RESUMEN

Groundwater nitrate (NO3-) contamination is a global concern. The distribution patterns, enrichment mechanisms, and human health risks of NO3- contaminated groundwater were investigated using 144 groundwater samples collected from domestic and irrigation wells in the piedmonts of the North China Plain (Beijing and Shijiazhuang areas). The results showed that the groundwater was neutral to weakly alkaline, and 47% of the groundwater samples had NO3- concentrations exceeding 50 mg/L, a threshold proposed by world health organization to threaten infants up to 3 months. Groundwater NO3- concentrations were generally higher in the Beijing piedmont than in the Shijiazhuang piedmont and decreased with depth in both piedmonts. High-NO3- (> 50 mg/L) groundwater was distributed sporadically spatially and mainly was of Ca-Mg-HCO3 hydrochemical facies. Stable isotopes (D and 18O) compositions and NO3-/Cl- ratios indicated that NO3- accumulation in groundwater was primarily due to use of N-fertilizers under agricultural practices, and was associated with groundwater recharge sources such as septic tank leakage and re-infiltration of reclaimed irrigation water. Water quality evaluation showed that groundwater quality was highly dependent on NO3- concentration, with entropy-weighted water quality index values increasing linearly with increasing NO3- concentrations. The potential health risk of high-NO3- groundwater was the most serious for infants in both the piedmonts. Therefore, reducing NO3- input from sources and drinking water intake is recommended to minimize the human health risk.

Asunto(s)

RESUMEN

Objective To establish a method for determining hydrogen sulfide(H2S)in blood and apply it to practical cases.Methods A delute solution was achieved by adding 0.8 mL saturated borax solution into 0.2 mL blood sample was diluted with.1 mL acetonitrile solution containing 0.1％formic acid was then taken in a test tube,followed by adding 0.1 mL dilute solution and 0.1 mL thiozine aqueous solution(1％).After thorough mixing,the mixture was left to stand for 30 minutes.Subsequently,the sample was subjected to liquid chromatography-tandem mass spectrometry(LC-MS/MS)analysis after centrifugation and membrane filtration.Results The results showed that H2S exhibited good linearity within the concentration range of 10～2 000 ng/mL,with the R2 value of 0.998 5.The detection limit was 5 ng/mL,and the quantification limit was 10 ng/mL.In three cases of H2S poisoning,sulfur ions were detected in the blood of the deceased individuals,with concentrations ranging from 0.17 to 0.56 μg/mL.Conclusion For the first time,this study established a LC-MS/MS method for determining H2S in blood,which can meet the detection needs of H2S poisoning cases.

RESUMEN

OBJECTIVES: To compare the pharmacokinetic and safety of the test group capecitabine tablets (0.5 g) and the reference group capecitabine tablets (0.5 g). METHODS: This study was registered at www.chinadrugtrials.org.cn under the registration number CTR20220138. 48 subjects with solid tumor were recruited and randomized to receive either the test group or the reference group at a dose of 2 g per cycle for three cycles of the entire trial. RESULTS: The point estimate of the geometric mean ratio of Cmax for the subject and reference groups was 1.0670, which was in the range of 80.00%-125.00%. And the upper limit of 95% confidence interval was -0.0450 < 0. The statistics of geometric mean ratio of AUC0-t and AUC0-∞ (test group/reference group) and their 90% confidence intervals were in the range of 80.00%-125.00%, thus the test group was bioequivalent to the reference group under the conditions of this postprandial test. There were no major or serious adverse events. Conclusion: The pharmacokinetic profiles of capecitabine under postprandial conditions were consistent between the two groups. The two groups were bioequivalent and had a similar favorable safety profile in Chinese patients with solid tumor.

Asunto(s)

RESUMEN

The respiratory system's complex cellular heterogeneity presents unique challenges to researchers in this field. Although bulk RNA sequencing and single-cell RNA sequencing (scRNA-seq) have provided insights into cell types and heterogeneity in the respiratory system, the relevant specific spatial localization and cellular interactions have not been clearly elucidated. Spatial transcriptomics (ST) has filled this gap and has been widely used in respiratory studies. This review focuses on the latest iterative technology of ST in recent years, summarizing how ST can be applied to the physiological and pathological processes of the respiratory system, with emphasis on the lungs. Finally, the current challenges and potential development directions are proposed, including high-throughput full-length transcriptome, integration of multi-omics, temporal and spatial omics, bioinformatics analysis, etc. These viewpoints are expected to advance the study of systematic mechanisms, including respiratory studies.

