Endoscopic submucosal dissection for duodenal-type follicular lymphoma.

Duodenal-type follicular lymphoma (D-FL) is a special type of follicular lymphoma, which tends to occur in the descending segment of the duodenum. The lesion is mostly limited to the mucosal layer. The treatment approach for D-FL has not been clearly established and the watch and wait (WW) approach is generally recommended as a major option. Since D-FL may be transformed into a more serious type of lymphoma, it is of clinical significance to explore active treatment methods. We diagnosed and successfully treated a case of D-FL with Endoscopic submucosal dissection (ESD). Because D-FL is limited to mucosa in the descending segment of the duodenum, ESD can completely dissect the lesion to achieve the purpose of complete resection. Compared with the WW, the method of WW after endoscopic therapy is more active, safe and effective.

POU2F1/DNMT3a Pathway Participates in Neuropathic Pain by Hypermethylation-Mediated LRFN4 Downregulation Following Oxaliplatin Treatment.

Evidence demonstrates that DNA methylation is associated with the occurrence and development of various neurological diseases. However, the potential target genes undergoing DNA methylation, as well as their involvement in the chemotherapy drug oxaliplatin-induced neuropathic pain, are still unclear. Here, Lrfn4, which showed hypermethylation in the promoter regions, was screened from the SRA methylation database (PRJNA587622) following oxaliplatin treatment. MeDIP and qPCR assays identified that oxaliplatin treatment increased the methylation in Lrfn4 promoter region and decreased the expression of LRFN4 in the spinal dorsal horn. The assays with gain and loss of LRFN4 function demonstrated that LRFN4 downregulation in spinal dorsal horn contributed to the oxaliplatin-induced mechanical allodynia and cold hyperalgesia. Moreover, oxaliplatin treatment increased the DNA methyltransferases DNMT3a expression and the interaction between DNMT3a and Lrfn4 promoter, while inhibition of DNMT3a prevented the downregulation of LRFN4a induced by oxaliplatin. We also observed that the transcriptional factor POU2F1 can bind to the predicted sites in DNMT3a promoter region, oxaliplatin treatment upregulated the expression of transcriptional factor POU2F1 in dorsal horn neurons. Intrathecal injection of POU2F1 siRNA prevented the DNMT3a upregulation and the LRFN4 downregulation induced by oxaliplatin. Additionally, intrathecal injection of DNMT3a siRNA or POU2F1 siRNA alleviated the mechanical allodynia induced by oxaliplatin. These findings suggested that transcription factor POU2F1 upregulated the expression of DNMT3a, which subsequently decreased LRFN4 expression through hypermethylation modification in spinal dorsal horn, thereby mediating neuropathic pain following oxaliplatin treatment.

Association between serum copper level and reproductive health of Women in the United States: a cross-sectional study.

Copper is an indispensable trace element in metabolism. This study aimed to investigate the relationship between copper and reproductive health, and possibly provide new insights for diagnosis and treatment. This study was based on data extracted from the NHANES database (2013-2014 and 2015-2016). The t-test, ANOVA, Chi-square test, multiple linear regression, and restricted cubic spline analysis were used. Serum copper levels were significantly higher in women with gestational diabetes than in those without gestational diabetes (P = 0.0150). Women with higher copper levels and smoking habits tended to deliver overweight babies (P = 0.028). Women with diabetes had higher serum copper and were prone to deliver overweight babies (P = 0.024). Serum copper levels showed a positive relationship with sex hormone-binding globulin (SHBG) levels (P < 0.0001). In this study, serum copper levels were found to be associated with reproductive health in women. Further studies are required to draw causal inferences.

[Effects of virtual reality in phase I cardiac rehabilitation training for elderly coronary heart disease patients after percutaneous coronary intervention].

