Identification of a Novel Streptomyces sp. Strain HU2014 Showing Growth Promotion and Biocontrol Effect Against Rhizoctonia spp. in Wheat.

Wheat sharp eyespot is a serious disease caused by the phytopathogens Rhizoctonia cerealis and R. solani. Some species in the genus Streptomyces have been identified as potential biocontrol agents against phytopathogens. In this investigation, the physiological, biochemical, phylogenetic, and genomic characteristics of strain HU2014 indicate that it is a novel Streptomyces sp. most closely related to Streptomyces albireticuli. Strain HU2014 exhibited strong antifungal activity against R. cerealis G11 and R. solani YL-3. Ultraperformance liquid chromatography-mass spectrometry on the four extracts from the extracellular filtrate of strain HU2014 identified 10 chemical constituents in the Natural Products Atlas with high match levels (more than 90%). In an antifungal efficiency test on wheat sharp eyespot, two extracts significantly reduced the lesion areas on bean leaves infected by R. solani YL-3. The drenching of wheat in pots with spore suspension of strain HU2014 demonstrated a control efficiency of 65.1% against R. cerealis G11 (compared with 66.9% when treated by a 30% hymexazol aqueous solution). Additionally, in vitro and pot experiments demonstrated that strain HU2014 can produce indoleacetic acid, siderophores, extracellular enzymes, and solubilized phosphate, and it can promote plant growth. We conclude that strain HU2014 could be a valuable microbial resource for growth promotion of wheat and biological control of wheat sharp eyespot.

Mesenteric lymph drainage alleviates acute kidney injury induced by hemorrhagic shock without resuscitation.

This study aimed to investigate the effect of mesenteric lymph drainage on the acute kidney injury induced by hemorrhagic shock without resuscitation. Eighteen male Wistar rats were randomly divided into sham, shock, and drainage groups. The hemorrhagic shock model (40 mmHg, 3 h) was established in shock and drainage groups; mesenteric lymph drainage was performed from 1 h to 3 h of hypotension in the drainage group. The results showed that renal tissue damage occurred; the levels of urea, creatinine, and trypsin in the plasma as well as intercellular adhesion molecule-1 (ICAM-1), receptor of advanced glycation end-products (RAGE), tumor necrosis factor-α (TNF-α), malondialdehyde (MDA), lactic acid (LA), and 2,3-DPG in the renal tissue were increased in the shock group after 3 h of hypotension. Mesenteric lymph drainage lessened the following: renal tissue damage; urea and trypsin concentrations in the plasma; ICAM-1, RAGE, TNF-α, MDA, and LA levels in the renal tissue. By contrast, mesenteric lymph drainage increased the 2,3-DPG level in the renal tissue. These findings indicated that mesenteric lymph drainage could relieve kidney injury caused by sustained hypotension, and its mechanisms involve the decrease in trypsin activity, suppression of inflammation, alleviation of free radical injury, and improvement of energy metabolism.

MicroRNA-mRNA functional pairs for cisplatin resistance in ovarian cancer cells.

Ovarian cancer is the leading cause of death in women worldwide. Cisplatin is the core of first-line chemotherapy for patients with advanced ovarian cancer. Many patients eventually become resistant to cisplatin, diminishing its therapeutic effect. MicroRNAs (miRNAs) have critical functions in diverse biological processes. Using miRNA profiling and polymerase chain reaction validation, we identified a panel of differentially expressed miRNAs and their potential targets in cisplatin-resistant SKOV3/DDP ovarian cancer cells relative to cisplatin-sensitive SKOV3 parental cells. More specifically, our results revealed significant changes in the expression of 13 of 663 miRNAs analyzed, including 11 that were up-regulated and 2 that were down-regulated in SKOV3/DDP cells with or without cisplatin treatment compared with SKOV3 cells with or without cisplatin treatment. miRNA array and mRNA array data were further analyzed using Ingenuity Pathway Analysis software. Bioinformatics analysis suggests that the genes ANKRD17, SMC1A, SUMO1, GTF2H1, and TP73, which are involved in DNA damage signaling pathways, are potential targets of miRNAs in promoting cisplatin resistance. This study highlights candidate miRNA-mRNA interactions that may contribute to cisplatin resistance in ovarian cancer.

