Causes of recurrence of paediatric inguinal hernia after single-port laparoscopic closure.

PURPOSE: This paper explores the causes of paediatric inguinal hernia (PIH) recurrence after single-port laparoscopic percutaneous extraperitoneal closure (SPLPEC). METHOD: From January 2015 to December 2020, the clinical data of 3480 children with PIHs who underwent SPLPEC were retrospectively reviewed, including 644 children who underwent SPLPEC with a homemade single-hook hernia needle from January 2015 to December 2016 and 2836 children who underwent the SPLPEC with a double-hook hernia needle and hydrodissection from January 2017 to December 2020. There were 39 recurrences (including communicating hydrocele) during the 2-5 years of follow-up. The findings of redo-laparoscopy were recorded and correlated with the revised video of the first operation to analyse the causes of recurrence. RESULT: Thirty-three males and 6 females experienced recurrence, and 8 patients had a unilateral communicating hydrocele. The median time to recurrence was 7.1 months (0-38). There were 20 cases (3.11%) in the single-hook group and 19 cases (0.67%) in the double-hook group. Based on laparoscopic findings, recurrence most probably resulted from multiple factors, including uneven tension of the ligation (10 cases), missing part of the peritoneum (14 cases), loose ligation (8 cases), broken knot (5 cases), and knot reaction (2 cases). All children who underwent repeat SPLPEC were cured by double ligations or reinforcement with medial umbilical ligament. CONCLUSION: The main cause of recurrence is improper ligation. Tension-free and complete PIH ligation are critical to the success of surgery, which requires avoiding the peritoneum skip area and the subcutaneous and muscular tissues. Redo-laparoscopic surgery was suitable for the treatment of recurrent inguinal hernia (RIH). For giant hernias, direct ligation of the internal ring incorporating the medial umbilical ligament (DIRIM) may be needed.

New Insight into the Potential Protective Function of Sulforaphene against ROS-Mediated Oxidative Stress Damage In Vitro and In Vivo.

Sulforaphene (SFE) is a kind of isothiocyanate isolated from radish seeds that can prevent free-radical-induced diseases. In this study, we investigated the protective effect of SFE on oxidative-stress-induced damage and its molecular mechanism in vitro and in vivo. The results of cell experiments show that SFE can alleviate D-gal-induced cytotoxicity, promote cell cycle transformation by inhibiting the production of reactive oxygen species (ROS) and cell apoptosis, and show a protective effect on cells with H2O2-induced oxidative damage. Furthermore, the results of mice experiments show that SFE can alleviate D-galactose-induced kidney damage by inhibiting ROS, malondialdehyde (MDA), and 4-hydroxyalkenals (4-HNE) production; protect the kidney against oxidative stress-induced damage by increasing antioxidant enzyme activity and upregulating the Nrf2 signaling pathway; and inhibit the activity of pro-inflammatory factors by downregulating the expression of Toll-like receptor 4 (TLR4)-mediated inflammatory response. In conclusion, this research shows that SFE has antioxidant effects, providing a new perspective for studying the anti-aging properties of natural compounds.

A Three-Phase Current Tacholess Envelope Order Analysis Method for Feature Extraction of Planetary Gearbox under Variable Speed Conditions.

Planetary gearboxes are the key components of large equipment, such as wind turbines, shield machines, etc. The operating state of the planetary gearbox is related to the safety of the equipment as a whole, and its feature extraction technology is essential. In assessing the problem of the non-stationarity of the current signal under variable speed conditions and the difficulty of evaluating the operating state of the planetary gearbox under a tacholess condition, a three-phase current, variable-speed tacholess envelope order analysis method is proposed. Firstly, a tacholess rotation speed estimation is completed by extracting the trend term of the instantaneous frequency of the asynchronous motor's three-phase currents. The motor slip rate is assumed to be constant. Then, the envelope order analysis signal is obtained by re-sampling in the angular domain. Finally, the features of the envelope order signal are extracted, and a linear discriminant analysis (LDA) algorithm is used to fuse multiple indexes to generate a comprehensive feature reflecting the operating status of the planetary gearbox. The results of the simulation analysis and experimental verification show that the proposed method is effective in evaluating the operating state of the planetary gearbox under variable speed conditions. Compared with the traditional time-frequency ridge extraction method, the tacholess speed estimation method can improve the instantaneous speed estimation accuracy. The comprehensive index of envelope order completes the planetary gearbox state identification process, and a 95% classification accuracy rate is achieved.