Asunto(s)

RESUMEN

PURPOSE: The study was aimed at evaluating the bioequivalence and safety of oseltamivir phosphate for suspension, provided by Shenzhen Beimei Pharmaceutical Co. Ltd. and manufactured by Hetero Labs Limited, and the reference product TAMIFLU® in healthy Chinese subjects. METHODS: A single-dose, randomized, two-phase, self-crossed model was adopted. Among 80 healthy subjects, 40 subjects in the fasting group and 40 subjects in the fed group. Subjects in the fasting group were randomized into two sequences according to the proportion of 1:1, each given 75 mg/12.5 mL of Oseltamivir Phosphate for Suspension or TAMIFLU®, and cross-administered after 7 days. Postprandial group is the same as fasting group. RESULTS: The Tmax of TAMIFLU® and Oseltamivir Phosphate for Suspension in the fasting group were 1.50 h and 1.25 h, which in the fed group were both 1.25 h. Geometrically adjusted mean ratios of the PK parameters of Oseltamivir Phosphate for Suspension along with TAMIFLU® under fasting and postprandial conditions were in the range of 80.00-125.00% at the 90% confidence interval (CI). The 90% CI of Cmax, AUC0-t, AUC0-∞ for fasting group and postprandial group were (92.39,106.50), (94.26,100.67), (94.32,100.89) and (93.61,105.83),(95.64,100.19),(96.06,102.66). Among the subjects on medication, a total of 18 subjects reported 27 adverse events, all of which were treatment-emergent adverse events (TEAEs), six of these TEAEs were rated as grade 2 in severity and the rest were as grade 1. The number of TEAEs in the test product and the reference product were 14,13 respectively. CONCLUSION: Two Oseltamivir phosphate for suspensions are safe and bioequivalent.

Asunto(s)

RESUMEN

PURPOSE: SHC014748M is a potent, novel selective PI3Kδ isoform inhibitor and is proposed for the treatment of non-Hodgkin lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma. This study investigated the pharmacokinetics, mass balance, metabolism and excretion of SHC014748M in Chinese male subjects following a single oral dose of 150 mg (100 µCi) [14C] SHC014748M. METHODS: Six healthy Chinese male subjects administrated an oral suspension of 150 mg (100 µCi) [14C] SHC014748M and the samples of blood, urine and feces were collected for measuring. Liquid chromatography-tandem mass spectrometry and liquid scintillation counter were utilized to obtain mass balance and the pharmacokinetic data. RESULTS: The median Tmax for [14C]-radioactivity was 1.6 ± 0.5 h after the oral administration of [14C] SHC014748M and the mean Cmax was 3863 ± 354 ng Eq./mL in plasma, while the mean Cmax, t1/2 values and AUC0-∞ values for total radioactivity in whole blood were 2466 ± 518 ng Eq./mL, 32.2 ± 30.5 h and 66,236 ± 44,232 h * ng Eq./mL, respectively. Fecal excretion was proposed as the predominant elimination route, accounting for a mean of 90.68 ± 11.38% of the administered dose, whereas the mean urine excretion was 6.00 ± 1.48% within 336 h post-dose. The proposed major metabolic pathway of [14C] SHC014748M in the human body were as follows: (I) monooxidation, (II) glucuronide acid conjugation, and (III) monoxide-hydrogenation. CONCLUSIONS: SHC014748M was absorbed, metabolized and excreted with unchanged SHC014748M as its main circulating component in plasma following oral administration. In addition, it was speculated that fecal excretion was the principal excretion pathway; meanwhile, monohydroxy, glucuronide conjugation, oxygen, and hydrogenation were the major clearance pathways of SHC014748M through urine and/or feces. TRIAL REGISTRATION: The trial registration number: CTR20202505.

