[Comparison of robotic-assisted single-incision-plus-one-port laparoscopic pyeloplasty and single-incision laparoscopic pyeloplasty in the treatment of pediatric ureteropelvic junction obstruction].

Objective: To compare the efficacy of robotic-assisted single-incision-plus- one-port laparoscopic pyeloplasty (R-SILP+1) with single-incision laparoscopic pyeloplasty (SILP) in pediatric ureteropelvic junction obstruction (UPJO). Methods: The clinical data of 47 children with UPJO who underwent surgery from October 2020 to September 2022 in the Department of Pediatric Surgery of Fujian Provincial Hospital were retrospectively analyzed. According to the surgical method chosen by parents, the children were divided into R-SILP+1 group and SILP group. Baseline data, operative time, intraoperative anastomosis time, volume of blood loss, postoperative hospitalization time, complications, total costs, preoperative and postoperative renal parenchymal thickness (PT), anterior posterior diameter of renal pelvis (APD), and differential renal function (DRF) before and after operation were compared between the two groups, and the clinical efficacy of the two kinds of operation was evaluated. Results: Among the 47 children, 27 were in R-SILP+1 group, including 16 males and 11 females, aged (6.6±3.5) years; 20 were in SILP group, including 12 males and 8 females, aged (6.5±3.5) years. The operations were successful in both groups without conversion to open operation. There were no significant differences between the two groups in baseline data, volume of blood loss, complications, APD and PT at postoperative 6 months, APD, PT and DRF at postoperative 12 months (all P>0.05). Compared with the SILP group, the operative time [(153.0±14.4) vs (189.9±32.6) minutes, P<0.001], intraoperative anastomosis time [(68.8±16.8) vs (97.5±12.0) minutes, P<0.001], postoperative hospitalization time [(6.0±1.3) vs (9.0±1.3) d, P<0.001] were shorter, but the total cost was higher[(57 390±7 664) vs (30 183±4 219) yuan RMB, P<0.001]. Conclusions: Compared with the SILP group, R-SILP+1 can achieve considerable efficacy in treating pediatric UPJO, and has certain advantages in shortening operative time, intraoperative anastomosis time, and postoperative hospitalization time. However, the cost is high.

[Mini-incision with endoscope-assisted surgery for bilateral congenital second branchial cleft fistula and a pedigree report].

Objective: To investigate the feasibility and efficacy of mini-incision with endoscope-assisted resection for bilateral congenital second branchial cleft fistula, and to report on a rare pedigree. Methods: The clinical data of 5 patients with bilateral congenital second branchial fistula admitted in Fujian Provincial Hospital from April 2007 to December 2018 were retrospectively reviewed, including 2 males and 3 females, aged from 3 to 31 years old. The surgical strateges and clinical experience of single mini-incision with endoscope-assisted fistulectomy were summarized, and a rare pedigree was reported. Results: In five patients, Case 1 to Case 4 were treated with bilateral endoscopic-assisted fistula high ligation with titanium clips and removal through a single small incision under general anesthesia. No obvious complications occurred after the operation. The patients were followed up for 40-164 months with no fistula recurrence. Case 5 gave up surgical resection and was followed up for 24 months with acute infection attack once. Case 2 and Case 4 came from the same family. In this family, 7 out of 31 members of four generations had second branchial cleft fistulas, of which 4 were bilateral and 3 were right. Pedigree analysis was consistent with autosomal dominant inheritance. No deafness, preauricular tag, external and middle ear deformity and kidney malformation were found in the family members. Conclusions: Bilateral congenital second branchial cleft fistula is rare. Surgical resection is the preferred treatment. Mini-incision with endoscopic-assisted fistula high ligation with titanium clip and resection has clear operative field, ideal cosmetic effect and definite curative effect.

[The application of transumbilical single incision plus one robotic-assisted surgery in choledochal cyst excision and hepaticojejunostomy in children].