Chronic exposure to fluoxetine of female mice before mating causes impaired stress resilience in female offspring.

Antidepressant agents have been proven their utilities in treating depression, but they also could serve as candidate drugs for misuse or abuse due to diverse pharmacologic properties. Potential detriments had also been multidimensionally investigated. However, there had been no study exploring whether treatment with antidepressants causes psychological and/or behavioral alterations in offspring. In this regard, we chronically treated normal female mice with different dosages (0, 10, and 20 mg/kg) of fluoxetine (FLU) for 2 weeks before mating them with drug-free male mice and then tested the offspring for anxiety/depression-like behaviors with the elevated plus maze and the tail-suspension test after exposing to acute or chronic stress in adult period. We found that there were significant increases for immobility time in the tail-suspension test as well as percentage of open arm entries and percentage of open arm time in the elevated plus maze test detected in the female offspring of the 20 mg group compared to both baseline and all other groups, with the exception that the female offspring of the 10 mg group showed an increased percentage of open arm entries after chronic stress exposure. Locomotor activity assessments showed that neither acute nor chronic stress protocol could significantly affect locomotor activities of mice. Conclusionally, we found that high-dosage FLU increased the risk of the female offspring developing into depression/anxiety-like behaviors after stress exposure, with chronic stress as the environmental-risk factor. Our study has important implications for the safe use of antidepressant agents and raises more concerns regarding long-term use of even second-generation antidepressants in clinical practice.

Intravenous Immunoglobulin Gamma (IVIG) versus IVIG Plus Infliximab in Young Children with Kawasaki Disease.

BACKGROUND Kawasaki disease (KD) is a serious disease characterized by systemic lesions of the skin and mucous membranes, as well as lymphomas and vascular inflammation. KD threatens the health and lives of children, especially young ones. Here, we compared the therapeutic effects of single intravenous immunoglobulin gamma (IVIG) vs. a combination of IVIG and infliximab in young children with Kawasaki disease (KD). MATERIAL AND METHODS A total of 154 children with KD, younger than 5 years old, were enrolled in the study from January 2013 to January 2017. The patients were randomly divided into an IVIG group and a combination of IVIG and infliximab treatment group. After systematic treatments, the therapeutic indicators of the 2 groups were compared. During the treatment process, body temperature and other important inflammatory indicators, including C-reactive protein (CRP), white blood cell count (WBC), and tumor necrosis factor alpha (TNF-α), were monitored in the first 4 days. RESULTS There were fewer refractory KD patients in the combined treatment group than in the IVIG group (4 vs. 14, p<0.001). KD patients in the combined treatment group had better outcomes with shorter fever durations and hospital stays, as well as less coronary artery dilation. However, there was no obvious differences in the incidence rate of coronary artery aneurysms between the 2 groups (p>0.05). Costs of administration were similar between groups (p>0.05). Body temperature, CRP, WBC, and TNF-α in the combined therapy group all showed an earlier drop than in the IVIG group, indicating a more effective anti-inflammation effect. CONCLUSIONS The introduction of IVIG combined with infliximab in the treatment of young children with KD has more advantages than single IVIG therapy and can be considered as a preferred treatment for KD. However, it would be necessary to further investigate whether there is a significant difference in aneurysm frequency and long-term outcome between these 2 strategies among a larger number of patients.

[Transumbilical single-port laparoscopy combined with improved double hernia needles for pediatric hydrocele].

