[The efficacy of chemotherapy re-challenge in third-line setting for metastatic colorectal cancer patients: a real-world study].

Objective: To explore the efficacy of chemotherapy re-challenge in the third-line setting for patients with metastatic colorectal cancer (mCRC) in the real world. Methods: The clinicopathological data, treatment information, recent treatment efficacy, adverse events and survival data of mCRC patients who had disease progression after treatment with oxaliplatin-based and/or irinotecan-based chemotherapy and received third-line chemotherapy re-challenge from January 2013 to December 2020 at Tianjin Medical University Cancer Institute and Hospital were retrospectively collected. Survival curves were plotted with the Kaplan-Meier method, and the Cox proportional hazard model was used to analyze the prognostic factors. Results: A total of 95 mCRC patients were included. Among them, 32 patients (33.7%) received chemotherapy alone and 63 patients (66.3%) received chemotherapy combined with targeted drugs. Eighty-three patients were treated with dual-drug chemotherapy (87.4%), including oxaliplatin re-challenge in 35 patients and irinotecan re-challenge in 48 patients. The remaining 12 patients were treated with triplet chemotherapy regimens (12.6%). Among them, as 5 patients had sequential application of oxaliplatin and irinotecan in front-line treatments, their third-line therapy re-challenged both oxaliplatin and irinotecan; 7 patients only had oxaliplatin prescription before, and these patients re-challenged oxaliplatin in the third-line treatment. The overall response rate (ORR) and disease control rate (DCR) reached 8.6% (8/93) and 61.3% (57/93), respectively. The median progression free survival (mPFS) and median overall survival (mOS) were 4.9 months and 13.0 months, respectively. The most common adverse events were leukopenia (34.7%) and neutropenia (34.7%), followed by gastrointestinal adverse reactions such as nausea (32.6%) and vomiting (31.6%). Grade 3-4 adverse events were mostly hematological toxicity. Cox multivariate analysis showed that gender (HR=1.609, 95% CI: 1.016-2.548) and the PFS of front-line treatments (HR=0.598, 95% CI: 0.378-0.947) were independent prognostic factors. Conclusion: The results suggested that it is safe and effective for mCRC patients to choose third-line chemotherapy re-challenge, especially for patients with a PFS of more than one year in front-line treatments.

[Inhibition of the TGF-ß/Smad3 signaling pathway by SB431542: A study of the intervention effect of SB431542 on silicotic fibrosis in rats].

Objective: To investigate the intervention effect of SB431542, which inhibits the TGF-ß/Smad3 signaling pathway, on silicotic fibrosis in rats. Methods: A total of 40 specific pathogen-free Sprague-Dawley rats were divided into normal saline control group, model group, SB431542 inhibitor group, and SB431542 inhibitor control group using a random number table, with 10 rats in each group. All rats except those in the normal saline control group were given non-exposed single intratracheal instillation of free silicon dioxide dust suspension 1 mL (50 mg/mL) ; the rats in the SB431542 inhibitor group were given intraperitoneal injection of SB431542 (5 mg/kg) on days 7 and 30 after dust exposure, those in the SB431542 inhibitor control group were given intraperitoneal injection of SB431542 cosolvent (5 mg/kg) on days 7 and 30 after dust exposure, and those in the normal saline control group were given intratracheal instillation of an equal volume of normal saline (5 mg/kg). On day 60 after dust exposure, the paraffin-embedded section of the right upper lobe of lung was collected for HE staining; the left upper lobe of lung was collected to measure the mRNA levels of fibronectin (FN) , collagen type I (COL-I) , and collagen type III (COL-III) by quantitative real-time PCR; the right inferior lobe of lung was collected to measure the protein levels of FN, COL-I, COL-III, phosphorylated Smad3 (p-Smad3) , and Smad3. Results: Compared with the normal saline control group, the model group had nodules with various sizes in lung tissue, with rupture of some alveolar septa, emphysema changes, and pulmonary interstitial fibrosis, as well as significant increases in the mRNA expression of FN, COL-I, and COL-III and the protein expression of FN, COL-I, COL-III, p-Smad3, and Smad3 in lung tissue (P<0.05) . Compared with the SB431542 inhibitor control group, the SB431542 inhibitor group had a relatively complete structure of lung tissue without marked nodules and with a small amount of exudate in alveolar space and the lumen of bronchioles, as well as significant reductions in the mRNA expression of FN, COL-I, and COL-III and the protein expression of FN, COL-I, COL-III, p-Smad3, and Smad3 in lung tissue (P<0.05) . There were no significant differences in the mRNA expression of FN, COL-I, and COL-III and the protein expression of FN, COL-I, COL-III, p-Smad3, and Smad3 between the model group and the SB431542 inhibitor control group (P>0.05) . Conclusion: SB431542 exerts an intervention effect on silicotic fibrosis by blocking the TGF-ß/Smad3 signaling pathway and reducing the expression of the downstream fibrosis factors FN, COL-I, and COL-III.