To explore the effectiveness and summarize the experiences of transumbilical single incision plus one robotic-assisted surgery surgery in the treatment of pediatric choledochal cyst. We retrospectively reviewed the medical records of 10 children who underwent choledochal cyst excision and hepaticojejunostomy from June to December 2020 at Fujian Provincial Hospital. The mean age was (4.6±1.7) years (range from 2 years to 8 years). The mean weight was (17.1±3.8) kg (range from 12.3 kg to 25.0 kg). The Todani classifications were type I (n=6) and type Ⅳ(n=4).The clinical symptoms were asymptomatic (n=4), abdominal pain (n=3), and abdominal pain with jaundice (n=3). Ten cases of transumbilical SILS+1 robotic-assisted choledochal cyst excision and hepaticojejunostomy were completed successfully. The average duration of operation was 204-227 min ((220.0±7.2) min), the mean intraoperative bleeding was (7.67±0.86) ml (range, 6-9 ml) without blood transfusion, average fasting time was (2.30±0.48) days (range, 2-3 days), the average hospitalization time was (4.70±0.67) days (range, 4-6 days) and the medical expense was (5.30±0.42) ten thousand yuan (range, 4-6 ten thousand yuan). Ten patients did not develop early complications such as acute cholangitis, ranging from 3 months to 6 months. Ultrasonography showed no dilation of ductuli hepaticus communis and intrahepatic bile duct occurred at the third month after surgery. With the development of minimally invasive techniques and enhanced recovery, the da Vinci robotic surgical system will be extensively used. Transumbilical SILS+1 robotic-assisted surgery has equal effect with routine robotic-assisted surgery. The incision is more subtle and excellent, but the operation should be taken by sophisticated surgeon.

[Analysis of sugammadex for antagonistic neuromuscular block in patients with radical resection of lung cancer under thoracoscope].

Objective: To investigate the efficacy and safety of sugammadex for antagonistic neuromuscular block in patients with radical resection of lung cancer under thoracoscope. Methods: One hundred patients undergoing radical resection of lung cancer under thoracoscope in Affiliated Cancer Hospital of Zhengzhou University from March to September in 2019, were randomly divided into control group (group C) and sugammadex group (group S). All patients were anaesthetized (induced and maintained) with intravenous target-controlled infusion of propofol and remifentanil, and intermittent intravenous injection of the neuromuscular block of rocuronium. During the operation, the bispectral index (BIS) was used to monitor the depth of anesthesia, and the neuromuscular block was assessed with TOF. Single-lung mechanical ventilation and double-lumen endotracheal intubation were carried out, and patient-controlled analgesia after operation were enforced. Patients in group C received neostigmine (2 mg) combined with atropine (0.5-1.0 mg) after thoracic closure, while patients in group S received sugammadex (2 mg/kg) at TOF count (≥2) after thoracic closure, and then double-lumen endotracheal tubes were extubated according to extubation indications. At these time points: T(0) (immediate before anesthesia induction), T(1) (immediate before tracheal intubation), T(2) (immediately after thoracic closure), T(3) (1 h after operation), T(4) (6 h after operation), T(5) (24 h after operation), T(6)(48 h after operation), the heart rate(HR) and mean arterial pressure (MAP) were recorded, QT interval (V3 ECG) were measured and calculated, indicators of liver function [alanine transaminase (ALT), aspartate transaminase(AST)], renal function [blood urea nitrogen (BUN), creatinine (Cre)] and clotting function [thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen (FIB)] were detected. The duration of operation, postoperative conditions within 48 hours after operation(the time of tracheal tube extubation, respiratory suppression/dysfunction, allergy, nausea and vomiting, itching of skin, abnormal sensation), pathological types and the postoperative hospital stay were recorded. Results: There were no significant differences of the age, sex ratio, body mass index (BMI), American Society of Anesthesiologists (ASA) grading ratio, duration of operation, pathological types and the postoperative hospital stay, HR, MAP and QT interval between two groups (all P>0.05). There were no remarkable differences of the levels of serum histamine, ALT, AST, BUN, Cre, TT, PT, APTT and FIB before and after administration of neuromuscular blockade antagonists (neostigmine or Sugammadex) in the same group patients (all P>0.05), also no significant differences between group C and group S at the same time points (all P>0.05). Average time of tracheal tube extubation in group S [(3.7±1.3) min] was sharply shorter than that in group C [(14.5±4.4) min, t=2.266, P<0.05)]. There were no patients with allergy, skin itching, sensory abnormality in these two groups. There were no significant difference of the incidence of postoperative nausea and vomiting between these two groups. There were 5 patients with respiratory depression in group C and no respiratory depression patient in group S, the difference was statistically significant between these two groups (χ(2)=5.263, P<0.05). Conclusion: Sugammadex is effective for antagonizing the neuromuscular blockade of rocuronium in patients with radical resection of lung cancer under thoracoscope, and can shorten the time of tracheal tube extubation after surgery.