OBJECTIVE: To compare the clinical effect of transumbilical single-port laparoscopy combined with improved double hernia needles with that of traditional open surgery in the treatment of hydrocele in children. METHODS: We retrospectively analyzed 35 cases (54 sides) of pediatric hydrocele treated by transumbilical single-port laparoscopy combined with improved double hernia needles (laparoscopy group). We recorded the operation time, intraoperative blood loss, hospital stay, scrotal edema, and postoperative complications and compared them with those of another 46 cases (58 sides) treated by traditional open surgery (open surgery group) during the same period. RESULTS: The laparoscopy group showed a significantly shorter operation time, less intraoperative blood loss, milder scrotal edema, and fewer hospital days than the open surgery group (all P<0.05). However, no statistically significant difference was found in the incidence of postoperative complications between the two groups (P>0.05). Subcutaneous emphysema developed in 2 patients in the laparoscopy group, which disappeared after 1－3 days of oxygen inhalation and other symptomatic treatment, while scrotal hematoma occurred in 1 and incision fat liquefaction in 2 patients in the open surgery group 3 days postoperatively, which healed after debridement suture and daily dressing, respectively. The patients were followed up for 3－6 months, which revealed no late complications in the laparoscopy group but 1 case of unilateral recurrence and 2 cases of offside recurrence in the open surgery group, all cured by laparoscopic internal ring ligation. CONCLUSIONS: Transumbilical single-port laparoscopy combined with improved double hernia needles is superior to traditional open surgery for the treatment of pediatric hydrocele and therefore deserves clinical generalization.

SlMYC2 mediates stomatal movement in response to drought stress by repressing SlCHS1 expression.

Drought stress limits plant development and reproduction. Multiple mechanisms in plants are activated to respond to stress. The MYC2 transcription factor is a core regulator of the jasmonate (JA) pathway and plays a vital role in the crosstalk between abscisic acid (ABA) and JA. In this study, we found that SlMYC2 responded to drought stress and regulated stomatal aperture in tomato (Solanum lycopersicum). Overexpression of SlMYC2 repressed SlCHS1 expression and decreased the flavonol content, increased the reactive oxygen species (ROS) content in guard cells and promoted the accumulation of JA and ABA in leaves. Additionally, silencing the SlCHS1 gene produced a phenotype that was similar to that of the MYC2-overexpressing (MYC2-OE) strain, especially in terms of stomatal dynamics and ROS levels. Finally, we confirmed that SlMYC2 directly repressed the expression of SlCHS1. Our study revealed that SlMYC2 drove stomatal closure by modulating the accumulation of flavonol and the JA and ABA contents, helping us decipher the mechanism of stomatal movement under drought stress.

Successful treatment of floating splenic volvulus: Two case reports and a literature review.

BACKGROUND: The floating spleen refers to the spleen moving away from the normal anatomical position to other parts of the abdominal cavity. CASE SUMMARY: In this report, we describe two cases of torsion of floating spleen, which were successfully treated by laparoscopic partial splenectomy and retroperitoneal fixation of the residual spleen. The clinical characteristics of previously reported cases are also discussed. CONCLUSION: In conclusion, laparoscopic partial resection of splenic volvulus infarction and extraperitoneal fixation of residual spleen are safe and reliable.

Decarboxylated osteocalcin, a possible drug for type 2 diabetes, triggers glucose uptake in MG63 cells.

BACKGROUND: Uncarboxylated osteocalcin (GluOC) has been reported to improve glucose metabolism, prevent type 2 diabetes, and decrease the severity of obesity in mice with type 2 diabetes. GluOC can increase glucose uptake in a variety of cells. Glucose metabolism is the main source of energy for osteoblast proliferation and differentiation. We hypothesized that decarboxylated osteocalcin (dcOC), a kind of GluOC, can increase glucose uptake in MG63 cells (osteoblast-like osteosarcoma cells) and influence their proliferation and differentiation. AIM: To investigate the effects of dcOC on glucose uptake in human osteoblast-like osteosarcoma cells and the possible signaling pathways involved. METHODS: MG63 cells (human osteoblast-like osteosarcoma cells) were treated with dcOC (0, 0.3, 3, 10, or 30 ng/mL) for 1 and 72 h, and glucose uptake was measured by flow cytometry. The effect of dcOC on cell proliferation was measured with a CCK-8 assay, and alkaline phosphatase (ALP) enzyme activity was measured. PI3K was inhibited with LY294002, and hypoxia-inducible factor 1 alpha (HIF-1α) was silenced with siRNA. Then, GPRC6A (G protein-coupled receptor family C group 6 subtype A), total Akt, phosphorylated Akt, HIF-1α, and glucose transporter 1 (GLUT1) levels were measured by Western blot to elucidate the possible pathways by which dcOC modulates glucose uptake. RESULTS: The glucose uptake of MG63 cells was significantly increased compared with that of the paired control cells after short-term (1 h) treatment with dcOC at different concentrations (0.3, 3, and 10 ng/mL groups, P < 0.01; 30 ng/mL group, P < 0.05). Glucose uptake of MG63 cells was significantly increased compared with that of the paired control cells after long-term (72 h) treatment with dcOC at different concentrations (0.3, 3, and 10 ng/mL groups, P < 0.01; 30 ng/mL group, P < 0.05). DcOC triggered Akt phosphorylation in a dose-dependent manner, and the most effective stimulatory concentration of dcOC for short-term (1 h) was 3 ng/mL (P < 0.01). LY294002 abolished the dcOC-mediated (1 h) promotion of Akt phosphorylation and glucose uptake without affecting GLUT1 protein expression. Long-term dcOC stimulation triggered Akt phosphorylation and increased the protein levels of HIF-1α, GLUT1, and Runx2 in a dose-dependent manner. Inhibition of HIF-1α with siRNA abolished the dcOC-mediated glucose uptake and substantially decreased GLUT1 protein expression. DcOC intervention promoted cell proliferation in a time- and dose-dependent manner as determined by the CCK-8 assay. Treatment with both 3 ng/mL and 10 ng/mL dcOC affected the ALP activity in MG63 cells after 72 h (P < 0.01). CONCLUSION: Short- and long-term dcOC treatment can increase glucose uptake and affect proliferation and ALP activity in MG63 cells. This effect may occur through the PI3K/Akt, HIF-1α, and GLUT1 signaling factors.