Asunto(s)

RESUMEN

BACKGROUND: Osteoarthritis (OA) is the most prevalent form of degenerative whole-joint disease. Before the final option of knee replacement, arthroscopic surgery was the most widely used joint-preserving surgical treatment. Emerging regenerative therapies, such as those involving platelet-rich plasma, mesenchymal stem cells, and microfragmented adipose tissue (MFAT), have been pushed to the forefront of treatment to prevent the progression of OA. Currently, MFAT has been successfully applied to treat different types of orthopedic diseases. AIM: To assess the efficacy and safety of MFAT with arthroscopic surgery in patients with knee OA (KOA). METHODS: A randomized, multicenter study was conducted between June 2017 and November 2022 in 10 hospitals in Zhejiang, China. Overall, 302 patients diagnosed with KOA (Kellgren-Lawrence grades 2-3) were randomized to the MFAT group (n = 151, were administered MFAT following arthroscopic surgery), or the control group (n = 151, were administered hyaluronic acid following arthroscopic surgery). The study outcomes were changes in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, the visual analog scale (VAS) score, the Lequesne index score, the Whole-Organ Magnetic Resonance Imaging Score (WORMS), and safety over a 24-mo period from baseline. RESULTS: The changes in the WOMAC score (including the three subscale scores), VAS pain score, and Lequesne index score at the 24-mo mark were significantly different in the MFAT and control groups, as well as when comparing values at the posttreatment visit and those at baseline (P < 0.001). The MFAT group consistently demonstrated significant decreases in the WOMAC pain scores and VAS scores at all follow-ups compared to the control group (P < 0.05). Furthermore, the WOMAC stiffness score, WOMAC function score, and Lequesne index score differed significantly between the groups at 12 and 24 mo (P < 0.05). However, no significant between-group differences were observed in the WORMS at 24 mo (P = 0.367). No serious adverse events occurred in both groups. CONCLUSION: The MFAT injection combined with arthroscopic surgery treatment group showed better mid-term clinical outcomes compared to the control group, suggesting its efficacy as a therapeutic approach for patients with KOA.

RESUMEN

Background: Cancer-associated fibroblasts (CAFs) play an important role in the tumorigenesis, immunosuppression and metastasis of colorectal cancer (CRC), and can predict poor prognosis in patients with CRC. The present study aimed to construct a CAFs-related prognostic signature for CRC. Methods: The clinical information and corresponding RNA data of CRC patients were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The Estimation of STromal and Immune cells in MAlignant Tumor tissues (ESTIMATES) and xCell methods were applied to evaluate the tumor microenvironment infiltration from bulk gene expression data. Weighted gene co-expression network analysis (WGCNA) was used to construct co-expression modules. The key module was identified by calculating the module-trait correlations. The univariate Cox regression and least absolute shrinkage operator (LASSO) analyses were combined to develop a CAFs-related signature for the prognostic model. Moreover, pRRophetic and Tumor Immune Dysfunction and Exclusion (TIDE) algorithms were utilized to predict chemosensitivity and immunotherapy response. Human Protein Atlas (HPA) databases were employed to evaluate the protein expressions. Results: ESTIMATES and xCell analysis showed that high CAFs infiltration was associated with adverse prognoses. A twenty-gene CAFs-related prognostic signature (CAFPS) was established in the training cohort. Kaplan-Meier survival analyses reveled that CRC patients with higher CAFs risk scores were associated with poor prognosis in each cohort. Univariate and multivariate Cox regression analyses verified that CAFPS was as an independent prognostic factor in predicting overall survival, and a nomogram was built for clinical utility in predicting CRC prognosis. Patients with higher CAFs risk scores tended to not respond to immunotherapy, but were more sensitive to five conventional chemotherapeutic drugs. Conclusion: In summary, the CAFPS could serve as a robust prognostic indicator in CRC patients, which might help to optimize risk stratification and provide a new insight into individual treatments for CRC.

