Evaluation of the cross-protection of the Vero cell-derived attenuated influenza vaccines with compound adjuvant, through intranasal immunization.

This study was to evaluate the sufficient safety and effect of the novel influenza vaccine program. It prepared new reassortant influenza virus, with high yield on Vero cells. According to the plaque counting, one dose LAIV was composed with 105 PFU of H1, H3, BY, and BV, respectively. Then mixed this LAIV with compound adjuvant, containing 500 µg/mL of carbopol971P and 50 µg/mL of tetanus toxin. That vaccination was called catt-flu. And it employed the GYZZ02 vaccine (commercialized freeze-dried LAIV, listed in China) as cohort analysis control. All mice received two doses of the vaccine, administered on days 0 and 14, respectively. That catt-flu program could induce more cross-protection with neutralizing antibody against heterogeneous types of influenza virus, not only based on HA but also NA protective antigen, through convenient nasal immunization, which had non-inferiority titter compared with the chicken embryo-derived GYZZ02 vaccine on safe and effect. The Vero cell-derived vaccine (LAIV) combined compound catt adjuvant (contain carbopol971P and tetanus toxin) could provide another safety and protective program of influenza vaccine by intranasal administration, as catt-flu program.

Diagnostic performance of IVUS-FFR analysis based on generative adversarial network and bifurcation fractal law for assessing myocardial ischemia.

Background: IVUS-based virtual FFR (IVUS-FFR) can provide additional functional assessment information to IVUS imaging for the diagnosis of coronary stenosis. IVUS image segmentation and side branch blood flow can affect the accuracy of virtual FFR. The purpose of this study was to evaluate the diagnostic performance of an IVUS-FFR analysis based on generative adversarial networks and bifurcation fractal law, using invasive FFR as a reference. Method: In this study, a total of 108 vessels were retrospectively collected from 87 patients who underwent IVUS and invasive FFR. IVUS-FFR was performed by analysts who were blinded to invasive FFR. We evaluated the diagnostic performance and computation time of IVUS-FFR, and compared it with that of the FFR-branch (considering side branch blood flow by manually extending the side branch from the bifurcation ostia). We also compared the effects of three bifurcation fractal laws on the accuracy of IVUS-FFR. Result: The diagnostic accuracy, sensitivity, and specificity for IVUS-FFR to identify invasive FFR ≤ 0.80 were 90.7% (95% CI, 83.6-95.5), 89.7% (95% CI, 78.8-96.1), 92.0% (95% CI, 80.8-97.8), respectively. A good correlation and agreement between IVUS-FFR and invasive FFR were observed. And the average computation time of IVUS-FFR was shorter than that of FFR-branch. In addition to this, we also observe that the HK model is the most accurate among the three bifurcation fractal laws. Conclusion: Our proposed IVUS-FFR analysis correlates and agrees well with invasive FFR and shows good diagnostic performance. Compared with FFR-branch, IVUS-FFR has the same level of diagnostic performance with significantly lower computation time.

Effect of electroacupuncture at the acupoints for Tiaozang Xingshen on cerebral metabolism in the patients with type 2 diabetes mellitus-associated cognitive dysfunction / 中国针灸

