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Abstract Background To reconstruct massive bone defects of the femoral diaphysis and proximal end with limited bilateral cortical bone after joint-preserving musculoskeletal tumor resections, two novel 3D-printed customized intercalary femoral prostheses were applied. Methods A series of nine patients with malignancies who received these novel 3D-printed prostheses were retrospectively studied between July 2018 and November 2021. The proximal and diaphyseal femur was divided into three regions of interest (ROIs) according to anatomic landmarks, and anatomic measurements were conducted on 50 computed tomography images showing normal femurs. Based on the individual implant-involved ROIs, osteotomy level, and anatomical and biomechanical features, two alternative 3D-printed prostheses were designed. In each patient, Hounsfield Unit (HU) value thresholding and finite element analysis were conducted to identify the bone trabecula and calcar femorale and to determine the stress distribution, respectively. We described the characteristics of each prosthesis and surgical procedure and recorded the intraoperative data. All patients underwent regular postoperative follow-up, in which the clinical, functional and radiographical outcomes were evaluated. Results With the ROI division and radiographic measurements, insufficient bilateral cortical bones for anchoring the traditional stem were verified in the normal proximal femur. Therefore, two 3D-printed intercalary endoprostheses, a Type A prosthesis with a proximal curved stem and a Type B prosthesis with a proximal anchorage-slot and corresponding locking screws, were designed. Based on HU value thresholding and finite element analysis, the 3D-printed proximal stems in all prostheses maximally preserved the trabecular bone and calcar femorale and optimized the biomechanical distribution, as did the proximal screws. With the 3D-printed osteotomy guide plates and reaming guide plates, all patients underwent the operation uneventfully with a satisfactory duration (325.00 ± 62.60 min) and bleeding volume (922.22 ± 222.36 ml). In the follow-up, Harris Hip and Musculoskeletal Tumor Society scores were ameliorated after surgery (P

Abstract The lactation capacity of dairy cows is critical to the productivity of the animals. Mastitis is a disease that directly affects the lactation capacity of cows. Staphylococcus aureus (S. aureus) is one of the most important pathogens that causes mastitis in dairy cows. The anti-inflammatory effect of Salvia miltiorrhiza polysaccharides (SMPs) has been demonstrated in mice and chickens. However, the effectiveness of SMPs in preventing and treating mastitis is unclear. Therefore, the purpose of this study was to explore the protective effect and mechanism of SMPs on mastitis caused by S. aureus. S. aureus was used to induce mastitis in rats, and three doses of SMPs (87.5, 175, 350 mg/kg, BW/d) were administered as treatments. The bacterial load, histopathology, and myeloperoxidase (MPO) and N-acetyl-β-D-glucosaminidase (NAGase) activities of mammary glands were observed and measured. Cytokines, including interleukin (IL)-1β, interleukin (IL)-6, and tumor necrosis factor α (TNF-α), were examined by qRT–PCR and ELISA. Key proteins in the NF-κB and MAPK signaling pathways were analyzed by Western blotting. The results showed that SMP supplementation could significantly reduce the colonization of S. aureus and the recruitment of inflammatory cells in mammary glands. S. aureus-induced gene transcription and protein expression of IL-1β, IL-6, and TNF-α were significantly suppressed in mammary glands. In addition, the increase in NF-κB and MAPK protein phosphorylation was inhibited by SMPs. These results revealed that supplementation with SMPs protected the mammary gland of rats against damage caused by S. aureus and alleviated the inflammatory response. This study provides a certain experimental basis for the treatment of S. aureus-induced mastitis with SMPs in the future.