RESUMEN

Pear fruits have been reported to contain abundant bioactive compounds and exhibit antidiabetic activity. In this study, Pingguoli pear (Pyrus pyrifolia cv.'Pingguoli') fermentation broth was sequentially extracted by five solvents with increasing polarity (petroleum ether, chloroform, ethyl acetate, n-butanol, and water) to evaluate its antioxidant and hypothermic activities, and then the main compounds of the fraction with the highest activity were assessed, which might be responsible for such activities. The results showed that the ethyl acetate fraction (EAF) exhibited the highest antioxidant activity according to DPPH (IC50 = 0.238 mg/mL), ABTS (IC50 = 0.293 mg/mL), and FRAP (IC50 = 0.193 mg/mL) assays. The in vitro hypoglycemic activity assay showed that EAF exhibited the strongest inhibitory effect, with IC50 values of 0.34 and 0.95 mg/mL for α-amylase and α-glucosidase, respectively. The glucose consumption in HepG2 cells treated with EAF was significantly increased to 252%, compare with control group. Liquid chromatography-mass spectrometry analysis implied that the main compounds, 3'-C-glucosylisoliquiritigenin, robustside D, caffeic acid, and chlorogenic acid may be potential candidates for the antioxidant and hypoglycemic activities of the EAF. This study suggested that EAF of Pingguoli pear fermentation broth could be utilized for development of potential functional food and antidiabetic agents.

Asunto(s)

RESUMEN

To study and prevent the water hazards of deep coal mines roof in the Inner Mongolia-Shaanxi (IM-S) mining area, it is essential to correctly evaluate the water-richness distributions of water-bearing aquifers in roof. This paper puts forward a sediment control method for water-richness law and zoning in the roof aquifers of deep Jurassic coals. To determine the vertical distance of direct water-bearing aquifers, the height of fractured water-conducting zone was detected by an underground network parallel electrical method. The plane and lateral spatial distribution patterns of the water-bearing aquifers and the control of the water-richness distribution was analyzed with the sediment control method. An evaluation system that consisted of four indicators, i.e., sedimentary environmental impact index, interlayer ratio of sandstone and mudstone, sandstone thickness, geophysical water-richness anomaly index was constructed. Furthermore, an Analytic Hierarchy Process (AHP) was introduced to establish the comprehensive zoning map. Finally, through the example analysis of Muduchaideng coal mine, the zoning evaluation results of water-richness were verified by the mine inflow. The findings of this study provide scientific guidance for prevention and control of mine water hazards in the IM-S mining area.

Asunto(s)

RESUMEN

Telitacicept, an injectable recombinant human B-lymphocyte stimulating factor receptor-antibody fusion protein, is a new dual B lymphocyte stimulator (BLyS)/APRIL (a proliferation-inducing ligand) inhibitor that effectively blocks proliferation of B lymphocytes. This study evaluates the pharmacokinetic characteristics, tolerability, and safety of a single subcutaneous injection of various doses (80, 160, and 240 mg) of telitacicept in healthy Chinese subjects. This trial is a single-center, randomized, open-label phase I clinical study that includes three dose groups (80, 160, and 240 mg) with 12 subjects in each dose group. The subjects were randomly assigned to different dose groups in a 1:1:1 ratio for a single subcutaneous administration trial. After a single dose, the maximum serum concentration (Cmax ) of total and free telitacicept was reached within 0.5-1 days. The elimination half-lives of total and free telitacicept at doses of 80-240 mg were 10.9-11.9 days and 11-12.5 days, respectively. The formation and elimination of the BLyS-telitacicept complex were much slower; the median time to Cmax was 15-57 days and was significantly prolonged with increasing dose. Only two of the 36 healthy subjects had positive antidrug antibodies with antibody titers of 1:15. The severity of adverse events was mild or moderate, and no higher treatment-emergent adverse events were reported. In conclusion, total telitacicept within a dose range of 80-240 mg and free telitacicept within a dose range of 160-240 mg had linear pharmacokinetic characteristics.

Asunto(s)

