A nomogram predicting the outcome of gallbladder cancer patients with different target organ metastases.

OBJECTIVE: Gallbladder cancer (GBC) is a highly aggressive malignancy that is associated with a high mortality rate globally. Unfortunately, distant metastases are often detected at the time of diagnosis. Therefore, we investigated the survival outcomes of gallbladder cancer patients with different metastases targeting organs, analyzed their prognosis, and explored their hidden clinical value. PATIENTS AND METHODS: Through data screening, a total of 398 patients with GBC with different target organ metastases were analyzed retrospectively, including patients with solitary bone metastasis, solitary liver metastasis, solitary lung metastasis, and multiple organ metastases. The survival results of different variables were plotted as Kaplan-Meier survival curves. Univariate and multivariate Cox regression models were used to screen study variables and identify independent prognostic factors. Finally, a nomogram was established to systematically evaluate the prognosis of patients with multiple organ metastasis. RESULTS: In the patient cohort, thirteen (3.3%) had solitary bone metastasis, 290 (72.9%) had solitary liver metastasis, 22 (5.5%) had solitary lung metastasis, and 73 (18.3%) had multiple organ metastases (including liver, lung, bone and brain metastases). Multivariate Cox analysis showed that the overall survival (OS) of patients with solitary lung metastasis was significantly better than that of patients with other organ metastasis (p = 0.038), while the difference in tumor cancer-specific survival (CSS) of this factor was not statistically significant (p > 0.05). Surgery and chemotherapy were independent prognostic protective factors for OS and CSS. The OS-related models exhibited a C-index of 0.74 (95% CI: 0.71-0.77), while the CSS-related models showed a slightly lower C-index of 0.73 (0.70-0.76). Both the OS- and CSS-related clinical prediction models had good accuracy. CONCLUSIONS: This study shows that different target organ metastases may affect the OS of patients with distant metastatic GBC. Patients receiving palliative surgery, primary site resection, radical surgery, and chemotherapy have significant survival benefits in terms of OS and CSS.

Comparison of laparoscopic common bile duct exploration and endoscopic retrograde cholangiopancreatography combined with laparoscopic cholecystectomy for patients with gallbladder and common bile duct stones a meta-analysis of randomized controlled trials.

OBJECTIVE: This study aimed to compare the efficacy and safety of laparoscopic common bile duct exploration (LCBDE) and endoscopic retrograde cholangiopancreatography (ERCP) combined with laparoscopic cholecystectomy (LC) to determine which one provides a better outcome for patients with gallbladder and common bile duct stones. MATERIALS AND METHODS: An electronic literature search was undertaken using Embase, Medline, PubMed, and Cochrane Library databases up to April 2022. For quality assessment of included studies, randomized controlled trials (RCTs) were assessed by utilizing the Jadad scale. The primary outcome includes surgical success rate, retained stone rate, stone clearance rate, major morbidity, and mortality. The second outcome includes conversion to open surgery rate, postoperative pancreatitis, bile leakage, cholangitis, hemorrhage, pneumonia, and surgical-site infection. RESULTS: 14 randomized controlled trials with 2,181 patients were included. No significant difference was seen between the two groups in terms of surgical success, stone clearance, retained stones, operation time, and total morbidity. LC-LCBDE had higher rate of bile leakage [relative risk (RR): 4.52; 95% confidence interval (CI): 2.19-9.31] and lower rate of postoperative pancreatitis (RR: 0.25; 95% CI: 0.13-0.46), cholangitis (RR: 0.17; 95% CI: 0.05-0.67), and hemorrhage (RR: 0.18; 95% CI: 0.07-0.42). CONCLUSIONS: Both LC+LCBDE and LC+ERCP are safe, effective, and minimal-invasive treatments for concomitant gallbladder and CBD stones. LC-LCBDE was associated with comparable effects compared with LC+ERCP in terms of surgical success rate, stone clearance rate, retained stones rate, operation time, and total morbidity. At the same time, LC-LCBDE had a higher rate of bile leakage and a lower rate of postoperative pancreatitis, cholangitis, and hemorrhage.

