Inhibition of the Tumor Suppressor Gene SPINK5 via EHMT2 Induces the Oral Squamous Cell Carcinoma Development.

Serine protease inhibitor Kazal-type 5 (SPINK5) has been revealed as a significant prognostic biomarker in oral squamous cell carcinoma (OSCC). However, there is little information regarding the detailed epigenetics mechanism underlying its dysregulation in OSCC. Using the Gene Expression Omnibus database, we identified SPINK5 as a significantly downregulated gene in OSCC tissues. Moreover, SPINK5 inhibited the malignant aggressiveness of HSC3 and squamous cell carcinomas (SCC)9 cells, whereas depletion of SPINK5 using shRNAs led to the opposite trend. The euchromatic histone lysine methyltransferase 2 (EHMT2) was found to bind to the SPINK5 promoter, and EHMT2 repressed the SPINK5 expression. SPINK5 reversed the stimulating effects of EHMT2 on the aggressiveness of HSC3 and SCC9 cells by impairing the Wnt/ß-catenin pathway. Wnt/ß-catenin inhibitor IWR-1 treatment reverted the malignant phenotype of OSCC cells in the presence of short hairpin RNA (sh)-SPINK5. Silencing of EHMT2 inhibited tumor growth and blocked the Wnt/ß-catenin signaling in OSCC, which was reversed by SPINK5 knockdown. Our study shows that SPINK5, mediated by the loss of EHMT2, can inhibit the development of OSCC by inhibiting Wnt/ß-catenin signaling and may serve as a treatment target for OSCC.

Synthesis of X@DRHC (X=Co, Ni, Mn) catalyst from comprehensive utilization of waste rice husk and spent lithium-ion batteries for efficient peroxymonosulfate (PMS) activation.

Highly efficient resource recycling and comprehensive utilization play a crucial role in achieving the goal of reducing resource wasting, environmental protection, and achieving goal of sustainable development. In this work, the two kinds waste resources of agricultural rice husk and metal ions (Co, Ni, and Mn) from spent lithium-ion batteries have been skillfully utilized to synthesize novel Fenton-like catalysts. Desiliconized rice husk carbon (DRHC) with rich pore structure and large specific surface area from rice husk has been prepared and used as scalable carrier, and dandelion-like nanoparticles cluster could be grown in situ on the surface of the carrier by using metal ions contained waste water. The designed catalysts (X@DRHC) as well as their preparation process were characterized in detail by SEM, TEM, BET, XRD and XPS, respectively. Meanwhile, their catalytic abilities were also studied by activating potassium peroxomonosulfate (PMS) to remove methylene blue (MB). The results indicate X@DRHC displays excellent degradation efficiency on MB with wide pH range and stable reusability, which is suitable for the degradation of various dyes. This work has realized the recycling and high-value utilization of waste resources from biomass and spent lithium-ion batteries, which not only creates an efficient way to dispose waste resources, but also shows high economic benefits in large-scale water treatment.

KRN7000 Reduces Airway Inflammation via Natural Killer T Cells in Obese Asthmatic Mice.

Although natural killer T cells (NKT cells) are altered in obese asthmatic mice, their function remains completely unclear. To further explore the potential mechanism of NKT cells in airway inflammation of obesity-associated asthma, we examined the effects of α-galactosylceramide (KRN7000) on airway inflammation in obese asthmatic mice. Male C57BL/6J mice were divided into five groups: (1) control; (2) asthma; (3) A + KRN, asthma with KRN7000; (4) obese asthma; and (5) OA + KRN, obese asthma with KRN7000. Cytometric bead array (CBA) was used to detect interleukin-4 (IL-4), IL-10, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) in the serum. Flow cytometry was used to detect NKT cells and CD69+ NKT cells. Airway inflammation was observed in pathological sections, and calmodulin (CaM) expression was observed by immunohistochemistry in lung tissues. Airway inflammation in the obese asthma group was more severe than that of the asthma group. Airway inflammation of the OA + KRN group was reduced more than that of the A + KRN group. CD69+ NKT cells were only significantly reduced in the OA + KRN group. The levels of serum IFN-γ and TNF-α increased more in the OA + KRN group than in the A + KRN group. CaM is widely expressed in the cytoplasm of the lung tissues and was sharply decreased in the OA + KRN group. KRN7000 can significantly reduce airway inflammation in obesity-associated asthma by regulating NKT cell cytokine secretion and intracellular calcium. These results may contribute to the development of novel therapeutic approaches.

