Self-rated health and health-related quality of life among cancer patients: the serial multiple mediation of anxiety and depression.

BACKGROUND: Health-related quality of life (HRQOL) in cancer patients has attracted increasing attention, which may be associated with self-rated health (SRH), anxiety, and depression. However, limited studies have focused on the mediating role of anxiety and depression in the relationship between SRH and HRQOL among cancer patients. Therefore, this study aims to explore the serial multiple mediating effects of anxiety and depression between SRH and HRQOL in cancer patients. METHODS: This cross-sectional study investigated a total of 565 hospitalized cancer patients in Anhui province in China from November 2020 to October 2021. SRH was assessed using a single-item measure, anxiety and depression were assessed using the Hospital Anxiety and Depression Scale (HADS) and HRQOL was assessed using the EuroQol-5 Dimension (EQ-5D, three-level version). Socio-demographic and clinical characteristics were analyzed using descriptive statistics. The relationships between SRH, anxiety, depression, and HRQOL were evaluated by Pearson correlation analysis. The serial multiple mediation of anxiety and depression was assessed by SPSS PROCESS macro. RESULTS: SRH, anxiety, depression and HRQOL were significantly correlated(P < 0.001). In comparison to the fair SRH, the good SRH exhibited a significantly positive direct effect (Effect = 0.2366, Bootstrap 95%CI: 0.0642 ~ 0.4090) and total effect on HRQOL (Effect = 0.4761, Bootstrap 95%CI: 0.2975 ~ 0.6546). Conversely, the poor SRH demonstrated a significantly negative total effect on HRQOL (Effect= -0.4321, Bootstrap 95%CI: -0.7544~ -0.1099). When considering the fair SRH as the reference group, the poor SRH displayed a negative indirect effect on HRQOL through the single mediation of anxiety (Effect= -0.1058, Bootstrap 95%CI: -0.2217~ -0.0107) and the serial mediation of anxiety and depression (Effect= -0.0528, Bootstrap 95%CI: -0.1233~ -0.0035). Conversely, the good SRH had a positive indirect impact on HRQOL through the single mediation of anxiety (Effect = 0.1153, Bootstrap 95%CI: 0.0583 ~ 0.1900) and depression (Effect = 0.0667, Bootstrap 95%CI: 0.0206 ~ 0.1234), as well as the serial mediation of anxiety and depression (Effect = 0.0575, Bootstrap 95%CI: 0.0192 ~ 0.1030). CONCLUSION: SRH can improve HRQOL through the decrease of anxiety and depression in cancer patients. Focusing on SRH would be beneficial for their mental health and HRQOL in cancer patients.

Amygdalin ameliorates alopecia areata on C3H/HeJ mice by inhibiting inflammation through JAK2/STAT3 pathway.

BACKGROUND: Evidence has demonstrated that Chinese medicine formula Xuefu Zhuyu decoction can markedly promote the formation of new hair in patients and mice with alopecia areata (AA). Amygdalin is one of the active components of Xuefu Zhuyu decoction, but its therapeutic effects and the underlying mechanisms on AA remains largely unrevealed. PURPOSE: Therefore, this study aims to investigate the therapeutic effects and to probe its molecular mechanisms of inflammation and immune regulation on AA model of C3H/HeJ mice. STUDY DESIGN: The C3H/HeJ female mice were divided into control, AA, rusolitinib (60 mg/kg), and amygdalin groups (60, 90, and 120 mg/kg, 0.2 ml/10 g, i.g.). METHODS: The optical microscope was used to observe the feature of the local skin, and the number of lanugo and terminal hair. H&E staining was performed to determine the degree of pathological damage to the skin. ELISA was performed to detect levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in mice serum. Flow cytometry was carried out to analyze the CD4+CD25+FOXP3+, CD4+ and CD8+ of skin tissue. And the levels of CD4+ and CD8+, p-JAK/JAK2, p-STAT3/STAT, and SOCS3 were detected by immunohistochemistry. Western blot and qRT-PCR were employed to examine the expression levels of IL-6, TNF-α, IFN-γ, JAK2, p-JAK, STAT, p-STAT3 and SOCS3 proteins and genes in skin tissues. RESULTS: Compared with AA group, amygdalin immensely increased the number of vellus hairs and decreased the number of terminal hairs determined by skin microscopy and H&E staining. ELISA, Western blot and qRT-PCR data showed that the levels of IL-6, TNF-α and IFN-γ in serum and skin tissues of AA mice were significantly increased, while amygdalin administration dramatically restrained the contents of the three pro-inflammatory factors. Flow cytometry and immunohistochemistry hinted that amygdalin observably enhanced the number of CD4+CD25+FOXP3+ and CD4+ cells, while inhibited the number of CD8+ positive cells in mice with AA. Moreover, amygdalin signally reduced JAK2/STAT3 pathway-related protein and gene levels in AA mice. CONCLUSION: Amygdalin could inhibit inflammatory response and improve immune function in the treatment of AA. The underlying molecular mechanism may be related to inhibition of JAK2/STAT3 pathway.