OBJECTIVES@#To investigate the cerebral metabolism in the patients with type 2 diabetes mellitus-associated cognitive dysfunction (T2DACD) and explore the mechanism of electroacupuncture (EA) at the acupoints for Tiaozang Xingshen (adjusting zangfu function and rescuing the spirit) in treatment of T2DACD, using magnetic resonance spectroscopy.@*METHODS@#Fifteen patients with T2DACD (observation group) and 22 healthy subjects (control group) were enrolled. In the observation group, the patients were treated with EA for Tiaozang Xingshen at Baihui (GV 20) and Shenting (GV 24), and bilateral Feishu (BL 13), Pishu (BL 20), Shenshu (BL 23), Zusanli (ST 36), Sanyinjiao (SP 6), Hegu (LI 4) and Taichong (LR 3). EA was operated with disperse-dense wave, 2 Hz/100 Hz in frequency and 0.1 mA to 1.0 mA in current intensity; 30 min each time, once daily. One course of EA consisted of 5 treatments, at the interval of 2 days and the intervention lasted 8 courses. Before treatment in the control group, before and after treatment in the observation group, the score of Montreal cognitive assessment scale (MoCA), the score of clinical dementia rating (CDR), Flanker paradigm, Stroop paradigm, Nback paradigm, the score of self-rating anxiety scale (SAS), the score of self-rating depression scale (SDS), and the score of Hamilton depression rating scale (HAMD) were evaluated separately; the glycolipid metabolic indexes (fasting plasma glucose [FPG], glycosylated hemoglobin type A1c [HbA1c], total cholesterol [TC], triacylglycerol [TG], high-density lipoprotein cholesterol [HDL-C] and low-density lipoprotein cholesterol [LDL-C]) were determined；with the magnetic resonance spectroscopy technique adopted, the metabolites in the basal ganglia area were detected. The correlation analysis was performed for the metabolite values with MoCA score, CDR score , Flanker paradigm, Stroop paradigm, and Nback paradigm.@*RESULTS@#Before treatment, compared with the control group, in the observation group, MoCA score was lower (P<0.001), CDR score and the levels of FPG and HbA1c were higher (P<0.001); the reaction times of Flanker non-conflict, Flanker conflict, Stroop neutrality, Stroop congruence, Stroop conflict, and 1-back were prolonged (P<0.05, P<0.001), and the accuracy of Flanker conflict, Stroop conflict, and 1-back decreased (P<0.05, P<0.01); the ratio of N-acetyl aspartate (NAA) to creatine (Cr) in the left basal ganglia area was dropped (P<0.001), and that of myo-inositol (MI) to Cr in the right side increased (P<0.05). In the observation group after treatment, compared with the levels before treatment, MoCA score was higher (P<0.001), the scores of CDR, SAS and HAMD were reduced (P<0.01, P<0.05), the reaction times of Flanker conflict and Stroop conflict shortened (P<0.001, P<0.05), and the accuracy of Flanker conflict and 1-back increased (P<0.001, P<0.05); the ratio of NAA to Cr in the left basal ganglia area and that of the gamma-aminobutyric acid (GABA) to Cr in the right increased (P<0.05), that of MI to Cr in the right decreased (P<0.05). Before treatment, in the observation group, the ratio of MI to Cr in the right basal ganglia area was positively correlated with the reaction time of Stroop congruence (r=0.671, P=0.012) and this ratio was positively correlated with the reaction time of Stroop conflict (r=0.576, P=0.039).@*CONCLUSIONS@#Electroacupuncture for "adjusting zangfu function and rescuing the mind" improves the cognitive function of T2DACD patients, which may be related to the regulation of NAA, MI and GABA levels in the basal ganglia.

Current status and hotspot of minimally invasive surgery for pancreatic head carcinoma / 中华外科杂志

With the improvement of laparoscopic equipment and surgical technology,pancreatic surgery has entered the "minimally invasive era".However,the use of minimally invasive pancreaticoduodenectomy in patients with pancreatic head cancer remains controversial.In recent years,China's pancreatic surgeons have been at the forefront of the world in terms of surgical technology,however,surgical philosophy, selection of indication,and perioperative management should be further stregthened. Additionally, the development of medical standards in various regions of China is seriously uneven,and minimally invasive pancreaticoduodenectomy still needs to be further standardized and popularized.Through this article,the author discusses the development status of minimally invasive surgery for pancreatic head cancer and related hot topics with fellow surgeons,in order to further improve the standard diagnosis and treatment of pancreatic cancer in China.

Spike-specific CXCR3+ TFH cells play a dominant functional role in supporting antibody responses in SARS-CoV-2 infection and vaccination

CD4+ T follicular helper (TFH) cells are required for high-quality antibody generation and maintenance. However, the longevity and functional role of these cells are poorly defined in COVID-19 convalescents and vaccine recipients. Here, we longitudinally investigated the dynamics and functional roles of spike-specific circulating TFH cells and their subsets in convalescents at the 2nd, 5th, 8th, 12th and 24th months after COVID-19 symptom onset and in vaccinees after two and three doses of inactivated vaccine. SARS-CoV-2 infection elicited robust spike-specific TFH cell and antibody responses, of which spike-specific CXCR3+ TFH cells but not spike-specific CXCR3- TFH cells and neutralizing antibodies were persistent for at least two years in more than 80% of convalescents who experienced symptomatic COVID-19, which was well coordinated between spike-specific TFH cell and antibody responses at the 5th month after infection. Inactivated vaccine immunization also induced spike-specific TFH cell and antibody responses; however, these responses rapidly declined after six months with a two-dose standard administration, and a third dose significantly promoted antibody maturation and potency. Functionally, spike-specific CXCR3+ TFH cells exhibited better responsiveness than spike-specific CXCR3- TFH cells upon spike protein stimulation in vitro and showed superior capacity in supporting spike-specific antibody secreting cell (ASC) differentiation and antibody production than spike-specific CXCR3- TFH cells cocultured with autologous memory B cells. In conclusion, spike-specific CXCR3+ TFH cells played a dominant functional role in antibody elicitation and maintenance in SARS-CoV-2 infection and vaccination, suggesting that induction of CXCR3-biased spike-specific TFH cell differentiation will benefit SARS-CoV-2 vaccine development aiming to induce long-term protective immune memory. HighlightsO_LISARS-CoV-2 infection elicited robust spike-specific TFH cell and antibody responses, which persisted for at least two years in the majority of symptomatic COVID-19 convalescent patients. C_LIO_LIInactivated vaccine immunization also elicited spike-specific TFH cell and antibody responses, which rapidly declined over time, and a third dose significantly promoted antibody maturation and potency. C_LIO_LISpike-specific CXCR3+ TFH cells exhibited more durable responses than spike-specific CXCR3- TFH cells, correlated with antibody responses and showed superior capacity in supporting ASC differentiation and antibody production than spike-specific CXCR3- TFH cells. C_LI