Targeting the HMGA2 oncogene by miR-498 inhibits non-small cell lung cancer biological behaviors.

OBJECTIVE: Previous study reported that miR-498 served as a tumor suppressor in non-small cell lung cancer (NSCLC), but the underlying mechanism remains largely unknown. The aim of this study is to investigate the role of miR-498 and its target gene HMGA2 in NSCLC progression. PATIENTS AND METHODS: The expression of miR-498 was assessed in clinical NSCLC specimens and cell lines using RT-PCR. Overexpression of miR-498 and transfection of pLenti-HMGA2 were performed in A549 cells. Cell proliferation, apoptosis, migration, and invasion were determined using cell counting kit-8 (CCK-8) assay, clone formation assay, flow cytometry, and transwell assay, respectively. Luciferase reporter assays were performed to analyze the regulation of putative target of miR-498. Western blot was used to detect the levels of HMGA2 in A549 cells. RESULTS: MiR-498 was found to be down-regulated in NSCLC tissues and cell lines. After miR-498 mimics transfection, cell proliferation, migration, and invasion were significantly suppressed in the NSCLC cells. Mechanistically, bioinformatic analysis predicted that miR-498 may target the 3'-UTR of HMGA2 and suppressed its translation, and was further confirmed by luciferase assay. Furthermore, restoration of HMGA2 expression completely rescued the inhibitory effect of miR-498 in NSCLC cells. CONCLUSIONS: This paper revealed that miR-498 may serve as a tumor suppressor in NSCLC through targeting HMGA2, suggesting that miR-498 could represent a novel target for effective therapies.

Development of an indirect enzyme-linked immunosorbent assay (ELISA) to differentiate antibodies against wild-type porcine reproductive and respiratory syndrome from the vaccine strain TJM-F92 based on a recombinant Nsp2 protein.

An accurate ELISA method to differentiate pigs infected with wild-type porcine reproductive and respiratory syndrome (PRRSV) strains from vaccinated ones would help to monitor PRRSV vaccination compliance. The recombinant protein GST-d120aa derived from the continuous deletion of 120 amino acids in the non-structural protein 2 region of the modified-live vaccine strain TJM-F92 was used to develop an indirect enzyme-linked immunosorbent assay (d120-ELISA) for differentiating serum antibodies against TJM-F92 from other PRRSV strains. At the optimized cut-off value which was calculated at an S/P of 0.25, it yielded a sensitivity of 90.7% and a specificity of 95.1%. Cross-reactivity tests suggested that the d120-ELISA was PRRSV-specific. Coefficient of variations of the repeatability tests ranged between 1.41-17.02%. The results suggest that the d120-ELISA is suitable for differentiating animals infected with wild-type strains from those immunized with MLV TJM-F92.

[The prevalence of metabolic syndrome among adults in rural areas of Ningxia Hui autonomous region].