Lipid nanoparticle encapsulated oleic acid induced lipotoxicity to hepatocytes via ROS overload and the DDIT3/BCL2/BAX/Caspases signaling in vitro and in vivo.

BACKGROUND: To date, Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver disease associated with clinical complications. Dietary fatty acids have been suggested to be involved in preventing or reversing the accumulation of hepatic fat. However, contradicting roles of monounsaturated fatty acids to the liver have been implicated in various human and murine models, mainly due to the insolubility nature of fatty acids. METHODS: High pressure homogenization methods were used to fabricate oleic acid embedded lipid nanoparticles (OALNs). The in vitro and in vivo models were used to validate the physiological effect of this OALNs via various cellular and molecular approaches including cell viability essay, fluorescent staining, electron microscope, RNAseq, qPCR, Western blots, and IHC staining. RESULTS: We successfully fabricated OALNs with enhanced stability and solubility. More importantly, lipid accumulation was successfully induced in hepatocytes via the application of OALNs in a dose-dependent manner. Overload of OALNs resulted in ROS accumulation and apoptosis of hepatocytes dose-dependently. With the help of transcriptome sequencing and traditional experimental approaches, we demonstrated that the lipotoxic effect induced by OALNs was exerted via the DDIT3/BCL2/BAX/Caspases signaling. Moreover, we also verified that OALNs induced steatosis and subsequent apoptosis in the liver of mice via the activation of DDIT3 in vivo. CONCLUSIONS: In all, our results established a potential pathogenic model of NAFLD for further studies and indicated the possible involvement of DDIT3 signaling in abnormal steatosis process of the liver.

Is Type 2 Diabetes Mellitus Associated with Spinal Degenerative Disorders?: Evidence from Observational and 2-Sample Mendelian Randomization Analyses.

BACKGROUND: Type 2 diabetes mellitus (T2DM) and spinal degenerative disorders (SDD) are common diseases that frequently coexist. However, both traditional observational studies and recent Mendelian randomization (MR) studies have demonstrated conflicting evidence on the association between T2DM and SDD. This comparative study explored and compared the association between T2DM and SDD using observational and MR analyses. METHODS: For observational analyses, cross-sectional studies (44,972 participants with T2DM and 403,095 participants without T2DM), case-control studies (38,234 participants with SDD and 409,833 participants without SDD), and prospective studies (35,550 participants with T2DM and 392,046 participants without T2DM with follow-up information until 2022) were performed to test the relationship between T2DM and SDD using individual-level data from the U.K. Biobank from 2006 to 2022. For MR analyses, the associations between single-nucleotide polymorphisms with SDD susceptibility obtained using participant data from the U.K. Biobank, which had 407,938 participants from 2006 to 2022, and the FinnGen Consortium, which had 227,388 participants from 2017 to 2022, and genetic predisposition to T2DM obtained using summary statistics from a pooled genome-wide association study involving 1,407,282 individuals were examined. The onset and severity of T2DM are not available in the databases being used. RESULTS: Participants with T2DM were more likely to have SDD than their counterparts. Logistic regression analysis identified T2DM as an independent risk factor for SDD, which was confirmed by the Cox proportional hazard model results. However, using single-nucleotide polymorphisms as instruments, the MR analyses demonstrated no causal relationship between T2DM and SDD. The lack of such an association was robust in the sensitivity analysis, and no pleiotropy was seen. CONCLUSIONS: Our results suggest that the association between T2DM and SDD may be method-dependent. Researchers and clinicians should be cautious in interpreting the association, especially the causal association, between T2DM and SDD. Our findings provide fresh insights into the association between T2DM and SDD by various analysis methods and guide future research and clinical efforts in the effective prevention and management of T2DM and SDD. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Fibula allograft transplantation combined with locking plate for treatment of recurrent monostotic fibular fibrous dysplasia: A case report.