RESUMEN

Purpose: Chronic rhinitis (CR) is a common chronic inflammation of the nasal mucosa. Nasal saline irrigation has been demonstrated to be an effective treatment for CR. In this study, we investigated the beneficial effects of hydrogen-rich saline irrigation as an anti-inflammatory irrigation therapy for CR and compared its effectiveness over saline irrigation. Hydrogen-rich saline (HRS) was investigated due to its antioxidant and anti-inflammatory properties. Methods: A total of 120 patients with CR were randomly divided into two groups, patients irrigated with HR (HRS group) and the control group irrigated with saline (NS group). A randomized, double-blind control study was performed. The main observation index in this study was the total score of nasal symptoms (TNSS). In addition, eosinophilic protein (ECP) of the nasal secretions, nasal nitric oxide (nNO) levels, and levels of regulatory T cells (Treg) and regulatory B cells (Breg) were also compared between the two groups. Furthermore, patients with allergic rhinitis (AR) and non-allergic rhinitis (NAR) were also evaluated based on serum-specific IgE positivity. Results: After treatment, TNSS and nasal ECP in the two groups decreased significantly (P<0.05), with patients in the HRS group showing significantly lower levels compared to the NS group (P<0.05). There were no significant differences in Treg and Breg levels between the two groups. Subgroup analysis showed that TNSS in the AR-HRS group showed a more significant reduction compared to the AR-NS group (P<0.05); however, there were no significant differences for the other inflammatory biomarkers (P>0.05). ECP levels were reduced significantly in the NAR subgroup compared to NS irrigation (P<0.05). There were no obvious adverse events observed in patients during the entire treatment period. Conclusion: Compared to saline irrigation, HRS nasal irrigation was found to improve CR clinical symptoms, especially in patients with AR. HRS could effectively be used for the clinical treatment of patients with CR.

RESUMEN

OBJECTIVES: The diagnosis of sepsis is challenging, the need for sensitive and specific diagnostic and prognostic biomarkers has not been met. Soluble CD25 (sCD25) is a readily available biomarker reported to represent the severity of the disease. This study aimed to assess the association between sCD25 and mortality in patients with sepsis. METHODS: In total, 329 adult patients with sepsis were screened through a prospective, observational study. We investigated the severity scores and sCD25 levels at admission to the intensive care unit (ICU), defined by sepsis (sepsis-3). The prognostic value of sCD25 was assessed using receiver operating characteristic (ROC) curves and binary logistic regression models in predicting unfavourable outcome. The correlations between variables and severity of disease were analysed by Spearman correlation tests. RESULTS: After entering the ICU, the sCD25 level and sequential organ failure assessment (SOFA) score were significantly higher in nonsurvivors than in survivors. The prognostic values estimated by the ROC curves were 0.678 for sCD25 and 0.945 for SOFA score at ICU admission. sCD25 had a modest ability to predict poor outcome. Logistic regression showed that increased levels of sCD25 were independently associated with unfavourable outcome. Spearman correlation tests showed that sCD25 levels were positively correlated with disease severity. CONCLUSIONS: In sepsis patients, increased sCD25 levels were independently associated with poor clinical outcomes. Further research is needed to improve the understanding of the pathophysiology of this relationship.

Asunto(s)

RESUMEN

Prostate cancer (PCa) is a most common malignancy in males. It has a greater heterogeneity than other cancers, which poses a real challenge to the clinical diagnosis, classification and prognostic monitoring. At present, high-, medium- and low-risk PCa patients are classified mainly by Gleason scores and the PSA level, which, however, fail to reveal the diverse molecular heterogeneity and precisely distinguish the molecular subtypes of PCa. With the development of high-throughput sequencing, more and more studies on the molecular classification of the malignancy have paved the theoretical ground for the early diagnosis, efficacy prediction and individualized treatment of PCa. This study reviews the molecular classification, prognosis prediction and individualized treatment of PCa to date, hoping to contribute to the development of the precise treatment of PCa.

Asunto(s)

RESUMEN

ObjectiveTo count and analyze the toxic traditional Chinese medicines and their characteristics in Chinese Materia Medica， so as to provide reference for the development and application of toxic drugs. MethodThe traditional Chinese medicines included in Chinese Materia Medica were screened one by one， and the inclusion criteria were "drug properties"， "usage and dosage" and "major poison， highly poisonous， poisonous， slightly poisonous， slightly poisonous" appearing in ancient books. Standard toxic traditional Chinese medicines were entered into an excel sheet for statistical analysis. ResultA total of 1 408 toxic Chinese medicines were included. The properties and flavors were mainly cold， bitter， pungent and sweet； the main meridians were liver， lung， spleen and stomach； the root， whole grass and leaves were the most used medicinal parts， and there were many toxic drugs. The pre-treatment methods are mainly sun-dried， fresh， fried， calcined， and sunburned； the efficacy categories are mainly heat-clearing drugs， rheumatism drugs， blood-activating and stasis-removing drugs； oral administration methods are mainly decoctions， pills， and powders ， mainly for external application， dipping， and coating； the dosage for oral administration is mostly 9-15 g， 3-9 g， 3-6 g， and an appropriate amount is mainly for external use. ConclusionThere are many toxic Chinese medicines clearly recorded in Chinese Materia Medica， but only 83 kinds of clearly toxic Chinese medicines are included in Chinese Pharmacopoeia， which need to be further strengthened by experimental observation and clinical data verification. The clinical application of toxic traditional Chinese medicine is mainly based on heat toxin blood syndrome and rheumatic arthralgia， which is closely related to its nature， taste and meridian return. Able to move， has the effect of activating Qi and activating blood， "sweet" can replenish energy and slow down， and has the effect of tonic， alleviation and pain relief， and mostly used for the treatment of heat syndrome， blood syndrome and arthralgia syndrome. However， there are certain limitations in the classification and processing conditions of toxic traditional Chinese medicines， which need to be further improved and scientifically verified.