Physcion 8-O-ß-glucopyranoside exhibits anti-growth and anti-metastatic activities in ovarian cancer by downregulating miR-25.

OBJECTIVE: Ovarian cancer ranks 5th leading cause of cancer-related death in females worldwide. Physcion 8-O-ß-glucopyranoside (PG) is an anthraquinone compound isolated from Rumex japonicus Houtt. This study aimed at investigating the effect of PG on ovarian cancer cells. PATIENTS AND METHODS: Cell viability was detected by CCK-8 assay. Colony formation assay evaluated whether PG could affect anchorage-independent growth. Whether PG affected cell cycle progression was examined by flow cytometry. The morphological changes caused by PG were visualized by microscopy. Apoptosis was quantitatively analyzed by flow cytometry. The effect of PG on cell migration and invasion was assessed by wound healing and transwell, respectively. The effect of PG on the expression of molecular markers was determined by Western blot. Microarray assay was performed to identify the potential target of PG. RESULTS: Results from the present study showed that PG decreased ovarian cancer cells viability. Colony formation assay also showed that PG suppressed the anchorage-independent growth of SKOV3 and OVCAR-3 cells. PG triggered cell cycle arrest at G1/G0 phase. The pro-apoptotic activity of PG was confirmed by flow cytometry, activation of caspase-3 and PARP, upregulation of Bax and downregulation of Bcl-2. The ability of PG to inhibit migration and invasion was evidenced by a decrease in wound healing and invasive cell number, as well as downregulation of MMP-2 and upregulation of TIMP-3. Microarray and qRT-PCR showed that miR-25 expression was downregulated by PG treatment. Moreover, our results indicated that the anti-cancer activities of PG were augmented by miR-25 knockdown and attenuated by ectopic miR-25 expression. CONCLUSIONS: PG exhibited anti-cancer activity in ovarian cancer by downregulating miR-25.

MiR-488 promotes fracture healing by targeting DKK1.

OBJECTIVE: The aim of this study was to evaluate the effect of miR-488 on fracture healing and to investigate the possible underlying mechanism. PATIENTS AND METHODS: The expression level of miR-488 in clinical cases was detected by quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR). After prediction of the potential target of miR-488 in websites, three groups were established to elucidate the effects of miR-488 and Dickkopf1 (DKK1) on osteoblasts function: the miR-NC group (negative control), the miR-488 mimics group (MC3T3-E1 cells transfected with miR-488 mimics) and the mimics + si-DKK1 group (MC3T3-E1 cells transfected with miR-488 mimics and si-DKK1). Subsequently, cell viability, apoptosis rate of osteoblasts and osteogenesis-associated markers were determined respectively. RESULTS: In the present study, we found that the expression of miR-488 in patients with osteoporosis was significantly lower than that of healthy controls. The potential target of miR-488 was predicted by three public databases. Luciferase reporter gene assay confirmed that DKK1 was a direct target of miR-488. Besides, the overexpression of miR-488 could significantly reduce the transcription and translation levels of DKK1. These results suggested that miR-488 had a negative regulatory effect on DKK1. Subsequent experiments demonstrated that decreased expression of DKK1 induced by miR-488 up-regulation could significantly improve cell viability and suppress cell apoptosis. Meanwhile, the expression levels of osteogenesis-associated markers were remarkably elevated. CONCLUSIONS: Our research revealed the role of miR-488 in promoting osteoblast function. This indicated that miR-488 could be a potential therapeutic target for fracture healing.

Maintenance of the contractile phenotype in corpus cavernosum smooth muscle cells by Myocardin gene therapy ameliorates erectile dysfunction in bilateral cavernous nerve injury rats.

