A detailed analysis of 16S rRNA gene sequencing and conventional PCR-based testing for the diagnosis of bacterial pathogens and discovery of novel bacteria.

This study represents the first analysis of the bacterial community in chickens affected by swollen head syndrome, utilizing 16S rRNA gene sequencing. Samples were obtained from clinical laying chickens and were examined for the presence of Avibacterium paragallinarum (APG) and Ornithobacterium rhinotracheale (ORT) using conventional polymerase chain reaction (PCR). From the samples, five APG-positive (APG) and APG-negative (N-APG) samples were chosen, along with five specific pathogen-free chickens, for 16S rRNA gene sequencing. Results showed that APG and ORT were widely detected in the chicken samples with swollen head syndrome (SHS, 9/10), while APG was detected in all five specific pathogen-free (SPF) samples. In contrast, conventional PCR sensitivity was found to be inadequate for diagnosis, with only 35.7% (5/14) and 11.1% (1/9) sensitivity for APG and ORT, respectively, based on 16S rRNA gene sequencing data. Furthermore, 16S rRNA gene sequencing was able to quantify the bacteria in the samples, revealing that the relative abundance of APG in the APG group ranged from 2.7 to 81.3%, while the relative abundance of APG in the N-APG group ranged from 0.1 to 21.0%. Notably, a low level of APG was also detected in all 5 SPF samples. The study also identified a significant number of animal and human common bacterial pathogens, including but not limited to Gallibacterium anatis, Riemerella columbina, Enterococcus cecorum, Mycoplasma synoviae, Helicobacter hepaticus, and Staphylococcus lentus. In conclusion, 16S rRNA gene sequencing is a valuable tool for bacterial pathogen diagnosis and the discovery of novel bacterial pathogens, while conventional PCR is not reliable for diagnosis.

Professional identity, job satisfaction, and turnover intention among Chinese novice nurses: A cross-sectional study.

The world is faced with challenges due to a growing aging population and the increasing burden of chronic disease. The acute shortage of nurses and high turnover rates, particularly among novice nurses, are of great concern in many countries. Several studies have shown that turnover intention among nurses is influenced by professional identity and job satisfaction. However, to the best of our knowledge, no studies have examined this issue in the context of novice nurses. Thus, the present study aimed to explore the relationship between professional identity, job satisfaction, and turnover intention among novice nurses in China. From March 18 to April 23, 2022, a cross-sectional survey was carried out involving 532 novice nurses recruited from four public hospitals in Sichuan Province, China. Among the sample, 526 questionnaires were retrieved, with an effective response rate of 98.87%. The mean scores for turnover intention, professional identity, and job satisfaction were 13.02 ±â€…3.94, 36.17 ±â€…7.98, and 111.02 ±â€…21.46, respectively. High turnover intention was observed among novice nurses, of whom 54.37% (286/526) had high or very high turnover intention. Professional identity and job satisfaction among novice nurses were moderate. In terms of demographic characteristics, "Whether living with relatives" and "Monthly income" had a statistically significant impact on the turnover intention of novice nurses (P < .05). Both professional identity (r = -0.459) and job satisfaction (r = -0.517) were significantly and moderately negatively correlated with turnover intention (P < .01). The results of the multivariate linear regression analysis revealed that variables including "Whether living with relatives," "Professional identity," "Control and responsibility for work," and "Benefits" jointly accounted for 29.9% of the variance related to turnover intention among novice nurses. "Whether living with relatives," "Professional identity," "Control and responsibility for work," and "Benefits" were highly predictive of turnover intention levels among novice nurses. Hence, potential predictors of turnover intention should be considered, and intervention research should be conducted to reduce the level of turnover intention among novice nurses.

The Adaptive Evolution in the Fall Armyworm Spodoptera frugiperda (Lepidoptera: Noctuidae) Revealed by the Diversity of Larval Gut Bacteria.