Calcium Participates in Migration of VSMCS Synergistically Induced by Cyclic Stretch and Platelet-Derived Microvesicles / 医用生物力学

Objective To investigate the synergistic effects of pathologically elevated cyclic stretch and platelet-derived microvesicles (PMVs) on migration of vascular smooth muscle cells (VSMCs) and the potential role of calcium in this process. Methods The FX-5000T strain loading system was used to apply cyclic stretch to VSMCs with magnitudes of 5% and 15%, which simulated physiological and hypertensive situation respectively in vitro; wound healing assay was used to analyze VSMCs migration; Ca2+-free medium was used to remove extracellular calcium; 2-APB (an antagonist of IP3R) was used to inhibit the release of intercellular stored calcium; GSK219 (an antagonist of TRPV4) and Nifedipine (an inhibitor of L-type voltage-gated calcium channel) were applied to block the activity of respective calcium channel; thrombin was used to stimulate platelets in vitro which simulated the hypertensive activation of PMVs in vivo. ResultsCompared with 5% cyclic stretch, 15% cyclic stretch significantly promoted VSMC migration. Removal of extracellular calcium inhibited VSMCs migration, but the application of GSK219 and Nifedipine did not affect the migration up-regulated by 15% cyclic stretch; while 2-APB which inhibited the release of intracellular stored calcium could also repress VSMCs migration under 15% cyclic stretch. PMVs further promoted VSMC migration under 15% cyclic stretch condition, and both extracellular calcium and intercellular stored calcium were involved in this process. Conclusions Both intracellular and extracellular calcium play important roles in VSMC migration induced by 15% cyclic stretch, and PMVs synergistically participate in the above process. The study is aimed to provide new mechanobiological insights into the molecular mechanism and clinical targets of vascular remodeling in hypertension.

[Evaluation of the Acute Toxicity and Genotoxicity of the Rice Biofortified with ß-Glucan].

OBJECTIVE: To provide a scientific evaluation of the food safety of the rice biofortified with ß-glucan. METHODS: The acute toxicity and genotoxicity of the rice were evaluated by 14-day feeding experiment, Ames experiment, erythrocyte micronucleus test and mouse lymphoma thymidine kinase gene ( TK) mutation assay respectively. RESULTS: In the acute toxicity test, there was no obvious toxicity of rice biofortified with ß-glucan, and no abnormality was found in anatomical observation. The median lethal dose (LD 50) to rats and mice wereall greater than 15 mg/kg, which belonged to the actual non-toxic level. Whether with S 9 activation or not, no genotoxicity was found to the tested strains TA97a, TA98, TA100, TA102 and TA1535. No induction of polychromatic erythrocytes and inhibition of bone marrow were found in erythrocyte micronucleus test. The results of TK gene mutation assay did not show the mutagenicity of ß-glucan bioaugmentation rice. All results of the three genotoxicity tests were negative. CONCLUSION: Under the current experimental conditions, ß-glucan biofortified rice showed no obvious acute toxicity and genotoxicity.

Identification of genes and pathways in human antigen-presenting cell subsets in response to polio vaccine by bioinformatical analysis.

BACKGROUND: Polio eradication has been achieved in the world except for three countries due to the widespread use of the inactivated poliovirus vaccine (IPV) and the live-attenuated oral poliovirus vaccine. Following polio eradication, the IPV would be the only polio vaccine available. However, the mechanisms of the interactions between IPV and human antigen-presenting cells (APCs) remain largely unclear. METHODS: To investigate the involvement of the IPV in human monocytes, we downloaded the gene chip GSE44721 from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified using the GEO2R analysis tool. Functional and pathway enrichment analyses were performed for DEGs using the Metascape database. DEG-associated protein-protein-interactions (PPIs) were established by the Search Tool for the Retrieval of Interacting Genes website and visualized by Cytoscape. RESULTS: There were 240 DEGs (51 upregulated and 189 downregulated genes) identified from the GSE44721 data set, and they were significantly enriched in several biological processes, including antigen processing and presentation of lipid antigen via MHC class Ib, adaptive immune response, and response to interferon-gamma. One hundred thirty-six nodes were screened from the DEG PPI network. There were six significant hub proteins (WDR36, MRTO4, RPF2, PPAN, CD40, and BMS1) that regulated the IPV in human monocytes. CONCLUSIONS: In summary, using bioinformatical analysis, we have information for the immunization activated by the IPV in monocytes. Moreover, hormones and cytokines regulate the activation of APCs.