BACKGROUND: Fibrous dysplasia is a congenital disorder in which normal bone is replaced by fibro-osseous tissue or irregular trabeculae of woven bone intermixed with mature collagenous tissue. A single or multiple bones are affected. This rare bone disorder has three clinical patterns including monostotic, polyostotic, and that associated with McCune-Albright syndrome. Most studies report primary fibrous dysplasia. However, a few cases of recurrent monostotic fibular fibrous dysplasia have been reported. Here, we report a therapeutic strategy for recurrent fibular fibrous dysplasia. CASE SUMMARY: A 4-year-old boy was admitted for persistent pain in the left lower limb and abnormal gait over the previous 9 mo. He had no history of present or past illness. Preoperative imaging data showed erosion-like changes with bone expansion of the left middle and lower fibular segment. Tumor tissue in the fibular bone marrow cavity was removed by curettage, and rapid intraoperative pathological examination suggested fibular fibrous dysplasia. An allograft was implanted into the fibular medullary cavity. However, he was readmitted with clinical symptoms including persistent pain, abnormal gait, and local swelling at the age of 6 years. He was diagnosed with recurrent fibular fibrous dysplasia based on the second medical examination. He underwent fibular bone tumor radical resection and longus fibular allograft transplantation combined with fibular bone locking plate and screws. Good host bone to allogenic bone graft fusion was observed by the physician on postoperative regular follow-up. CONCLUSION: Radical resection of fibrous dysplasia and longus fibula allograft combined with internal fixation for reconstruction are suitable for the treatment of recurrent monostotic fibular fibrous dysplasia.

Surgery for fibrous dysplasia associated with aneurysmal-bone-cyst-like changes in right proximal femur: A case report.

BACKGROUND: Fibrous dysplasia associated with aneurysmal bone cyst (ABC)-like changes in the right proximal femur has a low incidence. It is considered more difficult to make early diagnosis than for single fibrous dysplasia. CASE SUMMARY: A 14-year-old woman was admitted because of persistent pain in the right hip and abnormal gait over the previous 2 mo. She had no history of present or past illness. Preoperative photography, enhanced computed tomography, and magnetic resonance imaging showed ground-glass appearance with cortical scalloping and expansion of the right proximal femur and femoral neck. Pathological examination by preoperative puncture biopsy revealed fibrous dysplasia of the right proximal femur. The patient was diagnosed with fibrous dysplasia based on medical history, physical examination, and results of laboratory, imaging and pathological examinations. According to final pathological examination, the patient was diagnosed with fibrous dysplasia of the right proximal femur associated with ABC. Curettage and allograft along with fixation of compression screws was performed for fibrous dysplasia associated with ABC-like changes. No obvious allograft absorption, loosening of fixation, or secondary fracture were observed during 6-months' follow-up with re-examination by plain radiography and computed tomography. Fibrous dysplasia associated with ABC-like changes in the right proximal femur has a low incidence and early diagnosis is considered more difficult than for single fibrous dysplasia. CONCLUSION: We report a cases of fibrous dysplasia associated with ABC-like changes in the right proximal femur treated with curettage and allograft along with hip compression screws.

Explore the Anti-Acne Mechanism of Licorice Flavonoids Based on Metabonomics and Microbiome.

Acne vulgaris is one of the most common inflammatory dermatoses in dermatological practice and can affect any gender or ethnic group. Although in previous studies, we had found that licorice flavonoids (LCF) play an anti-acne role by inhibiting PI3K-Akt signaling pathways and mitochondrial activity, the mechanism of LCF regulating skin metabolism, serum metabolism and skin microbes is still unclear. Here, we performed a full spectrum analysis of metabolites in the skin and serum using UHPLC-Triple TOF-MS. The results showed that LCF could treat acne by regulating the metabolic balance of amino acids, lipids and fatty acids in serum and skin. Similarly, we performed Illumina Hiseq sequencing of DNA from the skin microbes using 16S ribosomal DNA identification techniques. The results showed that LCF could treat acne by regulating the skin microbes to interfere with acne and make the microecology close to the normal skin state of rats. In summary, this study confirmed the anti-acne mechanism of LCF, namely by regulating metabolic balance and microbial balance. Therefore, this discovery will provide theoretical guidance for the preparation development and clinical application of the drug.

[Association of serum EGFR protein concentration with the efficacy of Gefitinib in the treatment of advanced non-small cell lung cancer].