Insect gut microbes have important roles in host feeding, digestion, immunity, development, and coevolution with pests. The fall armyworm, Spodoptera frugiperda (Smith, 1797), is a major migratory agricultural pest worldwide. The effects of host plant on the pest's gut bacteria remain to be investigated to better understand their coevolution. In this study, differences in the gut bacterial communities were examined for the fifth and sixth instar larvae of S. frugiperda fed on leaves of different host plants (corn, sorghum, highland barley, and citrus). The 16S rDNA full-length amplification and sequencing method was used to determine the abundance and diversity of gut bacteria in larval intestines. The highest richness and diversity of gut bacteria were in corn-fed fifth instar larvae, whereas in sixth instar larvae, the richness and diversity were higher when larvae were fed by other crops. Firmicutes and Proteobacteria were dominant phyla in gut bacterial communities of fifth and sixth instar larvae. According to the LDA Effect Size (LEfSe) analysis, the host plants had important effects on the structure of gut bacterial communities in S. frugiperda. In the PICRUSt2 analysis, most predicted functional categories were associated with metabolism. Thus, the host plant species attacked by S. frugiperda larvae can affect their gut bacterial communities, and such changes are likely important in the adaptive evolution of S. frugiperda to host plants.

Anti-programmed death 1 antibody in the treatment of coexistent Mycobacterium fortuitum and lung cancer: A case report.

BACKGROUND: Nontuberculous mycobacterium (NTM) refers to all mycobacteria except Mycobacterium tuberculosis and Mycobacterium leprae, also known as environmental Mycobacterium. The patients with lung cancer and NTM are somewhat special; the two diseases are inevitably influenced by each other. It brings difficulties and challenges to the choice of treatment. Recently, cancer immunotherapy has been considered one of the pillars for the treatment of lung cancer. However, the clinical experience in the application of immune checkpoint inhibitors is scarce for lung cancer patients with pulmonary tuberculosis, and lung cancer with NTM is even more rare. Although it ameliorates lung cancer, immunotherapy with immune checkpoint inhibitors presents complications of infectious diseases, including tuberculosis and NTM. CASE SUMMARY: A 61-year-old male patient visited a doctor in May 2019. His admitting diagnoses were: (1) Cancer of the left lung with a pathological diagnosis of poorly differentiated non-small cell carcinoma, likely poorly differentiated adenocarcinoma, clinical stage IIIb (T3N3M0); and (2) Mycobacterium fortuitum (M. fortuitum) infection. We chose to proceed with pembrolizumab treatment. After two treatment cycles, a chest computed tomography scan showed a new irregular subpleural mass in the anterior segment of the left upper lobe of the lung, a reduction in the mediastinal enlarged lymph node, and no other obvious changes. Next, an ultrasound-guided biopsy of the new tumor was performed. Pathological examination showed that a large number of carbon particles were deposited in the alveolar tissue with histiocyte reaction and multinucleated giant cell formation. The tuberculosis (TB) specialist suggested that anti-TB therapy be combined with continued antitumor treatment. The patient continued to be treated with pembrolizumab. After 14 cycles, the lesion shrunk by 79%, there was no recurrence of M. fortuitum infection, and there were no intolerable adverse reactions. CONCLUSION: We have observed that in cases of lung cancer complicated with M. fortuitum infection, opportunistic pathogen infection recurrence can be overcome, and immunotherapy is most beneficial when TB doctors and oncologists cooperate to closely observe dynamic changes in M. fortuitum and lung cancer. Treatment should be maintained with low dosage anti-TB drugs after general anti-TB chemotherapy for 1 year; this may prevent opportunistic pathogen infection recurrence during immunotherapy.

Prevalence of smartphone addiction among Asian medical students: A meta-analysis of multinational observational studies.