Role of phenol red in the stabilization of the Sabin type 2 inactivated polio vaccine at various pH values.

To analyze the effects of phenol red at various pH values on the Sabin type 2 inactivated polio vaccine (sIPV2), several biophysical techniques were used to evaluate the particle size and capsid protein for conformation. sIPV2's size was assessed via transmission electron microscopy and dynamic light scattering. The effects of various pH values (from 4.0 to 7.0) on the biophysical characters of sIPV2 particles in solution were determined by dynamic light scattering and zeta potential. The results clearly indicated that aggregation and instability occurred in the solution of sIPV2 particles at a pH of 6.0. Under similar conditions, by dynamic light scattering and zeta potential, the virus particles in solution showed more dispersion and were stable with the addition of 0.05 mM phenol red. According to circular dichroism and intrinsic tryptophan fluorescence data, it was observed that the secondary and tertiary structures of the sIPV2 particles were more stable with the protection of phenol red. At a pH below 6.0, the sIPV2 solution with phenol red had more D-antigen content, which was confirmed by enzyme-linked immunosorbent assay and rat experiments. These results strongly suggested that phenol red improved the pH stability of the sIPV2. The study indicated the potential of phenol red in preserving vaccine potency of the sIPV2 at various pH values.

Application of a novel nanoemulsion adjuvant for rabies vaccine which stabilizes a Krebs cycle intermediate (SDH) in an animal model.

Rabies is the most lethal zoonotic, vaccine-preventable viral disease in the world. Its treatment is complicated by insufficient vaccine supply and the requirement for four to five repeated injections, as commercially available inactivated rabies lack adjuvant and have low immunogenicity. In this study, we focused on the role of a Krebs cycle intermediate, succinate dehydrogenase (SDH), in the innate immune response to cytokine production. We formulated a novel nanoemulsion adjuvant, Golden03, which stabilizes mouse SDH activity and contains more coenzyme Q10 and succinic acid than the classic MF59 adjuvant. Mice were immunized on days 1, 3, and 7, with seroconversion rate results suggesting that Golden03 significantly enhanced vaccine-stimulated antibody production against the rabies virus. Neutralizing antibody concentration testing by RFFIT indicated that treatment with Golden03 could result in antibody levels of up to 0.74 IU/mL 5 days post infection (DPI). ELISPOT for IFN-γ in mouse spleen cells showed that Golden03 enhanced immune responses at 14 DPI, inducing a rapid and powerful cellular response compared to the control group. Furthermore, the Vaccine-Golden03 group displayed no obvious weight loss or death after intracranial injection with CVS-11. An additional advantage is that Golden03 allowed for a three-quarter reduction in dose, while maintaining its efficacy and rapid stimulation effect. We suggest that Golden03 could be developed as a potential adjuvant for use in human rabies vaccine.

Effects of IRA and UV alone or in combination on skin photoaging in mice / 西安交通大学学报(医学版)

Objective: To detect the expression of MMP-13 in the skin of mice treated by near-infrared (IRA) and ultraviolet (UV) so as to observe their effects on skin photoaging and their interrelation and explore molecular mechanisms in IRA-induced skin photoaging. Methods: Male ICR mice were randomly divided into five groups: control group (without ray exposure), IRA group, UV group, IRA/UV group, and UV/IRA group. The mice in the latter four groups had their dorsal skin exposed to different radiated ray respectively. The levels of MMP-13 protein and mRNA in the exposed skin were detected by HE, immunohistochemical method, Western blot and real-time PCR. Results: Both skin lesions by visual inspection and H&E staining results showed that mice in the other four groups had skin photoaging in the exposed skin area compared with the control group. The levels of MMP-13 protein and mRNA in the exposed skin in IRA/UV and UV/IRA groups were significantly higher than those in the control mice (P<0.05). In addition, mice in IRA/UV group showed higher levels of MMP-13 protein and mRNA than those in UV/IRA group (P<0.05). Conclusion: ① IRA causes skin photoaging in mice. ② UV and IRA interact with each other, up-regulate the expression of MMP-13, and promote each other in the process of photoaging. ③ The effects of IRA and UV in combination on skin photoaging are closely related to order of exposure. Taken together, avoiding IRA exposure and the expression of MMP-13 play an important role in preventing skin wrinkle formation and treatment of photoaging in mice.