OBJECTIVE: To analyze the association between the EGFR protein level and the EGFR gene mutation status in advanced non-small cell lung cancer (NSCLC), and to explore whether the EGFR protein level is related to the efficacy and survival of the EGFR-TKI drug Gifitinib-treated patients with advanced NSCLC. METHODS: Ninety-nine cases were enrolled in this study. Pathological tissue specimens and paired peripheral blood samples were collected. Exons 19 and 21 of the EGFR gene mutation were detected by direct sequencing. The concentration of plasma EGFR protein was detected by ELISA. Univariate and multivariate statistical analyses of the efficacy and survival were performed using SPSS 13.0 software. RESULTS: The response rate (RR) and clinical benefit rate (CBR) of Gefitinib-treated patients were 51.5% and 79.8%, respectively. There were 35 (35.4%) with positive EGFR gene mutation of the 99 samples. The concentration limit of EGFR protein was 55.42 µg/L. The RR and CBR of patients with EGFR gene mutation was significantly higher than those without mutation (65.7% vs. 43.8%, P = 0.037; 94.3% vs. 71.9%, P = 0.008). The median PFS was prolonged (23 months vs. 10 months, P = 0.014). The CBR of patients with high EGFR protein expression (concentration ≥ 55.42 µg/L) was significantly higher than those with low expression (90.0% vs 64.1%, P = 0.004), and the median PFS was prolonged (21 months vs. 8 months, P = 0.016). EGFR protein level was an independent factor affecting the EGFR gene mutation status. The Correlation between EGFR gene mutation status and EGFR protein level was positive. CONCLUSIONS: Gefitinib is effective in the treatment of advanced NSCLC patients with EGFR gene mutation and high EGFR protein expression. EGFR protein level in peripheral blood may be a molecular biomarker in prediction of efficacy and survival of the Gefitinib treatment in patients with advanced NSCLC.

[Spatial and Temporal Distribution Characteristics of Levoglucosan and Its Isomers in PM2.5 in Beijing and Six Surrounding Cities].

Air PM2.5 samples from Beijing and six surrounding cities were collected during spring, summer, autumn, and winter. Levoglucosan (LG), mannosan (MN), and galactosan (GT) contents were analyzed by ion chromatography. The concentrations and distribution characteristics of the three anhydroglucoses with PM2.5 and organic carbon (OC) were compared. SPSS 24.0 was used to analyze the significant differences. The results indicated that the seasonal distributions of PM2.5, OC, and LG in the six cities were highly similar and followed the order winter > spring > autumn > summer. There were significant differences in the concentration levels of the three anhydroglucoses in the four seasons. Between Beijing and Tianjin, Baoding, and Shijiazhuang, there was no significant difference in the three anhydroglucose concentrations. However, significant differences in the three anhydroglucose concentrations appeared between Beijing, Ji'nan, and Zhengzhou. Based on the ratios of LG/MN and LG/(MN+GT) measured in the six cities, it could be determined that the biomass combustion sources in PM2.5 mainly came from crop straw and hardwood in this region. During the air pollution process in spring, LG stably existed in PM2.5 in Beijing, Tianjin, Shijiazhuang, and Ji'nan, indicating that this pollution process was weakly affected by biomass combustion.

[Pollution Characteristics and Source Apportionment of Ambient PM2.5 During Four Seasons in Yantai City].

PM2.5 samples were collected at three sites in Yantai City during all four seasons of 2016-2017, and the mass concentration and chemical composition characteristics were analyzed. The CMB model was used to calculate source apportionment of ambient PM2.5, and the backward trajectory cluster and PSCF were used to analyze the transport flow and potential source regions. The results showed that the average mass concentrations of PM2.5 in winter, spring, summer, and autumn in Yantai were (89.45±56.80), (76.78±28.44), (32.65±17.92) and (57.32±24.60) µg·m-3, respectively. The PM2.5 concentration showed a significant seasonal variation (P<0.01). The contribution of PM2.5 sources was as follows:secondary nitrate (20.3%) > crustal dust (15.7%) > vehicle exhaust (14.9%) > coal combustion (13.8%) > secondary sulphate (12.8%) > SOC (6.1%) > cement dust (5.5%) > sea salt source (2.9%). It can be seen that the predominant sources were secondary sources, crustal dust, vehicle exhaust, and coal combustion. The sources of nitrate in spring and of crustal dust were important contributors. The contribution of sulfate in summer was prominent, and the proportion of coal combustion was high in autumn and winter. Yantai City's airflow transport and potential source regions also showed significant seasonal changes:winters were mainly affected by short-distance transport in Yantai City; summers were mainly affected by the coastal of eastern Yantai City and local areas; springs and autumns were mainly affected by regional transmission in the northeast and in the eastern coastal areas of Shandong Province and by local sources in Yantai City.