Surgery Adherence and Survival Outcomes in Patients With Locally Advanced (IIA-IVA) Cancer of the Lower Esophagus: A SEER Database-Based Study.

BACKGROUND: Esophageal cancer is a prevalent malignant tumor of the upper gastrointestinal tract. The aim of this study was to examine the impact of surgical adherence on the prognosis of patients with locally advanced lower esophageal cancer and to analyze the factors that affect surgical adherence. METHODS: Patients diagnosed with locally advanced (IIA-IVA) lower esophageal cancer between 2004 and 2015 were screened from the Surveillance, Epidemiology, and End Results (SEER) database. We utilized multifactorial logistic regression to analyze the correlates affecting surgical adherence. Furthermore, we employed Kaplan-Meier curves and Cox regression to determine the impact of surgical adherence on cancer-specific survival (CSS) and overall survival (OS). RESULTS: Of the 4922 patients screened, 2372 individuals were advised to undergo surgery, out of which 2025 ultimately underwent the procedure while the remaining 347 refused. Lower surgical adherence was associated with older age, unmarried, SEER classification of "distant," and squamous cell carcinoma. Adherence to surgery proved to be an independent factor affecting OS and CSS. The Cox regression analysis showed that patients who refused surgery had lower OS (OR: 1.657; 95% CI: 1.429∼1.927; P < .001) and CSS (OR: 1.487; 95% CI: 1.309∼1.690; P < .001) than those who underwent surgery. Kaplan-Meier curves showed that patients who underwent surgical treatment had a better prognosis. DISCUSSION: Good surgical adherence can improve the prognosis of patients with locally advanced (IIA-IVA) lower esophageal cancer, while poor surgical adherence is associated with older age, unmarried, SEER classification of "distant," and squamous cell carcinoma.

Exosomes derived from umbilical cord-mesenchymal stem cells inhibit the NF-κB/MAPK signaling pathway and reduce the inflammatory response to promote recovery from spinal cord injury.

Spinal cord injury (SCI) is a serious traumatic disease of the central nervous system and leads to incomplete or complete loss of the body's autonomous motor and sensory functions, seriously endangering human health. Recently, exosomes have been proposed as important substances in cell-to-cell interactions. Mesenchymal stem cell (MSC)-derived exosomes exert good therapeutic effects and play a crucial role in neurological damage repair. However, the detailed mechanisms underlying their effects remain unknown. Herein, we found that compared to SCI rats, those subjected to umbilical cord MSC (UC-MSC)-derived exosomes injection showed an improved motor ability. Nevertheless, the transcriptome of BV2 microglia in different treatment groups indicated that the action pathway of exosomes might be the NF-κB/MAPK pathway. Additionally, exosomes from UC-MSCs could inhibit P38, JNK, ERK, and P65 phosphorylation in BV2 microglia and SCI rat tissues. Moreover, exosomes could inhibit apoptosis and inflammatory reaction and reactive oxygen species (ROS) production of BV2 microglia in vitro and in vivo. In conclusion, UC-MSCs-derived exosomes might protect SCI in rats by inhibiting inflammatory response via the NF-κB/MAPK signaling pathway, representing novel treatment targets or approaches for SCI.

Theoretical error analysis of spotlight-based instrument localization for retinal surgery.