Construction of influenza B virus vero cell adapted strain by genetic reassortment / 中华实验和临床病毒学杂志

Objective@#To construct influenza B virus Vero cell adapted strain by genetic recombination technology by using the influenza B virus Vero cell adapted strain as the parent strain.@*Methods@#The chick embryo and Vero cell were co-infected with influenza virus Vero cell adapted strain B/Malaysia/2506/2004 Va (Bv) and the vaccine strain B/massachusetts/2/2012 (BX-51B) recommended by WHO. The reassortants were screened with the anti-Bv serum. Plaque-purified reassortants were used to screen for Vero cell-adapted influenza B virus strains containing the surface antigen of the epidemic strain.@*Results@#A Vero cell-adapted influenza B virus strain was obtained with successive passage in Vero cells. The hemagglutination inhibition test and the one-way immunogold agar diffusion test both showed that the reassortant virus was homologous to NYMC BX-51B, and sequence analysis result showed that the reassortment virus has the same HA and NA gene with the vaccine strain.@*Conclusion@#B/Malaysia/2506/2004Va (Bv) can be used as a parent strain to prepare Vero cell vaccine against influenza B virus.

Comprehensive treatment of liver metastasis of pancreatic neuroendocrine neoplasms / 中国实用外科杂志

Pancreatic neuroendocrine neoplasms(p NENs)are noted for its great variety and wide heterogeneity.The incidence is increasing gradually.Liver metastasis is not the contraindication of surgery of p NENs.Surgery is consider as a significant role in the multi-disciplinary team about treating p NENs.Although p NENs liver metastasis is relatively rare,its overall prognosis is significantly better than that of patients with pancreatic cancer liver metastasis.It is of great significance to grasp the indications and principles of surgical treatment for improving the survival of patients.Despite the relevant guidelines for diagnosis and treatment,the choice of surgical treatment options and the grasp of surgical indications for p NENs liver metastasis are still controversial.All pancreatic centers should give full play to the advantages of MDT and formulate individualized treatment plans for patients.Meanwhile,hospitals at all levels should strengthen cooperation to reduce missed diagnosis,misdiagnosis and mistreatment,and further standardize the surgical diagnosis and treatment of p NENs liver metastasis in China.

Effect of broad-spectrum antibiotics on bacterial translocation in burned or septic rats / 中华医学杂志(英文版)

Background:@#Antibiotics are frequently used to treat critically ill patients, and its use is often accompanied by intestinal dysbiosis that might further lead to bacterial translocation (BT). Nevertheless, studies on the relationship between antibiotic therapy and BT are rare. In the present study, we investigated the effect of broad-spectrum antibiotics on BT in an experimental rat model of burn or sepsis injury.@*Methods:@#The septic rat model was simulated by a second insult with lipopolysaccharides after burn injury. Ninety-two male Sprague-Dawley rats were randomly divided into control, burn, and sepsis groups (n = 8 or 9, each group), and the latter two groups were then treated with imipenem or ceftriaxone for 3 or 9 days. The mesenteric lymph nodes, liver, lungs, and blood were collected at each time point under sterile conditions for quantitative bacterial culture and strain identification. The differences between the groups were compared by Fisher exact test or Mann-Whitney U test.@*Results:@#Only minimal Escherichia coli translocation to the mesenteric lymph nodes was observed in the normal control group, in which the BT rate was 12.5%. Burn injury did not affect the BT rate (Burn group vs. Control group, 12.5% vs. 12.5%, P = 1.000), whereas the BT rate showed an increased trend after the second insult with lipopolysaccharide (Sepsis group vs. Control group, 44.4% vs. 12.5%, P = 0.294), and many strains of Enterobacteria spp. were detected in distant organs (liver, lung, and blood) [Sepsis group vs. Control group, 0 (0,3) vs. 0 (0,0), U = 20, P = 0.045]. After the antibiotic treatment, BT to the distant organs was increased in burned rats [Burn IT3 group vs. Burn group, 0 (0,2) vs. 0 (0,0); Burn IT9 group vs. Burn group, 0 (0,1) vs. 0 (0,0); Burn CT9 group vs. Burn group, 0 (0,2) vs. 0 (0,0); all U = 20 and P = 0.076] but decreased in septic rats [Sepsis CT3 group vs. Sepsis group, 0 (0,0) vs. 0 (0,3), U = 20, P = 0.045]. The total amount of translocated bacteria, regardless of which antibiotic was used, was increased in burned rats [Burn IT9 group vs. Burn group, 2.389 (0,2.845) vs. 0 (0,2.301) Log10 colony-forming units (CFU)/g, U = 14, P = 0.034; Burn CT3 group vs. Burn group, 2.602 (0,3.633) vs. 0 (0,2.301) Log10 CFU/g, U = 10.5, P = 0.009], but there was a slightly decreased trend in septic rats [Sepsis IT9 group vs. Sepsis group, 2.301 (2,3.146) vs. 0 (0,4.185) Log10 CFU/g, U = 36, P = 0.721; Sepsis CT9 group vs. Sepsis group, 2 (0,3.279) vs. 0 (0,4.185) Log10 CFU/g, U = 32.5, P = 0.760]. Remarkably, the quantity of Enterococci spp. dramatically increased after broad-spectrum antibiotic treatment in both the burned and septic groups [Burn IT3 group vs. Burn group, 1 (0,5.164) vs. 0 (0,0) Log10 CFU/g, U = 16; Burn IT9 group vs. Burn group, 1 (0,2.845) vs. 0 (0,0) Log10 CFU/g, U = 16; Burn CT3 group vs. Burn group, 2.602 (0,3.633) vs. 0 (0,0) Log10 CFU/g, U = 8; Burn CT9 group vs. Burn group, 1 (0,4.326) vs. 0 (0,0) Log10 CFU/g, U = 16; Sepsis IT3 group vs. Sepsis group, 2.477 (0,2.903) vs. 0 (0,0) Log10 CFU/g, U = 4.5; Sepsis IT9 group vs. Sepsis group, 2 (0,3.146) vs. 0 (0,0) Log10 CFU/g, U = 9; Sepsis CT3 group vs. Sepsis group, 1.151 (0,2.477) vs. 0 (0,0) Log10 CFU/g, U = 18; Sepsis CT9 group vs. Sepsis group, 2 (0,3) vs. 0 (0,0) Log10 CFU/g, U = 13.5; all P < 0.05].@*Conclusions:@#Broad-spectrum antibiotics promote BT in burned rats but prevent BT in septic rats, especially preventing BT to distant organs, such as the liver and lung. Moreover, Enterococci spp. with high drug resistance and high pathogenicity translocated most after antibiotic treatment.

