Trend analysis of hemagglutinin and ovalbumin content for influenza virus split vaccines in 2021 / 中国生物制品学杂志

@#Objective To analyze the trend of the hemagglutinin(HA) and ovalbumin contents in the lot release of influenza virus split vaccines in 2021,and evaluate the quality and quality control level of the vaccines.Methods The HA and ovalbumin content data of influenza virus split vaccines from two domestic enterprises in 2021 were collected and collated. The mean value and standard deviation were calculated according to the first 40 batches of data of the enterprise in the year,and the warning limit and action limit were established. The trend analysis of the above indexes was carried out to evaluate the stability and consistency of the product quality of the enterprise. Statistical data comparison and consistency analysis were made between the test results of the batch inspected by the lot release institution and the results of the enterprise.Results Through the retrospective data analysis of quadrivalent influenza virus split vaccines from two vaccine enterprises A and B,it was found that the content of H1N1 subtype HA and ovalbumin in the two enterprises and the content of Bv HA in the B enterprise had out of trend(OOT)situations,while the trend of other items was stable. The results of paired student's t test or Wilcoxon signed-rank test of the samples inspected by the lot release institution showed that except Bv subtype HA(t = 1. 094 and 0. 742 respectively)and ovalbumin(w =-64 and 36 respectively)contents showed no statistically significant difference(P > 0. 05),the HA contents of H1N1(t = 3. 862,w = 232),H3N2(t = 8. 225 and3. 473 respectively)and By(t = 5. 616 and 4. 934 respectively)of the two enterprises had significant differences(P <0. 05). The results of enterprises were generally higher than the lot release institution. Bland-Altman test analysis found that the consistency between the test data of enterprise A's HA content and the data of the lot release institution was better than that of enterprise B.Conclusion The stability and consistency of data trends of active ingredients and main impurity ingredients of quadrivalent influenza virus split vaccine batches in 2021 were generally good. The trend analysis can identify potential problems in vaccine production,and enterprises should carefully implement trend analysis and effectively monitor the product quality of vaccines.

The role and clinical significance of microRNA-29a-3p in the development of hypopharyngeal carcinoma

Abstract Objective MicroRNA-29a-3p has been reported in a variety of cancers, but its role in hypopharyngeal cancer remains unclear. This study was to determine the role of microRNA-29a-3p in the occurrence and development of hypopharyngeal cancer. Methods 40 patients with hypopharyngeal cancer who underwent surgery in the Affiliated Hospital of Jining Medical University from April 2013 to November 2017 were selected for this study. The cancer tissue samples of the patients were collected, and the patients were followed up for three years. The expression of microRNA-29a-3p in tissue samples was detected by in situ hybridization with fluorescent probe, and the relationships among microRNA-29a-3p and clinicopathological factors, postoperative recurrent-metastasis, survival time were studied. Immunohistochemical was used to detect the expression of Ki67 and E-cadherin in tissue samples. Results Combined with HE staining results showed that microRNA-29a-3p expression was relatively high in non-cancer tissue cells (red blood cells and fibroblasts in tumor interstitial vessels), but was relatively low in cancer tissue and cells. According to the follow-up data of 40 patients with hypopharyngeal cancer, tumor size, T-stage, tumor differentiation, postoperative recurrent-metastasis of hypopharyngeal cancer patients were significantly negatively correlated with microRNA-29a-3p (p< 0.05). Immunohistochemica results further confirmed that microRNA-29a-3p was negatively correlated with the expression of Ki67 and E-cadherin. The survival time of patients positively related with microRNA-29a-3p expression (p< 0.05). Moreover, ROC curve analysis showed that the area under the curve of the combined detection of miRNA-29a-3p+Ki67+E-cadherin was larger than that of the single detection of the three indexes. Conclusions The expression of microRNA-29a-3p is closely related to the occurrence, development and prognosis of hypopharyngeal cancer, and it affects the proliferation and invasion. This indicates that microRNA-29a-3p serves as a therapeutic target for the occurrence and development of hypopharyngeal cancer. The evidence of study designs of this study is IV using "Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence".

Prediction of the Impact of CYP2C19 Polymorphism on Drug-Drug Interaction between Voriconazole and Tacrolimus Using Physiologically-Based Pharmacokinetic Modelling

Abstract Voriconazole increases tacrolimus blood concentration significantly when coadministrated. The recommendation of reducing tacrolimus to 1/3 in voriconazole package insert seems not to be satisfactory in clinical practice. In vitro studies demonstrated that the magnitude of inhibition depends on the concentration of voriconazole, while voriconazole exposure is determined by the genotype status of CYP2C19. CYP2C19 gene polymorphism challenges the management of drug-drug interactions(DDIs) between voriconazole and tacrolimus. This work aimed to predict the impact of CYP2C19 polymorphism on the DDIs by using physiologically based pharmacokinetics (PBPK) models. The precision of the developed voriconazole and tacrolimus models was reasonable by evaluating the pharmacokinetic parameters fold error, such as AUC0-24, Cmax and tmax. Voriconazole increased tacrolimus concentration immediately in all population. The simulated duration of DDIs disappearance after voriconazole withdrawal were 146h, 90h and 66h in poor metabolizers (PMs), intermediate metabolizers (IMs) and extensive metabolizers(EMs), respectively. The developed and optimized PBPK models in this study can be applied to assit the dose adjustment for tacrolimus with and without voriconazole.

