A novel heterozygous mutation in PTHLH causing autosomal dominant brachydactyly type E complicated with short stature.

BACKGROUND: Brachydactyly type E (BDE) is a general term characterized by variable shortening of metacarpals and metatarsals, with phalanges affected frequently. It can occur as an isolated form or part of syndromes and manifest a high degree of phenotypic variability. In this study, we have identified the clinical characteristics and pathogenic causes of a four-generation pedigree with 10 members affected by BDE and short stature. METHODS: After the informed consent was signed, clinical data and peripheral blood samples were collected from available family members. Karyotype analysis, array-CGH, next-generation sequencing, and Sanger sequencing were employed to identity the pathogenic candidate gene. RESULTS: No translocation or microdeletion/duplication was found in karyotype analysis and array-CGH; hence, a novel heterozygous mutation, c.146dupA. p.S50Vfs*22, was detected by next-generation sequencing in PTHLH gene, leading to a premature stop codon. Subsequently, the mutation was confirmed by Sanger sequencing and co-segregation analysis. CONCLUSION: In this study, we described a novel heterozygous mutation (c.146dupA. p.S50Vfs*22) of gene PTHLH in a Chinese family. The mutation could induce a premature stop codon leading to a truncation of the protein. Our study broadened the mutation spectrum of PTHLH in BDE.

Higher cefazolin concentrations in synovial fluid with intraosseous regional prophylaxis in knee arthroplasty: a randomized controlled trial.

BACKGROUND: Prophylactic antibiotics reduce the risk of periprosthetic joint infection. However, conventional systemic administration may not provide adequate tissue concentrations against more resistant organisms such as coagulase-negative staphylococci. Intraosseous regional administration is known to achieve significantly higher antibiotic tissue concentrations than systemic administration, but it is unclear how synovial fluid concentrations are affected. We aimed to compare synovial fluid cefazolin concentrations achieved by regional intraosseous versus systemic intravenous administration, and also to compare synovial fluid cefazolin concentrations with those in subcutaneous fat. METHODS: A total of 60 patients undergoing primary knee arthroplasty were randomized into 2 groups: group IO received 2 g interosseous cefazolin in 100 mL saline through a tibial cannula after tourniquet inflation and before skin incision; group IV received 2 g cefazolin in 100 mL saline via the median basilic or median cephalic vein 30 min before tourniquet inflation. Subcutaneous fat and synovial fluid samples were collected immediately after skin incision, and cefazolin concentrations were measured by high-performance liquid chromatography. RESULTS: The cefazolin concentration in synovial fluid was 391.3 ± 70.1 µg/ml in group IO and 17.6 ± 3.5 µg/ml in group IV. The cefazolin concentration in subcutaneous fat was 247.9 ± 64.9 µg/g in group IO and 11.4 ± 1.9 µg/g in group IV. CONCLUSION: Intraosseous regional administration results in several times higher tissue concentrations than systemic administration, especially in the synovial fluid.

Stable Harsh-Temperature Lithium Metal Batteries Enabled by Tailoring Solvation Structure in Ether Electrolytes.

For lithium metal batteries (LMBs), the elevated operating temperature results in severe capacity fading and safety issues due to unstable electrode-electrolyte interphases and electrolyte solvation structures. Therefore, it is crucial to construct advanced electrolytes capable of tolerating harsh environments to ensure stable LMBs. Here, we proposed a stable localized high-concentration electrolyte (LHCE) by introducing the highly solvating power solvent diethylene glycol dimethyl ether (DGDME). Computational and experimental evidence discloses that the original DGDME-LHCE shows favorable features for high-temperature LMBs, including high Li+-binding stability, electro-oxidation resistance, thermal stability, and nonflammability. The tailored solvated sheath structure achieves the preferred decomposition of anions, inducing the stable (cathode and Li anode)/interphases simultaneously, which enables a homogeneous Li plating-stripping behavior on the anode side and a high-voltage tolerance on the cathode side. For the Li||Li cells coupled with DGDME-LHCE, they showcase outstanding reversibility (a long lifespan of exceeding 1900 h). We demonstrate exceptional cyclic stability (∼95.59%, 250 cycles), high Coulombic efficiency (>99.88%), and impressive high-voltage (4.5 V) and high-temperature (60 °C) performances in Li||NCM523 cells using DGDME-LHCE. Our advances shed light on an encouraging ether electrolyte tactic for the Li-metal batteries confronted with stringent high-temperature challenges.