A de novo SCN8A heterozygous mutation in a child with epileptic encephalopathy: a case report.

BACKGROUND: Epilepsy is a complex disorder caused by various factors, including genetic aberrance. Recent studies have identified an essential role of the sodium channel Nav1.6, encoded by the gene SCN8A, in epileptic encephalopathy. CASE PRESENTATION: Using parent-offspring trio targeted-exome sequencing, we identified a de novo heterozygous missense mutation c.3953A > G (p.N1318S) in SCN8A in a 3-year-and-9-month Chinese female patient with early infantile epileptic encephalopathy and a normal magnetic resonance imaging of the brain. CONCLUSIONS: This de novo mutation was only detected in the patient but not in her parents. Bioinformatic analysis indicates the pathogenicity of this mutation. Administration of the sodium channel blocker well controlled seizures in the patient. Therefore, we recommend trio targeted-exome sequencing as a routine method for pathogenic variant screening in patients with intractable epilepsy and a normal MRI.

Long noncoding RNA PCAT6 inhibits colon cancer cell apoptosis by regulating anti-apoptotic protein ARC expression via EZH2.

Prostate cancer-associated ncRNA transcript 6 (PCAT6) is a long intergenic noncoding RNA that is involved in the progression of prostate and lung cancer, acting as a potential diagnostic and prognostic biomarker in nonsmall cell lung cancer. However, little is known about PCAT6 expression and its clinical significance in colon cancer. Here, we aimed to investigate the clinical significance of PCAT6 in colon cancer and its underlying mechanism. The expression of PCAT6 was analyzed in colon cancer tissues using public databases, and a series of in vitro and in vivo experiments was performed to investigate the biological functions of PCAT6 in colon cancer cells and the underlying mechanisms. Our results demonstrated that PCAT6 was upregulated in colon cancer tissues compared with that in noncancerous tissues, correlating with poorer clinical stages and a worse survival status. In vitro and in vivo experiments illustrated PCAT6 promoted cell growth and inhibited cell apoptosis in colon cancer. Mechanistically, PCAT6 enhanced the coenrichment of EZH2 and H3K4me3 at the apoptosis repressor with caspase recruitment domain (ARC) genomic region, promoting the transcriptional activity of ARC. Our data highlighted that PCAT6 acts as a key activator of ARC expression by forming a complex with EZH2, inhibiting cell apoptosis and contributing to colon cancer progression. These findings elucidated that PCAT6 may be a novel prognostic predictor and therapeutic target of colon cancer.

Specific Cancer Cytosolic Drug Delivery Triggered by Reactive Oxygen Species-Responsive Micelles.

Cytosolic drug delivery, a major route in cancer therapy, is limited by the lack of efficient and safe endosomal escape techniques. Herein, we demonstrate a reactive oxygen species (ROS)-responsive micelle composed of methoxy polyethylene glycol-b-poly(diethyl sulfide) (mPEG-PS) copolymers which can induce specific endosome escape in cancer cells by changes in the hydrophobicity of copolymers. Owing to the more ROS levels in cancer cells than normal cells, the copolymers can be converted into more hydrophilic and insert into and destabilize the cancer intracellular endosome membrane after cellular uptake. More importantly, we show that acid-intolerant drugs successfully maintain their bioactivity and cause selective cytotoxicity for cancer cells over normal cells. Our results suggest that the endosomal escape induced by hydrophobic-hydrophilic exchange of copolymers has great potential to locally and efficiently deliver biological agents (e.g., proteins and genes) in the cancer cell cytosol.

Arthroscopic anterior cruciate ligament reconstruction guided by fluoroscopy-based navigation system / 中华外科杂志

<p><b>OBJECTIVE</b>To introduce the process and outline of fluoroscopy-based navigation system assisted anterior cruciate ligament (ACL) reconstruction, and evaluate its feasibility and accuracy.</p><p><b>METHODS</b>From September 2005 to February 2006, there were 30 cases ACL rupture patients who received fluoroscopy-based navigation system assisted arthroscopy operations for ACL reconstruction (navigation group). At the same time, there were 40 patients who underwent traditional ACL operation (traditional group). For the navigation group, the proper placement of femoral and tibial tunnels was planned preoperatively in standard AP and lateral X-ray view. Intraoperative fluoroscopic images were taken and input into navigation computer system to form the virtual interactive working fields. After placement and registration, signals from patient trackers, which fixed on the distal femur and tibia respectively, and tool trackers, which attached with ACL tibial and femoral guide, were captured by the optic navigation camera and the navigation computer system could pursue the real-time position of the ACL tools and projected into working field to help precise placement of femoral and tibial tunnels. Then results of two groups were observed and evaluated.</p><p><b>RESULTS</b>For navigation group, the mean time extension was 20 min. The tibial tunnel position was measured in all these cases. The tibial tunnel position of navigation group was 45.90% (SD 2.36%), and the traditional group was 41.05% (SD 6.01%). The difference was statistically significant (P < 0.05).</p><p><b>CONCLUSION</b>Fluoroscopy-based navigation system assisted ACL reconstruction improves the accuracy and reproducibility of the tunnel placement.</p>