Primary laparoscopic endorectal pull-through procedure with or without a postoperative rectal tube for hirschsprung disease: a multicenter perspective study.

BACKGROUND: Hirschsprung-associated enterocolitis (HAEC) is a significant complication of HD both in the pre- and postoperative periods. This was a large multicenter series study to determine the effect of preserving a postoperative rectal tube on preventing HAEC after primary laparoscopic endorectal pull-through procedure. METHODS: Between 2014 and 2017, a total of 383 consecutive patients with rectosigmoid segment HD were randomly divided into group A (n = 190) and group B (n = 193). All of them underwent primary laparoscopic pull-through procedure, with the same postoperative treatment protocols except for group A with a rectal tube after surgery for 5 days, while group B did not have it. The mean time of follow-up was 2.0 ±â€¯0.53 years (0.5-3.6 years). Demographics, operative data, postoperative complications, and clinical outcomes were compared between these two groups. RESULTS: Outcomes within 1 month after surgery indicated a lower incidence of abdominal distention (4% vs 15.5%, P < 0.05) and postoperative HAEC (1.2% vs 6.8%, P < 0.05) in group A compared to group B. Beyond 1 month after surgery, the overall incidence of HAEC was not significantly different (12% vs 13.1%, P = 0.54). However, further analysis revealed that the patients who suffered HAEC twice or above twice in group A were significantly less than those in group B (3.6% vs 8.3%, p = 0.02). There were no significant differences in the defecation frequency and other complications. CONCLUSIONS: Primary laparoscopic endorectal pull-through procedure with a postoperative rectal tube can reduce the early-stage postoperative incidence of abdominal distension and HAEC and the risk of HAEC recurrence in the long term, and is beneficial to postoperative management. LEVEL OF EVIDENCE: Level 2.

Targeted inhibition of myeloid-derived suppressor cells in the tumor microenvironment by low-dose doxorubicin to improve immune efficacy in murine neuroblastoma.