BAG3 regulates bone marrow mesenchymal stem cell proliferation by targeting INTS7.

Background: BAG3 is an essential regulator of cell survival and has been investigated in the context of heart disease and cancer. Our previous study used immunoprecipitation-liquid chromatography-tandem mass spectrometry to show that BAG3 might directly interact with INTS7 and regulate bone marrow mesenchymal stem cell (BMMSCs) proliferation. However, whether BAG3 bound INTS7 directly and how it regulated BMMSCs expansion was unclear. Methods: BAG3 expression was detected by quantitative real-time PCR in BMMSCs after siRNA-mediated BAG3 knockdown. BMMSC proliferation was determined using the CCK-8 and colony formation assays. The transwell migration, flow cytometry and TUNEL assays were performed to measure BMMSC migration, cell cycle and apoptosis, respectively. Moreover, co-immunoprecipitation, protein half-life assay and western blotting analyses were used to determine the regulatory mechanism underlying the BAG3-mediated increase in BMMSC proliferation. Results: The results showed that knocking down BAG3 in BMMSCs markedly decreased their proliferative activity, colony formation and migratory capacity, and induced cell apoptosis as well as cell cycle arrest. Meanwhile, overexpression of BAG3 had the opposite effect. Bioinformatics and BAG3-INTS7 co-immunoprecipitation analyses revealed that BAG3 directly interacted with INTS7. Moreover, the downregulation of BAG3 inhibited the expression of INTS7 and promoted its ubiquitination. We also observed that BAG3 knockdown increased the levels of reactive oxygen species and the extent of DNA damage in BMMSCs. Notably, the upregulation of INTS7 or the addition of an antioxidant scavenger could rescue the BMMSC phenotype induced by BAG3 downregulation. Conclusions: BAG3 directly interacts with INTS7 and promotes BMMSC expansion by reducing oxidative stress.

Identification and Validation of Cyclin A2 and Cyclin E2 as Potential Biomarkers in Small Cell Lung Cancer.

INTRODUCTION: Small cell lung cancer (SCLC) is a special type of lung cancer sensitive to radiotherapy and chemotherapy but is prone to drug resistance and recurrence and has a very poor prognosis. This study aimed to explore the potential biomarkers and therapeutic targets for SCLC. METHODS: After batch normalization of GSE40275, GSE1037, and GSE44447 datasets, R was used to screen SCLC's differentially expressed genes (DEGs) and hub genes. We used immunohistochemistry (IHC) to assess the tissue's expression level of the hub gene. The clinical value of the hub gene was further evaluated based on the collected clinical-pathological data. RESULTS: In this study, a total of 230 DEGs (133 upregulated and 97 downregulated) were screened by the R package. The IHC showed that the expression of CCNA2 and CCNE2 in SCLC tissues was significantly higher than that in normal tissues (p < 0.01). Overexpression of CCNA2 was closely associated with the extensive period of NCCN (p = 0.004), tumor position (p = 0.046), and clinical stage (p = 0.002). The high expression levels of CCNE2 were related to high survival in chemotherapy patients (p = 0.019). CONCLUSION: CCNA2 and CCNE2 may serve as potential biomarkers of diagnosis and treatment for SCLC.

The effect of tibial component rotational alignment on clinical outcomes of mobile-bearing unicompartmental knee arthroplasty.

BACKGROUND: The optimal tibial component rotational alignment in unicompartmental knee arthroplasty has not been defined. This study aimed to explore the effect of tibial component rotational alignment on the clinical outcomes of UKA. METHODS: Clinical and follow-up data from 269 patients were retrospectively analysed. They were assigned into Groups A (- 5° to 0°), B (0°-3°), C (3°-6°) and D (> 6°) according to the external rotation of the tibial component to Akagi's line. The Knee Society Score clinical (KSS-c), Knee Society Score function (KSS-f), Forgotten Joint Score (FJS) and postoperative complications at 2 years postsurgically were analysed. RESULTS: The mean rotation of the tibial component relative to Akagi's line in 269 patients was 4.56 ± 3.79°. There were 15, 84, 89 and 81 patients in Groups A, B, C and D, respectively. The postoperative KSS-c and KSS-f in Groups B and C were significantly higher than those in Group D. No significant differences in KSS-c and KSS-f were detected between Groups B and C. The postoperative FJS in Group B was significantly higher than that in Group C, which was significantly higher in Group C than in Group D. There were 5, 8 and 15 cases of postoperative knee pain in Groups B, C and D, respectively, and the difference was statistically significant. CONCLUSION: Tibial component rotational alignment is of significance to Oxford Phase III UKA in patients. External rotation of the tibial component by 0°-3° is optimal to achieve satisfactory clinical outcomes.