Mouse Nerve Growth Factor Facilitates the Growth of Interspinal Schwannoma Cells by Activating NGF Receptors

OBJECTIVE: Nerve growth factor (NGF) is a member of the neurotrophic factor family and plays a vital role in the physiological processes of organisms, especially in the nervous system. Many recent studies have reported that NGF is also involved in the regulation of tumourigenesis by either promoting or suppressing tumor growth, which depends on the location and type of tumor. However, little is known regarding the effect of NGF on interspinal schwannoma (IS). In the present study, we aimed to explored whether mouse nerve growth factor (mNGF), which is widely used in the clinic, can influence the growth of interspinal schwannoma cells (ISCs) isolated from IS in vitro.METHODS: ISCs were isolated, cultured and identified by S-100 with immunofluorescence analysis. S-100-positive cells were divided into five groups, and separately cultured with various concentrations of mNGF (0 [phosphate buffered saline, PBS], 40, 80, 160, and 320 ng/mL) for 24 hours. Western blot and quantantive real time polymerase chain reaction (PCR) were applied to detect tyrosine kinase A (TrkA) receptor and p75 neurotrophin receptor (p75(NTR)) in each group. Crystal violet staining was selected to assess the effect of mNGF (160 ng/mL) on ISCs growth.RESULTS: ISCs growth was enhanced by mNGF in a dose-dependent manner. The result of crystal violet staining revealed that it was significantly strengthened the cells growth kinetics when cultured with 160 ng/mL mNGF compared to PBS group. Western blot and quantantive real time PCR discovered that TrkA receptor and mRNA expression were both up-regualated under the condition of mNGF, expecially in 160 ng/mL, while the exoression of p75(NTR) demonstrated no difference among groups.CONCLUSION: From these data, we conclude that exogenous mNGF can facilitate ISC growth by activating both TrkA receptor and p75(NTR). In addition, patients who are suffering from IS should not be administered mNGF in the clinic.

Effect of broad-spectrum antibiotics on bacterial translocation in burned or septic rats / 中华医学杂志(英文版)