The study aimed to examine the effects of virtual reality (VR) technology-based phase I cardiac rehabilitation (CR) program in elderly coronary heart disease (CHD) patients after percutaneous coronary intervention (PCI). Thirty-six cases of elderly CHD patients who underwent PCI in the First Affiliated Hospital of Chongqing Medical University from June 2022 to April 2023 were recruited by convenience sampling method. The patients were randomly assigned by means of random digital table method to two study groups: control group (n = 18), which received conventional nursing intervention after PCI, and experimental group (n = 18), which received a combined program of conventional nursing intervention together with CR program based on VR technology. The 6 min walk test (6MWT), Simple Physical Performance Battery (SPPB), SF-36 scale, Hospital Anxiety and Depression Scale (HADS) and Impact of Events Scale-Revised (IES-R) were tested before and after rehabilitation. Moreover, the incidence of major adverse cardiovascular events (MACE) was recorded at 3 months after PCI. After VR-based CR, the 6MWT distance and SPPB scores of patients in the experimental group were higher than those in control group (P < 0.05). The HADS scores and IES-R scores of the patients in the experimental group were lower than those in control group (P < 0.01), and the difference in SF-36 scale scores was not statistically significant between two groups (P > 0.05). The incidence of MACE was not significantly different at 3 months after PCI (P > 0.05). These results suggest that VR-based phase I CR program mitigates the degree of PCI postoperative stress, anxiety, and depression in elderly CHD patients, however, enhances the resistance to fatigue and does not increase the risk of adverse cardiac events, suggesting it is a safe intervention.

A multi-center, single-arm, phase II study of anlotinib plus paclitaxel and cisplatin as the first-line therapy of recurrent/advanced esophageal squamous cell carcinoma.

BACKGROUND: Anlotinib, a tyrosine kinase inhibitor, has shown encouraging anti-tumor activity in esophageal squamous cell carcinoma (ESCC). This study was designed to assess the efficacy and safety of anlotinib plus paclitaxel and cisplatin (TP) as first-line therapy for advanced ESCC. METHODS: In a multi-center, single-arm, phase II clinical trial, patients (aged > 18 years) with ESCC, which was judged to be locally advanced, recurrent, or metastatic, received 10 mg oral anlotinib once daily on days 1-14, 135 mg/m2 intravenous paclitaxel on day 1, and 60-75 mg/m2 intravenous cisplatin on days 1-3 every 3 weeks for a maximum of 4-6 cycles as the initial therapy in five centers in China. Subsequently, patients received anlotinib monotherapy (10 mg) as maintenance therapy until tumor progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS). RESULTS: Forty-seven patients were enrolled in this study between October 2019 and March 2021. The median follow-up was 14.04 months (IQR, 9.30-19.38). Of 46 with assessable efficacy, the median PFS and median overall survival were 8.38 months (95% CI, 6.59-10.17) and 18.53 months (95% CI, 13.11-23.95), respectively. The objective response rate was 76.1% (95% CI, 61.2-87.4%), with 4 (8.7%) complete responses and 31 (67.4%) partial responses. The disease control rate was 91.3% (95% CI, 79.2-97.6%). The median duration of response was 6.80 months (95% CI, 4.52-9.08), and 1 patient had an ongoing response for 23 months. Subgroup analysis revealed no association between clinical factors and survival or response. Of the 47 patients with assessable safety, the main grade ≥ 3 treatment-emergent adverse events (TEAEs) were neutropenia (17.0%), bone marrow suppression (12.8%), and vomiting (10.6%). No treatment-related deaths or serious TEAEs were observed. Notably, higher c-Kit levels were an independent factor for superior PFS (HR = 0.032; 95% CI, 0.002-0.606; P = 0.022). CONCLUSIONS: The study demonstrated a manageable safety profile and durable clinical response of anlotinib plus TP as first-line therapy in advanced ESCC, which suggested a potential therapeutic option for this population. TRIAL REGISTRATION: ClinicalTrials.gov NCT04063683. Registered 21 August 2019.

Disease Progression in Patients with Parkin-Related Parkinson's Disease in a Longitudinal Cohort.