Nickel-catalyzed divergent Mizoroki-Heck reaction of 1,3-dienes.

Developing efficient strategies to realize divergent arylation of dienes has been a long-standing synthetic challenge. Herein, a nickel catalyzed divergent Mizoroki-Heck reaction of 1,3-dienes has been demonstrated through the regulation of ligands and additives. In the presence of Mn/NEt3, the Mizoroki-Heck reaction of dienes delivers linear products under Ni(dppe)Cl2 catalysis in high regio- and stereoselectivities. With the help of catalytic amount of organoboron and NaF, the use of bulky ligand IPr diverts the selectivity from linear products to branched products. Highly aryl-substituted compounds can be transformed from dispersive Mizoroki-Heck products programmatically. Preliminary experimental studies are carried out to elucidate the role of additives.

Case report: Complete resection of invasive thymoma invading the superior vena cava and right atrium under cardiopulmonary bypass support.

Here we describe an uncommon case of a 48-year-old male patient with an invasive thymoma invading the superior vena cava, bilateral innominate veins, right internal jugular vein, right subclavian vein, right atrium, azygos vein, and part of the lung tissues. The tumor was resected entirely under cardiopulmonary bypass support, and the venous bypass using a vascular graft was successfully established between the left innominate vein and the right atrium. The postoperative course was uneventful, and the patient was discharged 15 days after surgery without complications.

Primary pulmonary choriocarcinoma in male: report a case with genetic testing and review of the literature.

Background: Primary pulmonary choriocarcinoma is an extremely rare malignant trophoblastic tumor with a poor prognosis. Most choriocarcinomas originated from gonads, such as the ovaries and testes. Review the previous literature, only 41 cases were reported. Case Description: We reported that a 65-year-old man found shadows in the lungs when undergoing the X-ray examination. Positron emission tomography (PET) was performed to exclude metastatic disease before surgery. The patient underwent three-dimension uniportal thoracoscopic left upper lung resection and lymph node dissection. The operation was uneventful, and he was discharged on the fourth day postoperatively. Postoperative pathology: malignant trophoblastic tumors (choriocarcinoma). After the operation, the patient has genetically tested, the mutations in tumor protein p53 (TP53), NRAS proto-oncogene (NRAS), and fibroblast growth factor receptor 1 (FGFR1) were found. Conclusions: Primary pulmonary choriocarcinoma is an extremely rare and highly malignant tumor difficult to detect in the early stage. By analyzing the previous literature, the patients with active treatment have more extended survival periods than the patients without treatment (P=0.0051). Patients, including surgery, had better survival than patients without surgery (P=0.027) depending on the different treatment regimens. Hence, once the diagnosis was confirmed, the comprehensive treatment of surgical resection combined with chemotherapy and radiotherapy is of great significance to improve the prognosis of patients.

Establishment and validation of a novel immune-related prognostic signature in malignant pleural mesothelioma.

Background: Immune-related genes (IRGs) play an important role in the tumor immune microenvironment and affect tumor prognosis. This study aimed to establish a prognostic signature for malignant pleural mesothelioma (MPM) patients. Methods: We obtained the relevant data of MPM patients in The Cancer Genome Atlas (TCGA), and univariate and multivariate Cox regression were used to construct the prediction signature and verify it with the external validation dataset GSE2549. A nomogram was then constructed, and its predictive ability was evaluated and analyzed the level of immune cell infiltration in different groups in the signature. Results: An IRG-related prognostic signature composed of INHBA, CAT, SORT1, TNFSF13B, and BIRC5 was constructed, with patients divided into high-risk and low-risk groups according to the risk score. The survival time of overall survival (OS), progression-free survival (PFS), disease-free interval (DFI), and relapse-free survival (RFS) in low-risk groups was longer than in high-risk groups. Furthermore, the signature had high predictive performance, and the receiver operating characteristic (ROC) of 1, 2, and 3 years could reach 0.853, 0.881, and 0.914, respectively. The predictive accuracy of the signature was verified by using the independent GSE2549 dataset. The levels of activated CD4 T cells, immature dendritic cells, and type 2 T helper cells were higher in high-risk patients. The gene set enrichment analysis (GSEA) analysis showed that a high concentration and P53 signal pathways were found in high-risk groups. Conclusions: This research developed and verified a new type of immune prognostic signature based on five IRGs, which can predict the prognosis of tumor patients and provide new ideas for individualized treatment.