Percutaneous pinning for the treatment of proximal humerus fractures / 中华外科杂志

<p><b>OBJECTIVE</b>The indication, surgical techniques and results had been discussed through clinical analysis of percutaneous pinning for the treatment of proximal humerus fractures.</p><p><b>METHODS</b>Forty-nine patients with 49 shoulders treated with percutaneous pinning had been reviewed with a mean follow-up period of 16.9 months. All were acute fractures, with a mean age of 40.4 years. There were 39 2-part surgical neck fractures, 6 impacted 2-part greater tuberosity fractures and 4 valgus-impaction 4-part fractures. SST (Simple Shoulder Test) questionnaire, ASES (American Shoulder & Elbow Surgeon) score, Constant-Murley score and UCLA score had been adopted for final evaluation at the latest follow-up.</p><p><b>RESULTS</b>The mean ASES score was 91.4, the mean VAS score was 1.7, the mean forward flexion was 146.7 degrees, external rotation 39.6 degrees, internal rotation at T(8)-T(9) level; the mean Constant-Murley score was 88.2; the mean UCLA score was 31.2; the mean number of questions for "yes" in SST questionnaire was 10.1. All fractures healed with a mean period of 8.8 weeks. No patient had been found for any evidence of humeral head necrosis at the latest follow-up The total satisfaction rate for pain relieve was 95.9% (47/49), and for functional recovery was 91.8% (45/49).</p><p><b>CONCLUSIONS</b>Most 2-part surgical neck fractures, impacted 2-part greater tuberosity fractures and 4-part valgus-impaction fractures are good indications for percutaneous pinning. With appropriate and intense rehabilitation, satisfactory results can be expected in percutaneous pinning for the treatment of certain types of proximal humerus fractures.</p>

Close needling for the treatment of calcifying tendinitis / 中华外科杂志

<p><b>OBJECTIVE</b>To study the effect of close needling in the treatment of calcifying tendonitis.</p><p><b>METHODS</b>Seventeen patients with calcifying tendonitis who had received close needling treatment were followed-up for 9.3 months on average. An 18-gauge or 16-gauge needle was used during needling. X-ray examination was given 4, 6, 8 and every 4 weeks after needling. SST (simple shoulder test) questionnaire, ASES (American Shoulder & Elbow Surgeon) score, constant-Murley score and UCLA score were adopted for evaluation before and after treatment.</p><p><b>RESULTS</b>Calcium deposition disappeared within 4 - 20 weeks mean 9.4 weeks in 15 of the 17 patients after needling for 1 - 3 times. Average ASES score before treatment was 47.7 (34 - 59), forward elevation was 90 degrees (70 degrees - 100 degrees ), external rotation was 15 degrees (0 degrees - 30 degrees ), and internal rotation was L3-4 (L1-buttock). Average constant-Murley score before treatment was 44.6 (34 - 54), UCLA score was 11.6 (8 - 15), and numbers of questions for "yes" in SST questionnaire was 3.4 (2 - 5). After needling the average ASES score was 87.1 (72 - 91), forward elevation was 143.5 degrees (120 degrees - 160 degrees ), external rotation was 40 degrees (30 degrees - 50 degrees ), internal rotation was T(8)-T(9), constant-Murley score was 87.8 (64 - 94), UCLA score was 29.5 (19 - 33), and numbers of questions for "yes" in SST questionnaire was 9.1 (6 - 12). Significant difference was found between before and after needling (ASES: P < 0.01, forward elevation, external rotation and internal rotation: P < 0.01, constant-Murley: P < 0.01, UCLA: P < 0.01, SST: P < 0.01).</p><p><b>CONCLUSIONS</b>Close needling is an effective method for the treatment of calcifying tendonitis. Symptoms and disability are greatly relieved non-surgically in most of patients. Care should be taken in differential diagnosis of degenerative calcification in chronic rotator cuff disease.</p>