[Relationship between gut microbiota and its metabolite dysregulation and postoperative cognitive dysfunction in elderly male C57BL/6J mice after laparotomy exploration].

Objective: To explore the relationship between gut microbiota and its metabolite dysregulation and postoperative cognitive dysfunction in elderly male C57BL/6J mice after laparotomy exploration. Methods: A total of 48 specific pathogen-free (SPF) male C57BL/6J mice, aged 16-17 months, were divided into two groups by random number table method: control group (n=24) and operation group (n=24). Mice in the operation group were induced with 1.4% isoflurane for 15 minutes, followed by a 10 minutes exploratory laparotomy anesthetized with 1.4% isoflurane and 100% oxygen, and anesthesia continued for 2 hours after surgery. Mice in control group were put in 100% oxygen for 2 hours. Feces and venous blood samples of both groups were collected 48 hours after surgery. Changes in the abundance and diversity of intestinal bacteria in the feces were detected by 16S rDNA gene sequencing. Functional changes of fecal metabolic profiles were detected by liquid chromatography tandem mass spectrometry (LC/MS) metabolomics and differential metabolite functions were analyzed. The serum level of interleukin (IL)-6, IL-1ß and tumor necrosis factor-α (TNF-α) were detected by Enzyme-linked immunosorbent assay (ELISA). The cognitive function of the mice was detected by Morris water maze test 3 days after operation. Results: The postoperative escape latency of mice in control group and operation group was (22.0±4.9) and (35.0±5.1) s, and the target quadrant residence time was (26.0±3.7) and (16.0±2.9) s, respectively. Compared with the control group, the postoperative escape latency of mice in the operation group was prolonged (P=0.035), and the residence time in the target quadrant was reduced (P=0.006). The difference of intestinal flora between the two groups was comparable. The expression levels of Escherichia coli, shigella and clostridium in the operation group were up-regulated, while the expression levels of rumen bacteria and butyricobacteria were down-regulated. Fecal metabolic profiles of mice in control group and operation group were obtained by LC/MS, and 14 and 21 different metabolites were screened in positive and negative ion modes, respectively. The different metabolites in positive ion mode were glutamic acid, 2-indoleic acid, kynuuric acid and glyceraldehyde. The negative ion pattern differential metabolites are methionine, aspartic acid, L-threonine, tyrosyl-threonine and 5-hydroxyindole-3-acetic acid. The identified differential metabolite pathways are mainly involved in amino acid, fatty acid and tryptophan metabolism and nucleotide synthesis. There were no significant differences in serum levels of IL-1ß, IL-6 and TNF-α between the two groups (all P>0.05). Conclusion: The dysregulated changes of gut microbiota and its metabolites are correlated with the occurrence of postoperative cognitive dysfunction in elderly male C57BL/6J mice. Anesthesia and surgery alter the structure of mice intestinal bacteria on the level of abundance, and change the metabolic balance and feces metabolomic phenotype.

[The association between baseline TPOAb and/or TgAb positivity and thyroid immune-related adverse events in patients with malignancies following treatment with immune checkpoint inhibitors].