The pathophysiology of erectile dysfunction post radical prostatectomy is not clearly clarified, and the low efficacy of traditional PDE5i treatment remains a major complaint in contemporary practice. This study aimed to demonstrate phenotypic modulation in bilateral cavernous nerve injury (BCNI) rats within 7 days, and subsequently validate gene therapy with Myocardin (Mycod) by maintaining a contractile phenotype in corpus cavernosum smooth muscle cells. Initially, 36 male rats were randomly divided into BCNI and negative control (NC) groups for histological and phenotypic molecular measurements at 3, 5, and 7 days. Afterwards, an additional 30 rats received a single intra-cavernous injection of 50 µL PBS, Ad-Myocd (1 × 1011  pfu/ml) or Ad-vector for 10 animals each, namely the NC+PBS, BCNI+Ad-Myocd, and BCNI+Ad-vector groups. Finally, the validity and mechanism of Myocd transfection was explored at 21 days in vivo and 48 h in vitro. Western blotting showed canonical declines in Myocd, α-SMA, and Calponin expression, as well as elevated Osteopontin (OPN) expression, before corporeal morphological and SM-to-collagen ratio changes at day 5 after injury. Overexpression of Myocd maintained the contractile phenotype of corpus cavernosum smooth muscle cells, ameliorated bilateral cavernous nerve injury rat erectile dysfunction, as well as promoted cell contractility and suppressed proliferative capacity. Simultaneously, confocal imaging revealed up-regulation and co-localization of serum response factor in gene-transferred cells. In conclusion, our study is the first to investigate corpus cavernosum smooth muscle cells phenotypes in the early stages of cavernous injury model rats, and Myocd reversed phenotypic modulation by activating serum response factor. The experimental results demonstrated the validity of gene therapy for erectile dysfunction.

Elevated Plasma Level of Interferon-λ1 in Chronic Spontaneous Urticaria: Upregulated Expression in CD8(+) and Epithelial Cells and Induction of Inflammatory Cell Accumulation.

Interferon- (IFN-) λ1 is regarded as a potent bio-active molecule in innate immunity. However, little is known about its role in chronic spontaneous urticaria (CSU). We therefore investigated expression of IFN-λ1 in CSU, its cellular location, and its influence on inflammatory cell accumulation by using flow cytometry analysis, skin tissue dispersion, immunohistochemical stain, and a mouse peritoneal inflammation model. The results showed that level of IFN-λ1 was 2.0-fold higher in plasma of the patients with CSU than the level in healthy control (HC) subjects. Among leukocytes examined, only CD8(+) T cells expressed more IFN-λ1 in CSU blood. Double labeling immunohistochemical staining revealed that IFN-λ1(+) inflammatory cells such as mast cells, eosinophils, B cells, neutrophils, and macrophages were mainly located in dermis, whereas epidermis tissue highly expressed IFN-λ1. IFN-λ1 induced a dose-dependent increase in number of eosinophils, lymphocytes, mast cells, macrophages, and neutrophils in the peritoneum of mice at 6 h following injection, which was inhibited by pretreatment of the animals with anti-intercellular adhesion molecule- (ICAM-) 1 and/or anti-L-selectin antibodies. In conclusion, IFN-λ1 is likely to play a role in the pathogenesis of CSU. Blocking IFN-λ1 production may help to reduce the accumulation of inflammatory cells in the involved CSU skin.

[Factors associated with adherence of highly active antiretroviral therapy among 386 HIV/AIDS patients in 3 provinces of China].

OBJECTIVE: To investigate adherence and the influence factors among patients who are on antiretrovirus therapy (ART) of 3 provinces in China. METHODS: This study selected 18-year-old and older AIDS patients as the survey objects who initiated anti-retrovirus therapy between April and September of 2014 and kept on the treatment for one year in Yunnan,Sichuan,and Hu'nan province. Information of demography, treatment and social support was collected by questionnaires. Adopt SSRS questionnaire to calculate the information of objective support, subjective support and utilization of social support. χ(2) test and logistic regression were performed to examine relationships between factors and adherence. RESULTS: A total of 386 patients with medication were investigated. Among them, there were 365 (94.6%) cases who were compliant to the ART, and 357 (92.5%) cases can take their pills on time, and 29 (7.5%) cases take their medication in excess of the prescribed time more than two hours. Social support score was 27.2 ± 7.3, including objective support score (5.6 ± 2.7), subjective support score (16.1 ± 4.8), and utilization of social support (5.5 ± 1.9). Multivariate logistic regression analysis revealed that adherence was significantly associated with the correct cognition of medication (OR (95%CI): 3.24 (1.17-9.00)), the self-awareness of the drug regimen was not complexity (OR (95%CI): 9.34 (3.27-26.68)), taking medication 1 time a day (OR (95%CI): 4.00 (1.35-11.84)), and the batter utilization of social support (OR (95%CI): 1.49 (1.06-2.01)). Married/cohabiting or farmers tend to be nonadherenced, while the OR (95%CI) was 0.24 (0.08-0.67) and 0.23 (0.08-0.69), respectively. CONCLUSION: The patients among these provinces were compliant to the ART, and most of them can take their pills on time. The social support score of these patients was lower than normal person. Participants who have correct cognition of medication, thinking their drug regimen was not complexity; Taking medication 1 time a day or have high level of utilization of social support showed a significantly higher level of self-reported adherence.