Objective: To investigate the prevalence of metabolic syndrome (MS) among adults in rural areas of Ningxia Hui autonomous region. Methods: A cross-sectional study was conducted in 10 639 adults enrolled with a multistage method from Jingyuan County. The MS was identified according to Chinese type 2 diabetes prevention guide (2013). Results: Among all the subjects, 17.4% of them met the MS definition with the standardized prevalence of 14.7% after adjustment of sex and age. The prevalence and standardized rate of MS in men were 19.9% and 17.3%, and in women were 15.3% and 13.5%.The prevalence of MS in men was higher than that in women(P<0.001) and increased with aging in both genders. The prevalence and standardized rate of abdominal obesity, hyperglycemia, hypertension, high triglycerides, and low HDL-C were 19.5% and 16.7%, 15.0% and 12.9%, 42.0% and 37.1%, 25.8% and 23.1%, 28.5% and 27.7%, respectively. The rate of abdominal obesity was higher in women than in men (20.5% vs 18.2%, P=0.004), whereas the rate of hypertension, high triglycerides, and low HDL-C were higher in men than in women (all P<0.01). The prevalence of having one parameter of the MS was 68.4%. Conclusion: The prevalence of MS is higher in rural areas of Ningxia Hui autonomous region, suggesting that a series of comprehensive prevention measures should be carried out to prevent and control the MS so as to improve the public health conditions in rural areas.

Mechanism underlying the bio-effects of an electromagnetic field based on the Huang-Ferrell model.

To understand the beneficial and harmful bio-effects of extremely low frequency electromagnetic fields, we studied the MAPK/ERK signaling pathway based on the Huang-Ferrell model. The sensitivity analysis method was used to study the influence of the model parameters on the activity of ERK, and to further investigate the key biochemical reactions and proteins. The results of the simulation show that an increase in the reaction rate of MAPK/ERK kinase had little effect on ERK activation and the steady-state molecular number. However, a decrease in the reaction rate of MAPK/ERK kinase significantly affected the trigger time of ERK activation and decreased the steady-state molecular number. Together with the biological significance of ERK activity, our findings indicate that the effects of electromagnetic fields are a result of the decrease in the reaction rate of MAPK/ERK kinase, which eventually determines whether these effects cause physical damage or are beneficial in treatment.

[Efficacy of antiretroviral therapy and influencing factors for people living with HIV/AIDS in designated hospitals in Harbin].

OBJECTIVE: To understand the efficacy of antiretroviral therapy for people living with HIV/AIDS and influencing factors; and provide evidence to improve the treatment of HIV infection and AIDS for the better life of the patients. METHODS: A cross sectional study was conducted in designated AIDS hospitals in Harbin. A questionnaire was used to collect the information of the patients receiving treatment in these hospitals. The statistical analysis was done with software SAS 9.2 and Excel 2010. Univariate analysis was performed with t test and multivariate analysis was performed with ordinal logistic regression model. Wilcoxon ranks sum test was conducted to compare the CD4(+) T lymphocyte counts. RESULTS: The number of the patients receiving antiretroviral therapy was in increase in recent years. The HIV infection route was mainly homosexual contact. The CD4(+)T lymphocyte count of the patients increased at different levels after ≥6 months treatment(P<0.01). Household income(P<0.05), adherence to treatment plan or not(P<0.05), social relationship(P< 0.05), concern of economic cost(P<0.01)medication compliance(P<0.01)and initial level of CD4(+) T lymphocyte(P<0.01)were the influencing factors for antiretroviral therapy efficacy. CONCLUSION: In designated hospitals in Harbin, the number of the patients receiving HIV antiretroviral therapy kept to increase and the efficacy of the treatment was obvious.

Effects of stocking density on behavior, productivity, and comfort indices of lactating dairy cows.