BACKGROUND: High prevalence of smartphone addiction among medical students may contribute to adverse physical and mental health outcomes. AIM: To estimate the prevalence of smartphone addiction, and explore the influencing factors and related mental health symptoms of smartphone addiction among Asian medical students. DESIGN: Systematic review and meta-analysis. METHODS: PubMed (MEDLINE), the Cochrane Central Register of Controlled Trials, and EMBASE were searched for relevant literature from the inception to September 10, 2021. Using Stata software 11.0, the meta-analysis of prevalence and the influencing factors of smartphone addiction were determined with 95% confidence intervals. RESULTS: Nineteen articles, published between 2014 and 2019, were included, producing medical student studies from seven different Asian countries. The included studies were conducted in India (n = 11) and Malaysia (n = 3), with China, Saudi Arabia, Turkey, Nepal, and Iran each contributing one study. Among a total of 5,497 medical students, the participants included 3,214 females, of whom 2,181 were medical students with smartphone addiction. The prevalence of smartphone addiction among Asian medical students was 41.93% (95% CI [36.24%, 47.72%]). The influencing factors of smartphone addiction among medical students included gender, duration of smartphone use, smartphone function, and marital status. Ten studies (52.63%) explored related mental health symptoms of smartphone addiction among Asian medical students. Smartphone addiction was positively correlated with poor sleep quality (r = .17-.31), stress (r = .30-.40), anxiety, depression, neuroticism, and general health among Asian medical students. CONCLUSION: Smartphone addiction is highly prevalent among Asian medical students. Smartphone addiction may adversely affect mental health, resulting in sleep disturbance, stress, anxiety, depression, and neuroticism. It is necessary to take appropriate precautionary actions and interventions to prevent smartphone overuse among medical students.

Association of physical activity and depressive symptoms with eating disorders among college students in Jinan / 中国学校卫生

Objective@#To understand the relationship between physical activity, depressive symptoms and eating disorders among college students, and to provide a theoretical basis for the intervention of eating disorders among college students.@*Methods@#A questionnaire survey including International Physical Activity Questionnaire, Patient Health Questionnaire Depression Scale and Eating Attitude Test was administered among 2 712 college students from three universities.@*Results@#Among the college students surveyed, 1 750(64.5%) did not meet the recommendations for physical activity, 962(35.5%) met the recommendation for physical activity; 488(18.0%) reported depressive symptoms, 452(16.7%) reported symptoms of eating disorders. There was a statistically significant difference in the incidence of eating disorders by genders, self-assessed learning pressure, physical activity and depressive symptoms(χ2=63.65, 23.17, 34.24, 70.66, P<0.05). After adjusting for demographic variables, the results of multiple Logistic regression analysis showed that physical activity and depressive symptoms were positively correlated with eating disorders(OR=1.59, 2.58, P<0.01). In the depression group, lower level of physical activity, was associated with higher rate of eating disorders.@*Conclusion@#Physical activity and depressive symptoms of college students were related to eating disorders. It is suggest that eating disorders might be alleviated by actively improving depressive symptoms and increasing physical activity.

MALAT1 Protected the Angiogenesis Function of Human Brain Microvascular Endothelial Cells (HBMECs) Under Oxygen Glucose Deprivation/re-oxygenation (OGD/R) Challenge by Interacting with miR-205-5p/VEGFA Pathway.

Long non-coding RNA MALAT1 was previously revealed to express abnormally in animal and cellular models of stroke, suggesting its indispensable role in stroke. The aims of the present study were to further investigate the functions of MALAT1 and to elucidate the underlying molecular mechanisms. Oxygen glucose deprivation/re-oxygenation (OGD/R) challenge was used in human brain microvascular endothelial cells (HBMECs) to mimic stroke injury in vitro. MALAT1 and miR-205-5p expression levels were evaluated by qRT-PCR. A tube formation assay was employed to verify the angiogenesis of HBMECs. Cell proliferation and apoptosis were evaluated using the ErdU assay and flow cytometry analysis, respectively. The interaction between miR-205-5p and MALAT1 was verified by dual-luciferase reporter assay. MALAT1 and miR-205-5p were both significantly upregulated in the serum of CIS patients and HBMECs under OGD/R, and the tube formation of HBMECs was damaged after OGD/R treatment. Silencing miR-205-5p remarkably promoted HBMEC proliferation and angiogenesis to resist OGD/R injury. Knockdown of MALAT1 markedly inhibited HBMEC proliferation and angiogenesis, and meanwhile promoted apoptosis induced by OGD/R treatment. Most importantly, MALAT1 acted as a competing endogenous RNA (ceRNA) of miR-205-5p via direct bonding with each other in HBMECs under OGD/R damage, indirectly upregulating the downstream targeted gene VEGFA. MALAT1 protected the angiogenesis function of HBMECs under OGD/R conditions by interacting with miR-205-5p/VEGFA pathway.

