The efficacy of levonorgestrelintrauterine system, drospirenone & ethinylestradiol tablets (II) and dydrogesterone in preventing the recurrence of endometrial polyps.

OBJECTIVE: To analyze the efficacy of levonorgestrelintrauterine system, Drospirenone & ethinylestradiol tablets (II), and dydrogesterone in preventing the recurrence of endometrial polyps after hysteroscopic endometrial polypectomy. METHODS: One hundred seventy patients who underwent hysteroscopic endometrial polypectomy in the Gynecology Department of Tianmen First People's Hospital in Hubei Province from January 2022 to June 2023 were randomly divided into the levonorgestrelintrauterine system group, Drospirenone & ethinylestradiol tablets (II) group, dydrogesterone group, and a control group. The recurrence rates, endometrial thickness, and menstrual volume changes at 6 and 12 months post-operation were compared among these four groups. RESULTS: The recurrence rates in the levonorgestrelintrauterine system group, Drospirenone & ethinylestradiol tablets (II) group, and dydrogesterone group were lower than the control group, with statistical significance (P < 0.01), with the levonorgestrelintrauterine system group having the lowest recurrence rate. The endometrial thickness at 6 and 12 months post-operation in the levonorgestrelintrauterine system group, Drospirenone & ethinylestradiol tablets (II) group, and dydrogesterone group was thinner than that of the control group and thinner than pre-operation, with statistical significance (P < 0.01). The menstrual volume at 3 months post-operation in the levonorgestrelintrauterine system group, Drospirenone & ethinylestradiol tablets (II) group, and dydrogesterone group was significantly less than the control group, and less than the pre-operation volume. CONCLUSION: Dydrogesterone, drospirenone & ethinylestradiol tablets (II), and levonorgestrelintrauterine system all play a role in preventing the recurrence of endometrial polyps, but levonorgestrelintrauterine system is significantly better than dydrogesterone and Drospirenone & ethinylestradiol tablets (II) in terms of postoperative recurrence rate, endometrial thickness, menstrual changes, and compliance, and is worth promoting in clinical application.

Early change of plasma Epstein-Barr virus DNA load and the viral lytic genome level could positively predict clinical outcome in recurrent or metastatic nasopharyngeal carcinoma receiving anti-programmed cell death 1 monotherapy.

PURPOSE: Patients with recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) have proven benefit from anti-programmed cell death 1 (anti-PD-1) monotherapy. Here, we retrospectively analyze the association of plasma Epstein-Barr virus (EBV) DNA load and tumor viral lytic genome with clinical outcome from 2 registered phase I trials. METHODS: Patients with RM-NPC from Checkmate 077 (nivolumab phase I trial in China) and Camrelizumab phase I trial between March 2016 and January 2018 were enrolled. Baseline EBV DNA titers were tested in 68 patients and EBV assessment was performed in 60 patients who had at least 3 post-baseline timepoints of EBV data and at least 1 post-baseline timepoint of radiographic assessment. We defined "EBV response" as 3 consecutive timepoints of load below 50% of baseline, and "EBV progression" as 3 consecutive timepoints of load above 150% of baseline. Whole-exome sequencing was performed in 60 patients with available tumor samples. RESULTS: We found that the baseline EBV DNA load was positively correlated with tumor size (spearman p < 0.001). Both partial response (PR) and stable disease (SD) patients had significantly lower EBV load than progression disease (PD) patients. EBV assessment was highly consistent with radiographic evaluation. Patients with EBV response had significantly improved overall survival (OS) than patients with EBV progression (log-rank p = 0.004, HR = 0.351 [95% CI: 0.171-0.720], median 22.5 vs. 11.9 months). The median time to initial EBV response and progression were 25 and 36 days prior to initial radiographic response and progression, respectively. Patients with high levels of EBV lytic genomes at baseline, including BKRF2, BKRF3 and BKRF4, had better progression-free survival (PFS) and OS. CONCLUSION: In summary, early clearance of plasma EBV DNA load and high levels of lytic EBV genes were associated with better clinical outcome in patients with RM-NPC receiving anti-PD-1 monotherapy.