Emotional responses of piglets under long-term exposure to negative and positive auditory stimuli.

The stress caused by sound is inevitable. The stress caused by noise and the positive effects of music can affect the endocrine of animals and their welfare. In this study, a total of 72 hybrid piglets (Large White × Duroc × Min pig) were randomly divided into 3 groups, including music (Mozart K.448, 60-70 dB), noise (recorded mechanical noise, 80-85 dB), and control (natural background sound, <40 dB) groups. S-IgA (secretory immunoglobulin A), IL-6 (interleukin-6), IL-8 (interleukin-8), and positive emotion-related behaviors were used as indicators to discuss whether noise induced stress and inflammation in piglets or whether music could have positive effects. Six hours of auditory exposure were given daily (10:00-16:00), which lasted for 56 days. Behavioral responses of the piglets were observed, and the concentrations of salivary S-IgA and serum IL-6 and IL-8 were measured. The results showed that the concentration of S-IgA increased in the noise and control groups on the 57th day (P < 0.05); S-IgA concentration in the music group was unchanged after long-term music exposure. The concentrations of IL-6 and IL-8 showed that long-term noise exposure might lead to stress and inflammation in piglets. Tail-wagging and play behaviors of the piglets in the music group were significantly greater than those in the noise and control groups, which implied that long-term music exposure improved the emotional state of the piglets in a restricted and barren environment.

LINC00958/miR-3174/PHF6 axis is responsible for triggering proliferation, migration and invasion of endometrial cancer.

OBJECTIVE: To reveal the role of LINC00958 in the progression of endometrial cancer (EC) and the underlying molecular mechanism. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was conducted to detect relative level of LINC00958 in EC specimens and cell lines. Its prognostic potential in EC was analyzed by Kaplan-Meier method. After in vitro knockdown of LINC00958, cell proliferative, migratory and invasive abilities in KLE and Ishikawa cells were evaluated by Cell Counting Kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU) and transwell assay. Dual-Luciferase reporter assay was carried out to identify the LINC00958/miR-3174/PHF6 axis, and their expression interaction was determined by Pearson correlation test. The role of miR-3174 in influencing LINC00958-induced phenotype changes of EC cells was determined through rescue experiments. RESULTS: LINC00958 was abnormally upregulated in EC specimens and cell lines, which was unfavorable to the prognosis of EC. Knockdown of LINC00958 reduced proliferative, migratory and invasive rates in KLE and Ishikawa cells. MiR-3174 shared a binding site in the 3'-untranslated region (3'-UTR) to that of LINC00958, which was lowly expressed in EC specimens and negatively linked to LINC00958 level. Overexpression of miR-3174 partially abolished the role of LINC00958 in accelerating the malignant phenotypes of EC cells. PHF6 was the downstream target of miR-3174 and it was upregulated in EC specimens. CONCLUSIONS: LINC00958 is upregulated in EC specimens, which is a prognostic factor of EC. It stimulates EC to proliferate, migrate and invade through the miR-3174/PHF6 axis.

MiR-150 suppressed cell viability, invasion and EMT via HMGA2 in oral squamous cell carcinoma.