RESUMEN

ObjectiveTo count and analyze the toxic traditional Chinese medicines and their characteristics in Chinese Materia Medica， so as to provide reference for the development and application of toxic drugs. MethodThe traditional Chinese medicines included in Chinese Materia Medica were screened one by one， and the inclusion criteria were "drug properties"， "usage and dosage" and "major poison， highly poisonous， poisonous， slightly poisonous， slightly poisonous" appearing in ancient books. Standard toxic traditional Chinese medicines were entered into an excel sheet for statistical analysis. ResultA total of 1 408 toxic Chinese medicines were included. The properties and flavors were mainly cold， bitter， pungent and sweet； the main meridians were liver， lung， spleen and stomach； the root， whole grass and leaves were the most used medicinal parts， and there were many toxic drugs. The pre-treatment methods are mainly sun-dried， fresh， fried， calcined， and sunburned； the efficacy categories are mainly heat-clearing drugs， rheumatism drugs， blood-activating and stasis-removing drugs； oral administration methods are mainly decoctions， pills， and powders ， mainly for external application， dipping， and coating； the dosage for oral administration is mostly 9-15 g， 3-9 g， 3-6 g， and an appropriate amount is mainly for external use. ConclusionThere are many toxic Chinese medicines clearly recorded in Chinese Materia Medica， but only 83 kinds of clearly toxic Chinese medicines are included in Chinese Pharmacopoeia， which need to be further strengthened by experimental observation and clinical data verification. The clinical application of toxic traditional Chinese medicine is mainly based on heat toxin blood syndrome and rheumatic arthralgia， which is closely related to its nature， taste and meridian return. Able to move， has the effect of activating Qi and activating blood， "sweet" can replenish energy and slow down， and has the effect of tonic， alleviation and pain relief， and mostly used for the treatment of heat syndrome， blood syndrome and arthralgia syndrome. However， there are certain limitations in the classification and processing conditions of toxic traditional Chinese medicines， which need to be further improved and scientifically verified.

RESUMEN

PURPOSE: To compare the pharmacokinetics, pharmacodynamics and safety of the new prolonged-release leuprorelin acetate microspheres for injection (3.75 mg) with the reference product Enantone® (3.75 mg). METHOD: 48 healthy male volunteers were enrolled and randomly received a single 3.75 mg dose of the test drug or Enantone®. RESULTS: There were no significant differences in Cmax, AUC0-t and AUC0-48 between the test group and reference group (P > 0.05). The 90% confidence intervals of the two groups were 87.49%~112.74%, 97.15%~154.25%, and 80.85%~109.01%, respectively. Twenty-eight days after administration, both groups reached 100.0% castration level; there was no difference in the time from administration to reaching castration level between the two groups (P > 0.05); However, the difference between the two groups in the duration of castration level was statistically significant (P < 0.05). There were no major or serious adverse events, and the severity was mild to moderate. CONCLUSION: The pharmacokinetic characteristics of leuprorelin in two groups were consistent. The two groups exhibited similar inhibitory effects on testosterone and more subjects in the test group maintained a longer castration time than those in the reference group.