Altered metabolites in guinea pigs with allergic asthma after acupoint sticking therapy: New insights from a metabolomics approach.

BACKGROUND: Clinical evidence gathered in Chinese communities suggested that acupoint sticking therapy could be an alternative treatment for asthma-related diseases. However, its underlying mechanism is still poorly understood. AIM/HYPOTHESIS: In this study, we aimed to investigate the mechanism of the anti-inflammatory effect of acupoint sticking application with 'Treatment of Winter Disease in Summer' (TWDS) prescription by using metabolomics. METHODS: Allergic asthma in guinea pig was sensitized and challenged by ovalbumin (OVA). Histopathological evaluation of the lung tissue was performed by hematoxylin and eosin (H&E) staining and Masson's trichrome staining. The levels of Th2 cytokine and IgE level in serum were measured using enzyme-linked immunoassay (ELISA). The mRNA expression levels of IL-4, IL-5, IL-13 and orosomucoid-like 3 (ORMDL3) were measured using quantitative reverse transcription polymerase chain reaction (RT-qPCR). Proteins of NF-κB signaling pathway were measured using western blot. The serum metabolomics profiles were obtained by using ultra-performance liquid chromatography combined with electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOF-MS). RESULTS: The overall results confirmed that AST with TWDS prescription had a significant protective effect against OVA-induced allergic asthma in guinea pig. This treatment not only attenuated airway inflammation and collagen deposition in the airway, but also decreased the levels of IL-4, IL-5, IL-13 and IgE in serum. In addition, metabolomics results indicated that metabolisms of phospholipid, sphingolipid, purine, amino acid and level of epinephrine were restored back to the normal control level. Moreover, results of the gene expression of ORMDL3 in lung tissues indicated that AST using TWDS could alter the sphingolipid metabolism. Further western blotting analysis also showed that its anti-inflammatory mechanism was by decreasing the phosphorylation of p65 and IκB. CONCLUSION: The study demonstrated that metabolomics provides a better understanding of the actions of TWDS acupoint sticking therapy on OVA-induced allergic asthma.

The Correlation between the Injury Patterns of the Medial Patellofemoral Ligament in an Acute First-Time Lateral Patellar Dislocation on MR Imaging and the Incidence of a Second-Time Lateral Patellar Dislocation.

Objective: To evaluate the correlation between the injury patterns of the medial patellofemoral ligament (MPFL) on magnetic resonance imaging in an acute first-time lateral patellar dislocation (LPD) and incidence of a second-time LPD. Materials and Methods: Magnetic resonance images were prospectively analyzed in 147 patients after an acute first-time LPD with identical nonoperative management. The injury patterns of MPFL in acute first-time LPDs were grouped by location and severity for the analysis of the incidence of second-time LPD in a 5-year follow-up. Independent t tests, chi-square tests and Kruskal-Wallis tests were performed as appropriate. Results: Forty-six cases (46/147, 31.3%) of second-time LPD were present at the 5-year follow-up. Fourteen (14/62, 22.6%) and 31 cases (31/80, 38.8%) were present in the partial and complete MPFL tear subgroups, respectively. Twenty-five cases (25/65, 38.5%), 11 cases (11/26, 42.3%), and 8 cases (8/47, 17%) were present in the isolated femoral-side MPFL tear (FEM), combined MPFL tear (COM), and isolated patellar-side MPFL tear (PAT) subgroups, respectively. Compared with the partial MPFL tears, complete tears showed higher incidence of a second-time LPD (p = 0.04). The time interval between the two LPDs was shorter in the complete MPFL tear subgroup (24.2 months) than in the partial tear subgroup (36.9 months, p = 0.001). Compared with the PAT subgroup, the FEM and COM subgroups showed a higher incidence of a second-time LPD (p = 0.025). The time intervals between the two LPDs were shorter in the FEM and COM subgroups (20.8 months and 19.2 months) than in the PAT subgroup (32.5 months, p = 0.049). Conclusion: A complete MPFL tear, isolated femoral-side tear and combined tear in a first-time LPD predispose a second-time LPD.