BACKGROUND: There was a paucity of follow-up studies in the disease progression of early-onset PD patients with Parkin mutations (Parkin-EOPD). Here we conducted a longitudinal study to investigate the progression of motor and cognitive features of Parkin-EOPD patients. METHODS: Genetic analysis was performed via target sequencing and multiplex ligation-dependent probe amplification. Thirty patients carrying homozygous or compound heterozygous Parkin mutations with at least 2 follow-up revisions were investigated as the Parkin-EOPD group. Fifty-two patients with at least 2 follow-up revisions, who did not have any known causative PD mutations, GBA or LRRK2 risk variants, a heterozygous Parkin mutation or 2 Parkin mutations without a segregation test, were defined as the genetically undefined EOPD (GU-EOPD) group. A linear mixed-effect model was implemented to evaluate longitudinal changes in motor symptoms and cognition. RESULTS: At baseline, the Parkin-EOPD group had a lower Unified Parkinson's Disease Rating Scale score (UPDRS-III) (off-medication) than the GU-EOPD group, without significant differences in cognition. A longitudinal study showed the estimated progression rate per year (standard error) of the UPDRS-III score (off-medication) was lower in the Parkin-EOPD group (0.203 [0.3162] points per year) than in the GU-EOPD group (1.056 [0.3001] points per year). The difference in the UPDRS-III score rate between the 2 groups was 0.853 (0.4183) (P = 0.042). The Parkin-EOPD group showed better maintenance of spatial processing ability compared with the GU-EOPD group (P = 0.027). CONCLUSION: Parkin-EOPD patients showed a slower deterioration of motor symptoms and a better spatial processing ability than GU-EOPD patients, which suggests that subtyping according to genetic features can help predict PD progression. © 2020 International Parkinson and Movement Disorder Society.

Propagated α-synucleinopathy recapitulates REM sleep behaviour disorder followed by parkinsonian phenotypes in mice.

Idiopathic rapid eye movement sleep behaviour disorder (RBD) is now recognized as an early manifestation of α-synucleinopathies. Increasing experimental studies demonstrate that manipulative lesion or inactivation of the neurons within the sublaterodorsal tegmental nucleus (also known as the subcoeruleus nucleus in humans) can induce RBD-like behaviours in animals. As current RBD animal models are not established on the basis of α-synucleinopathy, they do not represent the pathological substrate of idiopathic RBD and thus cannot model the phenoconversion to Parkinson's disease. The purpose of this study was therefore to establish an α-synucleinopathy-based RBD animal model with the potential to convert to parkinsonian disorder. To this end, we first determined the functional neuroanatomical location of the sublaterodorsal tegmental nucleus in wild-type C57BL/6J mice and then validated its function by recapitulating RBD-like behaviours based on this determined nucleus. Next, we injected preformed α-synuclein fibrils into the sublaterodorsal tegmental nucleus and performed regular polysomnographic recordings and parkinsonian behavioural and histopathological studies in these mice. As a result, we recapitulated RBD-like behaviours in the mice and further showed that the α-synucleinopathy and neuron degeneration identified within the sublaterodorsal tegmental nucleus acted as the neuropathological substrates. Subsequent parkinsonian behavioural studies indicated that the α-synucleinopathy-based RBD mouse model were not stationary, but could further progress to display parkinsonian locomotor dysfunction, depression-like disorder, olfactory dysfunction and gastrointestinal dysmotility. Corresponding to that, we determined α-synuclein pathology in the substantia nigra pars compacta, olfactory bulb, enteral neuroplexus and dorsal motor nucleus of vagus nerve, which could underlie the parkinsonian manifestations in mice. In conclusion, we established a novel α-synucleinopathy-based RBD mouse model and further demonstrated the phenoconversion of RBD to Parkinson's disease in this animal model.

Total Synthesis and Anti-Inflammatory Bioactivity of (-)-Majusculoic Acid and Its Derivatives.