Complete mitochondrial genome of a natural triploid crucian carp mutant, Carassius auratus var. pingxiangnensis, and phylogenetic analysis of different ploidies in crucian carp.

Carassius auratus var. pingxiangnensis is a natural triploid crucian carp mutant. In order to understand its placement and genetic background at the gene level, the characteristics of mitochondrial DNA sequences and phylogenetic relationship were examined. The results showed that the mitochondrial DNA is a circular double-stranded DNA molecule that is 16,576 bp in length with 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes, and a non-coding control region. Mitochondrial genes overlapped by a total of 40 bp in 11 different locations from 1 to 14 bp. The base composition of the C. auratus mitogenome was estimated to be 29.70% A, 26.74% C, 15.35% G, and 28.21% T. The central conserved blocks and the conserved blocks were compared and were similar among C. auratus var. pingxiangnensis and six other cyprinids with different ploidies. The origin of light strand replication was similar to that of other vertebrates; it was 33 bp, but the characteristic sequence motif 5ꞌ-GCCGG-3ꞌ at the base of the stem within tRNA(Cys) was mutated to 5ꞌ-GGCGG- 3ꞌ. Our phylogenetic analysis based on whole mitogenome sequences indicated that C. auratus var. pingxiangnensis was clustered with C. auratus and then sister-grouped with Carassius gibelio. The systemic developmental tree of crucian carp with different chromosome ploidies showed that diploid C. auratus auratus was clustered with triploid C. auratus auratus, sister-grouped with tetraploid C. auratus auratus, and clustered with other diploid, triploid, and tetraploid C. auratus.

Metabolic syndrome and risk for ED: a meta-analysis.

There are many recent observational studies on metabolic syndrome (MS) and the risk for ED, and it is still inconclusive whether MS increases the risk for ED. This meta-analysis aims to detect a relationship between MS and ED. We identified eligible studies by searching PubMed, Embase and the Cochrane Library for articles published before August 2013. Adjusted relative risks (RR) with 95% confidence interval (CI) were calculated using random-effects or fixed-effects models. A total of 10 studies involving 4092 participants were included in the meta-analysis. MS was associated with an increased incidence of ED (RR=1.60, 95% CI=1.27-2.02, P<0.001), with significant evidence of heterogeneity among these studies (P for heterogeneity <0.001, I(2)=92.9%). The subgroup and sensitivity analyses confirmed the stability of the results and no publication bias was detected. The present meta-analysis suggests that MS is significantly associated with the risk for ED. Large-scale and well-designed prospective studies are required to further investigate the association between MS and risk for ED.

The insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme gene and erectile dysfunction risk: a meta-analysis.

Erectile dysfunction (ED) is increasingly recognized as a public health problem. Several studies have reported the influence of the insertion/deletion (I/D) polymorphism in the Angiotensin-converting enzyme (ACE) gene on ED susceptibility, but the results remain controversial. To derive a more precise estimation of the relationship, a meta-analysis was conducted using data published previously by other groups. A total of six case-control studies, including 1039 cases and 927 controls, were selected. The pooled odds ratios (ORs) and respective 95% confidence intervals (CIs) were calculated by comparing the carriers of D-allele with the wild homozygotes (ID + DD vs. II). Comparisons of other genetic models were also performed (ID + II vs. DD, DD vs. II, DI vs. II and D vs. I). In the overall analysis, no significant association between the polymorphism and ED risk was observed (OR=1.07, 95% CI = 0.84 - 1.37, p = 0.575 for ID + DD vs. II). In the subgroup analysis by ethnic, no significant association was detected among Asian, Latino and European for the comparison of ID + DD vs. II (Asian: OR=1.27, 95% CI = 0.89 - 1.81; Latino: OR=0.76, 95% CI = 0.46 - 1.27; European: OR=1.06, 95% CI = 0.67 - 1.66). Results from other comparative genetic models also indicated the lack of associations between this polymorphism and ED risk. In conclusion, this meta-analysis indicates that the ACE I/D polymorphism might not contribute to the risk of ED.

Thymic stromal lymphopoietin: a promising therapeutic target for allergic diseases.