LncRNA NEAT1 promotes inflammatory response in sepsis-induced liver injury via the Let-7a/TLR4 axis.

BACKGROUND: Sepsis is a systemic inflammatory response that can lead to organ dysfunction and/or circulatory disorders in severe cases. The dysregulated inflammatory response plays a pivotal role in sepsis-induced liver injury. A variety of microRNAs and lncRNAs have been shown to be involved in the inflammatory response. However, their role in regulating sepsis-induced liver injury remains to be revealed. METHODS: Human hepatic tissue and healthy tissue were used for in vivo level detection. And Raw264.7 cells and Kupffer cells were used for in vitro modelling. The relative mRNA expression and the protein levels of TNF-α, IL-6 and IL-1ß were detected by q-PCR or by enzyme-linked immunosorbent assay (ELISA), respectively. The binding of lncRNA NEAT1/Let-7a and Let-7a/TLR4 was detected by dual-luciferase reporter assay. RNA Immunoprecipitation (RIP) was used to detect the targeting relationship between lncRNA NEAT1 and Let-7a. Western blotting (WB) was used to detect TLR4 expression in different cell models. RESULTS: The overexpression of lncRNA NEAT1 accompanied by Let-7a inhibition and TLR4 activation was found in sepsis-induced liver injury patients. Similarly, LPS stimulation upregulated lncRNA NEAT1 expression, and lncRNA NEAT1 inhibition decreased the levels of inflammatory cytokines in vitro. Let-7a inhibitor treatment as well as TLR4 overexpression rescued the expression of inflammatory cytokines in lncRNA NEAT1-knockdown cells. Moreover, Let-7a interacted with both lncRNA NEAT1 and TLR4. CONCLUSION: We demonstrate that lncRNA NEAT1 interacts with Let-7a, targeting TLR4 to contribute to the LPS-induced inflammatory response. Our assay can provide a potential therapeutic target for sepsis-induced liver injury.

Quench-Shield Ratiometric Upconversion Luminescence Nanoplatform for Biosensing.

Upconversion nanoparticles (UCNPs) possess several unique features, but they suffer from surface quenching effects caused by the interaction between the UCNPs and fluorophore. Thus, the use of UCNPs for target-induced emission changes for biosensing and bioimaging has been challenging. In this work, fluorophore and UCNPs are effectively separated by a silica transition layer with a thickness of about 4 nm to diminish the surface quenching effect of the UCNPs, allowing a universal and efficient luminescence resonance energy transfer (LRET) ratiometric upconversion luminescence nanoplatform for biosensing applications. A pH-sensitive fluorescein derivative and Hg(2+)-sensitive rhodamine B were chosen as fluoroionphores to construct the LRET nanoprobes. Both showed satisfactory target-triggered ratiometric upconversion luminescence responses in both solution and live cells, indicating that this strategy may find wide applications in the design of nanoprobes for various biorelated targets.

Bispyrene-fluorescein hybrid based FRET cassette: a convenient platform toward ratiometric time-resolved probe for bioanalytical applications.