BACKGROUND@#Antibiotics are frequently used to treat critically ill patients, and its use is often accompanied by intestinal dysbiosis that might further lead to bacterial translocation (BT). Nevertheless, studies on the relationship between antibiotic therapy and BT are rare. In the present study, we investigated the effect of broad-spectrum antibiotics on BT in an experimental rat model of burn or sepsis injury.@*METHODS@#The septic rat model was simulated by a second insult with lipopolysaccharides after burn injury. Ninety-two male Sprague-Dawley rats were randomly divided into control, burn, and sepsis groups (n = 8 or 9, each group), and the latter two groups were then treated with imipenem or ceftriaxone for 3 or 9 days. The mesenteric lymph nodes, liver, lungs, and blood were collected at each time point under sterile conditions for quantitative bacterial culture and strain identification. The differences between the groups were compared by Fisher exact test or Mann-Whitney U test.@*RESULTS@#Only minimal Escherichia coli translocation to the mesenteric lymph nodes was observed in the normal control group, in which the BT rate was 12.5%. Burn injury did not affect the BT rate (Burn group vs. Control group, 12.5% vs. 12.5%, P = 1.000), whereas the BT rate showed an increased trend after the second insult with lipopolysaccharide (Sepsis group vs. Control group, 44.4% vs. 12.5%, P = 0.294), and many strains of Enterobacteria spp. were detected in distant organs (liver, lung, and blood) [Sepsis group vs. Control group, 0 (0,3) vs. 0 (0,0), U = 20, P = 0.045]. After the antibiotic treatment, BT to the distant organs was increased in burned rats [Burn IT3 group vs. Burn group, 0 (0,2) vs. 0 (0,0); Burn IT9 group vs. Burn group, 0 (0,1) vs. 0 (0,0); Burn CT9 group vs. Burn group, 0 (0,2) vs. 0 (0,0); all U = 20 and P = 0.076] but decreased in septic rats [Sepsis CT3 group vs. Sepsis group, 0 (0,0) vs. 0 (0,3), U = 20, P = 0.045]. The total amount of translocated bacteria, regardless of which antibiotic was used, was increased in burned rats [Burn IT9 group vs. Burn group, 2.389 (0,2.845) vs. 0 (0,2.301) Log10 colony-forming units (CFU)/g, U = 14, P = 0.034; Burn CT3 group vs. Burn group, 2.602 (0,3.633) vs. 0 (0,2.301) Log10 CFU/g, U = 10.5, P = 0.009], but there was a slightly decreased trend in septic rats [Sepsis IT9 group vs. Sepsis group, 2.301 (2,3.146) vs. 0 (0,4.185) Log10 CFU/g, U = 36, P = 0.721; Sepsis CT9 group vs. Sepsis group, 2 (0,3.279) vs. 0 (0,4.185) Log10 CFU/g, U = 32.5, P = 0.760]. Remarkably, the quantity of Enterococci spp. dramatically increased after broad-spectrum antibiotic treatment in both the burned and septic groups [Burn IT3 group vs. Burn group, 1 (0,5.164) vs. 0 (0,0) Log10 CFU/g, U = 16; Burn IT9 group vs. Burn group, 1 (0,2.845) vs. 0 (0,0) Log10 CFU/g, U = 16; Burn CT3 group vs. Burn group, 2.602 (0,3.633) vs. 0 (0,0) Log10 CFU/g, U = 8; Burn CT9 group vs. Burn group, 1 (0,4.326) vs. 0 (0,0) Log10 CFU/g, U = 16; Sepsis IT3 group vs. Sepsis group, 2.477 (0,2.903) vs. 0 (0,0) Log10 CFU/g, U = 4.5; Sepsis IT9 group vs. Sepsis group, 2 (0,3.146) vs. 0 (0,0) Log10 CFU/g, U = 9; Sepsis CT3 group vs. Sepsis group, 1.151 (0,2.477) vs. 0 (0,0) Log10 CFU/g, U = 18; Sepsis CT9 group vs. Sepsis group, 2 (0,3) vs. 0 (0,0) Log10 CFU/g, U = 13.5; all P < 0.05].@*CONCLUSIONS@#Broad-spectrum antibiotics promote BT in burned rats but prevent BT in septic rats, especially preventing BT to distant organs, such as the liver and lung. Moreover, Enterococci spp. with high drug resistance and high pathogenicity translocated most after antibiotic treatment.

Mouse Nerve Growth Factor Facilitates the Growth of Interspinal Schwannoma Cells by Activating NGF Receptors

OBJECTIVE: Nerve growth factor (NGF) is a member of the neurotrophic factor family and plays a vital role in the physiological processes of organisms, especially in the nervous system. Many recent studies have reported that NGF is also involved in the regulation of tumourigenesis by either promoting or suppressing tumor growth, which depends on the location and type of tumor. However, little is known regarding the effect of NGF on interspinal schwannoma (IS). In the present study, we aimed to explored whether mouse nerve growth factor (mNGF), which is widely used in the clinic, can influence the growth of interspinal schwannoma cells (ISCs) isolated from IS in vitro. METHODS: ISCs were isolated, cultured and identified by S-100 with immunofluorescence analysis. S-100-positive cells were divided into five groups, and separately cultured with various concentrations of mNGF (0 [phosphate buffered saline, PBS], 40, 80, 160, and 320 ng/mL) for 24 hours. Western blot and quantantive real time polymerase chain reaction (PCR) were applied to detect tyrosine kinase A (TrkA) receptor and p75 neurotrophin receptor (p75(NTR)) in each group. Crystal violet staining was selected to assess the effect of mNGF (160 ng/mL) on ISCs growth. RESULTS: ISCs growth was enhanced by mNGF in a dose-dependent manner. The result of crystal violet staining revealed that it was significantly strengthened the cells growth kinetics when cultured with 160 ng/mL mNGF compared to PBS group. Western blot and quantantive real time PCR discovered that TrkA receptor and mRNA expression were both up-regualated under the condition of mNGF, expecially in 160 ng/mL, while the exoression of p75(NTR) demonstrated no difference among groups. CONCLUSION: From these data, we conclude that exogenous mNGF can facilitate ISC growth by activating both TrkA receptor and p75(NTR). In addition, patients who are suffering from IS should not be administered mNGF in the clinic.