Discovery, classification and application of the CPISPR-Cas13 system.

BACKGROUND: The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas system is an acquired immune system of bacteria and archaea. Continued research has resulted in the identification of other Cas13 proteins. OBJECTIVE: This review briefly describes the discovery, classification, and application of the CRISPR-Cas13 system, including recent technological advances in addition to factors affecting system performance. METHODS: Cas13-based molecular therapy of human, animal, and plant transcriptomes was discussed, including regulation of gene expression to combat pathogenic RNA viruses. In addition, the latest progress, potential shortcomings, and challenges of the CRISPR-Cas system for treatment of animal and plant diseases are reviewed. RESULTS: The CRISPR-Cas system VI is characterized by two RNA-guided higher eukaryotes and prokaryotes nucleotide-binding domains. CRISPR RNA can cleave specific RNA through the interaction between the stem-loop rich chain of uracil residues and the Cas13a protein. The CRISPR-Cas13 system has been applied for gene editing in animal and plant cells, in addition to biological detection via accurate targeting of single-stranded RNA. CONCLUSION: The CRISPR-Cas13 system offers a high-throughput and convenient technology for detection of viruses and potentially the development of anti-cancer drugs in the near future.

Effect of sitagliptin combined with Yiqi yangyin huoxue decoction on clinical efficacy and hemorheology in early diabetic nephropathy.

BACKGROUND: Early diabetic nephropathy (DN) is a complication of diabetes mellitus. It mainly affects kidney microvessels and glomerular function, and its timely and effective treatment is critical for early DN. However, the effects of treatments comprising simple Western medicine are not optimal. With the promotion and implementation of integrated Chinese and western medicine treatments, remarkable results have been achieved for many diseases. To this end, we explored the clinical efficacy of integrated traditional Chinese and western medicines for the treatment of early DN. AIM: To investigate the effect of sitagliptin tablets combined with Yiqi yangyin huoxue decoction on clinical efficacy and hemorheology in patients with early DN. METHODS: Through a retrospective analysis, 123 patients with early DN were admitted to the endocrinology clinic of the Changzhou NO. 7 People's Hospital from January 2021 to October 2022 and were selected as study subjects. After rigorous screening, 100 patients with early DN were enrolled. The control group (CG, n = 50) and the observation group (OG, n = 50) were divided according to the treatment method. The CG were treated with sitagliptin, and the OG were treated with sitagliptin plus the Yiqi yangyin huoxue decoction. Both groups were treated for 3 mo. For both groups, the baseline data and clinical efficacy were compared, and changes in blood glucose levels, lipid levels, renal function, and hematological indicators before (T0) and after (T1) treatment were assessed. RESULTS: The total effective rate for the OG was 94.00% and that of the CG was 80.00% (P < 0.05). After treatment (T1), the levels of fasting blood glucose, 2 h postprandial glucose, total cholesterol, triacylglycerol, and low-density lipoprotein cholesterol in OG patients were obviously lower than those in the CG (P < 0.05), and cystatin C, homocysteine, urinary microalbumin, and blood creatinine values in OG patients were also obviously lower than those in the CG (P < 0.05); erythrocyte deposition, plasma viscosity, whole blood high shear viscosity, and whole blood low shear viscosity were markedly lower in OG patients than in the CG (P < 0.05). CONCLUSION: Sitagliptin combined with Yiqi yangyin huoxue decoction has a remarkable effect when used to treat patients with early DN. Further, it is helpful in improving hemorheological indices and controlling disease progression.

Targeted heart repair by Tß4-loaded cardiac-resident macrophage-derived extracellular vesicles modified with monocyte membranes.

