promote the secretion of adiponectin insulin resistant adipocyte, its mechanism may be related to upregulating the expression of PPARgamma protein.

Fabrication of Luteolin Loaded Zein-Caseinate Nanoparticles and its Bioavailability Enhancement in Rats.

Luteolin loaded zein nanoparticles (Lut-ZNP) were prepared by using sodium caseinate as an electrostatic stabilizer. The formulation of the nanoparticles was optimized. Lut-ZNP were spray-dried, and the physicochemical properties were characterized by SEM, XRD, FT-IR and DSC. Then, the bioavailability of luteolin in rats was determined. Under the formulation of luteolin, zein and sodium caseinate with mass ratio of 1:5:15, the particle size, ζ-potential, encapsulation efficiency and loading efficiency of Lut-ZNP were 171.8 nm, -49.05 mV, 85.85% and 3.15%, respectively. Luteolin existed in the nanoparticles with amorphous form. Lut-ZNP exhibited good redispersibility in water after drying. Compared with free luteolin, the solubility, stability and release of luteolin in Lut-ZNP were greatly improved. Besides, the fecal excretion of luteolin in rats was significantly reduced after oral administration of Lut-ZNP. In addition to native luteolin, its metabolites including sulfate, glucuronidate and methylated glucuronidate were found in rat plasma. Lut-ZNP significantly increased the plasma concentrations of luteolin and its metabolites, and the bioavailability of luteolin was enhanced by 2.92 times.

Dynamic differentiation of F4/80+ tumor-associated macrophage and its role in tumor vascularization in a syngeneic mouse model of colorectal liver metastasis.

Tumor-associated macrophages (TAMs) are highly heterogeneous and play vital roles in tumor progression. Here we adopted a C57BL/6 mouse model imitating the late-stage colorectal liver metastasis (CRLM) by Mc38 colorectal cancer cell injection via the portal vein. With serial sections of CRLM biopsies, we defined 7-9 days post-injection as the critical period for tumor neovascularization, which was initiated from the innate liver vessels via vessel cooption and extended by vascular mimicry and thereof growth of CD34+cells. In samples with increasing-sized liver metastases, the infiltrated Ly6C+ CD11b+ F4/80- monocytes steadily gained the expression of F4/80, a Kupffer cell marker, before transformed into Ly6C- CD11bint F4/80+ cells, which, the same phenotype was also adapted by Ly6C- CD11b- F4/80+ Kupffer cells. F4/80+ TAMs showed proximity to neovascularization and tumor vessels, functionally angiogenic in vivo; and greatly promoted the activation of a few key angiogenic markers such as VEGFA, Ki67, etc. in endothelial cells in vitro. Depletion of macrophages or diversion of macrophage polarization during neovascularization impeded tumor growth and vascularization and resulted in greatly reduced F4/80+ TAMs, yet increased CD11b+ cells due to inhibition of TAM differentiation. In summary, our results showed dynamic and spatial-temporal F4/80+ TAM transformation within the tumor microenvironment and strengthened its role as perivascular and angiogenic TAMs in CRLM.

Luteolin-Loaded Nanoparticles for the Treatment of Melanoma.

Background and Purpose: Luteolin (LUT), a flavonoid found in various plants, has been reported to have potential therapeutic effects in melanoma. However, poor water solubility and low bioactivity have severely restricted the clinical application of LUT. Based on the high reactive oxygen species (ROS) levels in melanoma cells, we developed nanoparticles encapsulating LUT with the ROS-responsive material poly(propylene sulfide)-poly(ethylene glycol) (PPS-PEG) to enhance the water solubility of LUT, accelerate the release of LUT in melanoma cells, and further enhance its anti-melanoma effect, providing a viable solution for the application of LUT nano-delivery systems in melanoma therapy. Methods: In this study, LUT-loaded nanoparticles were prepared with PPS-PEG and named as LUT-PPS-NPs. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) were applied to determine the size and morphology of LUT-PPS-NPs. In vitro studies were carried out to determine the uptake and mechanism of LUT-PPS-NPs by SK-MEL-28 melanoma cells. According to the CCK-8 assay, the cytotoxic effects of LUT-PPS-NPs on human skin fibroblasts (HSF) and SK-MEL-28 cells were assessed. Apoptosis assays, cell migration and invasion assays, and proliferation inhibition assays with low and normal density plating were also applied to test the in vitro anti-melanoma effect. Additionally, melanoma models were established utilizing BALB/c nude mice and initially evaluated the growth inhibitory impact following intratumoral injection of LUT-PPS-NPs. Results: The size of LUT-PPS-NPs was 169.77 ± 7.33 nm with high drug loading (15.05 ± 0.07%). In vitro, cellular assays confirmed that LUT-PPS-NPs were efficiently internalized by SK-MEL-28 cells and showed low cytotoxicity against HSF. Moreover, LUT released from LUT-PPS-NPs significantly inhibited tumor cell proliferation, migration and invasion. Animal experiments showed that LUT-PPS-NPs inhibited tumor growth more than 2-fold compared with the LUT group. Conclusion: In conclusion, the LUT-PPS-NPs developed in our study enhanced the anti-melanoma effect of LUT.