Objective: To investigate the association between positive anti-thyroid peroxidase antibody (TPOAb) and/or anti-thyroglobulin antibody (TgAb) and the occurrence of thyroid immune-related adverse events (irAEs) in patients with malignant tumors who treated with immune checkpoint inhibitors (ICIs). Methods: A case-control study. A total of 116 patients with malignant tumor who received ICIs treatment and underwent thyroid function evaluation at Peking Union Medical College Hospital from January 2017 to April 2023 were enrolled retrospectively, including 77 males and 39 females, with a median age of (M(Q1, Q3)) 63.0 (55.0, 70.0) years. The patients were divided into the euthyroid group (n=58) and the thyroid irAEs group (n=58) according to whether thyroid irAEs occurred after ICIs treatment. The clinical characteristics and baseline anti-thyroid antibodies associated with the occurrence of thyroid irAEs after ICIs treatment in patients with malignant tumors were evaluated. Variables with statistical significance in univariate analysis were included in multivariate logistic regression model to analyze the risk factors for thyroid irAEs in patients with malignant tumors who received ICIs treatment. Results: In irAEs group, therewore 4 (3.4%) cases of clinical thyrotoxicosis, 23(19.8%) cases of subclinical thyrotoxicosis, 23 (19.8%) cases of clinical hypothyroidism, and 8(6.9%) cases of subclinical hypothyroidism. The positive rate of anti-thyroid antibodies at baseline in the thyrioid irAEs group was higher than that in the euthyroid group［16/58（27.6%）vs 3/58（5.2%），P=0.001］. After at least one course of ICIs treatment, the incidence of thyroid irAEs in patients with positive anti-thyroid antibodies at baseline was 84.2% (16/19), whereas it was 43.3% (42/97) in patients with negative anti-thyroid antibodies(P=0.001). Univariate logistic regression analysis showed that gender (OR=2.812, 95%CI:1.257-6.293), baseline thyroid autoantibodies were positive (OR=6.984, 95%CI: 1.909-25.547), baseline TgAb positivity (OR=8.909, 95%CI: 1.923-41.280), and baseline TPOAb positivity (OR=7.304, 95%CI: 1.555-34.308) were associated with thyroid irAEs (all P<0.05). Multivariate logistic regression analysis indicated that baseline TgAb positivity (OR=7.637, 95%CI: 1.617-36.072) was a risk factor for thyroid irAEs (P=0.01). Conclusions: The incidence of thyroid irAEs is higher in patients who are positive for baseline TPOAb and/or TgAb compared to those who are negative for TPOAb and TgAb. Patients with positive TgAb at baseline are at high risk of developing thyroid irAEs.

Clinical outcome of postoperative surgical site infections in patients with posterior thoracolumbar and lumbar instrumentation.

OBJECTIVES: Postoperative surgical site infection (SSI) is associated with high rates of disability, especially following instrumented spinal surgeries. The management of implant-associated SSI is challenging. This study analysed data from hospital databases to assess the incidence and characteristics related to postoperative SSI after posterior thoracolumbar and lumbar instrumentation. METHODS: Patient demographics, infection characteristics, details of treatment and perioperative factors were reviewed (January 2010-December 2020). Oswestry Disability Index (ODI), Patient Health Questionnaire-9 (PHQ-9) and Visual Analogue Scale (VAS) scores for back and leg pain were analysed preoperatively and postoperatively until final follow-up. RESULTS: Of the 27,881 procedures collected from the databases, 521 (1.8%) patients were diagnosed with SSI. Of these, 191 (36.7%) patients underwent at least one revision surgery for SSI. The infection rate was significantly higher in patients with lumbar spinal stenosis than in patients with scoliosis or kyphosis (P<0.01). The most commonly isolated pathogen was meticillin-susceptible Staphylococcus aureus (43.4%). The rate of complications secondary to antibiotic treatment was 7.8%, and long-term antibiotic suppression was reported in 15.2% of patients. Instrumentation was retained in 175 (91.6%) patients, and all SSIs were controlled without recurrence during follow-up. CONCLUSION: Analysis of 27,881 patients showed an average SSI rate of 1.8%. Patients with deep wound SSI can be treated successfully in most cases with retention of instrumentation. Early diagnosis, positive revision surgery with strict irrigation, thorough debridement and a long-term course of antibiotics are critical to eradicate infection, retain implants, decrease morbidity and achieve wound healing.

Male urethral diverticulum squamous cell carcinoma containing a calculus: a rare entity.

Male urethral diverticula with calculi have a low incidence. It is extremely rare when the diverticulum accompanied with carcinoma. We report a case of diverticulum of the male urethra containing giant calculi which developed into squamous cell carcinoma. The patient initially presented with lower urinary tract symptoms and a hard, painless perineal mass. We believe that the process of diagnosis and treatment is of great significance in clinical practice.

[Arthroscopic evaluation of tibial plateau fractures combined with meniscal tears and cruciate ligamentous injuries].