Capsaicin reverses the inhibitory effect of licochalcone A/ß-Arbutin on tyrosinase expression in b16 mouse melanoma cells.

INTRODUCTION: Melanin is synthesized by melanocytes, which are located in the basal layer of the skin. After synthesis, melanin is further deposited on the surface of the skin to form black spots or chloasma. Tyrosinase is a rate-limiting enzyme that plays an important role in melanogenesis. Currently, there are many drugs that inhibit tyrosinase expression to further reduce melanogenesis. Nevertheless, some of these could reverse the pharmacological effect of other drugs, when used simultaneously. MATERIALS AND METHODS: B16 mouse melanoma cells were treated with the tyrosinase inhibitors licochalcone A and ß-arbutin, alone or in combination with capsaicin, an alkaloid found in peppers. Cytotoxicity, melanin content, and tyrosinase activity and expression were determined. RESULTS: Licochalcone A/ß-arbutin inhibited tyrosinase expression and further hindered melanin synthesis when applied individually to B16 mouse melanoma cells. However, licochalcone A/ß-arbutin combined with 50 µmol/L capsaicin enhanced the expression of tyrosinase in these cells and further increased melanin content. CONCLUSION: Our data implied that capsaicin could reverse the inhibitory effect of licochalcone A/ß-arbutin on tyrosinase expression in B16 mouse melanoma cells. SUMMARY: B16 mouse melanoma cells were treated with the tyrosinase inhibitors licochalcone A and ß-arbutin, alone or in combination with capsaicin, an alkaloid found in peppers. Cytotoxicity, melanin content, and tyrosinase activity and expression were determined. Licochalcone A/ß-arbutin inhibited tyrosinase expression and further hindered melanin synthesis when applied individually to B16 mouse melanoma cells. However, licochalcone A/ß-arbutin combined with 50 µmol/L capsaicin enhanced the expression of tyrosinase in these cells and further increased melanin content. Our research implied that capsaicin could reverse the inhibitory effect of licochalcone A/ß-arbutin on tyrosinase expression in B16 mouse melanoma cells. Abbreviations used: B16: B16 mouse melanoma cells; L-DOPA: 3, 4-L-dihydroxyphenylalanine; TYR: Tyrosinase; USP: United States Pharmacopeia; FBS: Fetal bovine serum; EDTA: Ethylenediaminetetraacetic acid; DMSO: Dimethyl sulfoxide; RPMI: Roswell Park Memorial Institute; MTT3: 4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, NaOH: Sodium hydroxide; PBS: Phosphate-buffered saline; RIPA: Radio-immunoprecipitation assay; PMSF: Phenylmethanesulfonyl fluoride or phenylmethylsulfonyl fluoride; SDS: Sodium dodecyl sulfate, sodium salt; PVDF: Polyvinylidene fluoride; ECL: Enhanced chemiluminescence.

Amplification and overexpression of Aurora-A in esophageal squamous cell carcinoma.

Aurora-A/BTAK/STK15 gene which encodes a centrosome-associated kinase is located on chromosome 20q13.2, a highly amplified region in various human tumors. Recent studies have demonstrated the overexpression and amplification of Aurora-A in many malignant human cancers. The purpose of this study was to investigate the amplification and expression of Aurora-A in esophageal squamous cell carcinoma. Amplification of Aurora-A was determined by fluorescence in situ hybridization in 7 esophageal cancer cell lines and real-time PCR in 29 esophageal cancer samples. We detected Aurora-A expression in 7 esophageal cancer cell lines and 38 esophageal cancers samples by semi-quantitative reverse transcription-PCR and Western blot hybridization. The amplification of Aurora-A was detected in 27 of 29 (93.1%) esophageal cancer samples and 6 of 7 (85.7%) cancer cell lines. Aurora-A was overexpressed in 27 of 38 (71.1%) esophageal cancer samples and all 7 esophageal cancer cell lines. We conclude that Aurora-A is amplified and overexpressed in esophageal squamous cancer.