INTS7-ABCD3 Interaction Stimulates the Proliferation and Osteoblastic Differentiation of Mouse Bone Marrow Mesenchymal Stem Cells by Suppressing Oxidative Stress.

Increased adipocyte and decreased osteoblast differentiation, combined with the ectopic proliferation of bone marrow mesenchymal stem cells (BM-MSCs), represent the primary causes of osteoporosis. The dysregulation of numerous intracellular bioactive factors is responsible for the aberrant differentiation and growth of BM-MSCs. In this study, we focused on a new stimulative factor, integrator complex subunit 7 (INTS7), and its cooperative protein ATP-binding cassette subfamily D member 3 (ABCD3)/high-density lipoprotein-binding protein (HDLBP) in mouse BM-MSCs. We aimed to uncover the effects of the INTS7-ABCD3/HDLBP interaction on BM-MSC biological behaviors and the potential mechanism underlying these effects. Functional in vitro experiments showed that the suppression of the INTS7-ABCD3 interaction rather than HDLBP could impair BM-MSC proliferation and induce cell apoptosis. Moreover, Alizarin Red S and Oil Red O staining, respectively, revealed that INTS7 and ABCD3 knockdown but not HDLBP knockdown could decrease osteoblastic differentiation and accelerate the adipogenic differentiation of BM-MSCs. Mechanistically, reactive oxygen species (ROS) and histone γ-H2AX quantities significantly increased, whereas the levels of antioxidants declined due to INTS7 and ABCD3 inhibition in BM-MSCs. These findings indicated that the suppression of oxidative stress could be involved in the INTS7/ABCD3 co-regulatory mechanisms for BM-MSC proliferation and differentiation, identifying new potential candidates for osteoporosis therapy.

Development of a prognostic signature of patients with esophagus adenocarcinoma by using immune-related genes.

BACKGROUND: Esophageal adenocarcinoma (EAC) is an aggressive malignancy with a poor prognosis. The immune-related genes (IRGs) are crucial to immunocytes tumor infiltration. This study aimed to construct a IRG-related prediction signature in EAC. METHODS: The related data of EAC patients and IRGs were obtained from the TCGA and ImmPort database, respectively. The cox regression analysis constructed the prediction signature and explored the transcription factors regulatory network through the Cistrome database. TIMER database and CIBERSORT analytical tool were utilized to explore the immunocytes infiltration analysis. RESULTS: The prediction signature with 12 IRGs (ADRM1, CXCL1, SEMG1, CCL26, CCL24, AREG, IL23A, UCN2, FGFR4, IL17RB, TNFRSF11A, and TNFRSF21) was constructed. Overall survival (OS) curves indicate that the survival rate of the high-risk group is significantly shorter than the low-risk group (P = 7.26e-07), and the AUC of 1-, 3- and 5- year survival prediction rates is 0.871, 0.924, and 0.961, respectively. Compared with traditional features, the ROC curve of the risk score in the EAC patients (0.967) is significant than T (0.57), N (0.738), M (0.568), and Stage (0.768). Moreover, multivariate Cox analysis and Nomogram of risk score are indicated that the 1-year and 3-year survival rates of patients are accurate by the combined analysis of the risk score, Sex, M stage, and Stage (The AUC of 1- and 3-years are 0.911, and 0.853). CONCLUSION: The 12 prognosis-related IRGs might be promising therapeutic targets for EAC.

Comparison of Early Clinical Results for Femoral Neck System and Cannulated Screws in the Treatment of Unstable Femoral Neck Fractures.