Objectives: To investigate the types of meniscal tears and cruciate ligamentous injuries in patients with tibial plateau fracture(TPF) following arthroscopic examination. Methods: The clinical data of 216 patients with TPF who underwent closed reduction and internal fixation (CRIF) from January 2016 to January 2019 at Trauma Emergency center, the Third Hospital of Hebei Medical University were analyzed retrospectively. There were 147 males (147 knees) and 69 females (69 knees),aged 46.3 years (range: 18 to 80 years). All patients underwent closed reduction for the displaced fracture fragment with the use of bidirectional rapid redactor,and minimally invasive percutaneous plate osteosynthesis. Intra-operative arthroscopic examination was performed to exam the stability of meniscus and the continuity of cruciate ligamentous after CRIF. The percentages and types of meniscal tears and cruciate ligamentous injuries were recorded. Results: The overall percentages of meniscal tears associated with TPFs was 48.6%(105/216). The most common pattern of meniscal tears was longitudinal tears, accounting for 43.8% (46/105), and it occurred most frequently in Schatzker type Ⅱ (58.7%, 27/46). Furthermore, the percentage of meniscal complex tears was 17.1% (18/105), occurring most frequently in Schatzker type Ⅴ (9/18). The overall percentage of cruciate ligamentous injuries associated with TPFs was 17.1% (37/216), and the percentages of anterior cruciate ligament (ACL) injuries was 64.9%(24/37), the percentage of posterior cruciate ligament injuries was 35.1%(13/37). Avulsion fracture was the most common pattern in ACL injuries, accounting for 41.7% (13/24), and all occurred in the tibial insertion site. Conclusions: In the present study, the percentages of meniscal tears and ligamentous injuries in TPFs are 48.6% and 17.1%, respectively. The most common types are meniscal longitudinal tears and ACL injury, occurring most frequently in Schatzker type Ⅱ and Ⅳ, respectively. Recognition of concomitant meniscal tears and cruciate ligamentous injuries in TPFs is helpful for trauma physicians to choose the best surgical treatment.

Linoleic acid and α-linolenic acid inhibit conjugative transfer of an IncX4 plasmid carrying mcr-1.

AIMS: The aim of this study was to determine the effects of unsaturated fatty acids on clinical plasmids. METHODS AND RESULTS: Two unsaturated fatty acids, linoleic acid (LA) and α-linolenic acid (ALA) at final concentration 0, 0·03, 0·3 and 3 mmol l-1 , respectively, were used to assess the effects on conjugative transfer of a mcr-1-harbouring plasmid pCSZ4 (IncX4) in conjugation experiment. The inhibitory mechanisms were analysed by molecular docking and the gene expression of virB11 was quantitated by qRT-PCR. Target plasmid diversity was carried out by TrwD/VirB11 homology protein sequence prediction analysis. Our results showed that LA and ALA inhibit plasmid pCSZ4 transfer by binding to the amino acid residues (Phe124 and Thr125) of VirB11 with dose-dependent effects. The expression levels of virB11 gene were also significantly inhibited by LA and ALA treatment. Protein homology analysis revealed a wide distribution of TrwD/VirB11-like genes among over 37 classes of plasmids originated from both Gram-negative and Gram-positive bacteria. CONCLUSIONS: This study demonstrates representing a diversity of plasmids that may be potentially inhibited by unsaturated fatty acids. SIGNIFICANCE AND IMPACT OF THE STUDY: Our work reported here provides additional support for application of curbing the spread of multiple plasmids by unsaturated fatty acids.

[The relationship between HPV integration and prognosis of cervical cancer].

Objective: To investigate the relationship between human papillomavirus (HPV) integration and prognosis of cervical cancer patients. Methods: The data of 82 patients with cervical cancer treated in the Radiotherapy Department of Peking Union Medical College Hospital from October 2004 to June 2012 were retrospectively analyzed.The patients were divided into poor prognosis group (recurrence or metastasis after surgery and adjuvant radiotherapy) and good prognosis group based on a propensity score matching strategy.The HPV integration of the two groups were detected by whole exome sequencing to determine whether the integration sites were located in the common fragile sites (CFSs). HPV integration and integration into CFSs were compared between the two groups. Results: Among the enrolled 82 patients, 37 were divided in poor survival group and 45 in good survival group. A total of 90 integration breakpoints were identified, 30 of them occurred in poor prognosis group and 60 occurred in good prognosis group. In the poor prognosis group, HPV integration occurred in 20 patients, 13 of them were inserted in CFSs of 11 patients, and the numbers in good prognosis group were 26, 17, 11, respectively. There were no significantly statistical differences in the number of HPV integration events (P=0.289), HPV integration patients (P=0.735), CFSs integration events (P=0.427), and CFSs integration patients (P=0.591) between the two groups. In poor prognosis group, more CFSs integration events occurred in patients with metastasis than those in patients with only local recurrence (9 vs 2, P=0.003). Conclusions: No significant differences are observed in HPV integration and HPV integration into CFSs between cervical cancer patients with different prognoses. HPV integration into CFSs may be associated with distant metastasis.

