Objective To explore the changes in ionic pump functions of cardiomyocyte cell membrane and the effects of compound hyperosmotic saline solution. Method Ninety-six Wistar rats were randomized into two groups: hyperosmotic saline solution (HES, n=48) and 0.9% sodium chloride solution injection (NS, n=48). Hemorrhagic shock model was reproduced by a gradient volume-control phase exsanguination, combined with an adjustment phase, from femoral artery, with mean arterial pressure kept at 40kPa. At each time-point (pre-shock stage, shock, and 30min, 60min, 90min, 120min post-resuscitation), eight rats were used for various tests. The ATPase activity of cardiomyocyte cell membrane and the myocardial pathologic changes were investigated at different time points. Results Compared with shock stage, the ATPase activity of group HSH was significantly different (P

Objective To explore the changes in Ca2+ concentration and mitochondrial membrane potential in cultured myocytes in rat subjected to hypovolemia shock.Methods 84 Wistar rats were randomized into two groups:hypertonic solution resuscitation(HES,n=42)and 0.9% sodium chloride resuscitation(NS,n=42).At different timepoint(pre-shock stage,shock,post-resuscitation 5min,15min,30min,60min and 90min),the cultured cardiac myocytes,some were stained with JC-1,used fluo-4/AM as calcium probe,the others were assayed for Ca2+ mitochondrial membrane potential by flow cytomety.Results Ca2+ concentration of group HES at shock,post-resuscitation 5min,15min and 30min was higher than that of pre-shock stage,but mitochondrial membrane potential at post-resuscitation 60min and 90min was lower(P0.05).Ca2+ concentration and mitochondrial membrane potential of group HES at post-resuscitation 60min and 90min were more significantly different than that of group NS(P

Objective To modify anterior cruciate ligament (ACL)reconstruction to achieve better structure;to measure the tunnel's position and shape using three-dimensional computed tomography (CT)so as to show the change of the femoral bony tunnel.Methods Forty-five patients were diagnosed with an ACL tear and subsequently underwent the modified ACL reconstruction,using a minor-diameter drill to drill the femoral tunnel and then expand it to oval-shaped tunnel with the raspatory between July 2014 and 2015.All procedures were conducted by the same experienced surgeon (Ao Yf.).In all patients,CT was performed at one week after the ACL reconstruction to evaluate the femoral tunnel's positioning,then the CT-images were imported into the image processing software MIMICS to reconstruct the femoral bony tunnel to measure the tunnel's diameters of the section and the shape.The tunnel's position was evaluated using the quadrant method.Results In all the 45 patients,the graft could pass the tunnel.And no posterior tunnel wall blowout,neurological or vascular deficit was documented during the operation.According to the different methods of modification (6 to 7,6 to 8 and 7 to 8),the long diameters of the sections of the femoral bony tunnels were 8.34-± 0.52 mm,10.65 ± 0.72mm,9.27-± 0.11 mm,without significant difference from the theoretical value (8.16 mm,10.66 mm and 9.14 mm).However,the short diameters of the sections were 6.57--0.12 mm,6.74-± 0.13 mm,and 7.52 ± 0.05 mm,showing significant difference from the theoretical value (6mm,6mm and 7 mm).The average centre of the femoral tunnel was located at 26.4 ± 4.8％ of the femoral length and at 30.1 ± 5.6％ of the femoral height.Conclusion In this modified ACL reconstruction,a minor-diameter drill is used to drill the femoral tunnel and then expand it to oval-shaped tunnel with the raspatory,The graft was matched well with the bony tunnel intraoperatively.The three-dimensional CT shows that the femoral tunnels are well located within the anatomical ACL footprint,and its entrance is closer to the natural state.