OBJECTIVE: Oral squamous cell carcinoma (OSCC) accounts for 90% of head and neck cancers, and its 5-year overall survival is very poor. MiR-150 is usually downregulated and acts as tumor suppressor in multiple cancers. The aim of our study is to explore the functions of miR-150 in OSCC. PATIENTS AND METHODS: Expressions of miR-150 and HMGA2 mRNA in OSCC tissues and cells were analyzed by qRT-PCR. Methyl Thiazolyl Tetrazolium (MTT) and transwell assays were conducted to assess the cell viability and invasive abilities. Western blot was conducted to assess the protein levels of epithelial-mesenchymal transition (EMT) markers. Luciferase reporter assay was carried out to verify miR-150 directly binding to HMGA2 in SCC25 cells. RESULTS: MiR-150 was low expressed and HMGA2 was highly expressed in OSCC tissues and cells. Downregulation of miR-150 or upregulation of HMGA2 predicted poor prognosis of OSCC patients. MiR-150 overexpression inhibited the abilities of viability, invasive and the EMT by targeting HMGA2 in OSCC cells. HMGA2 was a target gene of miR-150 and its expression was regulated by altering the expression of miR-150 in OSCC cells. HMGA2 reversed partial roles of miR-150 on cell viability and invasion in OSCC. CONCLUSIONS: MiR-150 impaired cell viability, invasion and EMT via binding to HMGA2 of OSCC. Our research demonstrates that miR-150 plays a critical role in the progression of OSCC. miR-150 might be a candidate molecular marker and a novel therapy target for OSCC patients.

Tobacco smoking confers risk for severe COVID-19 unexplainable by pulmonary imaging.

BACKGROUND: COVID-19 is a new pneumonia. It has been hypothesized that tobacco smoking history may increase severity of this disease in the patients once infected by the underlying coronavirus SARS-CoV-2 because smoking and COVID-19 both cause lung damage. However, this hypothesis has not been tested. OBJECTIVE: Current study was designed to focus on smoking history in patients with COVID-19 and test this hypothesis that tobacco smoking history increases risk for severe COVID-19 by damaging the lungs. METHODS AND RESULTS: This was a single-site, retrospective case series study of clinical associations, between epidemiological findings and clinical manifestations, radiographical or laboratory results. In our well-characterized cohort of 954 patients including 56 with tobacco smoking history, smoking history increased the risk for severe COVID-19 with an odds ratio (OR) of 5.5 (95% CI: 3.1-9.9; P = 7.3 × 10-8 ). Meta-analysis of ten cohorts for 2891 patients together obtained an OR of 2.5 (95% CI: 1.9-3.3; P < 0.00001). Semi-quantitative analysis of lung images for each of five lobes revealed a significant difference in neither lung damage at first examination nor dynamics of the lung damage at different time-points of examinations between the smoking and nonsmoking groups. No significant differences were found either in laboratory results including D-dimer and C-reactive protein levels except different covariances for density of the immune cells lymphocyte (P = 3.8 × 10-64 ) and neutrophil (P = 3.9 × 10-46 ). CONCLUSION: Tobacco smoking history increases the risk for great severity of COVID-19 but this risk is achieved unlikely by affecting the lungs.

Glycyrrhizin improves inflammation and apoptosis via suppressing HMGB1 and PI3K/mTOR pathway in lipopolysaccharide-induced acute liver injury.

OBJECTIVE: Acute liver injury (ALI) is mainly characterized by the symptom of metabolic disorders, homeostasis unbalance, and loss of liver function. There are no effective treatment methods at present stage except the liver transplantation. Effective treatment for early ALI is of great significance for the treatment of liver injury thereof. Glycyrrhizin (GL) is a promising inhibitor of the high-mobility group box-1 gene (HMGB1) which is expressed much higher in an inflammatory injury. However, it is not clear whether GL improves ALI via the inhibition of HMGB1. The present study is to probe the function and mechanism of glycyrrhizin on acute liver injury. MATERIALS AND METHODS: The expression of HMGB1 and inflammation in liver macrophages were analyzed. Lipopolysaccharide (LPS) was used in stimulating the macrophages to activate inflammatory response and recombined human HMGB1 was used to resist the function of GL to explore whether GL acted via the target of HMGB1. Then, LPS injection was utilized to induce ALI in mice, and then we evaluated GL treatment in ALI model. RESULTS: The results showed that the expressions of HMGB1 and inflammatory factors were markedly increased in LPS-activated liver macrophages. GL inhibited the progress of macrophages inflammation by restraining HMGB1, and the administration of GL could reverse the effects of LPS-induced ALI in mice. Moreover, PI3K/mTOR pathway was significantly suppressed by GL application. CONCLUSIONS: These results suggest that GL prevents inflammation in liver macrophages via inhibition of HMGB1. GL restrains inflammation and cell apoptosis by inhibiting HMGB1 via PI3K/mTOR signaling pathway in ALI. GL may become a novel drug for the therapy of ALI in the future.