Retinal surgery is widely considered to be a complicated and challenging task even for specialists. Image-guided robot-assisted intervention is among the novel and promising solutions that may enhance human capabilities therein. In this paper, we demonstrate the possibility of using spotlights for 5D guidance of a microsurgical instrument. The theoretical basis of the localization for the instrument based on the projection of a single spotlight is analyzed to deduce the position and orientation of the spotlight source. The usage of multiple spotlights is also proposed to check the possibility of further improvements for the performance boundaries. The proposed method is verified within a high-fidelity simulation environment using the 3D creation suite Blender. Experimental results show that the average positioning error is 0.029 mm using a single spotlight and 0.025 mm with three spotlights, respectively, while the rotational errors are 0.124 and 0.101, which shows the application to be promising in instrument localization for retinal surgery.

Identification and validation of a novel cellular senescence-related lncRNA prognostic signature for predicting immunotherapy response in stomach adenocarcinoma.

Background: Cellular senescence is a novel hallmark of cancer associated with patient outcomes and tumor immunotherapy. However, the value of cellular senescence-related long non-coding RNAs (lncRNAs) in predicting prognosis and immunotherapy response for stomach adenocarcinoma (STAD) patients needs further investigation. Methods: The transcriptome and corresponding clinical information of STAD and cellular senescence-related genes were, respectively, downloaded from the Cancer Genome Atlas (TCGA) and CellAge databases. Differential expression analysis and coexpression analysis were performed to obtain cellular senescence-related lncRNAs. Univariate regression analysis and least absolute shrinkage and selection operator (LASSO) Cox analysis were conducted to establish the cellular senescence-related lncRNA prognostic signature (CSLPS). Next, the survival curve, ROC curve, and nomogram were developed to assess the capacity of predictive models. Moreover, principal component analysis (PCA), gene set enrichment analysis (GSEA), tumor microenvironment (TME), tumor mutation burden (TMB), microsatellite instability (MSI), and tumor immune dysfunction and exclusion (TIDE) score analysis were performed between high- and low-risk groups. Results: A novel CSLPS involving fifteen lncRNAs (REPIN1-AS1, AL355574.1, AC104695.3, AL033527.2, AC083902.1, TYMSOS, LINC00460, AC005165.1, AL136115.1, AC007405.2, AL391152.1, SCAT1, AC129507.1, AL121748.1, and ADAMTS9-AS1) was developed. According to the nomogram, the risk model based on the CSLPS was an independent prognostic factor and could predict 1-, 3-, and 5-year overall survival for STAD patients. GSEA suggested that the high-risk group was mainly associated with Toll-like receptor, JAK/STAT, NOD-like receptor, and chemokine signaling pathways. Further analysis revealed that STAD patients in the low-risk group with better clinical outcomes had a higher TMB, higher proportion of high microsatellite instability (MSI-H), better immune infiltration, and lower TIDE scores. Conclusion: A fifteen-CSlncRNA prognostic signature could predict survival outcomes, and patients in the low-risk group may be more sensitive to immunotherapy.

Self-Assembling Imageable Silk Hydrogels for the Focal Treatment of Osteosarcoma.

Background: The standard treatment for osteosarcoma comprises complete surgical resection and neoadjuvant chemotherapy, which may cause serious side effects and partial or total limb loss. Therefore, to avoid the disadvantages of traditional treatment, we developed self-assembling imageable silk hydrogels for osteosarcoma. Methods: We analysed whether iodine induced apoptosis in MG-63 and Saos-2 cells by using CCK-8 and flow cytometry assays and transmission electron microscopy. Western blotting was used to analyse the pathway of iodine-induced apoptosis in osteosarcoma cells. PEG400, silk fibroin solution, polyvinylpyrrolidone iodine (PVP-I), and meglumine diatrizoate (MD) were mixed to produce an imageable hydrogel. A nude mouse model of osteosarcoma was established, and the hydrogel was injected locally into the interior of the osteosarcoma with X-ray guidance. The therapeutic effect and biosafety of the hydrogel were evaluated. Results: Iodine treatment at 18 and 20 µM for 12 h resulted in cell survival rate reduced to 50 ± 2.1% and 50.5 ± 2.7% for MG-63 and Sao-2 cells, respectively (p < 0.01). The proportion of apoptotic cells was significantly higher in the iodine-treatment group than in the control group (p < 0.05), and apoptotic bodies were observed by transmission electron microscopy. Iodine could regulate the death receptor pathway and induce MG-63 and Saos-2 cell apoptosis. The hydrogels were simple to assemble, and gels could be formed within 38 min. A force of less than 50 N was required to inject the gels with a syringe. The hydrogels were readily loaded and led to sustained iodine release over 1 week. The osteosarcoma volume in the PEG-iodine-silk/MD hydrogel group was significantly smaller than that in the other three groups (p < 0.001). Caspase-3 and poly (ADP-ribose) polymerase (PARP) expression levels were significantly higher in the PEG-iodine-silk/MD hydrogel group than in the other three groups (p < 0.001). Haematoxylin and eosin (H&E) staining showed no abnormalities in the heart, liver, spleen, lung, kidney, pancreas or thyroid in any group. Conclusions: Self-assembling imageable silk hydrogels could be injected locally into osteosarcoma tissues with X-ray assistance. With the advantages of good biosafety, low systemic toxicity and minimal invasiveness, self-assembling imageable silk hydrogels provide a promising approach for improving the locoregional control of osteosarcoma.