OBJECTIVE: To compare early clinical effects of the femoral neck system (FNS) and three cannulated screws for the treatment of patients with unstable femoral neck fractures. METHODS: A retrospective analysis with pair matching of 81 patients who received FNS or cannulated screw internal fixation for Pauwels type-3 femoral neck fracture in our hospital from January 2019 to December 2019 was conducted. Patients who received FNS were the test group, and those who received cannulated screws comprised the control group. Matching requirements were as follows: same sex, similar age, and similar body mass index (BMI). A total of 30 pairs were successfully matched at a 1:1 ratio, including 12 males and 18 females. The average age of the patients in the FNS group was 54.53 ± 6.71 years. In the cannulated screw group, the average age of the patients was 53.14 ± 7.19 years. The operation time, intraoperative blood loss, hospital stay, hospitalization cost, postoperative visual analog scale (VAS) score, time to walking without crutches, Harris score, femoral head necrosis rate, and complication rate were compared between the groups. RESULTS: Postoperative re-examination of radiographs showed satisfactory reduction in all patients, and all patients were followed up for 10-22 months. Those in the FNS group had lower postoperative VAS scores, earlier times to walking without crutches, higher Harris scores at the last follow-up, and lower complication rates (P < 0.05). VAS scores were lower in the FNS group (3.13 ± 1.07 scores) than in the cannulated screw group (3.77 ± 1.04 scores) (P = 0.018). Patients in the FNS group (5.23 ± 1.33 months) recovered to walking without crutches earlier than did those in the cannulated screw group (6.03 ± 1.45 months) (P<0.001). In addition, a statistically higher postoperative Harris score was detected in the FNS group (86.16 ± 7.26) than in the cannulated screw group (82.37 ± 7.52) (P = 0.039). Overall, a higher incidence of complications was observed in the cannulated screw group (9/30) than in the FNS group (2/30) (P = 0.042). However, intraoperative blood loss and hospitalization costs were greater in the FNS group (P < 0.05). Intraoperative blood loss was greater in the FNS group (99.73 ± 4.69) than in the cannulated screw group (30.27 ± 9.04) (P<0.001). In addition, patients in the FNS group (46976 ± 2270 ¥) spent more on hospitalization costs than did those in the cannulated screw group (15626 ± 1732 ¥) (P<0.001). No statistically significant difference in operation time, hospital stay, or femoral head necrosis rate was observed between the two groups (P > 0.05). CONCLUSION: For patients with unstable femoral neck fractures, FNS has better clinical efficacy than cannulated screws, though it is also more expensive.

The prognostic value of an autophagy-related lncRNA signature in hepatocellular carcinoma.

BACKGROUND: lncRNA may be involved in the occurrence, metastasis, and chemical reaction of hepatocellular carcinoma (HCC) through various pathways associated with autophagy. Therefore, it is urgent to reveal more autophagy-related lncRNAs, explore these lncRNAs' clinical significance, and find new targeted treatment strategies. METHODS: The corresponding data of HCC patients and autophagy genes were obtained from the TCGA database, and the human autophagy database respectively. Based on the co-expression and Cox regression analysis to construct prognostic prediction signature. RESULTS: Finally, a signature containing seven autophagy-related lncRNAs (PRRT3-AS1, RP11-479G22.8, RP11-73M18.8, LINC01138, CTD-2510F5.4, CTC-297N7.9, RP11-324I22.4) was constructed. Based on the risk score of signature, Overall survival (OS) curves show that the OS of high-risk patients is significantly lower than that of low-risk patients (P = 2.292e-10), and the prognostic prediction accuracy of risk score (AUC = 0.786) is significantly higher than that of ALBI (0.532), child_pugh (0.573), AFP (0.5751), and AJCC_stage (0.631). Moreover, multivariate Cox analysis and Nomogram of risk score are indicated that the 1-year and 3-year survival rates of patients are obviously accuracy by the combined analysis of the risk score, child_pugh, age, M_stage, and Grade (The AUC of 1- and 3-years are 0.87, and 0.855). Remarkably, the 7 autophagy-related lncRNAs may participate in Spliceosome, Cell cycle, RNA transport, DNA replication, and mRNA surveillance pathway and be related to the biological process of RNA splicing and mRNA splicing. CONCLUSION: In conclusion, the 7 autophagy-related lncRNAs might be promising prognostic and therapeutic targets for HCC.

Identification of Potential Hub Genes and Therapeutic Drugs in Malignant Pleural Mesothelioma by Integrated Bioinformatics Analysis.