Clinical manifestations of erythrocyte membrane protein coding gene mutations in hereditary spherocytosis / 中华血液学杂志

Objective: To investigate the relationship between the erythrocyte membrane protein gene mutations and the clinical severity of hereditary spherocytosis (HS). Methods: Targeted sequencings were performed on 25 HS patients, correlation between HS mutations and patients' clinical characteristics were evaluated. Results: A total of 25 HS patients were enrolled, including 13 males and 12 females with median age of 20 (4-55) years, including 9 compensatory hemolysis patients, 9 patients with mild anemia, 3 patients with moderate anemia and 4 patients with severe anemia. Of them, 18 patients (72%) harbored HS-related mutations, including ANK1 mutation in 6 cases, SLC4A1 mutation in 6 cases, SPTB mutation in 5 cases and 1 case with EPB41 mutation. Seven patients (28%) didn't carry common HS mutations. SPTB and SLC4A1 mutations mainly affected male patients. There was no significant difference between the age of diagnosis (P=0.130) and HGB level (P=0.585) in patients with HS mutation and those without mutation, however, the EMA binding fluorescence intensity (P=0.015), AGLT50 (P=0.032) and EOF minimal hemolytic concentration (P=0.027) were significantly different in these two groups of HS patients. Conclusion: To screen erythrocyte membrane protein coding gene mutations could favor the diagnosis of HS, and patients without mutations have mild clinical phenotype.

Curative Effect of YU Yun Pulse-feeling-based Acupuncture Therapy for Treatment of Middle-late Liver Cancer / 广州中医药大学学报

Objective To investigate the curative effect of YU Yun pulse-feeling-based acupuncture therapy for the treatment of middle-late liver cancer. Methods A total of 60 middle-late liver cancer patients were divided into control group and treatment group by stratified randomization method,30 cases in each group. The control group was given integrated Chinese and western medicine therapy according to the clinical pathway, including anti-cancer treatment such as vascular interrention,molecular targeted therapy,chemotherapy,radio therapy, and focal ablation therapy,as well as chinese medicine treatment based on disease differentiation and syndrome differentiation. And the treatment group was given YU Yun pulse-feeling-based acupuncture therapy on the basis of treatment for the control group. The two groups received 12-week treatment, and then their curative effects were compared. Results The treatment group had better effect on increasing the survival rate, prolonging survival time, improving the scores of clinical symptoms, stabilizing tumor size, and increasing the scores of Karnofsky Performance Status (KPS)than the control group,the difference being significant (P < 0.05 or P <0.01). Conclusion YU Yun pulse-feeling-based acupuncture therapy exerts certain curative effect for the treatment of middle-late liver cancer.

A Metabonomics Study of Cervical Cancer by Ultra Performance Liquid Chromatography Coupled with Quadrupole Orbitrap Tandem Mass Spectrometry / 分析化学

This work aims to analyZe and compare the potential biomarkers between cervical cancer ( CC ) patients and healthy controls (HC).The urine samples of 11 CC patients (age (45.65 ± 5.6) years) and 11 HC patients (age (45.9 ± 3.2) years) were collected.The metabolites of urine samples from CC and HC were analyZed by using ultra performance liquid chromatography coupled with quadrupole orbitrap tandem mass spectrometry ( UHPLC-Q-Orbitrap MS/MS ) , which could provide evidence for early diagnose and disease pathway.The LC-MS data of urines were analyZed by principal components analysis ( PCA) and orthogonal partial least squares discriminant analysis ( OPLS-DA) to identify the potential biomarkers.Urine samples of CC patients were successfully discirminated from those of healthy controls.A total of twelve significant metabolites were found and identified as potential biomarkers according to the established UHPLC-Q-Orbitrap MS and MS/MS method.Identification of biomarkers between CC and HC patients may play an important role in the study of mechanism of UC and its pathway.