Longitudinal changes in prostate volume in a community-based cohort study of middle-aged and elderly men in rural China.

BACKGROUND: Prostate volume (PV) and its change rate are important for the progression of prostate disease, but studies on their estimates are inconsistent. OBJECTIVES: To investigate whether age, prostate-specific antigen (PSA), and other specific characteristics are associated with PV and its change rate. MATERIALS AND METHODS: A community-based cohort study was conducted in a rural area of China among male residents aged 40-80 years. PV was estimated at baseline and at 4 years of follow-up by trans-abdominal ultrasound. Annual PV change rate (PVCR) was calculated as change in volume divided by time interval. Baseline characteristics, including age, serum PSA, and hormones, were evaluated. And their relationships with PV or PVCR were assessed with Pearson correlation and multivariate linear regression analyses. RESULTS: Totally, 462 participants completed the follow-up with baseline PV (PV0 ) of 15.6 ± 5.5 ml. PV0 was highly correlated with age and PSA in pairwise correlations (Pearson r = 0.35 and 0.34, respectively, p < 0.01). Multivariate linear regression showed similar associations that PV0 tended to increase with age and PSA. The average PVCR was 0.7 ± 1.8 ml/year. In pairwise correlations, PVCR was inversely correlated with PV0 and positively correlated with PSA, while it was not significantly related to baseline age. Linear regression of PVCR on age and PSA in groups classified by PV0 quartile showed that age was not a significant estimator of PVCR, whereas PSA was. In each PV0 group, PVCR tended to increase with PSA. DISCUSSION AND CONCLUSION: PV was positively associated with age and PSA, and it tended to grow faster in men with smaller baseline PV and higher PSA. PSA can be a valuable parameter for estimating both the size and the growth speed of prostate. Although age is associated with prostate enlargement, it does not appear to be related to the longitudinal change rate of PV.

MIR22HG inhibits cell growth, migration and invasion through regulating the miR-24-3p/p27kip1 axis in thyroid papillary carcinomas.

OBJECTIVE: To explore the underlying mechanism of ncRNA (MIR22HG) in thyroid papillary carcinomas. PATIENTS AND METHODS: 40 pairs of thyroid papillary carcinomas tissues and adjacent normal tissues were collected from patients of the First Affiliated Hospital of Guangxi Medical University, who underwent oral surgery. qRT-PCR was applied to detect the expression of MIR22HG, miR-24-3p and p27kip1 in tissues and cells. Western blot was used to measure the protein level of p27kip1 in tissues and cells. Kaplan-Meier plot was used to analyze the overall survival rates in thyroid papillary carcinomas. Pearson's correlation analysis was used to analyze the correlation relationship among MIR22HG, miR-24-3p and p27kip1 expression. Flow cytometric assay was applied to measure cell apoptosis. Transwell assay was used to assess cell migration and invasion abilities. Luciferase reporter assay was applied to verify the molecular relationships among MIR22HG, miR-24-3p and p27kip1 in thyroid papillary carcinomas. RESULTS: LncRNA MIR22HG and p27kip expressed low while miR-24-3p expressed high in thyroid papillary carcinomas and cells. Overexpression of MIR22HG inhibited cell proliferation, migration and invasion, whereas promoted cell apoptosis in thyroid papillary carcinomas cells. However, these effects were reversed by upregulation of miR-24-3p. Further exploration showed that the promoted effects of miR-24-3p mimics on thyroid papillary carcinomas cells were suppressed by enhancing p27kip1 expression. Meanwhile, MIR22HG induced p27kip1 expression by binding miR-24-3p in thyroid papillary carcinomas. CONCLUSIONS: MIR22HG inhibited cell growth through modulating p27kip1 by decreasing miR-24-3p expression in thyroid papillary carcinomas, providing a new modulate mechanism and therapeutic targets in thyroid papillary carcinomas.