The first total synthesis of marine natural product, (-)-majusculoic acid (1) and its seven analogs (9-15), was accomplished in three to ten steps with a yield of 3% to 28%. The strategy featured the application of the conformational controlled establishment of the trans-cyclopropane and stereochemical controlled bromo-olefination or olefination by Horner-Wadsworth-Emmons (HWE) reaction. The potential anti-inflammatory activity of the eight compounds (1 and 9-15) was evaluated by determining the nitric oxide (NO) production in the lipopolysaccharide (LPS)-induced mouse macrophages RAW264.7. (-)-Majusculoic acid (1), methyl majusculoate (9), and (1R,2R)-2-((3E,5Z)-6-bromonona-3,5-dien-1-yl)cyclopropane-1-carboxylic acid (12) showed significant effect with inhibition rates of 33.68%, 35.75%, and 43.01%, respectively. Moreover, they did not show cytotoxicity against RAW264.7 cells, indicating that they might be potential anti-inflammatory agents.

Efficacy of low-dose versus high-dose simethicone with polyethylene glycol for bowel preparation: A prospective randomized controlled trial.

BACKGROUND AND AIM: Additional simethicone (SIM) can improve adequate bowel preparation and adenoma detection rate (ADR). However, there is no consensus on the optimal dose of SIM. In this study, we compared the adequate bowel preparation rate with supplementation of split-dose 2 L polyethylene glycol (PEG) with low-dose SIM (200 mg) versus high-dose SIM (1200 mg). METHODS: This was a prospective, randomized, observer-blinded trial involving consecutive subjects undergoing colonoscopy. The primary outcome was adequate bowel preparation as assessed by Boston Bowel Preparation Scale (BBPS) score. RESULTS: Four hundred subjects were randomly allocated to low-dose SIM or high-dose SIM group. Baseline characteristics were comparable in the two groups (P > 0.05). No significant between-group differences were observed with respect to total bubble scale (BS) (8.49 ± 1.00 vs 8.39 ± 1.10, P = 0.07), total BBPS score (8.70 ± 0.81 vs 8.29 ± 1.18, P = 0.98), ADR (33.68% vs 31.79%, P = 0.69) or withdrawal time (13 [range, 10-16] min vs 13 [10-15] min, P = 0.96). The intubation time in low-dose SIM group was significantly shorter than that in high-dose SIM group (8 (4-16) min vs 10 [6-17] min, P = 0.04). In addition, BS scores as well as diminutive ADR in right colon were superior in the low-dose SIM group (2.68 ± 0.59 vs 2.52 ± 0.73, P = 0.03 and 54.29% vs 30.30%, P = 0.046, respectively). CONCLUSION: Addition of low-dose SIM to split-dose 2 L PEG was as effective as addition of high-dose SIM with respect to adequate bowel preparation, ADR and patient tolerance. However, low-dose SIM was superior with respect to intubation time, right colon BS scores, right colon diminutive ADR and cost savings.

Survey and analysis of the nutritional status in hospitalized patients with malignant gastric tumors and its influence on the quality of life.

BACKGROUND/OBJECTIVES: The assessment of nutritional status and the quality of life in patients with gastric cancer has become one of the important goals of current clinical treatment. The purpose of this study was to assess the nutritional status in hospitalized gastric cancer patients by using patient-generated subjective global assessment (PG-SGA) and to analyze the influence of nutritional status on the patients' quality of life (QOL). METHODS: We reviewed the pathological diagnosis of gastric cancer for 2322 hospitalized patients using PG-SGA to assess their nutritional status and collected data on clinical symptoms, the anthropometric parameters (height, weight, body mass index (BMI), mid-arm circumference (MAC), triceps skin-fold thickness (TSF), and hand-grip strength (HGS). We also collected laboratory data (prealbumin, albumin, hemoglobin) within 48 h after the patient was admitted to the hospital. The 30-item European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) was used for QOL assessment in all patients. RESULTS: By using PG-SGA, we found 80.4% of the patients were malnourished (score ≥ 4) and 45.1% of the patients required urgent nutritional support (score ≥ 9). In univariate analysis, old age (> 65 years, p < 0.001), female (p = 0.007), residence in a village (p = 0.004), a lower level of education (p < 0.001), and self-paying (p < 0.001) were indicated as risk factors of patients with gastric cancer to be suffering from severe malnutrition. There was a negative correlation between PG-SGA and various nutritional parameters (p < 0.05). The quality of life was significantly different in gastric cancer patients with different nutritional status (p < 0.01). CONCLUSION: Malnutrition of hospitalized patients with gastric cancer in China is common and seriously affects the patients' quality of life. The nutritional status should be evaluated in a timely manner and reasonable nutritional intervention should be provided as soon as possible. The PG-SGA was fit for using as a clinical nutrition assessment method, being worthy of clinical application.