Prediction model of no-response before the first transarterial chemoembolization for hepatocellular carcinoma: TACF score.

Previous clinic models for patients with hepatocellular carcinoma (HCC) receiving transarterial chemoembolization (TACE) mainly focused on the overall survival, whereas a simple-to-use tool for predicting the response to the first TACE and the management of risk classification before TACE are lacking. Our aim was to develop a scoring system calculated manually for these patients. A total of 437 patients with hepatocellular carcinoma (HCC) who underwent TACE treatment were carefully selected for analysis. They were then randomly divided into two groups: a training group comprising 350 patients and a validation group comprising 77 patients. Furthermore, 45 HCC patients who had recently undergone TACE treatment been included in the study to validate the model's efficacy and applicability. The factors selected for the predictive model were comprehensively based on the results of the LASSO, univariate and multivariate logistic regression analyses. The discrimination, calibration ability and clinic utility of models were evaluated in both the training and validation groups. A prediction model incorporated 3 objective imaging characteristics and 2 indicators of liver function. The model showed good discrimination, with AUROCs of 0.735, 0.706 and 0.884 and in the training group and validation groups, and good calibration. The model classified the patients into three groups based on the calculated score, including low risk, median risk and high-risk groups, with rates of no response to TACE of 26.3%, 40.2% and 76.8%, respectively. We derived and validated a model for predicting the response of patients with HCC before receiving the first TACE that had adequate performance and utility. This model may be a useful and layered management tool for patients with HCC undergoing TACE.

[Nephro-protective effects of total triterpenoids from Psidium guajava leaves on type 2 diabetic rats].

OBJECTIVE: To investigate the nephro-protective effects of total triterpenoids from Psidium guajava leaves (TTPGL) on type 2 diabetic rats. METHODS: Diabetic rats were induced by intraperitoneal injection of streptozotocin (STZ, 35 mg/kg) and a high-fat diet. Diabetic rats were divided into five groups: diabetic model control, low-dose TTPGL-treated (60 mg/kg, L-TTPGL), medium-dose TTPGL-treated (120 mg/kg, M-TTPGL), high-dose TTPGL-treated (240 mg/kg, H-TTPGL) and rosiglitazone-treated (3 mg/kg, RSG). The rats received daily treatment for six weeks. At the end of the period,the levels of fasting blood glucose (FPG), fasting insulin (FINS), creatinine (Cr) and blood urea nitrogen (BUN) in serum were measured. Kidneys for histopathological evaluation were stained with Hematoxylin and Eosin (HE). RESULTS: Compared with normal control group, the level of FPG was increased, the insulin and insulin sensitivity index were decreased in the model group; The levels of BUN and Cr were increased with histopathological changes related to diabetic nephropathy in the kidney, which were the glomerular endothelium and mesangial cell proliferation, capillary narrowed, the base-membrane incrassation, glomerular swelling, cysts narrowed and tubules edema. Compared with the model group, the levels of FPG were decreased, serum insulin and insulin sensitivity index were increased significantly in M-TTPGL and H-TTPGL groups (P<0.01 or P<0.05); The levels of BUN and Cr were decreased significantly (P<0.01 or P<0.05) and the renal structural damages were improved significantly. CONCLUSION: TTPGL could decrease the level of blood glucose of diabetic rat effectively, increase the insulin sensitivity index and protect renal lesions in diabetic rats.

Ultrasensitive analysis of mirtazapine and its metabolites enantiomers in body fluids using ultrasound-enhanced and surfactant-assisted dispersive liquid-liquid microextraction followed by polymer-mediated stacking in capillary electrophoresis.