[Establishment of a model to assess the clinical efficacy of Gefitinib in treatment of non-small cell lung cancer].

OBJECTIVE: To establish a model to predict the clinical response of Gefitinib in non-small cell lung cancer (NSCLC). METHODS: The clinical outcomes of 262 consecutive advanced NSCLC patients to oral treatment of gefitinib 250 mg daily in the past 4 years were reviewed. DNA sequencing was used to detect the mutations in the exons 18, 19, 20, and 21 of the epidermal growth factor receptor (EGFR) tyrosine kinase domain in 55 patients who had enough tumor tissues. RESULTS: The response rate and disease control rate of gefitinib in the advanced NSCLC patients were 30.1% and 78.6% respectively. The median progression free survival and median overall survival were 6.0 and 16.0 months respectively, while the 1, 2 and 3-year survival rates of the NSCLC patients were 60.8%, 35.6%, and 18.3% respectively. The clinical response rate of the patients with EGFR mutation was 50.0%, significantly higher than that of those patients without mutation (16.1%; P = 0.009). In the majority of patients Gefitinib was well tolerated, and the common adverse effects were skin rash and diarrhea. Based on the results of our patients, we try to establish a model which may predict the response of patients by logistic multivariate regression analysis. Patients being female aged under 65, with adenocarcinoma, not smoking, taxone-unresistant and with EGFR mutation were more sensitive to gifitinib. However, COX multivariate regression analysis showed that only the age, histology, smoke status and EGFR mutation were valuable in selection of sensitive patients. So, we set up the cut-off value at 2 in the model based on these 4 factors. The response rate of the patients with 2 or more scores was 34.2%, significantly higher than that of the patients with the scores < 2 (9.3%, P = 0.001). The sensitivity would be doubled when the score increases by one point. CONCLUSION: A simple clinical model based on the patients' age, histology, smoking status and EGFR mutation has been established and is useful to determine the efficacy of gifitinib in NSCLC patients.

[Effects of low dose mifepristone on population and subsets of natural killer cells in human endometrium during receptive phase].

OBJECTIVE: To investigate the immunologic mechanism of low dose mifepristone as an anti-implantation contraceptive drug. METHODS: Endometrial biopsies were obtained from fourteen normally cycling women during the receptive phase. Each endometrial tissue, divided into three equal parts, was assigned to three groups: control group, 65 nmol/L mifepristone group (group A) and 200 nmol/L mifepristone group (group B). Endometrial explants were cultured in vitro. The numbers of natural killer cells and the percentages of CD3- CD56+ CD16- subset and CD3- CD56+ CD16+ subset were analysed by immunohistochemistry and flow cytometry. RESULTS: (1) The mean number of CD56+ NK cells in group A (148 +/- 11) and group B (150 +/- 12) were significantly higher when compared to the control group (121 +/- 7, P < 0.05). There was no significant difference between the two mifepristone-treated groups (P > 0.05). (2) The percentage of CD3- CD56+ Nk cells in group A (44 +/- 5)% and in group B (48 +/- 4)% were significantly higher when compared to the control group (35 +/- 3)% (P < 0.05), there was no significantly difference between the two mifepristone-treated groups (P > 0.05); The percentage of CD3- CD56+ CD16- subset in group A (42 +/- 5)% and in group B (45 +/- 5)% were significantly higher when compared to the control group (33 +/- 3)%, (P < 0.05), there was no significantly difference between the two mifepristone-treated groups (P > 0.05); the percentages of CD3- CD56+ CD16+ subset in three groups [(2.70 +/- 0.24)% (3.26 +/- 0.37)% and (2.33 +/- 0.29)%] were not significantly different (P > 0.05). CONCLUSION: Low dose mifepristones increase the number of CD56+ NK cells and the percentage of CD3- CD56+ CD16- NK subset, which might result in the disturbance of human endometrial immuno-microenvironment during receptive phase and lead to implantation failure.

Short article: A randomized-controlled study of sitagliptin for treating diabetes mellitus complicated by nonalcoholic fatty liver disease.