Recent studies have demonstrated the critical role of cardiac-resident macrophages (cMacs) in the maintenance of physiological homeostasis. However, recruitment of circulating monocyte-derived macrophages decreases cMac levels post-myocardial infarction (MI). Transplanting cMacs is not an ideal option due to their low survival rates and the risk of immunological rejection. However, extracellular vesicle therapy has the potential to provide a feasible and safe alternative for cardiac repair. In this study, cell membrane-modified extracellular vesicles (MmEVs) were developed for heart repair by modifying cMac-derived extracellular vesicles (mEVs) with monocyte membranes, resulting in immune evasion and sequential targeted localization to damaged regions through expression of CD47 on MmEVs and strong affinity between monocyte membrane proteins and CCL2. Additionally, to fully exploit the potential clinical application of MmEVs and achieve a better curative effect, thymosin ß4 (Tß4) was loaded into the nanoparticles, resulting in Tß4-MmEVs. In vitro experiments indicated that both the MmEVs and Tß4-MmEVs promoted cardiomyocyte proliferation and endothelial cell migration. Animal experiments suggested that MI mice treated with MmEVs and Tß4-MmEVs exhibited reduced myocardial fibrosis and increased vascular density compared to the control group. Thus, we posit that these targeted nanoparticles hold significant potential for MI adjuvant therapy and may open new avenues for cardiac repair and regeneration. STATEMENT OF SIGNIFICANCE: Extracellular vesicles (EVs) derived from bioactive parent cell sources involved in pathological and repair processes for cardiovascular disease have emerged as a compelling strategy for regenerative therapy. In this study, we constructed monocyte membrane-modified extracellular vesicles loaded with a drug (Tß4-MmEVs) for heart repair that exhibit extraordinary abilities of immune evasion and sequential localization to damaged regions owing to the presence of CD47 and the strong affinity between monocytes and damaged cardiomyocytes and endothelial cells. The bioactivities of Tß4-MmEVs on enhancing cardiomyocyte and endothelial cell proliferation were validated both in vitro and in vivo. Effective development and implementation of therapeutically membrane-modified nanoparticles from homologous origins can provide a reference for adjuvant therapy in clinical MI management.

4-1BB Targeting Immunotherapy: Mechanism, Antibodies, and Chimeric Antigen Receptor T.

4-1BB (CD137, TNFRSF9) is a type I transmembrane protein which binds its natural ligand, 4-1BBL. This interaction has been exploited to improve cancer immunotherapy. With ligand binding by 4-1BB, the nuclear factor-kappa B signaling pathway is activated, which results in transcription of corresponding genes such as interleukin-2 and interferon-γ, as well as the induction of T cell proliferation and antiapoptotic signals. Moreover, monoclonal antibodies that target-4-1BB, for example, Urelumab and Utomilumab, are widely used in the treatments of B cell non-Hodgkin lymphoma, lung cancer, breast cancer, soft tissue sarcoma, and other solid tumors. Furthermore, 4-1BB as a costimulatory domain, for chimeric antigen receptor T (CAR-T) cells, improves T cell proliferation and survival as well as reduces T cell exhaustion. As such, a deeper understanding of 4-1BB will contribute to improvements in cancer immunotherapy. This review provides a comprehensive analysis of current 4-1BB studies, with a focus on the use of targeting-4-1BB antibodies and 4-1BB activation domains in CAR-T cells for the treatment of cancer.

Ribavirin extends the lifespan of Caenorhabditis elegans through AMPK-TOR Signaling.

Aging is a process accompanied by widespread degenerative changes which are a major cause of human disease and disability. One goal of aging research is to develop interventions or drugs that can extend organism lifespan and treat age-related diseases. Here, we report the identification of a broad spectrum anti-viral agent, ribavirin, as a potential pharmacological aging intervention. Ribavirin extended the lifespan and healthspan of Caenorhabditis elegans by inhibiting Target of Rapamycin (TOR) signaling and activating AMP-activated protein kinase (AMPK). Moreover, our data indicate that ribavirin activated AMPK by reducing the levels of adenosine triphosphate (ATP) and lysosomal v-ATPase-Ragulator-AXIN Complex. Thus, our studies successfully identify ribavirin as a potential anti-aging drug, and indicate that its anti-aging effect is mediated via AMPK-TOR signaling.

Value of blood gas analysis and immunological indicators in early diagnosis and treatment monitoring of children with severe pneumonia and sepsis.