BACKGROUND: High agglomeration of myeloid-derived suppressor cells (MDSCs) in neuroblastoma (NB) impeded therapeutic effects. This study aimed to investigate the role and mechanism of targeted inhibition of MDSCs by low-dose doxorubicin (DOX) to enhance immune efficacy in NB. METHODS: Bagg albino (BALB/c) mice were used as tumor-bearing mouse models by injecting Neuro-2a cells, and MDSCs were eliminated by DOX or dopamine (DA) administration. Tumor-bearing mice were randomly divided into 2.5 mg/kg DOX, 5.0 mg/kg DOX, 50.0 mg/kg DA, and control groups (n = 20). The optimal drug and its concentration for MDSC inhibition were selected according to tumor inhibition. NB antigen-specific cytotoxic T cells (CTLs) were prepared. Tumor-bearing mice were randomly divided into DOX, CTL, anti-ganglioside (GD2), DOX+CTL, DOX+anti-GD2, and control groups. Following low-dose DOX administration, immunotherapy was applied. The levels of human leukocyte antigen (HLA)-I, CD8, interleukin (IL)-2 and interferon (IFN)-γ in peripheral blood, CTLs, T-helper 1 (Thl)/Th2 cytokines, perforin, granzyme and tumor growth were compared among the groups. The Wilcoxon two-sample test and repeated-measures analysis of variance were used to analyze results. RESULTS: The slowest tumor growth (F = 6.095, P = 0.018) and strongest MDSC inhibition (F = 14.632, P = 0.001) were observed in 2.5 mg/kg DOX group. Proliferation of T cells was increased (F = 448.721, P < 0.001) and then decreased (F = 2.047, P = 0.186). After low-dose DOX administration, HLA-I (F = 222.489), CD8 (F = 271.686), Thl/Th2 cytokines, CD4+ and CD8+ lymphocytes, granzyme (F = 2376.475) and perforin (F = 488.531) in tumor, IL-2 (F = 62.951) and IFN-γ (F = 240.709) in peripheral blood of each immunotherapy group were all higher compared with the control group (all of P values < 0.05). The most significant increases in the aforementioned indexes and the most notable tumor growth inhibition were observed in DOX+anti-GD2 and DOX+CTL groups. CONCLUSIONS: Low-dose DOX can be used as a potent immunomodulatory agent that selectively impairs MDSC-induced immunosuppression, thereby fostering immune efficacy in NB.

Molecular epidemiology and antimicrobial susceptibility of Clostridium difficile isolated from the Chinese People's Liberation Army General Hospital in China.

Clostridium difficile is a Gram-positive, spore-forming obligate anaerobe responsible for antibiotic-associated diarrhoea. Its virulence is associated with the production of endotoxins A and B and endospores, which can cause symptoms, such as diarrhoea, toxic megacolon, and pseudomembranous colitis. Given the increasing elderly population and the well-recognized problem of over-prescribing of broad-spectrum antibiotics, it is critical to have an understanding of molecular epidemiology and antimicrobial susceptibility in China. This study analyzed the toxin types and multilocus sequence typing (MLST) results of 74 clinical isolates of C. difficile after the glutamate dehydrogenase (GDH) screening test and anaerobic culture. The minimum inhibitory concentrations (MICs) of four different antibiotics were determined for all of the isolates, and the bacterial resistance mechanisms were investigated. Sixty-five strains (75%) were toxigenic, including 54 tcdA-positive, tcdB-positive, and cdtA/cdtB-negative strains (A+B+CDT-) and nine A-B+CDT- strains. Eleven strains (14.9%) were non-toxigenic. All clinical isolates were classified into 26 MLST genotypes, with the predominant type being ST-54 (18.9%). All isolates were susceptible to vancomycin. The tetracycline, clindamycin, and levofloxacin resistance rates were 1.4%, 36.5%, and 20.3%, respectively. The expression of tet(M), erm(B), and mutations of gyrA and/or gyrB were observed in the tetracycline-, clindamycin-, and levofloxacin-resistant isolates, respectively.

Simple and efficient polyoxomolybdate-mediated synthesis of novel graphene and metal nanohybrids for versatile applications.

The application of nanohybrids based on polyoxomolybdates, reduced graphene oxide (rGO) and/or metal nanoparticles (NPs) high-performance electrode materials in electrocatalysis and energy storage devices is promising but still limited due to the complexity and the cost of the synthesis. Here we introduce a simple polyoxomolybdate, [MoV4O8(OH)2(H2O)2(C4O4)2]2- (MoS), as reducing and stabilizing agent for the facile and one-pot syntheses of large quantity of highly stable MoS/rGO and MoS/Au NPs nanohybrids in aqueous solution without any catalyst or toxic co-solvent. They were characterized by various physical techniques and electrochemistry which confirm strong interaction between MoS and rGO sheets. We also used DFT calculations to investigate the affinity between MoS or its neutral form with graphene. The adsorption energy for the most stable configuration is -1.97 eV, indicating a strong adsorption process of MoS, which can also be confirmed by the distance (3.04 Å) and the charge transfer (0.86 e) between MoS and graphene. These observations are also consistent with the electrochemical results which underscore the excellent redox properties and high stability of MoS/rGO. Importantly, the MoS/rGO nanohybrids are excellent noble metal-free electrocatalysts for hydrogen peroxide reduction with high sensitivity, large detection range and low detection limit. Finally, the preliminary tests reveal that the electrode materials based on MoS/rGO and a low-cost carbon cloth (CC) composite MoS/rGO/CC may have a potential for an application in energy storage as performant and flexible supercapacitor, showing specific capacitance as high as 870 F g-1 at 10 mV s-1 and excellent stability after 5000 cycles.