INTRODUCTION: Malignant pleural mesothelioma (MPM) is closely linked to asbestos exposure and is an extremely aggressive tumor with poor prognosis. OBJECTIVE: Our study aimed to elucidate hub genes and potential drugs in MPM by integrated bioinformatics analysis. METHODS: GSE42977 was download from the Gene Expression Omnibus (GEO) database; the differentially expressed genes (DEGs) with adj.p value <0.05 and |logFC| ≥2 were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed by DAVID database. The STRING database was used to construct a protein-protein interaction network, and modules analysis and hub genes acquisition were performed by Cytoscape. The Gene Expression Profiling Interactive Analysis (GEPIA) database was used to assess the impact of hub genes on the prognosis of MPM patients. The Drug-Gene Interaction database (DGIdb) was used to select the related drugs. RESULTS: A total of 169 upregulated and 70 downregulated DEGs were identified. These DEGs are enriched in the pathway of extracellular matrix-receptor interaction, focal adhesion, PI3K-Akt signaling pathway, and PPAR signaling pathway. Finally, 10 hub genes (CDC20, CDK1, UBE2C, TOP2A, CCNB2, NUSAP1, KIF20A, AURKA, CEP55, and ASPM) were identified, which are considered to be closely related to the poor prognosis of MPM. In addition, 119 related drugs that may have a therapeutic effect on MPM were filtered out. CONCLUSION: These discovered genes and small-molecule drugs provide some new ideas for further research on MPM.

Alignment results of infrared computer-assisted navigation of total knee arthroplasty for end-stage knee osteoarthritis.

OBJECTIVE: Total knee arthroplasty (TKA) is one of the most conventional surgeries used to solve dyskinesia caused by knee joint degeneration; however, ambiguous prosthesis position and angle after TKA can cause serious complications. This study evaluated the outcomes of infrared computer-assisted navigation (ICAN) of TKA for end-stage knee osteoarthritis. METHODS: Forty-six end-stage knee osteoarthritis patients who underwent TKA were randomly divided into computer-assisted orthopedic surgery (CAOS) (n = 23) and non-CAOS (n = 23) groups. The intraoperative conditions, postoperative complications, soft tissue balancing, functional scores, and X-ray data were compared between groups. RESULTS: The CAOS group showed longer surgery time and higher range of motion than the non-CAOS group. No significant differences in American Knee Society Score (AKSS) and Oxford Knee Score were observed between the two groups. Compared to those in the non-CAOS group, the error of the lower limb line, angle of soft tissue balancing, separation of soft tissue, and angular deviation (α, ß, γ, δ) of the implants were much lower in the CAOS group. CONCLUSION: The ICAN system for TKA surgery was associated with less intraoperative blood loss and suitable position and angle in patients with end-stage knee osteoarthritis.

Circular RNA hsa_circ_0000073 contributes to osteosarcoma cell proliferation, migration, invasion and methotrexate resistance by sponging miR-145-5p and miR-151-3p and upregulating NRAS.

An increasing number of studies have demonstrated that circular RNAs (circRNAs), as promising therapeutic targets, are essential for diverse human diseases, especially cancer. However, the potential functions and complex mechanisms of most circRNAs in osteosarcoma (OS) are still not fully elucidated. In the present study, we obtained the expression profile of circRNAs from a GEO database (GSE96964) and identified hsa_circ_0000073 as a highly expressed candidate in OS. Overexpression of hsa_circ_0000073 accelerated the proliferation, migration, invasion and MTX resistance of OS cells, and knockdown of hsa_circ_0000073 resulted in the opposite effects. Mechanistically, hsa_circ_0000073 upregulated NRAS expression by targeting miR-145-5p and miR-151-3p in OS cells. In addition, the promotion of OS progression by hsa_circ_000007 was blocked by miR-145-5p and miR-151-3p-mediated NRAS inhibition. In conclusion, hsa_circ_0000073 facilitated the proliferation, migration, invasion and MTX resistance of OS cells through the inhibition of miR-145-5p and miR-151-3p-mediated downregulation of NRAS.

Interleukin-22 modulates cisplatin sensitivity of osteosarcoma cells by regulating the STAT3 signaling pathway.