The anti-apoptotic and anti-autophagic effects of EPO through PI3K/Akt/mTOR signaling pathway in MAC-T cells.

Lipopolysaccharide (LPS) is an important inflammatory and infected factor of bacterial mastitis, which treated bovine mammary epithelial cells (MAC-T) in our previous studies, as mastitis cells model in vitro. Erythropoietin (EPO) is a well-known hematopoietic hormone with antioxidative, anti-apoptotic, and anti-inflammatory roles. We hypothesized that EPO might regulate the apoptosis and autophagy to attenuate the inflammation of mastitis. Western blot, RT-PCR, transmission electron microscope analysis and Annexin V-FITC/PI were used to evaluate the regulation of EPO on apoptosis and autophagy in inflammatory MAC-T cells. These results demonstrated that EPO promoted the proliferation of MAC-T cells. Meanwhile, EPO had a better anti-inflammatory effect in MAC-T cells with LPS treatment. Certainly, EPO also showed anti-apoptotic and anti-autophagic effects. Interestingly, we found that the beneficial effect of EPO on inflammatory MAC-T cells depended on the PI3K/Akt/mTOR signaling pathway, which was involved in the regulation of apoptosis and autophagy. Generally, this study provides an insight for EPO to inhibit apoptosis and autophagy of inflammatory MAC-T cells via PI3K/Akt/mTOR signaling pathway.

Cannabidiol promotes apoptosis of osteosarcoma cells in vitro and in vivo by activating the SP1-CBX2 axis.

Osteosarcoma is the most common primary malignant bone tumor that often occurs in children, adolescents, and young adults. Cannabidiol plays an essential role in cancer treatment. However, its effects on osteosarcoma have not yet been addressed. In the present study, we investigated the pharmacological effects of cannabidiol on osteosarcoma. We found that cannabidiol effectively suppressed the proliferation and colony formation of osteosarcoma cells. Further studies showed that cannabidiol significantly promoted cell apoptosis and changes in cell apoptosis-related gene proteins in vitro. In addition, cannabidiol administration inhibited tumor growth and promoted the apoptosis of osteosarcoma cells in a mouse xenograft model. The in vitro study also demonstrated that SP1 contributes to chromobox protein homolog 2 (CBX2) reduction in cannabidiol-treated MG63 and HOS cells, and that cannabidiol may recruit SP1 into the CBX2 promoter regions to downregulate CBX2 expression at the transcriptional level and promote osteosarcoma cell apoptosis. Further, the result showed that cannabidiol suppressed osteosarcoma cell migration. In summary, cannabidiol effectively promoted the apoptosis of osteosarcoma cells in vitro and in vivo and suppressed tumor growth in a mouse xenograft model by regulating the SP1-CBX2 axis. This finding provides novel therapeutic strategies for osteosarcoma in the clinic.

Comprehensive analysis of a glycolysis and cholesterol synthesis-related genes signature for predicting prognosis and immune landscape in osteosarcoma.