Therapeutic effect of transforaminal endoscopic spine system in the treatment of prolapse of lumbar intervertebral disc.

OBJECTIVE: To investigate the clinical efficacy and safety of transforaminal endoscopic spine system (TESSYS) in treating the prolapse of lumbar intervertebral disc. PATIENTS AND METHODS: 462 patients with prolapse of lumbar intervertebral disc who were treated in our hospital from June 2012 to May 2016 were enrolled. All patients were randomly divided into 2 groups: the study group (n=231) and the control group (n=231). Patients in the study group received TESSYS, while those in the control group received conventional surgical treatment with posterior approach. Venous blood was collected before the surgery and 6 h, 12 h, 24 h, and 48 h after surgery. C reactive protein (CRP), interleukin-6 (IL-6), creatine phosphokinase (CPK) and white blood cell (WBC) in each patient were measured. The operation time, intraoperative blood loss, length of stay, postoperative ambulation time and complications were compared between the two groups. Clinical efficacy before and after surgery (1st day, 1st month, 3rd month, and 6th month after surgery) was evaluated according to visual analogue scale (VAS), Oswestry disability index (ODI) and modified MacNab criteria. RESULTS: The operation time, intraoperative blood loss, length of stay, postoperative ambulation time and complications of patients in the study group were less than those of the control group (p<0.05). There were no significant differences in VAS score and ODI score on the 1st day before surgery, 1st day, 1st, 3rd, and 6th month after surgery (p>0.05). According to the improved MacNab standard, the excellent and good rate was 87.88% in the study group and 84.85% in the control group, the difference was not statistically significant (p>0.05). There were no significant differences in CRP, IL-6, CPK and WBC between the two groups before surgery (p>0.05). Postoperative levels of CRP, IL-6, CPK, and WBC in study group were better than those in control group, the differences were statistically significant (p<0.05). CONCLUSIONS: TESSYS has the advantages of less bleeding, less traumatic reactions, fewer complications, rapid postoperative recovery, and exact short-term effect in treatment for prolapse of lumbar intervertebral disc.

Extracellular signal-regulated kinase activation in the spinal cord contributes to visceral hypersensitivity induced by craniofacial injury followed by stress.

BACKGROUND: We previously developed an animal model to examine mechanisms that underlie the emergence of visceral hypersensitivity modeling pain characteristics of temporomandibular disorder (TMD) patients with comorbid irritable bowel syndrome (IBS). In ovariectomized (OVx) rats with estradiol (E2) replacement, visceral hypersensitivity developed subsequent to masseter muscle inflammation followed by repeated forced swim (FS) stress. The purpose of this study was to investigate whether activation of extracellular signal-regulated kinase (ERK) in the spinal cord contributes to visceral hypersensitivity in this overlapping pain model. METHODS: In OVx with E2 replacement rats masseter muscle inflammation was followed by 3 day FS (comorbid condition). Depression-like behaviors were assessed by sucrose preference and in the elevated plus maze, and visceral sensitivity was measured by the visceromotor response (VMR) to colorectal distention. The protein level of ERK1/2 and phosphorylated ERK1/2 (p-ERK1/2) in the L6-S2 dorsal spinal cord was analyzed by western blot. KEY RESULTS: FS stress decreased sucrose consumption in E2 replaced rats in sucrose preference test. The expression of p-ERK1/2 in the L6-S2 dorsal spinal cord increased significantly in E2 with comorbid rats. Intrathecal injection of mitogen-activated protein kinase (MAPK) kinase (MEK) inhibitor PD98059 blocked the visceral hypersensitivity induced by masseter muscle inflammation combined with FS stress. CONCLUSIONS & INFERENCES: These data indicate that ERK1/2 activation contributes to the visceral hypersensitivity evoked by craniofacial inflammation pain combined with stress. The results may provide a new therapeutic avenue for alleviating overlapping pain conditions.