Thymic stromal lymphopoietin (TSLP), an interleukin 7-like cytokine, can trigger dendritic cell (DC)-mediated T-helper type 2 (Th2) inflammatory responses. Recent evidence demonstrates that cytokines TSLP and OX40 (CD134)/OX40 ligand seem to be important players in the maintenance of Th2 memory pool in the pathogenesis of asthma. Accumulating data reveal that the pathogenic T cells involved in asthma are likely to be inflammatory Th2 cells. TSLP is involved in the development of asthma through crosstalk with nuclear factor NF-ĸB. Progression of skin fibrosis in atopic dermatitis occurs via TSLP/TSLP receptor. TSLP-mediated dermal inflammation aggravates experimental allergic asthma. Also, TSLP polymorphisms are associated with susceptibility to asthma, atopic dermatitis, and eczema herpeticum. These findings suggest a master switch of TSLP in the initiation of allergic and adaptive inflammation through innate pathways at the epithelial cell-DC interface. The TSLP pathway is therefore a promising target for immunotherapy of allergic diseases.

Characterization of corpus cavernosum smooth muscle cell phenotype in diabetic rats with erectile dysfunction.

Phenotypic modulation from a contractile to a proliferative state within vascular smooth muscle cells has a critical role in the pathogenesis of a variety of cardiovascular diseases. To investigate the characterization of corpus cavernosum smooth muscle cell phenotype in diabetic rats with erectile dysfunction, a group of Sprague-Dawley rats (n=30) were induced by intraperitoneal injection of streptozotocin (60 mg kg(-1)) and screened by subcutaneous injection of apomorphine (100 µg kg(-1)) for the measurement and comparison of the penile erections, and then three different groups were defined. Primary corpus cavernosum smooth muscle cells were cultured and passaged. The cavernous tissue segments were subjected to quantitative real-time polymerase chain reaction to determine the expressions of smooth muscle α-actin (SMA), SM myosin heavy chain (SMMHC), smoothelin, calponin and myocardin. Cell contractility in vitro and western blot analysis of SMA and SMMHC in the cavernous tissues and cells were determined. Compared with the control group (n=8) and the diabetes mellitus group (n=5), the expressions of SMA, calponin, SMMHC, smoothelin and myocardin mRNA were decreased in the cavernous tissues in rats of the diabetic erectile dysfunction group (n=15; P=0.001 and 0.02, P=0.014 and 0.012, both P<0.001, P=0.005 and <0.001, P=0.003 and 0.035, respectively). The levels of SMA and SMMHC proteins showed a significant decrease in cavernous tissues and cultured cells in rats of the diabetic erectile dysfunction group. Cells of the diabetic erectile dysfunction group exhibited significantly less contractility compared with those of other groups (P<0.001). Corpus cavernosum SM cell possesses the ability to modulate the phenotype under hyperglycemic conditions, which could have a key role in the pathogenesis of diabetic erectile dysfunction.

Reduced expression of myocardin and serum response factor in the cavernous tissue of diabetic rats.

This study aimed to investigate the expression of myocardin and serum response factor (SRF) in the cavernous tissue of diabetic rats. The experimental diabetes model was induced in 8-week-old male Sprague-Dawley rats (200-220 g) by a single administration of streptozotocin. Both the diabetes mellitus group (DM group, n = 20) and the control group (NDM group, n = 10) were injected with a low dose of apomorphine to allow for the measurement and comparison of the corresponding penile erections. Western blot and qRT-PCR were used to determine the protein and mRNA expression levels of myocardin and SRF. Erectile function was significantly decreased in the DM group compared with the control group (P < 0.001). The mRNA and protein expression levels of myocardin and SRF were reduced in the cavernous tissue of diabetic rats compared with the control group (P < 0.001). It is concluded that diabetes inhibits the mRNA and protein expression of both myocardin and SRF in the cavernous tissue. This could play a key role in the development of erectile dysfunction in diabetic rats.

IL-9(+) IL-10(+) T cells link immediate allergic response to late phase reaction.