Background: Glycolysis and cholesterol synthesis are crucial in cancer metabolic reprogramming. The aim of this study was to identify a glycolysis and cholesterol synthesis-related genes (GCSRGs) signature for effective prognostic assessments of osteosarcoma patients. Methods: Gene expression data and clinical information were obtained from GSE21257 and TARGET-OS datasets. Consistent clustering method was used to identify the GCSRGs-related subtypes. Univariate Cox regression and LASSO Cox regression analyses were used to construct the GCSRGs signature. The ssGSEA method was used to analyze the differences in immune cells infiltration. The pRRophetic R package was utilized to assess the drug sensitivity of different groups. Western blotting, cell viability assay, scratch assay and Transwell assay were used to perform cytological validation. Results: Through bioinformatics analysis, patients diagnosed with osteosarcoma were classified into one of 4 subtypes (quiescent, glycolysis, cholesterol, and mixed subtypes), which differed significantly in terms of prognosis and tumor microenvironment. Weighted gene co-expression network analysis revealed that the modules strongly correlated with glycolysis and cholesterol synthesis were the midnight blue and the yellow modules, respectively. Both univariate and LASSO Cox regression analyses were conducted on screened module genes to identify 5 GCSRGs (RPS28, MCAM, EN1, TRAM2, and VEGFA) constituting a prognostic signature for osteosarcoma patients. The signature was an effective prognostic predictor, independent of clinical characteristics, as verified further via Kaplan-Meier analysis, ROC curve analysis, univariate and multivariate Cox regression analysis. Additionally, GCSRGs signature had strong correlation with drug sensitivity, immune checkpoints and immune cells infiltration. In cytological experiments, we selected TRAM2 as a representative gene to validate the validity of GCSRGs signature, which found that TRAM2 promoted the progression of osteosarcoma cells. Finally, at the pan-cancer level, TRAM2 had been correlated with overall survival, progression free survival, disease specific survival, tumor mutational burden, microsatellite instability, immune checkpoints and immune cells infiltration. Conclusion: Therefore, we constructed a GCSRGs signature that efficiently predicted osteosarcoma patient prognosis and guided therapy.

Accurate Identification and Early Diagnosis of Osteosarcoma through CRISPR-Cas12a-Based Average Telomerase Activity Detection.

Sensitive and reliable analysis of telomerase activity is important for clinical diagnosis, therapy, and prognosis of osteosarcoma. Telomerase activity is a complicated concept including both the amount of active telomerases and the length of the telomerases extension product. Still, few of the strategies formerly proposed distinguish the two aspects of telomerase activity. Herein, we propose a novel CRISPR-Cas12a-based fluorescent sensing platform that can output signals of both the amounts of telomerase and length of telomerase extension products with the assistance of an elegantly designed stem-loop probe and CRISPR-Cas12a system. On this basis, we induced a novel index, average telomerase activity, for accurate cancer reporting. Through systematic laboratory and clinical experiments, we have demonstrated that average telomerase activity can accurately distinguish cancer cells and has the potential for osteosarcoma staging.

Inhibition of PI3K/Akt/mTOR pathway by ammonium chloride induced apoptosis and autophagy in MAC-T cell.

Ammonia is a harmful gas with a pungent odor, participates in the regulation of a variety of apoptosis and autophagy, which in turn affects the growth and differentiation of cells. To test the regulation of NH3 on the apoptosis and autophagy of mammary epithelial cells, we selected NH4Cl as NH3 donor in vitro model. MTT and CCK-8 assay kits were employed to detect cell activity. Real-time quantitative PCR and western blot methods were used to detect the abundance of inflammatory molecules, apoptosis markers, and autophagy genes. We selected TUNEL kit and the Annexin-FITC/PI method to detect apoptosis. TEM analysis was used to detect autophagic vesicles, and MDC stain evaluated the formation of autophagosome. The results indicated that NH4Cl reduced cell viability in a concentration-dependent manner and promoted cell inflammatory response, apoptosis, and autophagy. NH4Cl stimulation notable increased the autophagosomes number. Interestingly, we also detected that the addition of LY294002 and Rapamycin inhibited the PI3K/Akt pathway and the mTOR pathway, respectively, resulting in changes in both apoptosis and autophagy. Therefore, we draw a conclusion that NH3 may regulate the apoptosis and autophagic response of bovine mammary epithelial cells through the PI3K/Akt/mTOR signaling pathway. Further investigations on ammonia's function in other physiological respects, will be critical to provide theoretical help for the improvement of production performance. It will be also helpful for controlling the harmful gas ammonia concentration in the livestock house to protect the health of dairy cows.

The antiinflammatory effects of Xuefu Zhuyu decoction on C3H/HeJ mice with alopecia areata.