STYK1 promotes the malignant progression of laryngeal squamous cell carcinoma through targeting TGF-ß1.

OBJECTIVE: The aim of this study was to uncover the expression characteristic and biological function of STYK1 in the progression of laryngeal squamous cell carcinoma (LSCC), and to explore the underlying mechanism. PATIENTS AND METHODS: Expression level of STYK1 in 44 paired LSCC and adjacent normal tissues was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The relationship between STYK1 level and clinical parameters of LSCC patients was analyzed. Subsequently, the regulatory effect of STYK1 on the proliferative ability of AMC-HN-8 and Hep-2 cells was evaluated by cell counting kit-8 (CCK-8) assay and colony formation assay. Dual-Luciferase reporter gene assay and rescue experiments were conducted to uncover the role of STYK1/TGF-ß1 axis in regulating the progression of LSCC. RESULTS: STYK1 was significantly up-regulated in LSCC tissues than that of adjacent normal tissues (p<0.05). LSCC patients with high expression level of STYK1 exhibited significantly higher clinical stage and lower survival rate (p<0.05). Knockdown of STYK1 remarkably attenuated viability and clonality in Hep-2 cells, while overexpression of STYK1 achieved the opposite trends in AMC-HN-8 cells (p<0.05). TGF-ß1 was confirmed to be the direct target binding STYK1, whose expression level was negatively regulated by STYK1. TGF-ß1 was significantly down-regulated in LSCC tissues  (p<0.05). Meanwhile, its low expression predicted significantly poor prognosis of LSCC patients. In addition, TGF-ß1 was responsible for STYK1-regulated malignant progression of LSCC. CONCLUSIONS: STYK1 is upregulated in LSCC and is closely associated with T stage and poor prognosis. Furthermore, STYK1 promotes the proliferative ability of LSCC cells through targeting TGF-ß1, thus aggravating the malignant progression of LSCC.

Transplantation of bone marrow mesenchymal stem cells alleviates spinal cord injury via inhibiting Notch signaling.

OBJECTIVE: To analyze the mechanism of action by which the bone marrow mesenchymal stem cells (BMMSCs) repair the spinal cord injury (SCI) in rats via the Notch signaling pathway. MATERIALS AND METHODS: A total of 75 male rats aged about 12 weeks old were equally divided into group A (sham operation group), group B (model group), and group C (model group + BMMSCs). The SCI model was established by Allen's method, and the differences in presenilin-1, Hes1 and Notch proteins among the three groups of rats were evaluated via immunohistochemical staining and Western blotting. RESULTS: Group B exhibited a lower Basso, Beattie, and Bresnahan (BBB) score at each time point than group A and group C (p<0.05), and the BBB score in group C was lower than that in group A (p<0.05). According to the average optical density analysis results of the immunohistochemically stained proteins, the optical density of presenilin-1 protein in group A was lower than that in both group B and group C (p<0.05), and group C exhibited a lower optical density of presenilin-1 protein than group B. In group A, the protein expression of Hes1 in the bone marrow tissues of rats was not evident and weakly positive. Compared with that in group A, it was substantially raised (p<0.05), and the strongly positively expressed Hes1 proteins were yellow or dark brown in group B. Compared with that in group B, the color of Hes1 proteins was lighter (p<0.05), and the positive level of Hes1 proteins was lowered in group C. Group A showed inconspicuously positively expressed Notch proteins, group B brown active Notch proteins, while group C several brown Notch proteins. The optical density of Notch proteins in group A was overtly lower than that in group B and group C (p<0.05), and it was significantly lower in group C than that in group B (p<0.05). Additionally, group B had an evidently higher expression level of Notch proteins than the other two groups (p<0.05), and the expression level of Notch proteins in group C was a little higher than that in group A (p<0.05). CONCLUSIONS: BMMSCs inhibit the Notch signals to promote the proliferation and differentiation of rat neurons, thereby repairing spinal neurons.

