Physical therapy for end-stage hemophilic arthropathy: a case report.

This report introduces a young adult who has been in bed for more than ten years with end-stage hemophilic arthropathy. He didn't have access to factor VIII (FVIII) in the early stage of hemophilia due to the high costs of clotting replacement therapy. As a result, he is experiencing some difficulties, such as joint contracture, muscular atrophy, severe pain, and poor function of cardiopulmonary. He came to visit us for a comprehensive rehabilitation program, and, finally, he achieved the basic goal of self-care in daily life.

LncRNA CRNDE promotes cell proliferation, migration and invasion of ovarian cancer via miR-423-5p/FSCN1 axis.

Ovarian cancer seriously threatens the health of women. LncRNA CRNDE is known to be upregulated in ovarian cancer. However, the mechanism by which CRNDE regulates the progress of ovarian cancer is largely unknown. MTT assay was applied to measure the cell viability. Colony formation assay was used to measure the cell proliferation. Cell migration was tested by wound healing, and Transwell assay was performed to detect cell invasion. In addition, the expression of miR-423-5p, CRNDE and FSCN1 were detected by RT-qPCR and western blotting, respectively. Meanwhile, dual-luciferase reporter assay and RIP assay were performed to explore the correlation between miR-423-5p and CRNDE (or FSCN1). CRNDE and FSCN1 were upregulated in ovarian cancer cells (SKOV3, CAOV-3, IGROV1, A2780 and C13K), while miR-423-5p was downregulated. Moreover, silencing of FSCN1/CRNDE significantly decreased proliferation, migration and invasion of ovarian cancer cells (SKOV3 and CI3K) via suppressing MMP-2 and MMP-9. In addition, CRNDE could sponge miR-423-5p, and FSCN1 was confirmed to be the direct target of miR-423-5p. Furthermore, CRNDE knockdown-induced inhibition of FSCN1 was notably reversed by miR-423-5p downregulation. Knockdown of CRNDE inhibited cell proliferation, migration and invasion of ovarian cancer via miR-423-5p/FSCN1 axis. Thus, CRNDE may serve a new target for ovarian cancer.

[Moxibustion Improved Transcutaneous Oxygen Tension and Exercise Capacity in Lower Limbs of Peripheral Arterial Disease].

OBJECTIVE: To observe the effects of moxibustion and treadmill exercise on transcutaneous oxygen tension and exercise capacity in lower limbs of peripheral arterial disease (PAD). METHODS: Totally 58 mild-to-moderate PAD patients were assigned to the control group (18 cases), the moxibustion group (20 cases), and the treadmill exercise group (20 cases) by random digit table. Patients in the control group received conventional drug therapy for 12 weeks. Patients in the moxibustion group and the treadmill exercise group additionally received moxibustion [at Zusanli (ST36), Sanyinjiao (SP6), Yongquan (KI1)] and treadmill exercise respectively, once per day, 5 times per week for 12 weeks in total. Ankle-Brachial Index (ABI) , transcutaneous oxygen tension (TcPO2), 6-min walking test (6MWT), and walking impairment questionnaire (WIQ) were assessed before and after treatment. RESULTS: Compared with the control group and the same group before treatment, there was no statistical difference in ABI in the moxibustion group and the treadmill exercise group (P > 0.05). But TcPO2, 6MWT, and WIQ were obviously elevated (P < 0.01). Besides, 6MWT and WIQ assessment of the treadmill exercise group were better than that of the moxibustion group (P < 0.01) after intervention. CONCLUSION: Moxibustion and treadmill exercise could improve the exercise capacity and TcPO2of lower limbers in PAD patients.

Delineation of fatty acid metabolism in gastric cancer: Therapeutic implications.

BACKGROUND: The prognosis of gastric cancer is extremely poor. Metabolic reprogramming involving lipids has been associated with cancer occurrence and progression. AIM: To illustrate fatty acid metabolic mechanisms in gastric cancer, detect core genes, develop a prognostic model, and provide treatment options. METHODS: Raw data from The Cancer Genome Atlas and Gene Expression Omnibus databases were collected and analyzed. Differentially expressed fatty acid metabolism genes were identified and incorporated into a risk model based on least absolute shrinkage and selection operator regression analysis. Then, patients from The Cancer Genome Atlas were assigned to high- and low-risk cohorts according to the mean value of the risk score as the threshold, which was verified in the Gene Expression Omnibus database. Relationships between chemotherapeutic sensitivity and tumor microenvironment features were assessed. RESULTS: An integrated evaluation was performed in this study. Fatty acid metabolism-related genes were used to construct the risk model. Patients classified into the high-risk cohort were considered to be resistant to chemotherapy based on results of the "pRRophetic" R package. Patients in the high-risk cohort were associated with type I/II interferon activation, increased inflammation level, immune cell infiltration, and tumor immune dysfunction based on the exclusion algorithm, indicating the potential benefit of immunotherapy in these patients. CONCLUSION: We constructed a fatty acid-related risk score model to assess the comprehensive fatty acid features in gastric cancer and validated its vital role in prognosis, chemotherapy sensitivity, and immunotherapy.