BACKGROUND: As a traditional and typical prescription of prominently activating blood circulation to remove blood stasis, Xuefu Zhuyu decoction (XZD) consists of 15 kinds of herbal medicine. Clinical investigations have showed that XZD could significantly promote the new hair generation of alopecia areata (AA) patients characterized by Qi stagnation and blood stasis. PURPOSE: The purpose of this study was executed to determine whether the mechanisms by which XZD stimulated newborn hair were related to its anti-inflammatory effects. METHODS: Clinical AA individuals were recruited to confirm the efficies of XZD. High performance liquid chromatography (HPLC) analysis was performed to qualitatively and quantitatively determine the contents of 15 compounds in XZD. Schrodinger molecular docking and in vivo surface plasmon resonance (SPR) techniques were used to evaluate the potential binding properties of compounds to target proteins. C3H/HeJ mice were randomly assigned to groups control, AA, and the XZD administration (6.5, 13.0 and 26.0 g/kg/d). Except for mice in control group, all the mice in the other groups were treated with a 21-day chronic unpredictable mild stress (CUMS) induced AA. Hematoxylin-eosin (H&E) staining was performed to determine the degree of pathological damage to the skin. Enzyme-linked immunosorbent assay (ELISA) was performed to detect levels of interleukin-6 (IL-6), interleukin-1 beta (IL-1ß) and tumor necrosis factor alpha (TNF-α) and in serum and skin tissues. Western blot, immunohistochemistry and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) were used to examine the expression levels of IL-6, IL-1ß, TNF-α and osteopontin proteins and genes in skin tissues. RESULTS: XZD could visibly promote hair regeneration of AA patients. The potential active ingredients in XZD prescription included at least amygdalin, hydroxysafflor yellow A, kaempferide, ferulic acid, catalpol, verbascoside, ß-ecdysone, platycodin D, paeoniflorin, naringin, neohesperidin, liquiritin, glycyrrhizic acid, saikosaponin A and saikosaponin D. The results of molecular docking and SPR analysis showed that verbascoside, liquiritin, kaempferide and amygdalin showed the best potential binding properties with IL-6, IL-1ß, TNF-α and osteopontin, respectively. Pathological evaluation showed that compared with the CUMS group, the administration of XZD significantly promoted hair regeneration, evidenced by increased number of skin hair follicles in C3H/HeJ AA mice. Compared with control group, ELISA data showed that the levels of IL-6, IL-1ß and TNF-α in serum and skin tissues of CUMS induced AA mice were significantly increased, while XZD administration dramatically restrained the contents of the three pro-inflammatory factors. Western blot, immunohistochemistry, and qRT-PCR results further demonstrated that XZD administration notably down-regulated the protein and gene expression levels of osteopontin, IL-6, IL-1ß and TNF-α in comparation with CUMS group. CONCLUSION: XZD could dramatically ameliorate CUMS-induced AA damage in the skin of C3H/HeJ mice, possibly by suppressing the levels of IL-6, IL-1ß, TNF-α and osteopontin.

Clinical application of carbon nanoparticles in lymphatic mapping during colorectal cancer surgeries: A systematic review and meta-analysis.

OBJECTIVE: To investigate the overall performance of carbon nanoparticles (CNs) for detecting lymph nodes (LNs) and node metastasis during colorectal cancer surgery. METHODS: The English and Chinese literature was searched until 29 April 2020. Studies were included if they were randomized controlled trials (RCTs) for colorectal resection and LN dissection that compared the use of CNs with a blank control in colorectal cancer surgery. Quality assessment and data extraction were performed, and a meta-analysis was conducted using ReviewManager 5.3 and Stata 15.1 software. RESULTS: A total of 17 RCTs comprising 1241 patients were included for analysis. Compared with the outcomes of the blank controls, the use of CNs resulted in an average of 5.21 more LNs per patient (weighted mean difference = 5.21, 95% confidence interval [CI] = 4.14-6.29, p < 0.001) and a 68% higher detection rate of micro LNs (relative risk [RR] = 1.68, 95% CI = 1.38-2.04, p < 0.001). In addition, more metastatic LNs were identified in stained nodes (RR = 1.56, 95% CI = 1.40-1.75, p < 0.001), but the total detection rate of metastatic nodes did not differ between the groups. CONCLUSION: CN is an effective lymphatic tracer in colorectal cancer surgeries. Further studies with larger sample sizes are needed to validate these findings.

H2S mediates apoptosis in response to inflammation through PI3K/Akt/NFκB signaling pathway.