OBJECTIVE: This study was designed to investigate the clinical value of blood gas analysis and related immunological indicators in the early diagnosis and treatment monitoring of children with severe pneumonia and sepsis. METHODS: A retrospective study was conducted on children with pneumonia and sepsis and healthy children undergoing physical examination in the First People's Hospital of Fuyang Hangzhou from January 2020 to December 2020. A total of 31 children with pneumonia and sepsis (observation group) and 31 healthy children (control group) were included. The levels of partial pressure of carbon dioxide (PaCO2), partial pressure of oxygen (PaO2), pH, immunoglobulin A (IgA), immunoglobulin M (IgM), immunoglobulin G (IgG), complement 3 (C3) and complement 4 (C4) were compared between the two groups. The changes of blood gas analysis indices and immune indices in the observation group before treatment (T0), as well as after 1 month (T1), 2 months (T2) and 3 months (T3) of treatment were dynamically analyzed. RESULTS: Compared with the control group, the level of PaCO2 was significantly increased, and the levels of PaO2, pH, IgA, IgM, IgG, C3 and C4 were significantly decreased in the observation group, showing statistically significant differences (P < 0.05). With the progress of treatment, the levels of PaO2, PH, IgA, IgM, IgG, C3 and C4 showed a slowly increasing trend, while PaCO2 gradually decreased, and the differences between T3 and T0 were statistically significant (P < 0.05). ROC curve analysis showed that PaCO2, PaO2, PH, IgA, IgM, IgG, C3 and C4 had good diagnostic value for severe pneumonia combined with sepsis (P < 0.05). CONCLUSION: Blood gas analysis and immune indices exhibited high precision in early diagnosis and treatment monitoring of children with severe pneumonia and sepsis.

Assessment of Risk Factors Associated with Severe Endometriosis and Establishment of Preoperative Prediction Model.

Approximately 10% (176 million) of women of reproductive age worldwide suffer from endometriosis, which has a high rate of postoperative recurrence. The objective of this study was to investigate the risk factors of severe endometriosis and establish a preoperative prediction model. A retrospective analysis of a database established between January 2020 and March 2022 including 491 women with a pathology-based endometriosis diagnosis was conducted. Subjects were divided into two groups: the non-severe group (ASRM ≤ 40) and the severe group (ASRM > 40). Age ≥ 40 years, bilateral lesions, pelvic nodules, adenomyosis, APTT, CA125 ≥ 34.5 U/mL, D-dimer ≥ 0.34 mg/L, and maximum cyst diameter ≥ 58 mm were independent correlation factors for severe endometriosis. The logistic regression equation for these factors showed good diagnostic efficiency (AUC = 0.846), which was similar to the model with intraoperative indicators (AUC = 0.865). Patients with severe endometriosis also had a shorter APTT and higher D-dimer and PLT, indicating hypercoagulability. In conclusion, we constructed a simple and feasible formula involving parameters that are preoperatively accessible to predict the severity of endometriosis. This study is of reference value for determining the timing of and alternatives to surgery. At the same time, attention should be paid to the primary prevention of venous thrombosis and cardiovascular metabolic diseases in patients with severe endometriosis.

Bifidobacterium bifidum and Bacteroides fragilis Induced Differential Immune Regulation of Enteric Glial Cells Subjected to Exogenous Inflammatory Stimulation.

Enteric glial cells (EGCs) are involved in intestinal inflammation. In this study, we will investigate how Bifidobacterium bifidum (B.b.) and Bacteroides fragilis (B.f.) influence EGC regulation. After pretreatment with lipopolysaccharide (LPS) and interferon-γ (IFN-γ), the expressions of major histocompatibility complex class II (MHC-II), CD80, CD86, glial cell line-derived neurotrophic factor (GDNF), toll-like receptor 2 (TLR-2), and tumor necrosis factor-α (TNF-α) in EGCs were detected using polymerase chain reaction and western blot after co-culture with the supernatants of B.b. or B.f. (multiplicity of infection, 40:1 or 80:1). Finally, EGCs were co-cultured with naive CD4+ T cells, and the expressions of interleukin (IL)-2, IL-4, IL-10, and IL-17 in supernatant were measured using enzyme-linked immunosorbent assay (ELISA). The mRNA expressions of MHC-II and CD86 in EGCs were increased after combined stimulation with LPS and IFN-γ. The expressions of MHC-II, GDNF, TLR-2, and TNF-α were all significantly upregulated in stimulated EGCs. The B.b. supernatant downregulated the expressions of MHC-II, GDNF, TLR-2, and TNF-α in stimulated EGCs, whereas the B.f. supernatant upregulated TLR-2 expression and downregulated MHC-II expression. The expressions of IL-4, IL-2, and IL-17 after co-culture of naive CD4+ T cells and stimulated EGCs were significantly increased. The supernatant of B.b. or B.f. downregulated the expressions of these cytokines. The low-concentration B.b. supernatant upregulated IL-10 expression. Conclusions B.b. and B.f. may influence intestinal inflammation by regulating MHC-II, GDNF, TLR-2, and TNF-α expression in EGCs and IL-4, IL-2, IL-17, and IL-10 secretion.