Strontium-doped lanthanum iron nickelate oxide as highly efficient electrocatalysts for oxygen evolution reaction.

Pursuing efficient and low-cost catalysts for the sluggish oxygen evolution reaction (OER) is imperative for the large-scale deployment of promising electrochemical technologies such as water splitting and CO2 electrochemical reduction. The earth-abundant perovskite catalysts based on LaNiO3-δ show promise in OER catalysis because of their relatively low cost and their optimal electronic structure but suffer from low electrode-area normalized activity. In this work, we partially substituted La with Sr and Ni with Fe to enable a remarkably high OER activity with an ultra-low overpotential of 374 ±â€¯3 mV vs RHE at a current density of 10 mA cm-2 normalized by electrode geometric area. This performance even surpasses the performance of benchmark RuO2. Our results show that Sr could promote OER-active sites including Ni(III), O2-2/O-, and optimal Ni/Fe ratios, which significantly improve the surface intrinsic activity at the perovskite surface. Therefore, this work not only developed a highly efficient earth-abundant catalyst towards OER, but also demonstrated the effective modulation of catalyst surface interactions through A-site doping for perovskite oxides for key applications such as water splitting, CO2 electrochemical reduction and N2 electrochemical fixations.

Novel SLCO2A1compound heterozygous mutation causing primary hypertrophic osteoarthropathy with Bartter-like hypokalemia in a Chinese family.

PURPOSE: Primary hypertrophic osteoarthropathy (PHO) is an inherited disease characterized by digital clubbing, periostosis and pachydermia with defects in the degradation of prostaglandin E2 (PGE2). Mutations in SLCO2A1 gene-encoding prostaglandin transporter (PGT) resulted in PHO, autosomal recessive 2 (PHOAR2). The spectrum of mutations and variable clinical complications of PHOAR2 has been delineated. In this study, we investigated a Chinese PHO family with a manifestation of Bartter-like hypokalemia. METHODS: Clinical manifestations were collected and genetic analyses were performed in the PHO family. RESULTS: The 33-year-old male proband had severe hypokalemia due to potassium loss from the kidney, while his brother had mild hypokalemia. After being treated with etoricoxib, the serum potassium level of the patient increased rapidly to the normal range which corresponded with the reduction in his serum PGE2 and PE2 metabolite (PGEM) levels. A novel SLCO2A1 compound heterozygous mutation of p.I284V and p.C459R was identified in two PHO patients in this family. CONCLUSIONS: The present findings supported that the Bartter-like hypokalemia is a new complication of PHOAR2 caused by the high level of PGE2. Etoricoxib was demonstrated to be effective for the renal hypokalemia in PHO patients.

[Survival and prognostic factors analysis of primitive neuroectodermal tumor].