The food contaminant, deoxynivalenol, modulates the Thelper/Treg balance and increases inflammatory bowel diseases.

The incidence of inflammatory bowel diseases (IBD) is increasing in both Western and developing countries. IBD are multifactorial disorders involving complex interactions between genetic, immune, and environmental factors such as exposure to food contaminants. Deoxynivalenol (DON) is the most prevalent mycotoxin that contaminates staple food and induces intestinal breakdown and inflammatory response. To delineate the role of DON oral exposure in IBD, we used a Dextran sulfate sodium (DSS) colitis model in rats fed with a DON-contaminated diet or a control diet for 4 weeks. Colitis was induced in the 4th week by increasing concentrations of DSS in the drinking water (0, 2, 3 or 5%). DON exacerbated body weight loss and accelerated the appearance of symptoms in animals treated with DSS. DON increased morphological damage, pro-inflammatory markers (myeloperoxidase, CXCL-1 and IL-1ß) and immune cell responses. In lamina propria of the rat with colitis, DON increased adaptive and innate immune responses after anti-CD3/28 or LPS stimulation, respectively. In the spleen, DON increased IFNγ secretion and reduced Treg populations. Interestingly, De-epoxy-DON (DOM-1) a detoxified form of DON did not have any consequences on colitis. These results suggest that DON is a risk factor in the onset of IBD.

Inhibition of ROCK activity regulates the balance of Th1, Th17 and Treg cells in myasthenia gravis.

Aberrant ROCK activation has been found in patients with several autoimmune diseases, but the role of ROCK in myasthenia gravis (MG) has not yet been clearly investigated. Here, we demonstrated that ROCK activity was significantly higher in peripheral blood mononuclear cells (PBMCs) from MG patients. ROCK inhibitor Fasudil down-regulated the proportions of Th1 and Th17 cells in PBMCs of MG patients in vitro. Intraperitoneal injection of Fasudil ameliorated the severity of experimental autoimmune myasthenia gravis (EAMG) rats and restored the balance of Th1/Th2/Th17/Treg subsets. Furthermore, Fasudil inhibited the proliferation of antigen-specific Th1 and Th17 cells, and inhibited CD4 + T cells differentiated into Th1 and Th17 through decreasing phosphorylated Stat1 and Stat3, but promoted Treg cell differentiation through increasing phosphorylated Stat5. We conclude that dysregulated ROCK activity may be involved in the pathogenic immune response of MG and inhibition of ROCK activity might serve as a novel treatment strategy for MG.

Short-term impact of breast cancer screening intervention on health-related quality of life in China: A multicentre cross-sectional survey.

OBJECTIVE: The impact of participating in breast cancer screening programmes on health-related quality of life (HRQoL)is poorly understood. METHODS: Based on a national breast cancer screening programme in China, a multicentre cross-sectional survey was conducted covering 12 provinces from September 2013 to December 2014. HRQoL of participants in the screening population and general population was evaluated by the three-levelEuroQol-five-Dimensions (EQ-5D-3L) instrument, and utility scores were generated through the Chinese value set. Univariate and multivariate regression analyses were performed to explore determinants of utility scores and anxiety/depression problems. RESULTS: For screening group and general population (n = 4756, mean age = 51.6 year old), the corresponding utility scores were 0.937 (95% CI, 0.933-0.941) and 0.953 (0.949-0.957) (P < .001). Pain/discomfort and anxiety/depression were the most common reported in both groups (51.4% and 34.3%, P < .001). Utility scores at prescreening, in-screening, and postscreening interview timings were 0.928 (0.921-0.935), 0.958 (0.948-0.969), and 0.938 (0.933-0.943), respectively (P < .001); the corresponding proportions of anxiety/depression reporting were 25.9%, 16.3%, and 21.1%, respectively (P = .004). Interview timing, geographical region, and insurance status were associated with HRQoL and anxiety/depression in women at high-risk of breast cancer. CONCLUSIONS: Utility scores of screening participants were significantly lower than that of general population in China, but the difference may be clinically insignificant. Further cohort studies using HRQoL measurements are needed.