The mechanism underlying late-phase allergic reactions (LPR) remains incompletely understood. This study aimed to investigate the role of a newly described subset of T cells, interleukin (IL)-9(+) IL-10(+) T cells, in the pathogenesis of LPR. Using a T helper type 2 (Th2) inflammatory mouse model, we examined the frequency of IL-9(+) IL-10(+) T cells in the jejunum by immunohistochemistry. The LPR in the jejunum was observed afterwards. The cytokine profile of IL-9(+) IL-10(+) T cells was characterized and the major cytokine that plays the critical role in the initiation of LPR was investigated. Abundant IL-9(+) IL-10(+) T cells as well as inflammatory cell extravasation in the jejunal sections were observed in sensitized mice 48 h after specific antigen challenge. IL-9(+) IL-10(+) T cells expressed high levels of macrophage inflammatory protein 1 (MIP1) that could be enhanced by T cell receptor activation. MIP1 facilitated macrophage extravasation in local tissue. Macrophage-derived MIP2 contributed to neutrophil infiltration in the intestine in LPR. Pretreatment with anti-MIP antibody inhibited the LPR in the intestine. IL-9(+) IL-10(+) T cells play an important role in LPR. This subset of T cells has the potential to be a novel therapeutic target in the treatment of LPR and LPR-related inflammation.

Exogenous cell-permeable C6 ceramide sensitizes multiple cancer cell lines to Doxorubicin-induced apoptosis by promoting AMPK activation and mTORC1 inhibition.

New chemotherapy-enhancing strategies are needed for better cancer therapy. Previous studies suggest that exogenous cell-permeable C6 ceramide may be a useful adjunct to the anti-tumor effects of chemotherapeutic agents (such as Taxol) against multiple cancers. Here we demonstrate that exogenous cell-permeable C6 ceramide largely sensitizes multiple progressive cancer cell lines to Doxorubicin-induced cell death and apoptosis. We found for the first time that Doxorubicin induces AMP-activated protein kinase (AMPK) activation in a reactive oxygen species-dependent manner. Activation of AMPK contributes to Doxorubicin-induced cancer cell death and apoptosis. Inhibition of AMPK by small interfering RNA knockdown or a pharmacological inhibitor reduces Doxorubicin-induced cancer cell apoptosis, whereas AMPK activator AICAR enhances it. Importantly, we found that C6 ceramide largely enhances Doxorubicin-induced activation of AMPK, which leads to mTOR complex 1 inhibition and chemo-sensitization. Our data suggest that the combination of C6 ceramide with traditional chemotherapy drugs such as Doxorubicin may have the potential to be used as a new therapeutic intervention against multiple cancers.

Specific immunotherapy suppresses Th2 responses via modulating TIM1/TIM4 interaction on dendritic cells.

BACKGROUND: Specific immunotherapy (SIT) is the only curable remedy for allergic disorders currently; however, the underlying mechanism is not fully understood yet. This study aimed to elucidate the mechanism of SIT on suppressing TIM4 (T cell immunoglobulin mucin domain molecule 4) expression in dendritic cells (DCs) and modulating the skewed T helper 2 (Th2) responses in patients with airway allergy. METHODS: Twenty patients with allergic rhinitis (AR) were treated with SIT for 3 months. Before and after SIT, the expression of TIM4 in peripheral DC and TIM1 in Th2 cells was examined. The role of Fc gamma receptor (FcgammaR) I and II in modulating the expression of TIM4 in DCs was investigated. RESULTS: The interaction of TIM1/TIM4 played a critical role in sustaining the polarization status of Th2 cells in AR patients. Cross-linking FcgammaRI by antigen/IgG complexes increased the production of TIM4 by dendritic cells via upregulating tumor necrosis factor-alpha in DCs. Exposure to microbial products promoted the expression of FcgammaRI in DCs that further increased the expression of TIM4. Exposure to specific antigens alone upregulated the expression of FcgammaRII in DCs, that suppressed the expression of TIM4. CONCLUSIONS: We conclude that SIT suppresses the skewed Th2 responses via disrupting the interaction of TIM1/TIM4 in antigen-specific Th2 cells.

The fabrication and characteristics of indium-oxide covered porous InP.

Uniform and vertical indium-oxide nanotube (IONT) arrays embedded well in n-type InP single crystal have been successfully prepared in situ by porous InP-template-assisted chemical vapor deposition (CVD). This IONT/InP nanostructure reveals high sensitivity to humidity at room temperature, which is ascribed to the ultrahigh surface-to-volume ratio of this nanostructure and the large number of oxygen defected states in IONTs. Such a nanostructure of IONT arrays embedded in a III-V semiconductor substrate could be expected to have potential applications, such as superior gas sensors. This work provides a novel approach for fabricating low-melting metal oxide semiconductor nanotubes.