The study was designed to explore the improvement effect of CSPCM (compound small peptide of Chinese medicine) on intestinal immunity and microflora through the treatment of different doses of CSPCM. A total of 100 male Kunming mice were weighed and divided into five groups, namely, group A (control group), group B (model group), group C (0.1 g/kg·bw CSPCM), group D (0.2 g/kg·bw CSPCM), and group E (0.4 g/kg·bw CSPCM). The use of CTX (cyclophosphamide) caused a series of negative effects: the secretion of IL-2, IL-22, TNF-α, sIgA, length of the villi, and the area of Pey's node were significantly reduced (P < 0.05); the depth of crypt and the percent of CD3+ and CD4+ cells were significantly increased (P < 0.05); the cecal flora taxa decreased; the abundance of Firmicutes and Lactobacillus increased; and the abundance of Bacteroidetes, Deferribacteres, Proteobacteria, Mucispirillum, Bacteroides, and Flexisprra decreased. The addition of CSPCM improved the secretion of cytokines and the development of intestinal villi, crypts, and Pey's node. The number of CD3+ and CD4+ cells in groups C, D, and E was significantly higher than that in group B (P < 0.05). Compared with group B, the abundance of Firmicutes in groups C, D, and E was decreased, and the Bacteroidetes, Deferribacteres, and Proteobacteria increased. The abundance of Lactobacillus decreased, while that of Mucispirillum, Bacteroides, and Flexisprra increased. It is concluded that cyclophosphamide is extremely destructive to the intestinal area and has a great negative impact on the development of the small intestine, the intestinal immune system, and the intestinal flora. The CSPCM can improve the negative effects of CTX.

The etiology of multiple sclerosis (MS) is not clear, and the treatment of MS presents a great challenge. This study aimed to investigate the pathogenesis and potential therapeutic targets of MS and to define target genes of matrine, a quinolizidine alkaloid component derived from the root of Sophorae flavescens that effectively suppressed experimental autoimmune encephalomyelitis (EAE), an animal model of MS. To this end, the GSE108000 gene data set in the Gene Expression Omnibus Database, which included 7 chronic active MS lesions and 10 control samples of white matter, was analyzed for differentially expressed genes (DEGs). X cell was used to analyze the microenvironmental differences in brain tissue samples of MS patients, including 64 types of immune cells and stromal cells. The biological functions and enriched signaling pathways of DEGs were analyzed by multiple approaches, including GO, KEGG, GSEA, and GSVA. The results by X cell showed significantly increased numbers of immune cell populations in the MS lesions, with decreased erythrocytes, megakaryocytes, adipocytes, keratinocytes, endothelial cells, Th1 cells and Tregs. In GSE108000, there were 637 DEGs, including 428 up-regulated and 209 down-regulated genes. Potential target genes of matrine were then predicted by the network pharmacology method of Traditional Chinese medicine, and 12 key genes were obtained by cross analysis of the target genes of matrine and DEGs in MS lesions. Finally, we confirmed by RT-PCR the predicted expression of these genes in brain tissues of matrine-treated EAE mice. Among these genes, 2 were significantly downregulated and 6 upregulated by matrine treatment, and the significance of this gene regulation was further investigated. In conclusion, our study defined several possible matrine target genes, which can be further elucidated as mechanism(s) of matrine action, and novel targets in the treatment of MS.

Background. Hepatocellular carcinoma (HCC) remains an important cause of cancer death. The molecular mechanism of hepatocarcinogenesis and prognostic factors of HCC have not been completely uncovered. Methods. In this study, we screened out differentially expressed lncRNAs (DE lncRNAs), miRNAs (DE miRNAs), and mRNAs (DE mRNAs) by comparing the gene expression of HCC and normal tissue in The Cancer Genome Atlas (TCGA) database. DE mRNAs were used to perform Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Then, the miRNA and lncRNA/mRNA modules that were most closely related to the survival time of patients with HCC were screened to construct a competitive endogenous RNA (ceRNA) network by weighted gene coexpression network analysis (WGCNA). Moreover, univariable Cox regression and Kaplan-Meier curve analyses of DE lncRNAs and DE mRNAs were conducted. Finally, the lasso-penalized Cox regression analysis and nomogram model were used to establish a new risk scoring system and predict the prognosis of patients with liver cancer. The expression of survival-related DE lncRNAs was verified by qRT-PCR. Results. A total of 1896 DEmRNAs, 330 DElncRNAs, and 76 DEmiRNAs were identified in HCC and normal tissue samples. Then, the turquoise miRNA and turquoise lncRNA/mRNA modules that were most closely related to the survival time of patients with HCC were screened to construct a ceRNA network by WGCNA. In this ceRNA network, there were 566 lncRNA-miRNA-mRNA regulatory pairs, including 30 upregulated lncRNAs, 16 downregulated miRNAs, and 75 upregulated mRNAs. Moreover, we screened out 19 lncRNAs and 14 hub mRNAs related to prognosis from this ceRNA network by univariable Cox regression and Kaplan-Meier curve analyses. Finally, a new risk scoring system was established by selecting the optimal risk lncRNAs from the 19 prognosis-related lncRNAs through lasso-penalized Cox regression analysis. In addition, we established a nomogram model consisting of independent prognostic factors to predict the survival rate of HCC patients. Finally, the correlation between the risk score and immune cell infiltration and gene set enrichment analysis were determined. Conclusions. In conclusion, the results may provide potential biomarkers or therapeutic targets for HCC and the establishment of the new risk scoring system and nomogram model provides the new perspective for predicting the prognosis of HCC.