Systematic sequential therapy for ex vivo liver resection and autotransplantation: A case report and review of literature.

BACKGROUND: Perihilar cholangiocarcinoma (pCCA) is a highly malignant tumor arising from the biliary tree. Radical surgery is the only treatment offering a chance of long-term survival. However, limited by the tumor's anatomic location and peri-vascular invasion, most patients lose the chance for curative treatment. Therefore, more methods to increase the resectability of tumors as well as to improve outcomes are needed. CASE SUMMARY: A 68-year-old female patient had a hepatic hilar mass without obvious symptoms. Laboratory results showed hepatitis B positivity. Magnetic resonance imaging indicated that the mass (maximum diameter: 41 mm) invaded the left and right branches of the main portal vein, as well as the middle, left and right hepatic veins; enlarged lymph nodes were also detected in the hilum. The patient was diagnosed with pCCA, and the clinical stage was determined to be T4N1M0 (stage IIIC). Considering the tumor's anatomic location and vascular invasion, systematic conversion therapy followed by ex vivo liver resection and autotransplantation (ELRA) was determined as personalized treatment for this patient. Our original systemic sequential therapeutic strategy (lenvatinib and tislelizumab in combination with gemcitabine and cisplatin) was successfully adopted as conversion therapy because she achieved partial response after three cycles of treatment, without severe toxicity. ELRA, anastomotic reconstruction of the middle hepatic vein, right hepatic vein, root of portal vein, inferior vena cava and right hepatic artery, and lymph node dissection were performed at one month after systemic therapy. Pathological and immunohistochemical examination confirmed the diagnosis of pCCA with lymph node metastasis. Although the middle hepatic vein was partially obstructed four months later, hepatic vein stent implantation successfully addressed this problem. The patient has survived for 22 mo after the diagnosis, with no evidence of recurrence or metastasis. CONCLUSION: An effective therapeutic strategy for conversion therapy greatly increases the feasibility and efficiency of ELRA.

Primary repair of esophageal atresia gross type C via thoracoscopic magnetic compression anastomosis: A case report.

BACKGROUND: Esophageal atresia (EA) is a life-threatening congenital malformation in newborns, and the traditional repair approaches pose technical challenges and are extremely invasive. Therefore, surgeons have been actively investigating new minimally invasive techniques to address this issue. Magnetic compression anastomosis has been reported in several studies for its potential in repairing EA. In this paper, the primary repair of EA with magnetic compression anastomosis under thoracoscopy was reported. CASE SUMMARY: A full-term male weighing 3500 g was diagnosed with EA gross type C. The magnetic devices used in this procedure consisted of two magnetic rings and several catheters. Tracheoesophageal fistula ligation and two purse strings were performed. The magnetic compression anastomosis was then completed thoracoscopically. After the primary repair, no additional operation was conducted. A patent anastomosis was observed on the 15th day postoperatively, and the magnets were removed on the 23rd day. No leakage existed when the transoral feeding started. CONCLUSION: Thoracoscopic magnetic compression anastomosis may be a promising minimally invasive approach for repairing EA.

Delineation of a SMARCA4-specific competing endogenous RNA network and its function in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common malignancy worldwide, and the mortality rate continues to rise each year. SMARCA4 expression has been associated with poor prognosis in various types of cancer; however, the specific mechanism of action of SMARCA4 in HCC needs to be fully elucidated. AIM: To explore the specific mechanism of action of SMARCA4 in HCC. METHODS: Herein, the expression level of SMARCA4 as well as its association with HCC prognosis were evaluated using transcriptome profiling and clinical data of 18 different types of cancer collected from The Cancer Genome Atlas database. Furthermore, SMARCA4-high and -low groups were identified. Thereafter, gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to identify the function of SMARCA4, followed by construction of a SMARCA4-specific competing endogenous RNA (ceRNA) network using starBase database. The role of SMARCA4 in immunotherapy and its association with immune cells were assessed using correlation analysis. RESULTS: It was observed that SMARCA4 was overexpressed and negatively correlated with prognosis in HCC. Further, SMARCA4 expression was positively associated with tumor mutational burden, microsatellite stability, and immunotherapy efficacy. The SNHG3/THUMP3-AS1-miR-139-5p-SMARCA4 ceRNA network was established and could be assumed to serve as a stimulatory mechanism in HCC. CONCLUSION: The findings of this study demonstrated that SMARCA4 plays a significant role in progression and immune infiltration in HCC. Moreover, a ceRNA network was detected, which was found to be correlated with poor prognosis in HCC. The findings of this study could contribute towards the identification of predictive markers for immunotherapy and a novel mechanism of action for HCC treatment.

EPAC Negatively Regulates Myelination via Controlling Proliferation of Oligodendrocyte Precursor Cells.