Objective: To investigate the clinical features and prognosis of primitive neuroectodermal tumor (PNET). Methods: The clinical data of 99 patients with PNET from February 1, 1998 to February 1, 2017 were retrospectively analyzed. Univariate analysis was performed using Kaplan-Meier and Log rank test. Multiviate Cox regression was applied to analyzed independent prognostic factor for patient survival. Results: Among the 99 patients, 81 were peripheral PNET(pPNET) and 18 were central PNET (cPNET) . Biopsy was performed exclusively in 16 cases, with R0 resection in 61 cases, with R1 resection in 4 cases, and with R2 resection in 18 cases. Twelve patients underwent surgery only, nine had chemotherapy only, and one received radiotherapy only. There were 72 patients who had combined treatment including chemotherapy, and 48 patients had combined therapy including radiotherapy. The one-year, three-year and five-year overall survival(OS) rates of the 99 PNET patients were 79.2%, 63.9% and 56.1% respectively, and median OS time was 14.0 months. The one-year, three-year and five-year progression free survival (PFS) rates of these patients were 42.7%, 25.7% and 19.8% respectively, and median PFS time was 8.0 months. The univariate analysis revealed that lymph node metastasis, surgical resection, numbers of cycles of chemotherapy and radiotherapy dose were the main factors affecting the OS (all P<0.05). Gender, age, lymph node metastasis, staging, and chemotherapy cycles were related to PFS in PNET patients (P<0.05). Multivariate analysis showed that the degree of surgical resection, chemotherapy cycle, and radiotherapy dosage were independent influencing factors of OS in PNET patients (risk ratio=1.856, 0.398, and 0.408, respectively, all P<0.05), and gender was an independent factor influencing PFS in PNET patients (risk ratio=0.494, P<0.05). Conclusions: Comprehensive therapy is the main therapy for PNET patients. The surgical resection, cycles of chemotherapy and radiotherapy dosage are independent prognostic factors for patient's OS.

Exploration on the relationship between the elderly osteoporosis and cardiovascular disease risk factors.

OBJECTIVE: To explore and discuss the correlation between osteoporosis and the risk factors of cardiovascular diseases in the elderly. PATIENTS AND METHODS: A total of 1240 patients, who were hospitalized in our hospital from January 2012 to January 2017, with the age ≥ 65 years old, were selected. All the patients were divided into osteoporosis group and normal bone mass group according to their bone mineral density. The general conditions, biochemical indexes, combined cardiovascular diseases, and the related risk factors, were recorded and analyzed. RESULTS: The proportion of patients with coronary heart diseases, hyperlipidemia, diabetes mellitus, and smoking in osteoporosis group was significantly higher than that in normal bone mass group (p < 0.05). Results of binary logistic regression analysis showed that homocysteine (HCY), low density lipoprotein (LDL) and total cholesterol (TC) were the major risk factors of osteoporosis in the elderly patients. High-density lipoprotein (HDL) and body weight were protective factors for senile patients with osteoporosis. Female, hypertension, coronary heart diseases, hyperlipidemia, and diabetes mellitus were the main risk factors of complication in the elderly patients with osteoporosis. CONCLUSIONS: Senile osteoporosis is closely correlated with cardiovascular diseases and related risk factors, including hypertension, coronary heart disease as well as hyperlipidemia, and should be early prevented and treated.

Comparison of clinicopathological features and prognosis of gastric cancer located in the lesser and greater curve.

PURPOSE: Little is known about the features of gastric cancer located in the lesser and greater curve. This study aims to investigate the clinicopathological features and prognosis of gastric cancer located in the lesser and greater curve. PATIENTS: From September 2008 to March 2015, 780 gastric cancer patients were enrolled in the present study. The associations between locations and features of patients were analyzed. RESULTS: There were 571 male (73.2 %) and 209 female (26.8 %) patients. The median age was 56 years (ranged 21-86). There were 684 tumors located in the lesser curve (87.7 %) and 96 located in the greater curve (12.3 %). The incidence of melena was significantly lower in patients with tumors located in the lesser curve than that in the greater curve (8.5 vs 15.6 %, P = 0.024). The median size of tumors in the lesser curve was significantly larger than that in the greater curve (5.0 (0.3-15) vs 4.0 cm (0.5-15), P = 0.001). The remaining clinicopathological features were comparable between the two groups (all P > 0.05). Tumor location was not a risk factor for the prognosis of gastric cancer by univariate and multivariate analysis (both P > 0.05). The postoperative complications (all P > 0.05) and prognoses (P = 0.279) were comparable between tumors located in the lesser and greater curve. CONCLUSIONS: The ratio of gastric cancer located in the lesser to greater curve was 7.1:1. Compared with tumors located in the greater curve, the incidence of melena was significantly lower and the tumor size was significantly larger in tumors located in the lesser curve. The prognoses were comparable between tumors located in the lesser and greater curve.

Expression of microRNA-106b and its clinical significance in cutaneous melanoma.