The aim of the study is to evaluate the effects of the single and mixed decoction of Thallus laminariae (kelp) and Glycyrrhiza glabra (licorice) on the metabolism and their difference. The mixed decoction of kelp and licorice and the single decoction were made and intragastrically administered to the SD rats. The effect on system metabolism, the toxicity of liver and kidney were assessed by GC-MS profiling of the endogenous molecules in serum, routine biochemical assays and histographic inspection of tissues from SD rats, separately. The mixed decoction of kelp and licorice induced more obvious pathological abnormalities in SD rats than a single decoction of kelp, while the extracts of licorice did not show any pathological change. Neither the mixed, nor the single decoction showed abnormal histopathology. After intragastric administration of extracts for 5 days, the mixed decoction induced a decrease of ALT (no significant change in the groups of single decoction) and an increase of BUN (so did the single decoction of kelp). Metabolomic profile of the molecules in serum revealed that the metabolic patterns were all obviously affected for the three groups, i.e., the mixed and single decoction of kelp and licorice. The rats given with the single decoction of kelp showed a similar pattern to that of the mixed decoction, indicating that the kelp primarily contributed the perturbation of metabolism for the mixed decoction. All three groups induced a decrease of branched chain amino acids, TCA cycle intermediates and glycolysis intermediates (e.g., pyruvic acid and lactic acid) and an increase of 3-hydroxybutyric acid. Kelp decoction showed stronger potential in reducing TCA cycle intermediates and glycolysis intermediates than the other two groups, while the levels of branched chain amino acids were the lowest after licorice extracts were given. These results suggested that the effect of the mixed decoction on metabolism was closely associated with both kelp and licorice. The continuous administration of single decoction of kelp and the mixed decoction of licorice and kelp resulted in pathological abnormalities in kidney of SD rats. The mixed decoction of kelp and licorice distinctly perturbed sera molecules and hence system metabolism, which showed associated with those of kelp and licorice. Although the metabolic effect was associated with both kelp and licorice, the results suggested kelp contributed to it primarily.
Animals ; Glycyrrhiza ; chemistry ; Kelp ; chemistry ; Kidney ; drug effects ; Liver ; drug effects ; Metabolomics ; Plant Preparations ; pharmacology ; Rats ; Rats, Sprague-Dawley

BACKGROUND:At present,the pathogenesis of osteoarthritis is still unclear,and there is a lack of effective means to control the disease.Research on osteoarthritis is mostly concentrated in the field of immunity,and there are few studies in the field of oxidative stress. OBJECTIVE:To explore the roles of oxidative stress and immune infiltration in osteoarthritis and to predict related miRNAs and therapeutic agents. METHODS:The GSE55235 dataset(10 samples of osteoarthritis and 10 healthy control samples)and the GSE55457 dataset(10 samples of osteoarthritis and 10 healthy control samples)were obtained from the GEO database for merging to obtain their differentially expressed genes that were combined with oxidative stress genes to get the differentially expressed genes of oxidative stress.The differentially expressed genes of oxidative stress were analyzed for KEGG and GO enrichment,and the osteoarthritis pathways and biological processes were evaluated using GSEA enrichment analysis.The protein-protein interaction network was constructed using the STRING online website and Cytoscape software,and the Degree algorithm was run to get the key genes.The GSE1919 dataset was obtained from the GEO database as a validation dataset,and the key genes were analyzed by variance analysis and receiver operating characteristic curve analysis to get the core genes.In addition,immune infiltration was evaluated by CIBERSORT and the correlation between core genes and immune cells was explored.miRNA prediction of core genes was performed using TargetScan and target drugs were predicted using the DSigDB database. RESULTS AND CONCLUSION:Sixty-five differentially expressed genes and five core genes(IL1B,CXCL8,MYC,NFKBIA,JUN)associated with oxidative stress were identified.Enrichment analysis showed that differentially expressed genes associated with oxidative stress were concentrated in the pathways of oxidative stress,interleukin-17,osteoclast differentiation,fluid shear stress and atherosclerosis.The area under the receiver operating characteristic curve for the five core genes exceeded 0.85,indicating their excellent specificity and sensitivity in diagnosing bone and joint conditions,as well as their close association with immune cells.The predicted miRNA was has-miR-3937,and the therapeutic small-molecule drugs were metformin,ionomycin and celecoxib.To conclude,oxidative stress and immune infiltration exist in osteoarthritis,and immune infiltration is involved in activating oxidative stress.The core genes and predicted miRNAs can be used as novel markers for the diagnosis of osteoarthritis,and small molecule drugs are predicted to treat osteoarthritis.

Objective:To study the feasibility of magnetic resonance imaging(MRI)technique with amide proton transfer(APT)in predicting the prognosis of cerebral stroke.Methods:A total of 71 patients with acute cerebral stroke who admitted to the Nanjing First Hospital,Nanjing Medical University from September 2022 to May 2023 were selected.All of them underwent the test of National Institute of Health Stroke Scale(NIHSS),and received the MRI examination with chemical exchange saturation transfer(CEST).According to the modified Rankin scale(mRS)values of 1-month follow-up,they were divided into favorable recovery group(mRS<2,44 cases)and poor group(mRS≥2,27 cases).The asymmetric magnetization transfer ratio(MTRasym)image(APT)was obtained by analyzing data with special software.And then,the difference(△APTw)of APT values between ischemic zone and contralateral normal tissue was further calculated.The △APTw values of two groups were compared and analyzed,and the Pearson correlation analysis was adopted to analyze the correlation among △APTw,NIHSS and mRS.The receiver operating characteristics(ROC)curve was drawn,and the area under curve(AUC)of ROC curve was calculated.Results:There were significant positive correlations among △APTw,NIHSS and mRS scores(R2=0.659,0.522,P<0.001),and the differences of △APTW,NIHSS and mRS scores between the favorable recovery group and poor group were significant(t=5.73,6.36,13.92,P<0.05),respectively.The AUC value was 0.886,and the sensitivity and specificity of prediction were respectively 77.8%and 95.5%.The positive and negative predictive values were respectively 91.3%and 87.5%.Conclusion:APT imaging technique has feasibility in predicting the prognosis of acute cerebral ischemic stroke.