Clinical Characteristics and Prognosis of Anti-AChR Positive Myasthenia Gravis Combined With Anti-LRP4 or Anti-Titin Antibody.

Objective: This study aimed to summarize the clinical characteristics and prognosis of patients with anti- acetylcholine receptor (AChR) positive myasthenia gravis (MG) with a combination of anti-LRP4 or Titin antibodies. Methods: A total of 188 patients with generalized MG before immunotherapy were retrospectively collected and then divided into three groups: single anti-AChR positive-MG (AChR-MG, 101 cases), anti-AChR combined with anti-low-density lipoprotein receptor-related protein four-positive MG (AChR+LRP4-MG, 29 cases), and anti-AChR combined with anti-Titin-positive MG (AChR+Titin-MG, 58 cases). Clinical manifestations, therapeutic responses to immunotherapy, and follow-up information were analyzed. Results: Of the 188 seropositive MG patients, 29 (15.4%) were positive for both AChR and LRP4 antibodies, and 58 (30.9%) were positive for both AChR and Titin antibodies. The mean disease onset ages in the three groups were 47.41 ± 7.0, 49.81 ± 9.2, and 48.11 ± 6.5 years, respectively. AChR+LRP4-MG showed female predominance (27.6% were males and 72.4% were females), with mild overall clinical symptoms. The AChR+Titin-MG group showed shorter times for conversion to generalized MG (5.14 ± 0.0 months) than the AChR-MG group (11.69 ± 0.0 months) and the AChR+LRP4-MG group (13.08 ± 0.5 months; P < 0.001 in both cases). Furthermore, AChR+Titin-MG group had increased bulbar dysfunction, higher incidences of thymoma (32.8 vs. 19.8% and 3.4%, P=0.035), more severe quantitative MG scores, as assessed by both QMG scores [15.5 (11.75-22.5) vs. 13 (8-19), P = 0.005; and 9 (6-14) P < 0.001], and MG-ADL scores [10 (8-13) vs. 8 (5-13), P = 0.018; and 6 (4-8), P < 0.001]. Treatment for AChR+Titin-MG was largely dependent on corticosteroids and immunosuppressive agents (56.7 vs. 19.2% and 16.7%, p = 0.028). The rates of achieving s(MMS) or better within 2 years following immunotherapy in the three groups were 51.5, 62.1, and 51.7%, respectively (P = 0.581). Conclusion: Clinical symptoms of anti-AChR positive MG combined with Titin antibody were more severe and progressed faster than those in the AChR + LRP4 and AChR groups. Regardless of antibody status, all patients responded well to immunotherapy and had relatively good prognoses.

LINC01605 knockdown induces apoptosis in human Tenon's capsule fibroblasts by inhibiting autophagy.