Purpose: The purpose of this study was to evaluate the efficacy of brachytherapy combined with or without hormone therapy in patients with localized prostate cancer.Methods and Materials: We systemically searched the Medline, Web of Science, Cochrane Library and Embase databases for studies published between the databases' dates of inception and February 2019. The primary endpoints were the 5-year overall survival (OS) rates, 5-year biochemical progression-free survival (bPFS) rates and 10-year bPFS rates. The results were expressed as the relative risk (RR) and 95% confidence interval (CI). Based on the heterogeneity evaluated with the I2 statistic, a meta-analysis was performed using either a random- or fixed-effects model.Results: A total of 16 cohort studies including 9,359 patients met all the criteria for inclusion in the analysis. Our data showed that brachytherapy (BT) combined with hormone therapy (HT) increased the patients' 5-year bPFS rates (RR = 1.04, 95% CI: 1.01–1.08, P = 0.005) and 10-year bPFS rates (RR = 1.12, 95% CI: 1.02–1.23, P = 0.001) compared with BT monotherapy. However, BT combined with HT did not increase the patients' 5-year OS rates (RR = 1.02, 95% CI: 0.99–1.095, P = 0.1) compared with BT monotherapy.Conclusions: BT combined with HT can increase the bPFS rates of patients with localized prostate cancer, but it does not improve patients' OS rates.

Background/Aims: BushenShugan Formula (BSF) is a traditional Chinese medicine that has therapeutic effects on middle- and late-stage lung adenocarcinoma in clinical application. It was reported that Bushen Chinese medicine suppressed the onset of pre-metastatic niches in a murine model of spontaneous lung metastasis. However, the mechanisms of BSF on human lung adenocarcinoma remain unknown. Methods: Cell proliferation was determined by CCK8 and colony formation. Cell apoptosis and cell cycle were detected by flow cytometry. Cancer stem cells properties were examined by spheroid body formation. The migration and invasion abilities were analyzed by wound healing assay and transwell invasion assay. The mRNA expressions were determined by qRT-PCR. Western blotting analysis showed the protein levels. Results: BSF was shown to inhibit the proliferation of A549 cells in time- and concentration-dependent manners. Colony formation assays also indicated the antiproliferative effect of BSF against A549 cells. Cellular mechanistic studies demonstrated that BSF arrested the cell cycle in G2/M phase and induced apoptosis. Importantly, BSF could inhibit the epithelial-mesenchymal transition(EMT) of A549 cells through PI3K/AKT/NF-κB pathway. Conclusions: BSF effectively inhibited tumour growth, suggesting that it is a promising anticancer treatment for further clinical development.

Background/Aims: Retinoic acid receptor beta (RAR beta) is a retinoic acid receptor gene that has been shown to play key roles during multiple cancer processes, including cell proliferation, apoptosis, migration and invasion. Numerous studies have found that methylation of the RAR beta promoter contributed to the occurrence and development of malignant tumors. However, the connection between RAR beta promoter methylation and prostate cancer (PCa) remains unknown. This meta-analysis evaluated the clinical significance of RAR beta promoter methylation in PCa. Materials and Methods: We searched all published records relevant to RAR beta and PCa in a series of databases, including PubMed, Embase, Cochrane Library, ISI Web of Science and CNKI. The rates of RAR beta promoter methylation in the PCa and control groups (including benign prostatic hyperplasia and normal prostate tissues) were summarized. In addition, we evaluated the source region of available samples and the methods used to detect methylation. To compare the incidence and variation in RAR beta promoter methylation in PCa and non-PCa tissues, the odds ratio (OR) and 95% confidence interval (CI) were calculated accordingly. All the data were analyzed with the statistical software STATA 12.0. Results: Based on the inclusion and exclusion criteria, 15 articles assessing 1,339 samples were further analyzed. These data showed that the RAR beta promoter methylation rates in PCa tissues were significantly higher than the rates in the non-PCa group (OR=21.65, 95% CI: 9.27-50.57). Subgroup analysis according to the source region of samples showed that heterogeneity in Asia was small (I2=0.0%, P=0.430). Additional subgroup analysis based on the method used to detect RAR beta promoter methylation showed that the heterogeneity detected by MSP (methylation-specific PCR) was relatively small (I2=11.3%, P=0.343). Conclusion: Although studies reported different rates for RAR beta promoter methylation in PCa tissues, the total analysis demonstrated that RAR beta promoter methylation may be correlated with PCa carcinogenesis and that the RAR beta gene is particularly susceptible. Additional studies with sufficient data are essential to further evaluate the clinical features and prognostic utility of RAR beta promoter methylation in PCa.