A simple, rapid, and sensitive technique for measuring mirtazapine and its metabolites enantiomers in human fluids, such as urine and serum, was developed by applying ultrasound-enhanced and surfactant-assisted dispersive liquid-liquid microextraction (USA-DLLME) integrated with poly(diallyldimethylammonium chloride) (PDDAC)-mediated stacking in capillary electrophoresis (CE). The parameters that affect extraction and stacking performance, such as the extraction volume, surfactant types, surfactant concentrations, salt additives, extraction time, solution pH, and background electrolytes, were comprehensively studied and optimized to achieve optimal detection performance. Under optimal extraction conditions (injection of 120 µL of C2H2Cl4 into 1 mL of a sample solution containing 0.05 mM Brij-35 at pH 10.0) and separation conditions (0.9% PDDAC, 10 mM phosphate, pH 3.0, and 20 mM dimethyl-ß-cyclodextrin), on-line CE stacking of mirtazapine-related chiral drugs was achieved by the two strategies: (i) neutral DM-ß-CD sweep low concentrations of DL-NaSSA and (ii) DL-NASSA is stacked by the difference in the viscosity between the PDDAC and sample zone. An approximately 2,800-4000-fold improvement in detection sensitivity was revealed for mirtazapine, N-demethylmirtazapine, and 8-hydroxymirtazapine enantiomers. The linear ranges for the quantification of all analyte enantiomers were 1.2-150 nM, with a coefficient of determination higher than 0.99; the relative standard deviations in the migration time and peak areas for six analytes were less than 1.8% and 5.8%, respectively. The proposed system provided the limits of detection (signal-to-noise ratio of 3) of the six analytes as 0.3-0.5 nM. The recovery of the six separated analytes spiked in urine and serum samples was revealed to be 82.7%-109.5% and 91%-112.8%, respectively. This advanced technique with high sensitivity enhancement factors was successfully employed to analyze mirtazapine and its metabolites enantiomers in urine and serum samples with reliability.

Compensatory roles of Protein Related to DAN and Cerberus (PRDC) decrease in pulmonary arterial hypertension.

Bone morphogenetic protein (BMP) signaling is commonly suppressed in patients with pulmonary arterial hypertension (PAH), but the compensatory mechanism of BMP signaling suppression is incompletely elucidated. This study aimed to investigate the role of PRDC, an antagonist of BMPs, in PAH and the underlying mechanism. Human lungs were collected and rat PAH was induced (monocrotaline, 60 mg/kg). BMP cascade and PRDC were detected in lungs and distal pulmonary artery smooth muscle cells (dPASMCs). In vitro cell experiments and in vivo supplementation of PRDC in hypertensive rats were subsequently performed. PRDC and BMP cascade all decreased in human and rat hypertensive lungs. Cell experiments confirmed that BMP2/4 inhibited dPASMCs proliferation by increasing cell cycle inhibitors (p21, p27), prevented dPASMCs migration by down-regulating MMP2/9 and up-regulating TIMP1/2 expression, and promoted dPASMCs apoptosis by up-regulating Bax, caspase3/9 and down-regulating Bcl-2 expression, as well as enhancing caspase3/7 activity, while, PRDC reversed the effects of BMP2/4 on dPASMCs proliferation, migration and apoptosis. In vivo trial found that PRDC supplementation deteriorated rat PAH in terms of pulmonary hemodynamics, vasculopathies and right ventricle hypertrophy. Taken together, compensatory decrease of PRDC in hypertensive lungs theoretically slow down the natural course of PAH, suggesting its therapeutic potential in PAH.

Network pharmacology analysis of the mechanism of Huisheng oral liquid in the treatment of lung cancer.

Background: To study the active ingredient and possible mechanism of Huisheng oral liquid in the treatment of lung cancer by network pharmacology. Methods: The active ingredient and drug targets of Huisheng oral liquid were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Traditional Chinese Medicine Integrated Database (TCMID), and lung cancer targets were screened using the Gene Expression Omnibus (GEO) database. The drug targets of the effective components of Huisheng oral liquid were matched with disease targets and the obtained intersecting targets were imported into the Search Tool for the Retrieval of Interaction Gene/Proteins (STRING) database to construct a protein-protein interaction (PPI) network. R software and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database were used for Gene Ontology (GO) and KEGG enrichment analyses, and Cytoscape software was used to construct a Huisheng oral liquid component target-lung cancer target network. The function and pathway of the therapeutic target of Huisheng oral liquid for lung cancer were analyzed. Results: A total of 1,376 differentially expressed genes (DEGs) of lung cancer were obtained, and 185 potential effective components of Huisheng oral liquid in the treatment of lung cancer were obtained, including quercetin, luteolin, kaempferol, and baicalein. There were 36 intersecting targets between Huisheng oral liquid and lung cancer, and the key targets for lung cancer treatment were CDKN1A, CCNB1, MDM2, CDK1, ErbB2, E2F1, EGFR, etc. Huisheng oral liquid mainly regulates the p53 signaling pathway. Conclusions: The mechanism of Huisheng oral liquid in the treatment of lung cancer is mainly reflected in regulating tumor cell apoptosis, inhibiting angiogenesis, and improving immunity.

Effects and dose-response relationships of exercise intervention on weight loss in overweight and obese children: a meta-regression and system review.