Glaucoma is an irreversible disease that causes blindness. Formation of a hypertrophic scar (HS) is the main cause of failure of glaucoma surgery. The long non-coding RNA LINC01605 is closely associated with the formation of HS; however, the function of LINC01605 in the formation and development of HS remains unclear. For this study, firstly, human Tenon's capsule fibroblasts (HTFs) and corneal epithelial cells (control cells) were collected from patients (n=5) with POAG who underwent glaucoma filtration surgery at Fuyang People's Hospital. Immunofluorescence analysis was performed to detect the expression levels of vimentin (one of the main components of medium fiber and plays an important role in the cytoskeleton and motility), keratin (the main component of cytoskeletal proteins) and LC3 (an autophagy marker). In addition, reverse transcription-quantitative PCR analysis was performed to detect LINC01605 expression. Besides, the Cell Counting Kit-8 assay was performed to assess the viability of human Tenon's capsule fibroblasts (HTFs). Next, flow cytometry was performed to detect HTF apoptosis. Furthermore, western blot analysis was performed for Bax, Bcl-2, Pro-caspase-3, cleaved caspase-3, phosphorylated (p-)Smad2, Smad2, α-SMA, MMP9, ATG7, p62, beclin 1, p-AMPK and AMPK in HTFs to determine the mechanism by which LINC01605 regulates the formation and development of HS. Moreover, a Transwell assay was performed to detect the migratory ability of HTFs. The results demonstrated that LINC01605 was significantly upregulated in HS tissues compared with that in normal (control/healthy) tissues. In addition, vimentin was highly expressed in HTFs, whereas keratin was expressed at a low level. Also, in HTFs, LINC01605 knockdown inhibited cell viability by inducing apoptosis, decreasing Smad2 activation and inhibiting autophagy. Furthermore, LINC01605 knockdown significantly inhibited the migratory ability of HTFs. Transfection with LINC01605 small interference RNAs significantly downregulated the expression levels of p-Smad2, α-SMA and MMP9 in HTFs. Furthermore, LINC01605 knockdown notably inhibited the viability and migration, and induced the apoptosis of HTFs, the effects of which were reversed following treatment with TGF-ß. Taken together, the results of the present study suggested that LINC01605 knockdown may inhibit the viability of HTFs by inducing the apoptotic pathway. These findings may provide novel directions for the treatment of HS.

Multiple intestinal hemangioma concurrent with low-grade appendiceal mucinous neoplasm presenting as intussusception-a case report and literature review.

BACKGROUND: Cases with intussusception caused by either intestinal hemangiomas or appendiceal mucinous neoplasms are extremely rare. CASE PRESENTATION: In this study, we reported a 47-year-old male presented with paroxysmal abdominal pain and postprandial bloating for 3 days. CT results indicated a high possibility of secondary intussusception in ascending colon. Histopathology indicated a mixed type of cavernous and capillary hemangioma, combined with low-grade appendiceal mucinous neoplasms (LAMNs) and intestinal obstruction. The patient underwent laparotomy and right hemicolectomy. Finally, the patient was followed up for 4 months with no disease progression. CONCLUSIONS: Rare studies reported the intestine hemangiomas coincided with appendix low-grade mucinous tumor. Its manifestations are not specific, which is a challenge in the preoperative diagnosis. For cases with intussusception that was not observed in time, it may lead to intestinal necrosis and diffuse peritonitis. Additionally, the ruptured mucinous tumor in the appendix may lead to pathogenesis of pseudomyxoma peritonei. Therefore, accurate diagnosis and appropriate surgery-based treatment contribute to the improvement of prognosis and severe outcomes among these patients.

Circular RNA hsa_circ_0072309 promotes tumorigenesis and invasion by regulating the miR-607/FTO axis in non-small cell lung carcinoma.

Emerging evidence has demonstrated that circular RNAs (circRNAs) are abnormally expressed in non-small cell lung carcinoma (NSCLC). However, the contributions of circRNAs to the tumorigenesis of lung adenocarcinoma (LUAD), one of the subtypes of NSCLC, remain unclear. Based on a microarray assay, we found that hsa_circ_0072309 was significantly upregulated in NSCLC compared with matched normal samples. Moreover, functional experiments demonstrated that hsa_circ_0072309 promotes the proliferation, migration, and invasion of NSCLC cells. In vitro precipitation of circRNAs, luciferase reporter assays, and biotin-coupled microRNA capture assays were carried out to investigate the mechanisms by which hsa_circ_0072309 regulates NSCLC. Through the above work, we found that hsa_circ_0072309 interacted with miR-607 via its miRNA response element to upregulate the expression of FTO, an m6A demethylase and downstream target of miR-607, thus promoting tumorigenesis of NSCLC. In total, our findings indicated the oncogenic role of hsa_circ_0072309 in NSCLC and provide a potential target for treatment.