Differentially expressed lncRNAs and mRNAs identified by NGS analysis in colorectal cancer patients.

Long noncoding RNAs (lncRNAs) play an important role in gene regulation, but their impact on the pathogenesis of colorectal cancer and the biological function of cancer cells is unclear. In this study, we used next-generation sequencing to study the differences in the expression profiles of lncRNAs and mRNAs in colorectal cancer tissues. We analyzed the differentially expressed genes by Gene Ontology/Kyoto Encyclopedia of Genes and Genomes (GO/KEGG) enrichment and predicted new lncRNA functions. Our results revealed that compared with lncRNAs and mRNAs in nontumor colorectal tissues, 1019 lncRNAs (512 upregulated, 507 downregulated) and 3221 mRNAs (1606 upregulated, 1615 downregulated) were differentially expressed in tumor colorectal tissues (fold change >2 and P < 0.05). We validated some of these genes by qPCR. Furthermore, we identified some new lncRNAs differently expressed in colorectal cancer samples from patients in northern China. We confirmed the function of lncRNA-FIRRE-201 and SLCO4A1-AS1-202 in colorectal cancer cells to provide an experimental basis for studies on their roles in the occurrence and development of colorectal cancer and in the regulation of networks.

[Conditioned mediums of different rat cerebral microvascular endothelial cells against damage of ischemia and ischemia/reperfusion neurons].

OBJECTIVE: Using the method of lactate dehydrogenase (LDH) assay, to observe the activities of rat cerebral microvascular endothelial cells (CMECs) intervened by Tongluo Jiunao Injection (TLJNI), a traditional Chinese compound drug removing toxin to dredge brain collaterals, and then further study the effects of different kinds of conditioned mediums (CMECs-CM) of cerebral microvascular endothelial cells on ischemia and ischemia/reperfusion cerebral cortex cells, and to probe into the drug pharmacological mechanisms of CMECs in modulating the neurons. METHODS: Three kinds of CMECs (normal, ischemic and ischemic/reperfusional) were all treated by TLJNI previously, and then the three pairs of CMECs-CM without serum were collected respectively for LDH assay. Rat cerebral cortex neurons were also primarily cultured and then divided into similar three groups (normal, ischemic and ischemic/reperfusional). The neuron responses caused by CMECs-CM at different concentrations were observed by using LDH transudation rate assay. RESULTS: The LDH release values of ischemic and ischemic/reperfusional CMECs with TLJNI treatment were obviously reduced (P<0.01) compared with the same kinds of CMECs untreated. For ischemic neurons, both conditioned medium of ischemic CMECs (Is-CM) and conditioned medium of ischemic CMECs with drug treatment (IsT-CM) in high concentration of 100% increased the LDH transudation rate (P<0.01), while in low concentration of 10%, IsT-CM reduced the transudation rate (P<0.05). For ischemia/reperfusion neurons, all kinds of CMECs-CM reduced the transudation rate respectively (P<0.05 or P<0.01). As far as each group concentration was concerned, 10% or 50% showed relatively stronger effects, and both conditioned medium of normal CMECs (N-CM) group and conditioned medium of ischemic/reperfusional CMECs (Rp-CM) group had statistical significance (P<0.05 or P<0.01). For normal neurons, all kinds of CMECs-CM increased the transudation rate respectively (P<0.05 or P<0.01). As far as each group concentration was concerned, only conditioned medium of normal CMECs (N-CM) had statistical significance (P<0.05 or P<0.01). CONCLUSION: The study shows that TLJNI is capable of preventing the damage of CMECs from both ischemia and ischemia/reperfusion states. Chinese drug can restrain the brain ischemia and ischemia/reperfusion damage by the media that CMECs modulate the neurons, demonstrating the pharmacological mechanisms of TLJNI. This work also indicates that there exist some active substances against ischemia/reperfusion injury secreted from CMECs-CM with TLJNI treatment.