The present study aimed to investigate the regulatory mechanisms by which interleukin (IL)-22 regulates cisplatin (DDP) sensitivity in osteosarcoma cells. Firstly, reverse transcription-quantitative (RT-q) PCR and western blotting demonstrated that IL-22 expression was significantly increased in osteosarcoma tissues and cell lines compared with the adjacent normal tissues and the normal osteoblast hFOB1.19 cells. Subsequently, the MG63 osteosarcoma cell line and cisplatin-resistant MG63/DDP osteosarcoma cell line were treated with different concentrations of cisplatin (2.5, 5.0, 10, 20, 40 and 80 µg/ml), and the half maximal inhibitory concentration (IC50) was calculated based on the MTT assay. The results showed that the IC50 of DDP in MG63/DDP cells was significantly higher than that in MG63 cells. Furthermore, IL-22 expression was higher in MG63/DDP cells compared with MG63 cells. Subsequently, the effects of IL-22 downregulation and overexpression on MG63/DDP and MG63 cells were assessed using the MTT assay, flow cytometry, RT-qPCR and western blotting. The IL-22 small interfering (si) RNA in MG63/DDP cells significantly decreased the IC50 of DDP and decreased the cell viability of MG63/DDP cells. Furthermore, IL-22 RNA interference decreased BCl-2 expression and phosphorylation of STAT3, induced apoptosis, and increased the expression of Bax and cleaved caspase-3. The IL-22 overexpression plasmid had opposite effects to the observations in IL-22 siRNA-transfected MG63 cells. Overall, the present study indicated that IL-22 regulated the cell viability and apoptosis of osteosarcoma cells by regulating the activation of the STAT3 signaling pathway and affecting the expression of apoptosis-associated genes, and thereby mediating the sensitivity of osteosarcoma cells to cisplatin.

Effects of the ratios of marrow cavity diameter to intramedullary nail diameter from different layers on blood loss during perioperative period for femoral intertrochanteric fractures.

The study aimed to investigate the effect of ratios of marrow cavity diameter to intramedullary nail diameter from different layers on hidden blood loss (HBL), overt blood loss (OBL) and total blood loss (TBL) during using proximal femoral nail antirotation-Asian version (PFNA)-II for femoral intertrochanteric fractures.We retrospectively studied 70 patients treated in our hospital recently. We recorded postoperative hematocrit (Hct) and OBL during operation. TBL and HBL were calculated using CROSS equation. The ratios of marrow cavity diameter to intramedullary nail diameter from different layers, including start of funnel, end of funnel and femoral isthmus, were measured. The mean of the ratio from frontal and lateral X-ray were designated as R. We classified all included participants into a high and a low matching group according to z-score of R within each layer. TBL, HBL, and OBL were compared between the 2 groups. We applied multiple linear regression analysis between the HBL as a dependent variable and gender, age, body mass index, fracture type, and R as independent variables.The present study indicated a significant reduction in the HBL and TBL in the high matching group compared to low matching group on three layers, whereas it showed no significant difference in OBL between the 2 groups on three layers. It showed that R values from start of funnel and end of funnel were significantly associated with HBL.Matching rate of PFNA II at the funnel might be an important factor for HBL and TBL postoperatively.

Pyruvate is an effective substitute for glutamate in regulating porcine nitrogen excretion.

This study was performed to determine if pyruvate, which acts as a critical intermediate in energy metabolism, can substitute the role of glutamate as a metabolic fuel and effectively reduce nitrogen excretion in pigs. First, the experiment in vitro was carried out to investigate the effects of culturing porcine small intestinal epithelial cell line with pyruvate on the oxidation. Then, barrows weighing 40 kg were used in the experiment investigating the changes of nitrogen balance in response to addition of pyruvate to low-protein diets. Last, barrows (40 kg), which were surgically fitted with permanent catheters in the mesenteric vein, portal vein, hepatic vein, and carotid artery, were used to investigate the effects of supplementing low-protein diets with calcium pyruvate on the net portal fluxes of amino acids (AAs) and the consumption of AAs in the liver. The results showed that culturing cells with sodium pyruvate significantly reduced the number of glutamate oxidation (P < 0.05). Addition of calcium pyruvate to low-protein diets significantly reduced urinary nitrogen excretion from 13.2 g/d (18.0% crude protein, CP) to 10.3 g/d (15.0% CP) or 7.80 g/d (13.5% CP) and total nitrogen excretion from 22.5 g/d (18.0% CP) to 17.8 g/d (15.0% CP) or 14.2 g/d (13.5% CP) (P < 0.05), without obviously negative effects on the nitrogen retention (P > 0.05). Addition of calcium pyruvate to low-protein diets significantly decreased essential AA consumption rate in the liver (P < 0.05). This diet modification reduced the net portal fluxes of NH3, glycine, and alanine, as well as urea production rate in the liver (P < 0.05). The results indicated that pyruvate is an effective substitute for glutamate as a supplement in low-protein diets, reducing porcine nitrogen excretion and nitrogen consumption.