BACKGROUND: This study aimed to evaluate the efficacy and safety of sitagliptin for treating Chinese patients with type 2 diabetes mellitus (T2DM) with nonalcoholic fatty liver disease (NAFLD). METHODS: In total, 72 Chinese T2DM patients with NAFLD were divided randomly into two groups of 36 patients each group. All 72 patients were assigned to receive either sitagliptin or diet and exercise for 52 weeks between January 2013 and December 2015. The outcomes' measurements included serum levels of hemoglobin A1c, fasting plasma glucose, aspartate aminotransferase, and alanine aminotransferase. RESULTS: Seventy patients completed the study. Sitagliptin showed greater efficacy than the diet and exercise in decreasing the hemoglobin A1c and fasting plasma glucose levels at weeks 13, 26, 39, and 52. In addition, no significant changes in the average aspartate aminotransferase and alanine aminotransferase levels were found during the 52-week follow-up in both the sitagliptin and the control groups. CONCLUSION: The results of this study indicate that sitagliptin is an effective and safe treatment for patients with T2DM and NAFLD.

Knockdown of c-Myc expression by RNAi inhibits MCF-7 breast tumor cells growth in vitro and in vivo.

INTRODUCTION: Breast cancer is the leading cause of cancer death in women worldwide. Elevated expression of c-Myc is a frequent genetic abnormality seen in this malignancy. For a better understanding of its role in maintaining the malignant phenotype, we used RNA interference (RNAi) directed against c-Myc in our study. RNAi provides a new, reliable method to investigate gene function and has the potential for gene therapy. The aim of the study was to examine the anti-tumor effects elicited by a decrease in the protein level of c-Myc by RNAi and its possible mechanism of effects in MCF-7 cells. METHOD: A plasmid-based polymerase III promoter system was used to deliver and express short interfering RNA (siRNA) targeting c-myc to reduce its expression in MCF-7 cells. Western blot analysis was used to measure the protein level of c-Myc. We assessed the effects of c-Myc silencing on tumor growth by a growth curve, by soft agar assay and by nude mice experiments in vivo. Standard fluorescence-activated cell sorter analysis and TdT-mediated dUTP nick end labelling assay were used to determine apoptosis of the cells. RESULTS: Our data showed that plasmids expressing siRNA against c-myc markedly and durably reduced its expression in MCF-7 cells by up to 80%, decreased the growth rate of MCF-7 cells, inhibited colony formation in soft agar and significantly reduced tumor growth in nude mice. We also found that depletion of c-Myc in this manner promoted apoptosis of MCF-7 cells upon serum withdrawal. CONCLUSION: c-Myc has a pivotal function in the development of breast cancer. Our data show that decreasing the c-Myc protein level in MCF-7 cells by RNAi could significantly inhibit tumor growth both in vitro and in vivo, and imply the therapeutic potential of RNAi on the treatment of breast cancer by targeting overexpression oncogenes such as c-myc, and c-myc might be a potential therapeutic target for human breast cancer.

[Expression of survivin and its significance in esophageal cancer].

OBJECTIVE: To detect the expression of survivin in esophageal cancer and elucidate its function in esophageal cancer. METHODS: Expression of surviv in was detected in paired normal and tumor tissues from patients with esophageal cancer by semi-quantitative RT-PCR. A dominant-negative survivin (surT34A) was transfected into esophageal cancer EC9706 cells (EC9706surT34A). Colony formation and apoptosis of the parental and surT34A-transfected EC9706 cells were examined in soft agar and by flow cytometry, respectively. RESULTS: Survivin mRNA expression of tumor tissues was higher than normal tissues in 18/27 (66.7%) samples. The expression level of survivin mRNA in tumor tissues (2.08 +/- 1.32) was significantly higher than that in normal tissues (1.22 +/- 1.09). EC9706 surT34A cells formed fewer colonies on agar than the non-transfected ones. After serum withdrawal, EC9706surT34A had higher apoptotic ratio than control, but survivin could reduce the apoptotic ratio. CONCLUSION: Overexpression of survivin is a common eventin esophageal cancer. The dominant-negative survivin can partially inhibit the malignant phenotype of esophageal cancer.