Pyrene excimer possesses a large Stokes shift and long fluorescence lifetime and has been widely applied in developing time-resolved biosensing systems to solve the autofluorescence interference problems in biological samples. However, only a few of pyrene excimer-based small molecular probes have been reported so far. Ratiometric probes, on the other hand, can eliminate interferences from environmental factors such as instrumental efficiency and environmental conditions by a built-in correction of the dual emission bands but are ineffective for endogenous autofluorescence in biosystems. In this work, by combining the advantages of time-resolved fluorescence technique with ratiometric probe, we reported a bispyrene-fluorescein hybrid FRET cassette (PF) as a novel ratiometric time-resolved sensing platform for bioanalytical applications, with pH chosen as a biorelated target. The probe PF showed a fast, highly selective, and reversible ratiometric fluorescence response to pH in a wide range from 3.0 to 10.0 in buffered solution. By employing time-resolved fluorescence technique, the pH-induced fluorescence signal of probe PF can be well-discriminated from biological autofluorescence background, which enables us to detect pH in a range of 4.0-8.0 in cell media within a few seconds. It has also been preliminarily applied for ratiometric quantitative monitoring of pH changes in living cells with satisfying results. Since many fluorescein-based fluorescence probes have been developed, our strategy might find wide applications in design ratiometric time-resolved probes for detection of various biorelated targets.

A simple and pH-independent and ultrasensitive fluorescent probe for the rapid detection of Hg2+.

Development of fluorescent probes for Hg(2+) has become a hot topic in modern chemical research due to its high toxicity. In this paper, we for the first time report the synthesis and application of a thioether spirocyclic rhodamine B derivative (TR) as an efficient fluorescent probe for Hg(2+). TR was synthesized using a simple procedure under mild condition. By employing a thioether spirocycle instead of classic spirolactam as recognition unit, our proposed probe TR is acidity-insensitive, and exhibits a pH-independent and ultrasensitive response to Hg(2+). The probe works well within a wide pH range from 3.5 to 11.5, and exhibits a 350-fold fluorescence enhancement upon 0.5 equiv of Hg(2+) triggered, with a detection limit of 2.5 nM estimated for Hg(2+). In virtue of the strong thiophilic characteristic of Hg(2+), the response of the probe to Hg(2+) is instantaneous and highly selective, which make it favorable for cellular Hg(2+) imaging applications. It has been preliminarily used for highly sensitive monitoring of Hg(2+) level in living cells with satisfying resolution, demonstrating its value of the practical applications in biological systems.

Prognostic value of chemotherapy-induced leukopenia in small-cell lung cancer.

OBJECTIVE: Chemotherapy is the standard treatment for small-cell lung cancer (SCLC), and leukopenia is a common side effect. This study assesses whether chemotherapy-induced leukopenia is a predictor of efficacy and whether it is associated with the survival of SCLC patients. METHODS: A retrospective analysis was conducted on data from 445 patients with SCLC who received standard chemotherapy for 4 to 10 cycles. The World Health Organization grading system classifies leukopenia during chemotherapy as follows: absent (grade 0), mild (grades 1 and 2), or severe (grades 3 and 4). The primary endpoint is overall survival (OS). RESULTS: The association between chemotherapy-induced leukopenia and OS was assessed. According to a multivariate Cox model with time-varying covariates, the hazard ratio of death was significantly lower among patients with mild leukopenia than among patients with severe leukopenia at 0.687 (0.506 to 0.943) and 1.414 (1.147 to 1.744), respectively. The median survival was 13 months (95% CI: 11 to 15 months) for patients who did not experience leukopenia, 17 months (95% CI: 14 to 18 months) for those with mild leukopenia, and 14 months (95% CI: 13 to 16 months) for those with severe leukopenia (absent vs. mild vs. severe leukopenia, P=0.047). CONCLUSION: Leukopenia during chemotherapy is associated with the survival of SCLC patients. Mild leukopenia is strongly associated with longer survival time.

Effect of titanium preoxidation on wrought pure titanium to ceramic bond strength.