The objective of this study was to investigate the effects of different stocking densities of 82 (0.82 cows per freestall and feed bin), 100, and 129% on behavior, productivity, and comfort indices of lactating Holstein dairy cows. Twenty-seven lactating cows (15 primiparous and 12 multiparous) were assigned to 1 of the 3 treatments, which were balanced for parity, milk yield, days in milk, and body weight in a 3×3 Latin square design with 14-d periods. After 7 d of adaptation to the treatments, lying time and bouts were recorded at 1-min intervals for 3 d, DMI and feeding time were monitored electronically by feed bins, and rumination time was quantified at 2-h periods for 5 d during each period. The cow comfort index, stall standing index, stall perching index, and stall use index (SUI) were calculated using 10-min scan samples of video recording from d 8 to 10 of each period. Milk yield was recorded from d 8 to 12 and milk composition was determined from composite samples on d 12 in each period. Daily lying time, lying bouts, and bout duration did not differ among the stocking densities. The ratio of lying time ≥12 h/d (the number of cows with daily lying time ≥12 h/d divided by number of cows per pen) was higher for cows housed at 82% stocking density compared with those housed at 100% stocking density, with stocking density of 129% intermediate. Hourly lying time was lower at 100% stocking density compared with 82 and 129% stocking densities during the peak period (2300-0400 h), determined based on diurnal pattern of lying time. Daily dry matter intake, feeding time, and feeding rate were not affected by stocking density. After morning milking, dry matter intake and feeding time was reduced at 129 versus 82% stocking density during peak feeding time (0600-0800 h), determined based on diurnal patterns of feeding behavior. Stocking density had no effect on rumination time, milk yield and milk composition. The ratio of SUI ≥85% (mean of the number of SUI ≥85% divided by the number of SUI at 10-min scan samples during a 24-h period) was lower at 129 versus 82% stocking density, with stocking density of 100% intermediate. During peak lying time after evening milking (2300-0400 h), both cow comfort index and SUI were higher at 129 than at 100% stocking density. The SUI was lower 2h after morning milking (0800-0900 h) for cows housed at 129% compared with those housed at 82 and 100% stocking densities. In conclusion, when compared with 100% stocking density, understocking contributed to natural behaviors of cows that including lying, feeding, and rumination behavior, whereas overstocking did not cause negative effect on behavior, productivity, and comfort indices of cows in this study.

Effect of RNAi-mediated silencing of Livin gene on biological properties of colon cancer cell line LoVo.

This study aimed to investigate the effect of RNAi-mediated silencing of the Livin gene on biological properties of the colon cancer cell line LoVo. Interference vectors pSilencer4.1-Ll and pSilencer4.1-L2 targeting the Livin gene were constructed and transfected into LoVo cells. The expression of the Livin gene was determined by RT-PCR and Western blotting. The apoptosis, cell cycle, colony formation, proliferation of LoVo cells, as well as their sensitivity to cisplatin, were detected by flow cytometry, colony formation assay and MTT. Livin mRNA and protein expression in LoVo cells could be effectively silenced by pSilencer4.1-Ll but not pSilencer4.1-L2. In the pSilencer4.1-Ll transfection group, the apoptosis rate of LoVo cells was significantly higher than in the control group (24.2 ± 3.2 vs 8.1 ± 1.4%, P < 0.01), and after 72 h, cell proliferation was clearly decreased (about 70% inhibition). Compared with the control group, the colony formation rate in pSilencer4.1-Ll transfection group was obviously decreased (15 ± 4.6 vs 85 ± 5.8%, P < 0.01), with increased proportion of S phase cells (45.7 ± 4.9 vs 28.0 ± 3.0%, P < 0.01), decreased proportion of G1 phase cells (43.0 ± 5.2 vs 62.8 ± 5.1%, P < 0.01), and increased sensitivity to cisplatin (apoptosis rate increased from 43.4 ± 6.9 to 65.3 ± 6.2%, P < 0.01). pSilencer4.1-Ll can effectively silence Livin gene expression in LoVo colon cancer cells, inhibit cell proliferation and colony formation, induce apoptosis, and enhance sensitivity to cisplatin.

Amorphous nickel hydroxide nanospheres with ultrahigh capacitance and energy density as electrochemical pseudocapacitor materials.

Among numerous active electrode materials, nickel hydroxide is a promising electrode in electrochemical capacitors. Nickel hydroxide research has thus far focused on the crystalline rather than the amorphous phase, despite the impressive electrochemical properties of the latter, which includes an improved electrochemical efficiency due to disorder. Here we demonstrate high-performance electrochemical supercapacitors prepared from amorphous nickel hydroxide nanospheres synthesized via simple, green electrochemistry. The amorphous nickel hydroxide electrode exhibits high capacitance (2,188 F g(-1)), and the asymmetric pseudocapacitors of the amorphous nickel hydroxide exhibit high capacitance (153 F g(-1)), high energy density (35.7 W h kg(-1) at a power density of 490 W kg(-1)) and super-long cycle life (97% and 81% charge retentions after 5,000 and 10,000 cycles, respectively). The integrated electrochemical performance of the amorphous nickel hydroxide is commensurate with crystalline materials in supercapacitors. These findings promote the application of amorphous nanostructures as advanced electrochemical pseudocapacitor materials.