Hypothermic Machine Perfusion's Protection on Porcine Kidney Graft Uncovers Greater Akt-Erk Phosphorylation.

BACKGROUND: To investigate the potential mechanisms of hypothermic machine perfusion (HMP)'s beneficial effects on kidney graft over static cold storage (SCS) in vitro. METHODS: Ten kidneys of 5 Bama miniature male pigs were paired into 2 groups: SCS group and HMP group. Preservation solutions were taken at 0, 1, 3, and 6 hours for the measurement of K+, Na+, Cl-, blood urea nitrogen (BUN), creatinine (Cr), and lactate dehydrogenase (LDH) using the standard laboratory methods. Renal cortex were harvested at 6 hours for the following measurement: lactic acid (LD), adenosine triphosphate (ATP), malondialdehyde (MDA), neutrophil accumulation (MPO), interleukin-10 (IL-10), and transforming growth factor-ß (TGF-ß). Ischemia-induced apoptosis and the protein expression levels of total Akt, phospho-Akt, total Erk, and phospho-Erk were analyzed by Western blotting. RESULTS: Almost all of the tested metabolites in preservation solutions were reduced with time in the HMP group. Levels of Na+, Cl-, BUN, Cr, K+, and LDH were lower in the HMP group compared with the SCS group, with differences in the first 4 reaching statistical significance. HMP alleviated ATP degradation and LD accumulation, diminished the MDA (P < .05) and MPO (P = .227) levels, and greatly raised IL-10 and TGF-ß (P < .05) expression. A marked decrease of proapoptotic and a large increase of antiapoptotic markers (P < .05) along with greatly raised Akt (P < .05) and Erk (P < .01) phosphorylation was observed in the kidney of the HMP group compared with the SCS group. CONCLUSION: HMP's kidney graft protection involves inhibition of accumulation of toxic metabolites, oxidative damage, and apoptosis along with upregulation of the Akt and Erk signaling pathway.

Effects of the Zhikang capsule on healing of the flap after radical breast cancer surgery.

This study aimed to investigate the effect and mechanism of trauma flap healing promoted by the Zhikang capsule after radical breast cancer surgery. The enrolled breast cancer patients were randomly divided into two groups: treatment and observation. The patients in the treatment group were treated with the Zhikang capsule in addition to the conventional dressing changes, while patients in the observation group underwent only the regular dressing changes. Serum samples of 98 breast cancer patients (with complete clinical data) who underwent modified radical mastectomy were collected and analyzed for expressions of transforming growth factor beta (TGF-ß) and basic fibroblast growth factor (bFGF). The drainage fluid amount and tissue necrosis rate were found to be lower in the treatment group than in the observation group. Moreover, bFGF expression in peripheral blood was higher in the treatment group than in the observation group. However, no significant difference was found between the two groups in the expression of TGF-ß in peripheral blood. In conclusion, Zhikang capsule is effective in promoting flap healing after radical breast cancer surgery, and the increase of bFGF expression in peripheral blood may be the underlying mechanism.

The effect of low-nitrogen and low-calorie parenteral nutrition combined with enteral nutrition on inflammatory cytokines and immune functions in patients with gastric cancer: a double blind placebo trial.