OBJECTIVES: Hydrogen sulfide (H2S) is involved in regulating cell apoptosis and proliferation. However, The effects and mechanism of H2S on the apoptosis of mammary epithelial cells that suffer from an inflammatory response remain unknown. RESULTS: An inflammatory cell model was used to explore whether exogenous H2S regulates lipopolysaccharides (LPS)-induced cell proliferation and apoptosis. We found that H2S affected cell viability, the inflammatory response and apoptosis in LPS-treated cells in a concentration-dependent manner. Moreover, exogenous H2S rescued LPS-induced cystathionine γ-lyase (CSE) inhibition and cystathionine ß-synthase (CBS) synthesis. Interestingly, in cells undergoing inflammation-induced apoptosis, H2S activated the PI3K/Akt and NFκB signal pathways both tested concentrations. Akt appeared to be a key crosstalk molecule that played a "bridge" role. CONCLUSIONS: H2S regulates LPS-induced inflammation and apoptosis by activating the PI3K/Akt/NFκB signaling pathway. Hence, NaHS may be clinically useful for preventing or treating mastitis.

Percutaneous Endoscopic Interlaminar Lumbar Discectomy with Local Anesthesia for L5-S1 Disc Herniation: A Feasibility Study.

BACKGROUND: General anesthesia (GA), which is routinely applied in patients who undergo percutaneous endoscopic interlaminar lumbar discectomy (PEILD) of L5-S1 disc herniation, is closely associated with postoperative cognitive dysfunction (POCD) in the elderly. Local anesthesia (LA) is an alternative pain control protocol that has not yet been fully evaluated. OBJECTIVES: To evaluate the feasibility of LA in PEILD compared with GA. STUDY DESIGN: A retrospective study. SETTING: This study took place at the First Affiliated Hospital of Harbin Medical University. METHODS: A total of 120 patients (aged 60-85 years) diagnosed with L5-S1 disc herniation and with American Society of Anesthesiologists fitness grade I or II between March 2016 and August 2017 were enrolled in the current study. Patients were randomly divided into LA group and GA group. For LA, 0.25% lidocaine was injected layer-by-layer into skin, subcutaneous tissue, fasciae, lumbar facet joint, muscle, and ligamentum flavum followed by injection of 1.33% lidocaine into epidural space; for GA, propofol, sufentanil, and cisatracurium were infused intravenously at 1 to 2 mg/kg, 0.3 µg/kg, and 0.15 mg/kg, respectively. Visual Analog Scale (VAS), Oswestry Disability Index (ODI), and MacNab Criteria (MNC) evaluated the feasibility of LA as pain control protocol in comparison to GA before and after operation. The development of POCD was assessed by the Mini-Mental State Examination 1 and 7 days postsurgery. Feasibility of LA as a pain control protocol was also evaluated by patient's willingness to receive the same surgical procedure immediately and 24 hours after the surgery, and intraoperative fluoroscopy use, blood loss, surgery duration, postoperative bed confinement, and duration and cost of hospital stay were also evaluated. RESULTS: Patients in both LA and GA groups had comparable VAS grade, ODI, and MNC pre- and post-PEILD, with significant pain reduction after operation. However, POCD developed only in GA group but not in LA group. In addition, compared with GA, LA group did not require postoperative bed confinement, had significantly shorter hospital stay, and lower hospital cost. Low intraoperative VAS grade and willingness to receive the same procedure reflected the acceptance of LA by patients. LIMITATIONS: The development of POCD was examined only 7 days after operation. The follow-up should be extended to 3 months and 2 years postoperation. CONCLUSIONS: LA has satisfactory pain control and low-risk of POCD in PEILD and is well accepted by patients. The benefits of LA are no postoperative bed confinement, faster recovery, shorter hospital stay, and lower hospital cost. KEY WORDS: L5-S1 disc herniation, older patients, percutaneous endoscopic interlaminar lumbar discectomy, local anesthesia, general anesthesia, postoperative cognitive dysfunction, American Society of Anesthesiologists grade, Oswestry Disability Index, MacNab Criteria, Mini-Mental State Examination.

Glycemic control and adipokines after periodontal therapy in patients with Type 2 diabetes and chronic periodontitis.