Molecular analysis and frequency of Staphylococcus aureus virulence genes isolated from bloodstream infections in a teaching hospital in Tianjin, China.

Staphylococcus aureus is an important cause of bloodstream infections worldwide. We examined the prevalence of genes that encode erythromycin ribosome methylase and bacterial toxins in S. aureus collected from bloodstream infections. Sixty different S. aureus isolates were obtained from blood cultures of patients who were admitted to a Teaching Hospital in Tianjin from January 2006 to August 2011. The susceptibility of the isolates to 16 antibiotics was tested. Methicillin-resistant S. aureus (MRSA) was identified using the disk diffusion method with cefoxitin. PCR was used to detect genes that encode the staphylococcal enterotoxins, Panton-Valentine leukocidin, toxic shock syndrome toxin 1 and erythromycin ribosome methylase. Molecular analysis of the MRSA strains was done using pulsed-field gel electrophoresis (PFGE) and staphylococcal cassette chromosome mec (SCCmec) typing. The positivity rates of mecA, ermA, ermB, and ermC in the isolates were 13/60, 10/60, 18/60, and 18/60, respectively. Among the 60 isolates, 30 harbored enterotoxin genes, with sea as the most frequent toxin gene (33%), followed by sec (15%), sed (12%), and seb (5%). The see and tst genes were not found in any of the isolates. The pvl gene was detected in four strains. Eleven MRSA isolates were of the SCCmec type III; two MRSA isolates could not be determined through SCCmec typing. PFGE analysis of the 13 MRSA isolates produced 8 distinct pulsotypes. Virulence genes and erythromycin ribosome methylase genes were highly prevalent in these isolates. The PFGE results demonstrated that the MRSA spread through cloning, mainly involving SCCmec type III.

Genetic evidence for domestic raccoon dog rabies caused by Arctic-like rabies virus in Inner Mongolia, China.

An outbreak of rabies affected domestic raccoon dogs on an animal farm in Inner Mongolia, China in 2007. A study was conducted to characterize the aetiological agent and clarify the origin of the rabies virus. Brain tissues were obtained from five rabid raccoon dogs. Viral nucleoprotein antigen was detected in the brain tissues and five rabies viruses were isolated from these rabid animals. Phylogenetic analysis of the N and G gene sequences showed that these isolates were closely related to Arctic-like rabies viruses isolated from the far-eastern region of Russia and South Korea, but distinct from the rabies viruses that are widely distributed in endemic areas in China. Epidemiological data suggested that the likely source of infection was from one wild raccoon dog that was captured and placed in the same type of pen used for domestic raccoon dogs.

Effects of intrathecal galanin on nociceptive responses in rats with mononeuropathy.

The present study was performed on rats with experimental mononeuropathy induced by left common sciatic nerve loose ligation. Unilateral sciatic nerve loose ligation induced decreases of the hindpaw withdrawal latency to the hot-plate test, cold-plate test and the Randall Selitto test. Sciatic nerve loose ligation induced hyperesponsiveness to touch at room temperature also. Intrathecal administration of either 3 or 6 nmol of galanin, but not 1 nmol, induced significant bilateral increases in hindpaw withdrawal latencies to the hot-plate test, cold-plate test and the Randall Selitto tests in rats with left mononeuropathy. The results indicate that galanin may play important roles in transmission of presumed nociceptive information in the spinal cord of mononeuropathic rats.

Annealing behavior of barriers in ion-implanted LiNbO3 and LiTaO3 planar waveguides.

We formed planar waveguides in LiNbO(3) and LiTaO(3) crystals by megaelectron volt He-ion implantation. The dark modes of both waveguides are measured and their refractive-index profiles are described according to the parameterized index profile reconstruction method. The extraordinary indices of both ion-implanted waveguides exhibit quite different profiles. We compare the thermal stability of barriers in ion-implanted LiNbO(3) and LiTaO(3) waveguides by annealing at different temperatures. The results show that the barrier in a LiTaO(3) planar waveguide has higher thermal stability than that in a LiNbO(3) waveguide. The experiments also show that annealing at a temperature higher than 400 degrees C results in recrystallization of the barrier.