Carcinoma cuniculatum in maxillary gingiva mimicking verruciform xanthoma: a case report.

Carcinoma cuniculatum (CC) is a rare and well-differentiated clinicopathological variant of squamous cell carcinoma (SCC) that is not common in head and neck. It is defined histologically by the infiltrative pattern of a deep, broad, and complex proliferation of stratified squamous epithelium with keratin cores and keratin-filled crypts. It has a propensity for local invasion and rare metastasis. This case report describes a 39-year-old man who was referred to our hospital with painful swelling in the right maxillary gingiva for 1 month and restriction of mouth opening for 1 week. Two biopsy examinations were negative for the diagnosis of malignancy, and the patient was misdiagnosed with verruciform xanthoma before an accurate diagnosis of CC. The biopsy reports were not in line with the imaging findings and clinical manifestations. Finally, he was diagnosed based on the combination of clinical manifestations and the pathological findings. Our case report provided a thorough clinical and histopathologic case of CC in maxillary gingiva, together with a brief review of the literature. In addition, we highlighted the difficulties in arriving at this uncommon diagnosis, and discussed the diagnosis of CC based on the combination of clinical manifestations and the pathological findings. To our knowledge, this is a very rare case of CC of the gingiva mimicking verruciform xanthoma.

Research progress on the source, production, and anti-cancer mechanisms of paclitaxel.

Paclitaxel, a tetracyclic diterpenoid compounds, was firstly isolated from the bark of the Pacific yew trees. Currently, as a low toxicity, high efficiency, and broad-spectrum natural anti-cancer drug, paclitaxel has been widely used against ovarian cancer, breast cancer, uterine cancer, and other cancers. As the matter of fact, natural paclitaxel from Taxus species has been proved to be environmentally unsustainable and economically unfeasible. For this reason, researchers from all over the world are devoted to searching for new ways of obtaining paclitaxel. At present, other methods, including artificial cultivation of Taxus plants, microbial fermentation, chemical synthesis, tissue and cell culture have been sought and developed subsequently. Meanwhile, the biosynthesis of paclitaxel is also an extremely attractive method. Unlike other anti-cancer drugs, paclitaxel has its unique anti-cancer mechanisms. Here, the source, production, and anti-cancer mechanisms of paclitaxel were summarized and reviewed, which can provide theoretical basis and reference for further research on the production, anti-cancer mechanisms and utilization of paclitaxel.

miR-219a-1 inhibits colon cancer cells proliferation and invasion by targeting MEMO1.

Colon cancer is the third most common cancer worldwide. Many miRNAs have been reported to be involved in colon cancer progression. However, there are only a few studies on the role of miR-219a-1 in colon cancer, and the molecular mechanisms involved remain unclear. The aim of this study was to investigate the miR-219a-1 level in patients with colon cancer and to explore both the effects and regulatory mechanisms of miR-219a-1 in the malignancy of colon cancer cells. Real-time PCR and western blot analysis were used to analyze the expression levels of miR-219a-1 and mediator of ErbB2-driven cell motility 1. Cell Counting Kit-8, transwell and wound-healing assays were performed to investigate the malignant ability of colon cancer cells. A luciferase assay was performed to explore whether miR-219a-1 could directly bind to 3'-UTR region of MEMO1. miR-219a-1 was found to be downregulated in colon cancer cell lines and in patients with colon cancer. Additionally, miR-219a-1 could inhibit colon cancer cell proliferation, invasion and migration. We identified MEMO1 as a novel potential target gene of miR-219a-1. Luciferase assays showed that miR-219a-1 could directly bind to 3'-UTR of MEMO1. Overexpression of miR-219a-1 in colon cancer cells could inhibit the expression of MEMO1. Furthermore, MEMO1 was upregulated in patients with colon cancer, which was inversely correlated with miR-219a-1 levels. In conclusion, our study revealed that miR-219a-1 exerts anti-tumor effects and regulates colon cancer cell proliferation, invasion and migration by targeting MEMO1, suggesting that miR-219a-1 could act as a therapeutic target in colon cancer.