The mechanism by which chronic periodontitis (CP) affects type 2 diabetes (T2DM) remains unclear. Therefore, the aim of this study is to evaluate the effects of periodontal therapy (PT) on the glycemic control and adipokines of patients with T2DM and CP with the purpose of elucidating the possible mechanisms by which CP influences T2DM. Forty-four patients with T2DM and CP were randomly divided into two groups according to whether they underwent PT. Periodontal status, blood glucose, and the levels of serum tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), adiponectin (APN), and fibroblast growth factor-21 (FGF-21) were measured at baseline and after 3 months. The results revealed that the probing depth (PD) and attachment loss (AL) were significantly improved, the serum levels of TNF-α and IL-6 were significantly decreased, and APN and FGF-21 exhibited substantial increases in the intervention group after 3 months (p < 0.05), whereas no significant changes were observed in the control group. The glycated hemoglobin (HbA1c) levels in both groups decreased significantly after 3 months compared with baseline (p < 0.05), but the intervention group exhibited a significantly greater change (p < 0.05). In conclusion, PT may relieve periodontal inflammation, which causes a reduction of insulin-antagonizing adipokines and an increase in insulin-sensitizing adipokines, thereby eliciting an improvement in glycemic control.

Research of the effect of miR-663 on the proliferation of prostate cancer cells, and the correlations of miR-663 with pathological grade and clinical stage.

PURPOSE: To investigate the effect of miR-663 on the proliferation of prostate cancer (PCa) cells, and the correlations of miR-663 with pathological grade and clinical stage. METHODS: PC-3 and DU-145 PCa cell lines were transfected by artificially synthesized miR-663 and its antisense plasmid, and cell proliferation was assessed using 5-ethynyl-2'-deoxyuridine and methyl thiazolyl tetrazolium assays. Real-time polymerase chain reaction (RT-PCR) was applied to assess the expression of miR-663 in tissue samples collected from 46 patients who were diagnosed with PCa but did not receive any treatment. Another 20 healthy subjects served as controls. According to morphologic and clinical data of tumor tissues in hematoxylin & eosin stained sections, we investigated the correlations of miR-663 with the pathological grade and clinical stage of PCa. METHODS: miR-663 transfection significantly increased the proliferation of PC-3 and DU-145 cells, while transfection of the miR-663 antisense plasmid inhibited the proliferation of PC-3 and DU-145 cells. This suggested that miR-663 can promote the metastasis of PCa. Through detection of the tissue expression of miR-663, the highest and lowest expression of miR-663 were found in the PCa group and healthy group, respectively. Therefore, increased expression of miR-663 in PCa patients was associated with the grade of malignancy . The expression of miR-663 was positively correlated with pathological stage (p<0.05; r=0.7404), and with the clinical stage (p<0.05;r=0.8610), suggesting that miR-663 is closely correlated with the pathological grade and clinical stage of PCa. RESULTS: PDGFRα and PDGFRß were frequently expressed on malignant PCs. We found that increased PDGFRß expression was strongly associated with advanced disease and adverse prognosis. The expression of PDGFRα and MDV were not correlated with specific features. CONCLUSION: miR-663 can significantly increase the proliferation of PCa cells, and its expression is closely correlated with the pathological grade and clinical stage of PCa. Thus, miR-663 is expected to serve as a key predictor of disease stage progression.

Role of Stat3 Signaling in Control of EMT of Tubular Epithelial Cells During Renal Fibrosis.

BACKGROUND/AIMS: Transforming growth factor ß 1 (TGFß1) plays a critical role in the epithelial-to-mesenchymal transition (EMT) of renal tubular epithelial cells (TECs) during renal injury, a major cause of acute renal failure, renal fibrosis and obstructive nephropathy. However, the underlying molecular mechanisms remain ill-defined. Here, we addressed this question. METHODS: Expression of TGFß1, Snail, and phosphorylated Stat3 was examined by immunohistochemistry in the kidney after induction of unilateral ureteral obstruction (UUO) in mice. In vitro, primary TECs were purified by flow cytometry, and then challenged with TGFß1 with/without presence of specific inhibitors for phosphorylation of SMAD3 or Stat3. Protein levels were determined by Western blotting. RESULTS: We detected significant increases in Snail and phosphorylated Stat3, an activated form for Stat3, in the kidney after induction of UUO in mice. In vitro, TGFß1-challenged primary TECs upregulated Snail, in a SMAD3/Stat3 dependent manner. CONCLUSION: Our study sheds light on the mechanism underlying the EMT of TECs after renal injury, and suggests Stat3 signaling as a promising innovative therapeutic target for prevention of renal fibrosis.