Increasing evidence suggests that a cyclic adenosine monophosphate (cAMP)-dependent intracellular signal drives the process of myelination. Yet, the signal transduction underlying the action of cAMP on central nervous system myelination remains undefined. In the present work, we sought to determine the role of EPAC (exchange protein activated by cAMP), a downstream effector of cAMP, in the development of the myelin sheath using EPAC1 and EPAC2 double-knockout (EPACdKO) mice. The results showed an age-dependent regulatory effect of EPAC1 and EPAC2 on myelin development, as their deficiency caused more myelin sheaths in postnatal early but not late adult mice. Knockout of EPAC promoted the proliferation of oligodendrocyte precursor cells and had diverse effects on myelin-related transcription factors, which in turn increased the expression of myelin-related proteins. These results indicate that EPAC proteins are negative regulators of myelination and may be promising targets for the treatment of myelin-related diseases.

Screening and validating the core biomarkers in patients with pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PAAD) is one of the most common malignant tumors in digestive system. To find the new therapeutic targets and explore potential mechanisms underlying PAAD, the bioinformatics has been performed in our study. The PAAD gene expression profile GSE28735 was chosen to analyze the differentially expressed genes (DEGs) between PAAD carcinoma tissues and normal adjacent tissues from 45 patients with PAAD. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed using Database for Annotation, Visualization and Integrated Discovery (DAVID). Moreover, a protein-protein interaction (PPI) network was also constructed to help us screen the top 20 hub genes in this profile and demonstrated the underlying interactions among them. The Gene Expression Profiling Interactive Analysis (GEPIA) was further performed in order to valid the mRNA levels of top5 up-regulated and top5 down-regualted DEGs, apart from exploring their association with survival rate as well as tumor stage. Finally, Q-PCR was further employed to valid the top5 up-regulated and top5 down-regulated genes in patients with PAAD. In our study, there were a total of 444 DEGs captured (271 up-regulated genes and 173 down-regulated genes). Among these DEGs, the top5 up-regulated genes were CEACAM5, SLC6A14, LAMC2, GALNT5 and TSPAN1 while the top5 down-regulated genes were GP2, CTRC, IAPP, PNLIPRP2 and PNLIPRP1. GO analysis disclosed that the DEGs were predominantly enriched in cell adhesion, lipid metabolism, integrin binding, proteolysis and calcium ion binding. KEGG analysis disclosed that the enriched pathway included pancreatic secretion, protein digestion and absorption, fat digestion and absorption, ECM-receptor interaction, focal adhesion and PI3K-Akt signaling pathway. Survival analysis unveiled that the high expression levels of SLC6A14, GALNT5 and TSPAN1 may correlate with the poor prognosis while high expression levels of IAPP may contribute to a better prognosis in patients with PAAD. Additionally, the levels of CEACAM5, SLC6A14, LAMC2 and GALNT5 were also associated with tumor stage. Furthermore, according to the connectivity degree of these DEGs, we selected the top20 hub genes, namely ALB, FN1, EGF, MMP9, COL1A1, COL3A1, FBN1, CXCL12, POSTIN, BGN, VCAN, THBS2, KRT19, MET, MMP14, COL5A2, GCG, MUC1, MMP1 and CPB1, which were expected to be promising therapeutic targets in PAAD. Collectively, our bioinformatics analysis showed that DEGs and hub genes may be defined as new biomarkers for diagnosis and for guiding the therapeutic strategies of PAAD.

Expression of growth differentiation factor 9 (GDF9), ALK5, and claudin-11 in adult alpaca testis.

Growth differentiation factor 9 (GDF9) is an oocyte-derived factor critical for folliculogenesis. Recently, in vitro data showed that GDF9 inhibited the localization of tight junction (TJ) proteins, suggesting that GDF9 could potentially regulate spermatogenesis in vivo, via inhibition of Sertoli cell TJ function. The purpose of the present study was to determine the expression and localization of GDF9, its receptor, ALK5, and its latent target protein, claudin-11 (one of TJ proteins) in adult alpaca testis using Western blot and immunohistochemistry. Western blotting results demonstrated that GDF9, ALK5 and claudin-11 were expressed in the adult alpaca testis. Immunohistochemistry revealed that GDF9 was expressed stage-specifically in the cytoplasm of pachytene spermatocytes and round spermatids of the adult alpaca seminiferous epithelium. Type I receptor, ALK5 was mainly localized in the cytoplasm of round spermatids and Leydig cells, and to a lesser extent in the cytoplasm of pachytene spermatocytes and Sertoli cells. Its latent target protein, claudin-11, was perpendicular or parallel to the basal lamina in the basal part of Sertoli cells. These results indicated that GDF9, as a paracrine and autocrine growth factor derived from round spermatids and pachytene spermatocytes, is involved in regulating spermatogenesis via action on germ cells or somatic cells (i.e. Leydig cells, Sertoli cells).