OBJECTIVE: The aim of this study is to investigate the effect of low-nitrogen and low-calorie parenteral nutrition (PN) combined with enteral nutrition (EN) on the inflammatory cytokines and immune function in patients with gastric cancer. PATIENTS AND METHODS: Between May 2012 and May 2014, 90 patients undergoing surgery for gastric cancer in our institution were involved in this double blind placebo study and randomly divided into experimental group and control group, 45 patients of each group. Patients in the control group would receive total parenteral nutrition (TPN) whereas patients in the experimental group would be supported with low-nitrogen and low-calorie PN combined with EN. RESULTS: On the 7th postoperative day 7, levels of IgA, IgM and IgG in experimental group were significantly higher than those in the control group and preoperative values (p < 0.05). CRP level was significantly lower than that of controls and preoperatively (p < 0.05). Levels of IL-2 and TNF-α were significantly higher than those of controls and preoperatively (p < 0.05). CONCLUSIONS: As low-nitrogen and low-calorie PN combined with EN can effectively improve the immune function, reduce the inflammatory reactions and improve the postoperative quality of life (QoL) and prognosis in patients with gastric cancer, it is suitable for clinical application.

Effect of curcumin on p38MAPK expression in DSS-induced murine ulcerative colitis.

The aim of this study was to determine the therapeutic effect of curcumin on dextran sulfate sodium-induced ulcerative colitis (UC) and to explore the related mechanism. Sixty mice were randomly divided into 6 groups. A group was the normal control group; B group was the model group; C group was the 1.5 mg/kg dexamethasone group based on the B group; and D, E and F groups were 15, 30, and 60 mg/kg curcumin groups, respectively, based on the B group. The mice were killed 7 days after treatment; the expression of TNF-α and MPO in colon tissue was determined with ELISA, and colon p-p38MAPK and p38MAPK mRNA expression was evaluated by immunohistochemistry and RT-PCR, respectively. In the C, D, E, and F groups, TNF-α and MPO levels significantly decreased (P < 0.05), and the expression of p-p38MAPK also significantly decreased (P < 0.01). The expression of p38MAPK mRNA in the C, D, E, and F groups decreased (P < 0.01), and there was a statistically significant difference between the E and F groups (P < 0.01). Curcumin had a therapeutic effect, which probably played a role in UC treatment by inhibiting the p38MAPK signaling pathway, thereby reducing the release of TNF-α.

ß-Catenin/LEF1 transactivates the microRNA-371-373 cluster that modulates the Wnt/ß-catenin-signaling pathway.

The microRNA-371-373 (miR-371-373) cluster is specifically expressed in human embryonic stem cells (ESCs) and is thought to be involved in stem cell maintenance. Recently, microRNAs (miRNAs) of this cluster were shown to be frequently upregulated in several human tumors. However, the regulatory mechanism for the involvement of the miR-371-373 cluster in human ESCs or cancer cells remains unclear. In this study, we explored the relationship between this miRNA cluster and the Wnt/ß-catenin-signaling pathway, which has been shown to be involved in both stem cell maintenance and tumorigenesis. We show that miR-371-373 expression is induced by lithium chloride and is positively correlated with Wnt/ß-catenin-signaling activity in several human cancer cell lines. Mechanistically, three TCF/LEF1-binding elements (TBEs) were identified in the promoter region and shown to be required for Wnt-dependent activation of miR-371-373. Interestingly, we also found that miR-372&373, in turn, activate Wnt/ß-catenin signaling. In addition, four protein genes related to the Wnt/ß-catenin-signaling pathway were identified as direct targets of miR-372&373, including Dickkopf-1 (DKK1), a well-known inhibitor of Wnt/ß-catenin signaling. Using a lentiviral system, we showed that overexpression of miR-372 or miR-373 promotes cell growth and the invasive activity of tumor cells as knockdown of DKK1. Taken together, our study demonstrates a novel ß-catenin/LEF1-miR-372&373-DKK1 regulatory feedback loop, which may have a critical role in regulating the activity of Wnt/ß-catenin signaling in human cancer cells.

The axial frontonasal flap for reconstruction of large nasal-tip defects based on modified nasal subunits in East Asians.