Administration of allogeneic mesenchymal stem cells in lengthening phase accelerates early bone consolidation in rat distraction osteogenesis model.

BACKGROUND: Distraction osteogenesis (DO) is a surgical technique to promote bone regeneration which may require long duration for bone consolidation. Bone marrow-derived mesenchymal stem cells (MSCs) have been applied to accelerate bone formation in DO. However, the optimal time point for cell therapy in DO remains unknown. This study sought to determine the optimal time point of cell administration to achieve early bone consolidation in DO. We hypothesized that the ratio of circulating MSCs to peripheral mononuclear cells and the level of cytokines in serum might be indicators for cell administration in DO. METHODS: Unilateral tibial osteotomy with an external fixator was performed in adult Sprague Dawley rats. Three days after osteotomy, the tibia was lengthened at 0.5 mm/12 h for 5 days. At first, 5 rats were used to analyze the blood components at 6 different time points (3 days before lengthening, on the day lengthening began, or 3, 6, 10, or 14 days after lengthening began) by sorting circulating MSCs and measuring serum levels of stromal cell-derived factor 1 (SDF-1) and interleukin 1ß. Then, 40 rats were used for cell therapy study. A single dose of 5 × 105 allogeneic MSCs was locally injected at the lengthening site on day 3, 6, or 10 after lengthening began, or 3 doses of MSCs were injected at the three time points. Sequential X-ray radiographs were taken weekly. Endpoint examinations included micro-computed tomography analysis, mechanical testing, histomorphometry, and histology. RESULTS: The number of circulating MSCs and serum level of SDF-1 were significantly increased during lengthening, and then decreased afterwards. Single injection of MSCs during lengthening phase (on day 3, but not day 6 or 10) significantly increased bone volume fraction, mechanical maximum loading, and bone mineralization of the regenerate. Triple injections of MSCs at three time points also significantly increased bone volume and maximum loading of the regenerates. CONCLUSION: This study demonstrated that bone consolidation could be accelerated by a single injection of MSCs during lengthening when the ratio of peripheral MSCs to mononuclear cells and the serum SDF-1 presented at peak levels concurrently, suggesting that day 3 after lengthening began may be the optimal time point for cell therapy to promote early bone consolidation.

MiR-324-5p/PTPRD/CEBPD axis promotes papillary thyroid carcinoma progression via microenvironment alteration.

MiR-324-5p is overexpressed in papillary thyroid carcinoma (PTC) with lymph node metastasis and promotes malignant phenotypes of KTC-1 cell line. However, the detailed regulatory mechanism remains unknown. Tumor microenvironment plays a key role in tumor progression. CCAAT enhancer-binding protein delta (CEBPD) is important in immune and inflammatory responses. In this study, we investigated the interaction between miR-324-5p/PTPRD/CEBPD axis and tumor microenvironment in PTC progression. K1 and KTC-1 were transfected by lenti-CEBPD or CEBPD-sh vectors. Supernatant from different groups was harvested and added into culture media of human macrophages and HUVEC. Cell viability, colony formation, invasive and migrated cell number, and gap closure rate were elevated in lenti-CEBPD group. Compared with the control, supernatant from lenti-CEBPD group contained more abundant levels of VEGF and IL-4/IL-13, which, respectively, induced higher HUVEC invasion/migration rates and more obvious M2 marker (CD206) and genes (PPAR-γ and MRC-1) expression in macrophages. By means of luciferase reporter assay and gene manipulation, we identified that CEBPD was negatively regulated in PTC by protein tyrosine phosphatase receptor delta (PTPRD) which was the target of miR-324-5p. CEBPD-shRNA was also proved to reverse the effect of PTPRD-sh1 or miR-324-5p mimic on IL-4/IL-13 expression and HUVEC invasion. These results suggested that miR-324-5p/PTPRD/CEBPD axis was involved in the progression of PTC by inducing HUVEC invasion/migration and macrophage M2 polarization via VEGF and IL4/IL13, respectively.