Asunto(s)

RESUMEN

Myocardial fibrosis (MF) is one of the leading causes of end-stage heart disease. Many studies have confirmed that inflammation caused by aldosterone may play an important role in the process of MF. A selective 11ß-hydroxysteroid dehydrogenase type 2 (11ß-HSD2) enzyme inhibitor can reduce the inactivation of cortisol, allowing cortisol to compete for mineralocorticoid receptors. This study investigated the protective effect of a novel selective 11ßHSD2 inhibitor (WZ51) on MF and described its underlying mechanism. The administration of WZ51 in rats with MF significantly alleviated myocardial injury, accompanied by a decrease in lactate dehydrogenase and the creatine kinase myocardial band. Furthermore, WZ51 significantly inhibited the development of MF and increased the protein level of 11ß-HSD2. The results of this study demonstrate that 11ß-HSD2 plays an important pathological role in MF. Thus, WZ51 may be a potential therapeutic agent for the treatment of this condition.

RESUMEN

Steroid-associated necrosis of the femoral head (SANFH) is one of the most common and refractory chronic diseases with increasing incidence. The typical pathological changes of SANFH include decreased osteogenic differentiation, enhanced intramedullary adipocytes deposition and impaired osseous circulation. In this study, we investigated the effects and potential mechanisms of Platelet-rich plasma (PRP) on SANFH. Sixty Sprague-Dawley rats were randomly divided into the control, PRP donor, model, and PRP groups. Compared to the model group, PRP treatment significantly increased the hemorheological indexes and serum levels of bone gla-protein (BGP) and vascular endothelial growth factor (VEGF), while decreased the levels of triglyceride (TG) and total cholesterol (TC). Meanwhile, Micro-CT and histopathological stain (Hematoxylin-eosin and Alcian blue-hematoxylin/orange G staining) were performed on the femoral head for morphological and histopathological evaluation, indicating that bone trabecular microstructure and bone mineral density (BMD) were significantly improved after PRP treatment. Immunohistochemical analysis revealed that PRP remarkably up-regulated the expression of osteogenic markers including ß-catenin and alkaline phosphatase (ALP), angiogenic markers containing VEGF and platelet endothelial cell adhesion molecule-1 (CD31), while down-regulated adipogenic markers involving fatty acid-binding protein (FABP-4), and peroxisome proliferator-activated receptor gamma (PPAR-γ) in SANFH rat models. In summary, for the first time, PRP was demonstrated to prevent the development of SANFH through stimulating bone formation and vascularization as well as retarding adipogenesis.

Asunto(s)

RESUMEN

OBJECTIVES: This study aimed to evaluate the bioequivalence, safety, tolerability and immunogenicity of the biosimilar trastuzumab (SIBP-01) compared to Herceptin®. METHODS: In this Phase I randomized double-blind parallel-group trial, 100 healthy male volunteers were randomized in a1:1 ratio to receive a single 6 mg•kg-1 intravenous dose of SIBP-01 or Herceptin®. Serum concentrationswere analyzed using a validated ELISA. RESULTS: The two groups had similar baseline characteristics. The geometric mean ratios (90% CI) of Cmax, AUC0-t and AUCinf between the trial group and the reference group were 93.55%-104.27%, 91.98%-102.35% and 91.88%-102.34%, respectively; the geometric mean ratios (90% CI) of AUC0-t and AUCinf in the sensitivity analysis were 92.29%-102.63% and 91.81%-102.16%, respectively. These values were within the prespecified equivalence margins, establishing the bioequivalence of SIBP-1 and Herceptin®. AEs were similar across all subjects in the SIBP-01 and Herceptin® arms, with treatment-related AEs reported by 72.00% and 80.00%, respectively. In each group, there was one AE that caused a subject to discontinue the study. EXPERT OPINION: Trastuzumab (Herceptin®) is significantly more effective than chemotherapy in reducing exacerbations and tumor cell growth, and its adverse events are far lower than chemotherapy. Herceptin®is very expensive for most patients in China. The protein molecular primary structure of the biosimilar trastuzumab (SIBP-01) is consistent with Herceptin®, with highly similar high level structure, biologocal activity and purity.But there are few studies comparing the bioequivalence of SIBP-01 and Herceptin® in healthy subjects and cancer patients 2. CONCLUSIONS: This study showed the PK similarity of SIBP-01 to Herceptin®. SIBP-01 was safe and well tolerated in healthy male volunteers, with no significant differences from the reference drug in safety or immunogenicity 4.

Asunto(s)