STATEMENT OF PROBLEM: The creation of high bond strength between machined computer-manufactured pure titanium and porcelain remains a problem. However, machined titanium does not form the thick titanium oxide film found in cast titanium. PURPOSE: The purpose of this study was to investigate the effects of different preoxidation treatments on the bond strength of a machined pure titanium ceramic system. MATERIAL AND METHODS: Specimens of commercially pure titanium (25 × 3 × 0.5 mm) were divided equally into 6 groups (n=8), which received different preoxidation treatments (3 hour natural oxidation; 600°C, 650°C, 700°C, 750°C, and 800°C for 3 minutes). Bond strengths were evaluated by using a 3-point bend test. The results were analyzed by using 1-way ANOVA and the least significant difference test. Twelve additional specimens of commercially pure titanium (15 × 3 × 0.5 mm) were cut for interface observation and divided equally into 6 groups that received the preoxidation treatments described previously. Scanning electron microscopy and energy dispersive spectrum were used to observe microscopic features of the interface between Ti and ceramic. RESULTS: The bond strength values of the 6 groups ranged from 23.72 ±2.53 MPa to 36.99 ±3.92 MPa, with significant differences (P<.05). The specimen that received 750°C preoxidation had the highest bond strength. The main interface elements of the 6 groups were O, Si, Ti, Sn, Al, Na, and K. Ti showed a sigmoidal diffusion curve in each group, and Si showed a sigmoidal diffusion curve in most groups. Sn was enriched in each group's interface. CONCLUSIONS: Preoxidation under vacuum before porcelain firing can effectively improve the bond strength of machined pure titanium-porcelain systems.

Through bond energy transfer: a convenient and universal strategy toward efficient ratiometric fluorescent probe for bioimaging applications.

Fluorescence resonance energy transfer (FRET) strategy has been widely applied in designing ratiometric probes for bioimaging applications. Unfortunately, for FRET systems, sufficiently large spectral overlap is necessary between the donor emission and the acceptor absorption, which would limit the resolution of double-channel images. The through-bond energy transfer (TBET) system does not need spectral overlap between donor and acceptor and could afford large wavelength difference between the two emissions with improved imaging resolution and higher energy transfer efficiency than that of the classical FRET system. It seems to be more favorable for designing ratiometric probes for bioimaging applications. In this paper, we have designed and synthesized a coumarin-rhodamine (CR) TBET system and demonstrated that TBET is a convenient strategy to design an efficient ratiometric fluorescent bioimaging probe for metal ions. Such TBET strategy is also universal, since no spectral overlap between the donor and the acceptor is necessary, and many more dye pairs than that of FRET could be chosen for probe design. As a proof-of-concept, Hg(2+) was chosen as a model metal ion. By combining TBET strategy with dual-switch design, the proposed sensing platform shows two well-separated emission peaks with a wavelength difference of 110 nm, high energy transfer efficiency, and a large signal-to-background ratio, which affords a high sensitivity for the probe with a detection limit of 7 nM for Hg(2+). Moreover, by employing an Hg(2+)-promoted desulfurization reaction as recognition unit, the probe also shows a high selectivity to Hg(2+). All these unique features make it particularly favorable for ratiometric Hg(2+) sensing and bioimaging applications. It has been preliminarily used for a ratiometric image of Hg(2+) in living cells and practical detection of Hg(2+) in river water samples with satisfying results.

[Clinical study of submental artery island myocutaneous flap for reconstruction of oral and maxillofacial defects following operation].

OBJECTIVE: To evaluate the outcome and indication of the reconstruction of oral and maxillofacial postoperative defects by submental artery island myocutaneous flaps. METHODS: Sixty eight cases with the reconstruction of oral and maxillofacial defects by submental artery island myocutaneous flaps from January 2006 to May 2010 were analysed retrospectively. Primary lesions included carcinomas originating from tongue (28 cases), palate (13 cases), mouth floor (9 cases), gingiva (4 cases), buccal mucosa (6 cases), lip (3 cases), and other malignant or benign tumors (5 cases). The ages ranged from 25 to 84 years (mean 58 years); 47 males and 21 females. The sizes of skin paddle varied from a minimum of 4 cm × 4 cm to a maximum of 15 cm × 10 cm. RESULTS: Of the 68 flaps, 62 were survival, 4 had partial necrosis but healed with treatments, and 2 failed due to complete necrosis. Appearance and functions of recipient sites were satisfactory. The followed-up time was 3 - 24 months, local recurrence occurred in 5 cases and cervical lymph node metastases were found in 15 patients. CONCLUSION: Submental island flap is reliable for the reconstruction of postoperative defects in early oral cancer without regional lymph node metastasis or in benign tumor.