The nasal tip is a prominent landmark on the face, and skin carcinomas of this area are very common. Moderate and large deep skin defects of the nasal tip normally represent a difficult reconstructive challenge. Nasal-tip reconstruction techniques have evolved to allow not only filling of the gap, but cosmetic and functional retention. Numerous flap options are available to reconstruct the defect of the tip of the nose. In this paper, we report the technique of the axial frontonasal flap and its use in reconstruction of large nasal-tip defects in East Asians. The axial frontonasal flap described is a good alternative for reconstruction of nasal-tip defects > 15 mm in diameter, with excellent aesthetic results. This technique is reliable, yields excellent functional and cosmetic results, and we believe that it is a valuable alternative to other techniques of reconstruction for defects of the nasal tip.

Association of TNF-alpha promoter polymorphisms with the outcomes of hepatitis B virus infection in Chinese Han population.

Host genetic factors and environment factors including hepatitis B virus (HBV) genotypes are widely studied for the different outcomes of HBV infection. Recent studies suggest that tumour necrosis factor-alpha (TNF-alpha) plays a pivotal role in the viral clearance and host immune response to HBV, and the capacity for TNF-alpha production in individuals is influenced by a major genetic component. In this study, we aimed to explore whether the single-nucleotide polymorphisms (SNPs) of TNF-alpha promoter are associated with the outcomes of HBV infection in the Chinese Han population. One hundred and forty-three spontaneously recovered HBV subjects and 196 chronic hepatitis B patients were recruited in this case-control study in the Beijing area of China. Polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) and sequence-specific primer-PCR (SSP-PCR) were used to detect the SNPs of five sites in the TNF-alpha promoter (-238G/A, -308G/A, -857C/T, -863C/A, -1031T/C). The frequency distributions of genotypes and haplotypes in two groups were analysed by EPI and EH programs. The presence of the -238GG genotype was significantly correlated with persistence of HBV infection (OR = 4.08, P = 0.02), and -857TT genotype appeared in relation to the spontaneous clearance of HBV (OR = 0.47, P = 0.03). Frequency of haplotype GGCCT (-238/-308/-857/-863/-1031) in the chronic HB group was significantly lower than that in spontaneously recovered group (P = 0.03), and frequencies of haplotypes GGCAT and GGTAT in the chronic HB group were significantly higher than those in the spontaneously recovered group (P = 0.0001, P = 0.0004). In conclusion, TNF-alpha promoter polymorphisms are independently associated with different outcomes of HBV infection.

A new approach to repairing cleft palate and acquired palatal defects with distraction osteogenesis.

Cleft palate (CP) is one of the most common human congenital deformities, and acquired palate defects after trauma or tumour resection are also common. In this study, distraction osteogenesis (DO) for CP and other palatal bone defects was evaluated. Twenty cats were assigned randomly to 3 groups of (1) 15, (2) 3 and (3) 2 cats. In groups 1 and 2, a rectangular ostectomy, in the posterior of the palatal bone shelf, was performed in the sagittal axis to establish the CP defect model. At the same time, a pure titanium intraoral distractor was fixed to molar teeth with brackets and to the palatal bone shelf across the defect with titanium miniscrews bilaterally. Four weeks later, a secondary transport disc (TD) osteotomy was performed, and gradual DO treatment started at 0.4mm twice a day, after 6 days of latency. DO was performed until the TD reached the opposite margin over the gap in 5-6 days. Three cats each of group 1 were killed at 2, 4, 6, 8 and 12 weeks after completion of DO. In group 2, the bone and soft-tissue defects were untreated until death 6 weeks later. Group 3 cats (control) were killed after 6 weeks. The TD successfully recombined with the opposite palatal bone stump, and proportional expansion of the overlay mucoperiosteal flap was achieved. Intramembranous bone formation was revealed: parallel collagen bundles gradually deposited on new bone trabeculae while the proliferative osteoblasts produced bone matrix. The bone defect was finally reconstructed by de novo osteogenesis. The control group was observed to have no spontaneous repairing. These results suggest that the CP defect was reconstructed by osteogenesis in situ, and the soft tissues expanded simultaneously to achieve functional correction. The intraoral distractor provided both effective distraction and stability.