MicroRNA-106b (miR-106b) is overexpressed in various types of cancers and is associated with the regulation of carcinogenic processes. However, its clinical significance in cutaneous melanoma has not been reported. qRT-PCR was performed to examine the expression of miR-106b in 15 cases of dysplastic nevi, 17 cases of melanoma metastases, and 97 cases of primary cutaneous melanoma tissue samples. Survival rate was determined with Kaplan-Meier and statistically analyzed with the log-rank method between groups. Survival data were evaluated through multivariate Cox regression analysis. Significant differences in miR-106b expression were shown between dysplastic nevi and primary cutaneous melanomas (P < 0.01), between primary melanomas and metastatic cutaneous melanomas (P < 0.01), and between primary cutaneous melanomas and metastatic cutaneous melanomas (P < 0.001). We found that high miR-106b expression was correlated with Breslow thickness (P = 0.002), tumor ulceration (P = 0.002), and advanced clinical stage (P < 0.001). The patients with high miR-106b expression showed shorter 5-year overall survival than those with low miR-106b expression (P = 0.02; log-rank test). Multivariate regression analysis showed that the status of miR-106b expression was an independent prognostic factor for overall survival (HR = 2.09, 95%CI: 1.11-10.26, P = 0.02). This study showed that miR-106b may contribute to the progression of cutaneous melanoma and its up-regulation may be independently associated with poor prognosis of cutaneous melanoma. This suggests that miR-106b might serve as a promising biological marker for further risk stratification in the management of cutaneous melanoma.

Apoptotic-induced cleavage shifts HuR from being a promoter of survival to an activator of caspase-mediated apoptosis.

Little is known about the cellular mechanisms modulating the shift in balance from a state of survival to cell death by caspase-mediated apoptosis in response to a lethal stress. Here we show that the RNA-binding protein HuR has an important function in mediating this switch. During caspase-mediated apoptosis, HuR is cleaved to generate two cleavage products (CPs). Our data demonstrate that the cleavage of HuR switches its function from being a prosurvival factor under normal conditions to becoming a promoter of apoptosis in response to a lethal stress. In the absence of an apoptotic stimuli, HuR associates with and promotes the expression of caspase-9 and prothymosin α (ProT) mRNAs, and pro- and antiapoptotic factors, respectively, both of which have been characterized as important players in determining cell fate. During the early steps of caspase-mediated apoptosis, however, the level of caspase-9 protein increases, while ProT remains unchanged. Under these conditions, the two HuR-CPs selectively bind to and stabilize caspase-9 mRNA, but do not bind to ProT. Hence, taken together, our data show that by maintaining a threshold of expression of proapoptotic factors such as caspase-9 in response to a lethal stress, the HuR-CPs help a cell to switch from resisting death to undergoing apoptosis.

Wnt10b promotes growth of hair follicles via a canonical Wnt signalling pathway.

BACKGROUND: Wnt10b (wingless-related mouse mammary tumour virus integration site 10b) plays various roles in a wide range of biological actions, including hair-follicle development. AIM: To assess the roles that Wnt10b plays in postnatal hair-follicle growth. METHODS: Adenovirus vectors AdWnt10b, AdGFP, AdGFP plus AdRFP, AdWnt10b plus AdFrzB, and AdWnt10b plus AdSimBC were co-cultured separately with vibrissae. In situ protein expression of Wnt10b, ß-catenin and Lef1 was determined by immunohistochemistry, and the proliferation status of the hair follicle was detected by 5-bromo-2-deoxyuridine (BrdU) labelling. The presence of Wnt signalling molecules in the three stages of hair-follicle growth was detected by PCR-based microarray. RESULTS: AdWnt10b-infected cells were able to secrete bioactive Wnt10b, and when this was added into the basal medium, the vibrissae grew faster than in control medium or in medium containing canonical Wnt signalling antagonists. The in situ protein expression of Wnt10b was consistent with that of ß-catenin and Lef1. The expression locus of Wnt10b was almost the same as the proliferating cells labelled by BrdU in the anagen hair follicle. CONCLUSIONS: Wnt10b may promote hair-follicle growth by inducing the switch from telogen to anagen via a canonical Wnt signalling pathway to promote the proliferation of matrix cells.