Clinical studies on the treatment of cancer cachexia with megestrol acetate plus thalidomide.

BACKGROUND: The management of cancer-related anorexia/cachexia syndrome (CACS) is a great challenge in clinical practice. To date, practice guidelines for the prevention and treatment of CACS are lacking. The authors conducted a randomized study to confirm the effectiveness and safety of treatment of CACS utilizing megestrol acetate (MA) plus thalidomide. METHODS: One hundred and two candidates with CACS were randomly assigned to two treatment groups (trial group and control group): the trial group received MA (160 mg po, bid) plus thalidomide (50 mg po, bid), while the control group received MA (160 mg po, bid) alone. Treatment duration was 8 weeks. RESULTS: Analysis of the trial group demonstrated a significant increase from baseline in body weight (<0.01), quality of life (p = 0.02), appetite (p = 0.01), and grip strength (p = 0.01), and a significant decrease in fatigue, Glasgow Prognostic Score (p = 0.05), Eastern Cooperative Oncology Group performance status (p = 0.03), IL-6 (p < 0.01), and tumor necrosis factor-α (p = 0.02). In contrast, in the control group, endpoints with a significant improvement from baseline included body weight (p < 0.02) and appetite (p = 0.02). The mean changes in the endpoints from baseline in the trial group were significantly greater compared with the control group: in the primary endpoints, body weight (p = 0.05), fatigue (p < 0.01) and quality of life (p = 0.01), and in the secondary endpoints, grip strength (p = 0.05), Glasgow Prognostic Score (p = 0.02), Eastern Cooperative Oncology Group performance status (p = 0.02), IL-6 (p < 0.01) and tumor necrosis factor-α (p = 0.01). Toxicity was found to be relatively negligible in both groups. CONCLUSION: A combination regimen of MA and thalidomide is more effective than MA alone in the treatment of CACS.

RIP1 mediates the protection of geldanamycin on neuronal injury induced by oxygen-glucose deprivation combined with zVAD in primary cortical neurons.

Caspase-dependent apoptosis is considered one of the most important cell death pathways. When the apoptotic process is blocked, a form of programmed necrosis called necroptosis occurs. Apoptosis and necroptosis may share some regulatory mechanisms. Recent studies indicated that receptor interacting protein 1 (RIP1), an Hsp90-associated kinase, is an important regulatory switch between apoptosis and necroptosis. In this study, we showed that oxygen-glucose deprivation (OGD) combined with a caspase inhibitor zVAD (OGD/zVAD)-induced RIP1 protein expression in a time-dependent manner. We found that geldanamycin (GA), a benzoquinone ansamycin, protected against neuronal injury induced by OGD/zVAD treatment in cultured primary neurons. More importantly, GA decreased RIP1 protein level in a time- and concentration-dependent manner. In this study, we found that GA also decreased the Hsp90 protein level, which caused instability of RIP1 protein, resulting in decreased RIP1 protein level but not RIP1 mRNA level after GA treatment. We concluded that the GA-mediated protection against OGD/zVAD-induced neuronal injury was associated with enhanced RIP1 protein instability by decreasing Hsp90 protein level. GA and its derivatives may be promising for the prevention of neuronal injury during ischemic injury.

RPL1, a gene involved in epigenetic processes regulates phenotypic plasticity in rice.

Organisms can adjust their phenotype in response to changing environmental conditions. This phenomenon is termed phenotypic plasticity. Despite its ubiquitous occurrence, there has been very little study on the molecular mechanism of phenotypic plasticity. In this study, we isolated a rice (Oryza sativa L.) mutant, rice plasticity 1 (rpl1), that displayed increased environment-dependent phenotypic variations. RPL1 was expressed in all tissues examined. The protein was localized in the nucleus and its distribution in the nucleus overlapped with heterochromatin. The rpl1 mutation led to an increase in DNA methylation on repetitive sequences and a decrease in overall histone acetylation. In addition, the mutation affected responses of the rice plant to phytohormones such as brassinosteroid, gibberellin, and cytokinin. Analysis of the putative rice brassinosteroid receptor OsBRI1, a key hormone signaling gene, indicated that RPL1 may be involved in the regulation of epigenomic modification of the gene. These data suggest that RPL1 regulated phenotypic plasticity likely through its involvement in epigenetic processes affecting responses of the plant to phytohormones.