Protective effects of ginsenoside Rg1 against oxygen-glucose-deprivation-induced apoptosis in neural stem cells.

Oxygen-glucose deprivation (OGD) causes neural damages through stroke-induced ischemia. Neural stem cells (NSCs) have been shown to alleviate ischemia-induced neural damages. However, ischemia reduces NSC survival. Ginsenoside Rg1 exerts anti-inflammatory and anti-oxidative effects, and repairs brain injury-related neural damages. We aimed to investigate whether ginsenoside Rg1 could prevent NSCs from OGD insult. Using multiple techniques, we explored neuroprotective effects of ginsenoside Rg1 on OGD-insulted NSCs. 6h treatment of OGD most significantly decreased NSC viability, and 10-20µM ginsenoside Rg1 efficiently protected NSCs against OGD insult. Annexin V-FITC/propidium iodide (PI) double staining results confirmed that ginsenoside Rg1 significantly reduced the OGD-induced apoptosis in NSCs. OGD-insulted NSCs with ginsenoside Rg1 treatment displayed reduced expressions of pro-apoptotic proteins cleaved Caspase3 and Bax, and elevated expression of anti-apoptotic protein Bcl-2 than the NSCs with OGD insult. Moreover, ginsenoside Rg1 reduced OGD-induced oxidative stress, and inhibited the expression of p-p38 and p-JNK2. Ginsenoside Rg1 protects NSCs against OGD-induced cell apoptosis through regulating the expression of apoptotic signal proteins. In addition, ginsenoside Rg1 attenuates OGD-induced oxidative stress and inhibits p38/JNK2 phosphorylation in NSCs. Our study provides solid evidence for neuroprotective effects of ginsenoside Rg1 and reveals the underlying mechanisms.

Triptolide reverses the Taxol resistance of lung adenocarcinoma by inhibiting the NF-κB signaling pathway and the expression of NF-κB-regulated drug-resistant genes.

Paclitaxel (or Taxol®) is a first-line chemotherapeutic drug for the treatment of non-small cell lung cancer; however, resistance to the drug is an important factor, which influences the outcome of chemotherapy. The present study aimed to investigate the role of triptolide (TPL) in reversing Taxol­resistant human lung adenocarcinoma and to elucidate the underlying molecular mechanism of resistance reversal mediated by TPL. It was hypothesized that this experimental approach would assist in solving the problem of chemotherapeutic resistance in non­small cell lung cancer, thereby improving the clinical outcomes. The human Taxol­resistant lung adenocarcinoma cell line, A549/Taxol, was established. The resistance index of the cell line was calculated, according to the half maximal inhibitory concentration (IC50) of A549/Taxol IC50 of A549, to be 51.87. The levels of apoptosis and the cell cycle in the A549/Taxol cell line were assessed to confirm the effects of TPL at three different concentrations (0.03, 0.3 and 3 µmol/l) and treatment durations (2, 4, 6 and 12 h) by flow cytometric analysis, and the inhibition of the NF­κB signaling pathway and the expression of NF­κB­regulated drug­resistant proteins were determined by immunofluorescence and western blotting, respectively. The administration of TPL promoted cell apoptosis in the A549/Taxol lung adenocarcinoma Taxol­resistant cell line and also promoted cell cycle regulation. The drug was also able to elicit a reversal of the drug resistance. TPL inhibited the nuclear factor­κB (NF­κB) signaling pathway and the expression of NF­κB­regulated drug­resistant genes, including those for FLICE­like inhibitory protein, X­linked inhibitor of apoptosis protein, Bcl­2, Bcl­xL and cyclo­oxygenase­2. TPL exerted a marked drug­resistance­reversal effect on human lung adenocarcinoma Taxol resistance, and the effect was revealed to be dose­ and time­dependent. In conclusion, TPL exerted its role in the process of resistance reversal by inhibiting the NF­κB signaling pathway, and the transcription and expression of NF-κB-regulated drug-resistant genes.

Anti-cancer effects of COX-2 inhibitors and their correlation with angiogenesis and invasion in gastric cancer.