Stimulative effects of gusuibu (Drynaria baronii) injection on chick embryo bone primordium calcification in vitro.

Through tissue culture and isotope tracing, it was found that Gusuibu (Drynaria baronii) injection (GI) significantly promoted calcification of the cultivated chick embryo bone primordium (CEBP), increased ALP activity in the cultivated tissue, and accelerated synthesis of proteoglycan. It was also confirmed that the promotion of proteoglycan synthesis was an important factor in the promotion of calcification.

Effects of 3-morpholinosydnonimine-N-ethylcarbamide on hypoxia-induced mechanical and electric responses of isolated pig coronary artery.

AIM: To study effects of 3-morpholinosydnonimine-N -ethylcarbamide (SIN-1) on hypoxia-induced mechanical and electric activities of the isolated pig coronary artery. METHODS: Mechanical tension and membrane potential were measured simultaneously. RESULTS: Hypoxia initially caused a transient vascular smooth muscle cell membrane hyperpolarization followed by a membrane depolarization in isolated pig coronary artery. Subsequent addition of SIN-1 100 mumol . L-1 or verapamil (Ver) 10 mumol . L-1 led to membrane repolarization and relaxation of the vascular smooth muscle. Nitro-L-arginine (NLA) 0.2 mmol . L-1 and KCI 40 mmol . L-1 also induced membrane depolarization and vasoconstriction, which were similarly suppressed by SIN-1 or Ver. CONCLUSION: Hypoxic contractile response in isolated pig coronary artery is mediated by an increased Ca2+ influx via suppression of nitric oxide release.

Association between HLA antigens and families with psoriasis vulgaris.

This paper typed HLA-A, B, C and DR antigens in patients with psoriasis vulgaris and healthy persons in 12 families. The phenotype frequencies of HLA-A1, B13, B17, Cw4 and Cw6 in the patients were higher than those in the controls. The analysis of haplotype segregation showed that HLA haplotypes in families with more psoriatic cases were marked deviation from random distribution. One or two HLA haplotypes sharing among affected siblings occurred more frequently than expected. The result of Lods score for six families showed that there was a close linkage between the gene of psoriasis vulgaris and HLA antigens. The gene of psoriasis was coincided with the recessive hereditary mode.

Establishment and characterization of two epithelial tumor cell lines (HNE-1 and HONE-1) latently infected with Epstein-Barr virus and derived from nasopharyngeal carcinomas.

Two epithelial tumor cell lines were established from biopsy specimens of 2 nasopharyngeal carcinomas (NPC) and designated HNE-1 and HONE-1. Uncloned HNE-1 cells were found to be Epstein-Barr virus (EBV) DNA-positive when examined by Southern blot analysis up to passage 35, after which the EBV genome could no longer be detected. A similar loss of EBV DNA took place in uncloned HONE-1 cells. However, HONE-1 clone 40 cells are still EBV DNA-positive up to passage 42 thus far and cell cultures contain 85-90% EBV nuclear antigen (EBNA)-positive cells. The HNE-1 cell line has been passaged more than 100 times and the uncloned HONE-1 cells more than 90 times. The tumorigenicity of the HNE-1 and HONE-1 cells was demonstrated by tumor induction in nude mice. Karyotypic analysis of the HNE-1 cells demonstrated an aneuploidy with a modal chromosomal number of 74 at passages 5 and 101 at passage 20; 18 marker chromosomes were identified. We have continued to map the EBV genome latently associated with the HNE-1 and HONE-1 cells using the Bam HI, EcoRI or Hind III restriction enzymes. Using EcoRI fragments A-K as probes, we found that HNE-1 EBV DNA is different from B95-8 and HR-1 EBV DNA in the EcoRI-C region. The Bam HI map for HONE-1 EBV DNA is very similar to the B95-8 map; it contains the Bam HI-Y fragment but without Bam HI B' and WI'. Differences were observed between HONE-1 EBV DNA and B95-8 DNA using the Hind III restriction enzyme. There was no evidence of spontaneous expression of the latent EBV genome in HNE-1 cells, and attempts to induce replication of the latent EBV genome and rescue infectious virus have failed, suggesting a tightly restricted virus genome.