[Comparison of the effect of rh-endostatin on intratumoral and myocardial micrangium in mice].

OBJECTIVE: To compare the effect of rh-endostatin on micrangium in tumor and myocardial tissue in nude mice. METHODS: Nude mice were randomized into 4 groups (10 mice in each group), blank control group (without tumor burden, received NS 100 µl×d(-1) injection), drug control group (without tumor burden, received rh-endostatin 400 µg×d(-1) injection), model group (with tumor burden, received NS 100 µl×d(-1) injection) and treatment group (with tumor burden, received rh-endostatin 400 µg×d(-1) injection) for 28 days. The tumor volume and body weight of the mice were measured before and after administration. The expression of CD34, MMP-2, MMP-9, HIF-1α and VEGF in the myocardium and tumor were detected by immunohistochemistry. The vascular structure was observed by immunoenzymatic CD34 and Masson double staining. RESULTS: The increase of tumor volume of the treatment group [(48.18 ± 37.31) mm(3)] was significantly lower than that in the model group [(113.80 ± 73.27) mm(3)). The changes of body weight was not significant different among the four groups. After treated with rh-endostatin, the expressions of MMP-9 and VEGF in tumors were significantly down-regulated, but the expressions of MMP-2 and HIF-1α in the tumor were not. The microvessel density (MVD) in the tumors of treatment group was significantly decreased compared with that of model group. The proportion of tumor vessels covered by collagen in the treatment group was increased compared with that of the model group. However, MVD and micrangium in myocardium were not changed significantly. CONCLUSION: Rh-endostatin can decrease the expression of MMP-9, VEGF and MVD, inhibit the tumor growth and normalize tumor micrangium in tumor but not weaken the MMPs and MVD of mature micrangium in myocadium.

Correlation of genes associated with drug response to prognosis of large cell lung carcinoma.

Platinum-based chemotherapy remains the main treatment of advanced lung cancer. However, platinum resistance has become a major treatment obstacle. Novel therapies, particularly tyrosine kinase inhibitors of the epidermal growth factor receptor (EGFR-TKI) and agents that target vascular endothelial growth factor (VEGF), have improved the treatment. Both chemotherapy and targeted therapy have their molecular mechanisms. This study aimed to determine the mutation, amplification, or expression status and interrelationships of the epidermal growth factor receptor (EGFR), K-Ras proto-oncogene, excision repair cross-complementation group 1 (ERCC1), and VEGF genes as well as their correlations to prognosis of large cell lung carcinoma (LCLC) after EGFR-targeted therapy, chemotherapy, and anti-VEGF therapy. EGFR and K-Ras mutations in 60 specimens of LCLC were detected by direct DNA sequencing. EGFR, ERCC1, and VEGF protein expression was detected by immunohistochemistry (IHC). EGFR gene copy number was detected by fluorescence in situ hybridization (FISH). One (1.7%) patient had an EGFR L858M point mutation in exon 21, 3 (5.0%) had K-Ras mutations, and 10 (19.6%) had EGFR amplification (FISH positive). Positive rates of EGFR, ERCC1, and VEGF proteins were 38.3%, 56.7%, and 70.0%, respectively. EGFR amplification was positively correlated to EGFR protein expression (r = 0.390, P = 0.005). The positive rate of VEGF protein was significantly higher in patients with lymph node metastasis than in those without (84.6% vs. 58.8%, P = 0.046). No significant correlations were observed among the EGFR, K-Ras, ERCC1, and VEGF genes. EGFR gene amplification and the low rate of EGFR mutation suggest that patients with LCLC are likely to obtain little benefit from anti-EGFR therapies.