Osteosarcoma （OS） is the most common primary malignant bone tumor originating from mesenchymal stem cells， which features high degree of malignancy， strong invasiveness， easy early metastasis， and high recurrence rate. The clinical manifestations of OS are pain， local mass， limited movement， and pathological fracture. OS mainly occurs in children， adolescents， and the elderly， seriously threatening physical and mental health of patients， as well as their quality of life. The currently available therapies for OS are surgery， chemoradiotherapy， and the combination of the two. Although the therapeutic effect has been improved， tumor recurrence and metastasis and multidrug resistance still occur. Thus， the therapeutic effect is not satisfactory， especially in improving the overall survival rate of patients with metastatic OS. As a result， clinicians and researchers have been making efforts to find an effective therapy. In recent years， the mechanism of curcumin （CUR） against OS has attracted wide attention. CUR， a pigment extracted from the rhizomes or tubers of many plants， such as Curcuma longa， C. rcenyujin， and C. phaeocaulis， has a variety of pharmacological effects. Scholars have found that CUR has the effects of inhibiting proliferation， inducing apoptosis， and reversing multidrug resistance （MDR） of tumor cells， but also it has poor water solubility and low bioavailability， which limit the clinical application. This paper mainly discusses the mechanism of CUR against OS， the existing problems， new treatment methods， and future research directions， which is expected to provide new ideas for scientific researchers and provide a reference for the development and utilization of CUR in the future.

OBJECTIVE To evaluate the correlation between the solid dispersion(SD) powder properties and the relative crystallinity(RC) during SD recrystallization. METHODS Andrographolide was used as model drug, polyvinylpyrrolidone K30, polyethylene glycol 8000, Poloxam 188, Soluplus® as carrier materials, 12 SD powders were prepared by three preparation processes, and then the SD powder properties were determined. Afterwards, the principle component analysis and partial least squares analysis(PLS) were used to evaluate the correlation between the SD powder properties and RC during SD recrystallization. RESULTS The correlation model was successfully established by partial least square method between the SD powder properties and the RC. The VIP value of particle size parameter D(0.5) was >1.2, which indicated that the particle size was the key factor affecting the recrystallization of SD powder. CONCLUSION In practical work, SD powder with different particle size parameters can be obtained by different preparation methods or by adjusting the process parameters of the selected preparation method, so as to improve the recrystallization stability of SD.

Asthenoteratozoospermia is one of the most severe types of qualitative sperm defects. Most cases are due to mutations in genes encoding the components of sperm flagella, which have an ultrastructure similar to that of motile cilia. Coiled-coil domain containing 103 (CCDC103) is an outer dynein arm assembly factor, and pathogenic variants of CCDC103 cause primary ciliary dyskinesia (PCD). However, whether CCDC103 pathogenic variants cause severe asthenoteratozoospermia has yet to be determined. Whole-exome sequencing (WES) was performed for two individuals with nonsyndromic asthenoteratozoospermia in a consanguineous family. A homozygous CCDC103 variant segregating recessively with an infertility phenotype was identified (ENST00000035776.2, c.461A>C, p.His154Pro). CCDC103 p.His154Pro was previously reported as a high prevalence mutation causing PCD, though the reproductive phenotype of these PCD individuals is unknown. Transmission electron microscopy (TEM) of affected individuals' spermatozoa showed that the mid-piece was severely damaged with disorganized dynein arms, similar to the abnormal ultrastructure of respiratory ciliary of PCD individuals with the same mutation. Thus, our findings expand the phenotype spectrum of CCDC103 p.His154Pro as a novel pathogenic gene for nonsyndromic asthenospermia.
Asthenozoospermia/pathology* ; Dyneins/genetics* ; Homozygote ; Humans ; Male ; Microtubule-Associated Proteins ; Mutation ; Mutation, Missense ; Sperm Tail/metabolism*