Background/Aims: In contrast to men, women have experienced a rapid increase in lung cancer mortality. Numerous studies have found that the sex differences in lung cancer are due to reproductive hormones. Experiments in female mice with and without ovariectomy were performed to explore the possible mechanism by which sex hormones (and their receptors) influence lung cancer. Methods: Twenty-four female C57BL/6 mice aged 56-62 days were randomly divided into the ovariectomized group and the control group. In the ovariectomized group, the bilateral ovaries were removed via the dorsal approach, while the control group underwent a sham operation with bilateral ovarian fat resection at the same sites. After 3 weeks of recovery, Lewis lung cancer cells were transplanted into these mice by subcutaneous inoculation of a tumour cell suspension to establish the ovariectomized lung cancer model. Beginning on the 6th day after subcutaneous inoculation, mouse weight and transplanted tumour volume were measured every 3 days. After 3 weeks, all the mice were killed by cervical dislocation, and we measured the tumour weight. Mouse serum and tumour tissues were removed. Then, the serum levels of E2 (oestradiol) and T (testosterone) were detected by ELISA; the protein expression levels of AR (androgen receptor), ERα (oestrogen receptor α) and ERβ (oestrogen receptor β) were detected by Western Blot and IHC (immunohistochemistry); and the mRNA expression levels of AR, ERα and ERβ were detected by qRT-PCR (quantitative real-time polymerase chain reaction) in the ovariectomized and control groups. Results: Compared with the control group, both mouse weight and transplanted tumour volume increased rapidly in the ovariectomized group, and the transplanted tumour weight was significantly heavier in the ovariectomized group (1.83±0.40 and 3.13±0.43, P

Abstract Recently, numerous genome wide association studies (GWAS) and other case-control association studies examining the relationship between interleukin-7 receptor α chain (IL7RA) gene rs3194051, rs987107, rs11567686, and rs11567685 variants and multiple sclerosis (MS) risk have been conducted, but the conclusions have been inconsistent. The main objective of this meta-analysis was to more precisely explore the association of these four IL7RA variants with MS development. Twenty-seven eligible studies involving 9734 cases and 10436 controls were included in the present meta-analysis. Power calculation, publication bias, sensitivity analysis and cumulative meta-analysis were performed to derive a reliable conclusion. Our study indicated three IL7RA loci were significantly associated with increasing MS risk (rs3194051: recessive model: OR = 1.22, 95% CI 1.08–1.38; rs987107: recessive model: OR = 1.44, 95% CI 1.22–1.69; and rs11567686: dominant model: OR = 1.18, 95% CI 1.01–1.37). Additionally, IL7RA rs11567685 variants might not be related to MS development. In all, IL7RA locus polymorphisms could play an important role in the predisposition to MS, which could contribute to a better understanding the pathogenesis of multiple sclerosis.

The aim of this work was to analyze the expression of Ki-67 in ovary, testis of aging mice with anthocyanidin extract from Summer-black-grape. ICR mice (the aging group and the anthocyanidin-groups (50 mg/kg/D-group, 75 mg/kg/D-group and 100 mg/kg/D-group) were employed to evaluate the effect of grape anthocyanidin on reproductive system. The results showed that the anthocyanidin had strong scavenging ability for free radicals, the level of oxidation in serum of mice treated with anthocyanidin was low, and the pathological changes were not obvious. In the anthocyanidin group, the Ki-67 positive particles in the testis and ovary tissue were significantly decreased. The anthocyanidin of Summer-black-grape reduces the expression of Ki-67 protein in the testis or ovary of aging mice. In gonadal cells of aging mice, the anthocyanidin were shown protective effect in the proliferation. [ABSTRACT FROM AUTHOR]