cas9 Enhances Bacterial Virulence by Repressing the regR Transcriptional Regulator in Streptococcus agalactiae.

Clustered regularly interspaced palindromic repeats (CRISPR) and their associated cas genes have been demonstrated to regulate self-genes and virulence in many pathogens. In this study, we found that inactivation of cas9 caused reduced adhesion and intracellular survival of the piscine Streptococcus agalactiae strain GD201008-001 and significantly decreased the virulence of this strain in zebrafish and mice. Further investigation indicated that the regR transcriptional regulator was upregulated in the Δcas9 mutant. As regR mediates the repression of hyaluronidase, a critical factor involved in opening the blood-brain barrier (BBB) in mice, cas9-mediated repression of regR transcription is important for S. agalactiae to open the BBB and thereby cause meningitis in animals. This study expands our understanding of endogenous gene regulation mediated by CRISPR-Cas systems in bacteria.

A homozygous missense variant in HSD17B4 identified in a consanguineous Chinese Han family with type II Perrault syndrome.

BACKGROUND: Perrault syndrome is a rare multisystem disorder that manifests with sensorineural hearing loss in both sexes, primary ovarian insufficiency in females and neurological features. The syndrome is heterogeneous both genetically and phenotypically. CASE PRESENTATION: We reported a consanguineous family (two affected sisters) with Perrault syndrome. The proband had the characteristics of Perrault syndrome: ovarian dysgenesis, bilateral hearing loss and obvious neurological signs. Target genetic sequencing and triplet repeat primed PCR (TP-PCR) plus capillary electrophoresis was conducted to detect causative mutations in the proband. The detected variant was further confirmed in the proband and tested in other family members by Sanger sequencing. Both the proband and her sister were found homozygous for the novel variant HSD17B4 c.298G > T (p.A100S) with their parents heterozygous. Detected by western blot, the protein expression of HSD17B4 mutant was much lower than that of the wild type in SH-SY5Y cells transfected by HSD17B4 wild type or mutant plasmid, which indicated the pathogenicity of the HSD17B4 mutation. CONCLUSIONS: Our findings supported that HSD17B4 was one of the genes contributing to Perrault syndrome with the likely pathogenic variant c.298G > T (p.A100S). Special manifestations of cerebellar impairment were found in cases caused by HSD17B4 mutations. Besides, attention should be paid to distinguish Perrault syndrome from D-bifunctional protein deficiency and hereditary ataxia.

Sika pilose antler type I collagen promotes BMSC differentiation via the ERK1/2 and p38-MAPK signal pathways.