AIM: To observe the anti-cancer effects of COX-2 inhibitors and investigate the relationship between COX-2 inhibitors and angiogenesis, infiltration or metastasis in SGC7901 cancer xenografts. METHODS: Thirty athymic mice xenograft models with human stomach cancer cell SGC7901 were established and divided randomly into 3 groups of 10 each. Sulindac, one non-specific COX inhibitor belonging to non-steroidal anti-inflammatory drugs (a series of COX inhibitors known as NSAIDs) and celecoxib, one selective COX-2 inhibitor (known as SCIs) were orally administered to mice of treatment groups. Immunohistochemistry was used to examine the expression of PCNA, CD44v6 and microvessel density (MVD). Apoptosis was detected by using TUNEL assay. RESULTS: Tumors in sulindac and celecoxib groups were significantly smaller than those in control group from the second week after drug administration (P<0.01). In treatment group, the cell proliferation index was lower (P<0.05) and apoptosis index was higher (P<0.05) than those in control groups. Compared with the controls, microvessel density was reduced (P<0.01) and expression of CD44v6 on tumor cells was weakened (P<0.05) in treatment groups. CONCLUSION: COX-2 inhibitors have anticancer effects on gastric cancer. They play important roles in angiogenesis and infiltration or metastasis of stomach carcinoma. The anticancer effects of COX-2 inhibitors may include inducing apoptosis, suppressing proliferation, reducing angiogenesis and weakening invasiveness.

Gender differences in associations of serum ferritin and diabetes, metabolic syndrome, and obesity in the China Health and Nutrition Survey.

SCOPE: This study examines gender differences in associations of serum ferritin and diabetes, metabolic syndrome (MetS), and obesity in Chinese. METHODS AND RESULTS: Based on a nationwide, population-based China Health and Nutrition survey this study included 8564 men and women aged 18 years or older. Anthropometric and fasting blood glucose, insulin, lipids, ferritin, and transferrin data were collected. Ferritin concentrations were higher in men than women (201.55 ± 3.6 versus 80.46 ± 1.64 ng/mL, p < 0.0001). The prevalences of MetS, diabetes, obesity, and overweight were 8.05, 8.97, 4.67, 25.88% among men and 14.23, 6.58, 5.81, 26.82% among women, respectively. Elevated ferritin concentrations were associated with higher body mass index, waist circumference, lipids, insulin, glucose (all p < 0.0001). Serum ferritin concentrations increased gradually with aging among women. The inverted U-shaped association between serum ferritin and age was observed among men. Elevated concentration of ferritins were significantly related with higher risk of MetS (p < 0.0001), obesity (p = 0.010), overweight (p < 0.0001), and diabetes (p < 0.0001) among men, but not among women. CONCLUSION: There was a gender difference in associations between ferritin and MetS, obesity, and diabetes in Chinese adults. Further evaluations of the variation in gender on these associations are warranted to understand the mechanisms behind gender differences.

An unconditioned stimulus retrieval extinction procedure to prevent the return of fear memory.

BACKGROUND: Conditioned fear memories can be updated by extinction during reconsolidation, and this effect is specific to the reactivated conditioned stimulus (CS). However, a traumatic event can be associated with several cues, and each cue can potentially trigger recollection of the event. We introduced a technique to target all diverse cues associated with an aversive event that causes fear. METHODS: In human experiments, 161 subjects underwent modified fear conditioning, in which they were exposed to an unconditioned stimulus (US) or unreinforced CS to reactivate the memory and then underwent extinction, spontaneous recovery, and reinstatement. In animal experiments, 343 rats underwent contextual fear conditioning under a similar protocol as that used in the human experiments. We also explored the molecular alterations after US reactivation in rats. RESULTS: Presentation of a lower intensity US before extinction disrupted the associations between the different CS and reactivated US in both humans and rats. This effect persisted for at least 6 months in humans and was selective to the reactivated US. This procedure was also effective for remote memories in both humans and rats. Compared with the CS, the US induced stronger endocytosis of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid glutamate receptors 1 and 2 and stronger activation of protein kinase A, p70S6 kinase, and cyclic adenosine monophosphate response element binding protein in the dorsal hippocampus in rats. CONCLUSIONS: These findings demonstrate that a modified US retrieval extinction strategy may have a potential impact on therapeutic approaches to prevent the return of fear.