The aim of this study was to determine the effect of different exercise doses on weight loss in obese/overweight children. PubMed, Embase, SPORTDiscus, and the Cochrane library were searched from inception to November 2020 for randomized controlled trials. Fourty six trials involving 2,599 obese/overweight children were finally included. Different exercise dose interventions had different impacts. Exercise intervention reduce body weight (BW) by 1.46 kg (95% CI, -2.35 to -0.56, p=0.001), body fat percentage (BF%) by 2.24 (95% CI, -2.63 to -1.84, p<0.001) and body mass index (BMI) by 1.09 kg/m2 (95% CI, -1.45 to -0.73, p<0.001). Each MET-h/week was association with 0.147 kg (95% CI, -0.287 to -0.007, p=0.039) decrease in BW, 0.060 (95% CI, -0.118 to -0.002, p=0.042) decrease in BF%, and 0.069 kg/m2 (95% CI, -0.125 to -0.014, p=0.015) decrease in BMI. The findings suggest that there is a positive liner between exercise dose and weight loss, each MET-h/week associated with 0.147 kg, 0.060 and 0.069 kg/m2 decrease in body weight, BF%, BMI, respectively.

Adverse skin reactions induced by sintilimab in advanced lung squamous carcinoma: a case report and review of the literature.

Background: Sintilimab is an immune checkpoint inhibitor (ICI). It can induce immune-related Adverse Events (irAEs). Severe adverse skin reactions are rare, but the mortality rate is high. We report the first case of successful treatment of adverse skin reactions using traditional Chinese medicine (TCM). Case Description: Here we present the case of a 67-year-old male with advanced lung squamous carcinoma. After 8 cycles of chemotherapy, the patient's disease progressed and the treatment regimen was adjusted to sintilimab combined with albumin paclitaxel and cisplatin. Thirty-two days after this cycle, the patient reported a sporadic rash with pruritus on the face, front chest, and both upper limbs. The area of rash was 40%, and the adverse reaction was grade 3. The level of interleukin-related indicators was above normal. The patient's skin symptoms disappeared after treatment with hormones, TCM, and other drugs. The patient's adverse skin reaction was due to an immune-related toxicity caused by sintilimab, so treatment with sintilimab was suspended. The albumin-paclitaxel plus cisplatin regimen was continued to treat lung cancer. Conclusions: Although rare, case of fatal adverse reaction caused by sintilimab have been reported. We recommend early monitoring and recognition of symptoms. During management, high-dose hormones combined TCM may be helpful.

[The role of semaphorin 4D in the mechanism of bisphosphonate-related osteonecrosis of the jaw in rats].

PURPOSE: To study the expression level of semaphorin 4D (Sema4D) in bisphosphonate-related osteonecrosis of the jaw (BRONJ) and to explore its possible role in the occurrence of BRONJ. METHODS: BRONJ-like rat model was established by intraperitoneal injection of zoledronic acid assisted with tooth extraction. The maxillary specimens were extracted for imaging and histological examination, and bone marrow mononuclear cells(BMMs) and bone marrow mesenchymal stem cells(BMSCs) of each group were obtained in vitro for co-culture. Trap staining and counting were performed on monocytes after osteoclast induction. RAW264.7 cells were induced by osteoclast orientation under bisphosphonates(BPs) environment, and Sema4D expression was detected. Similarly, MC3T3-E1 cells and BMSCs were induced to osteogenic orientation in vitro, and the expression level of osteogenic and osteoclastic related genes ALP, Runx2, and RANKL was detected under the intervention of BPs, Sema4D and Sema4D antibody. Statistical analysis of the data was performed using GraphPad Prism 8.0 software. RESULTS: BRONJ-like rat model was successfully constructed. Two weeks after tooth extraction, the healing of the tooth extraction wound in the experimental group was significantly limited, and the tooth extraction wound was exposed. H-E staining results showed that regeneration of new bone in the extraction socket of the experimental group was significantly restricted, dead bone was formed, and the healing of the soft tissue was limited. The results of trap staining showed that the number of osteoclasts in the experimental group was significantly less than that in the control group. Micro-CT results showed that bone mineral density and bone volume fraction in the extraction socket of the experimental group were significantly lower than those of the control group. Immunohistochemical results showed that compared with the control group, the expression level of Sema4D in the experimental group was significantly increased. In vitro studies showed that compared with the control group, the osteoclast induction of BMMs in the experimental group was significantly lower than that in the control group. BMSCs in the experimental group significantly reduced the induction of osteoclasts. Osteoclastic induction experiments revealed that bisphosphonates could effectively inhibit the formation of osteoclasts, and the expression of Sema4D was significantly reduced. Osteogenic induction experiment found that Sema4D significantly reduced the expression of Runx2 and RANKL genes in osteoblasts, while the expression of ALP gene decreased and the expression of RANKL up-regulated after adding Sema4D antibody. CONCLUSIONS: BPs can interfere with normal bone healing time by up-regulating the expression of Sema4D in tissues, leading to coupling disorder between osteoclasts and osteoblasts with inhibition of the maturation of osteoclasts, thereby inhibiting the growth of osteoblasts. Differentiation and expression of related osteogenic factors mediate the development of BRONJ.