CONTEXT: Sika pilose antler type I collagen (SPC-I) have been reported to promote bone marrow mesenchymal stem cell (BMSC) proliferation and differentiation. However, the underlying mechanism is still unclear. OBJECTIVE: This study investigates the molecular mechanisms of SPC-I on the BMSC proliferation and differentiation of osteoblast (OB) in vitro. MATERIAL AND METHODS: The primary rat BMSC was cultured and exposed to SPC-I at different concentrations (2.5, 5.0 and 10.0 mg/mL) for 20 days. The effect of SPC-I on the differentiation of BMSCs was evaluated through detecting the activity of alkaline phosphatase (ALP), ALP staining, collagen I (Col-I) content, and calcified nodules. The markers of osteoblastic differentiation were evaluated using RT-PCR and Western-blot analysis. RESULTS: SPC-I treatment (2.5 mg/mL) significantly increased the proliferation of BMSCs (p < 0.01), whereas, SPC-I (5.0 and 10.0 mg/mL) significantly inhibited the proliferation of BMSCs (p < 0.01). SPC-I (2.5 mg/mL) significantly increased ALP activity and Col-I content (p < 0.01), and increased positive cells in ALP staining and the formation of calcified nodules. Additionally, the gene expression of ALP, Col-I, Osteocalcin (OC), Runx2, Osterix (Osx), ERK1/2, BMP2 and p38-MAPK, along with the protein expression of ERK1/2, p-ERK1/2, p-p38 MAPK were markedly increased in the SPC-I (5.0 mg/mL) treatment group (p < 0.01) compared to the control group. DISCUSSION AND CONCLUSIONS: SPC-I can induce BMSC differentiation into OBs and enhance the function of osteogenesis through ERK1/2 and p38-MAPK signal transduction pathways and regulating the gene expression of osteogenesis-specific transcription factors.

Canine influenza virus coinfection with Staphylococcus pseudintermedius enhances bacterial colonization, virus load and clinical presentation in mice.

BACKGROUND: Canine influenza virus (CIV) and Staphylococcus pseudintermedius (Sp) are pathogens that cause respiratory disease in dogs. Considering bacterial infections following influenza are a leading cause of illness and death, it is of particular meaning to investigate the interaction between these two pathogens. In this study, BALB/c mice were used as a mouse model to assess whether inoculation with CIV H3N2 followed by S. pseudintermedius 72 h later resulted in exacerbation of disease. Disease was characterized by assessment of body weight loss, titration of virus and bacteria, histopathology, and cytokine production. RESULTS: There was a significantly greater decrease in body weight in the co-infected group compared with the CIV-only and SP-only groups. CIV inoculation increased bacterial colonization, whereas secondary infection with S. pseudintermedius elevated the viral RNA load of CIV in tissues. The histological lesions in the brain, spleen and lung were more severe in the CIV/Sp group than in the singly treated groups. Infection with CIV alone, Sp alone or coinfection stimulated a significantly higher release of cytokines, such as interferon-gamma (IFN)-γ, interleukin 6 (IL)-6, tumor necrosis factor (TNF-α) and lymphotactin (Lptn), than was observed in the mock-infected group (PBS). Moreover, the levels of IFN-γ in the spleen and lung were higher in the CIV/Sp group compared with the CIV-only and Sp-only groups. CONCLUSION: Our findings provide the first demonstration that the secondary infection of mice with Sp leads to increased clinical signs and lesions during canine influenza.

[Effects of sika pilose antler type collagen on ROS1728 cell and its molecular mechanism].

In this paper, effect and molecular mechanism of sika pilose antler type I collagen(SPC-I) of ROS1728 cell were explored. For the SPC-I provides the theory basis for the treatment of osteoporosis. The adherent method was used to cultivate rat osteosarcoma osteogenesis sample cell line ROS1728. The effect of SPC-I on ROS1728 cells proliferation was tested by CCK-8 method. Runx2, osernix, ALP, Coll-I, OC osteogenesis related genes expression was tested by RT-PCR, and Runx2 protein expression was tested by Western-bolt. Results showed that 5 g•L ⁻¹ SPC-I could inhibit ROS1728 cell proliferation, and significantly promote the expression of ROS1728 cell specific transcription factor Runx2 and osterix mRNA, Runx2 protein and marker gene ALP, Coll-I, OC mRNA expression(P<0.01). 2.5 g•L ⁻¹ and 10 g•L ⁻¹ SPC-I could significantly inhibit the ROS1728 cell proliferation(P<0.01), and inhibit the expression of related genes. In conclusion, 5 g•L ⁻¹ SPC-I could inhibit ROS1728 cell proliferation, obviously enhance ROS1728 cell function, promote ROS1728 cell differentiation, maturation.