Cerebrolysin alleviates early brain injury after traumatic brain injury by inhibiting neuroinflammation and apoptosis via TLR signaling pathway

Purpose: Traumatic brain injury (TBI) is a major cause of death and disability. Cerebrolysin (CBL) has been reported to be anti-inflammatory by reducing reactive oxygen species (ROS) production. However, the neuroprotection of CBL in TBI and the potential mechanism are unclear. We aimed to investigate the neuroprotection and mechanisms of CBL in TBI. Methods: The TBI model was established in strict accordance with the Feeney weight-drop model of focal injury. The neurological score, brain water content, neuroinflammatory cytokine levels, and neuronal damage were evaluated. The involvement of the early brain injury modulatory pathway was also investigated. Results: Following TBI, the results showed that CBL administration increased neurological scores and decreased brain edema by alleviating blood­brain barrier (BBB) permeability, upregulating tight junction protein (ZO­1) levels, and decreasing the levels of the inflammatory cytokines tumor necrosis factor­α (TNF­α), interleukin­1ß (IL­1ß), IL­6, and NF­κB. The TUNEL assay showed that CBL decreased hippocampal neuronal apoptosis after TBI and decreased the protein expression levels of caspase­3 and Bax, increasing the levels of Bcl­2. The levels of Toll­like receptor 2 (TLR2) and TLR4 were significantly decreased after CBL treatment. In TBI patients, CBL can also decrease TNF­α, IL­1ß, IL­6, and NF­κB levels. This result indicates that CBL­mediated inhibition of neuroinflammation and apoptosis ameliorated neuronal death after TBI. The neuroprotective capacity of CBL is partly dependent on the TLR signaling pathway. Conclusions: Taken together, the results of this study indicate that CBL can improve neurological outcomes and reduce neuronal death against neuroinflammation and apoptosis via the TLR signaling pathway in mice.

Association between childhood abuse experiences and health risk behaviors among college students / 中国学校卫生

Objective@#To understand the association between childhood abuse experience and health risk behaviors among college students, providing references for childhood abuse and health risk behavior prevention.@*Methods@#During Mar. to Apr. of 2016, 918 college students from 2 universities in Nanchong city were selected through cluster sampling, the survey included general demographic characteristics, childhood abuse experiences and health risk behaviors. Chi square test was used for univariate analysis, and Logistic regression was used for multivariate analysis.@*Results@#A total of 720(78.43%) of participants reported at least one type of health risk behaviors, overeating was the most common type[595(64.81%)]. The number of adolescent reporting smoking, drinking 5 or more beers at a time, fighting and suicidal ideation was 146(15.90%), 271(29.52%), 224(24.40%), 205( 22.33 %), respectively. Multivariate Logistic regression analysis showed that a significant positive association between experiencing at least one kind of childhood abuse and the behaviors of fighting, suicidal ideation, and overeating; between childhood emotional neglect with smoking and suicidal ideation; between childhood emotional abuse with fighting, suicidal ideation, and overeating; and between childhood sexual abuse with smoking( P <0.05).@*Conclusion@#Health risk behavior in college students is popular. Childhood abuse can increase the risk of health risk behaviors of college students.

Advances in studies on steroidal alkaloids and their pharmacological activities in genus Veratrum / 中国中药杂志

Genus Veratrum plants contain a diversity of steroidal alkaloids, so far at least 184 steroidal alkaloids attributed to cevanine type(A-1～A-69), veratramine type(B-1～B-21), jervanine type(C-1～C-31), solanidine type(D-1～D-10) and verazine type(E-1～E-53), respectively, have been isolated and identified in the genus Veratrum. Their pharmacological activities mainly focused on decreasing blood pressure, anti-platelet aggregation and anti-thrombosis, anti-inflammatory and analgesic, and antitumor effect. This paper classified and summarized the 184 kind of steroidal alkaloids from the Veratrum plants and their major pharmalogical activities in order to provide the scientific basis for the further development and utilization of active alkaloids.

Effects of TGF-β1 on the migration of oral cancer-associated fibroblasts in two and three dimensional co-culture models / 口腔疾病防治

Objective@#To observe the effect of transforming growth factor-β1 (TGF-β1) on the migration of oral carcinoma associated fibroblasts (CAFs) with two-dimensional culture model and three-dimensional model.@*Methods @# Under two-dimensional culture conditions, CAFs stimulated by TGF-β1 with the addition of 10 ng/mL medium were used as the experimental group, and untreated CAFs were used as the control group. The migration of CAFs with the stimulation of TGF-β1 was measured by cell scratch assay and transwell assay. CAFs positive for green fluorescent protein (GFP) were cultured by retrovirus transfection. Human tongue squamous cell carcinoma cells SCC25, GFP(+) CAFs and CAFs with three-dimensional cell co-culture models were established. The three-dimensional model cultured under the stimulation of TGF-β1 with 10 ng/mL medium was used as the experimental group, and the three-dimensional model without TGF-β1 was used as the control group. The migration of CAFs with the stimulation of TGF-β1 was also measured by the three-dimensional models.@*Results@# It was verified that 10 ng/mL TGF-β1 promoted the migration of CAFs in the two-dimensional culture model. The three-dimensional co-culture models of SCC25, GFP(+) CAFs and CAFs were successfully established. The migration of SCC25 and CAFs was detected in the three-dimensional model. However, 10 ng/mL TGF-β1 had little effect on their migration.@*Conclusion@#The effect of TGF-β1 in vitro on the migration of oral CAFs was associated with different culture models in two and three dimensions.

Detection of MSX1 gene mutations in patients with congenital tooth loss in Van der Woude syndrome / 口腔疾病防治

Objective@#To explore the relationship between MSX1 gene detection and tooth loss in a Van der Woude syndrome (VWS) family @* Methods @# DNA was extracted from the venous blood of 2 patients with dental hy⁃podontia in the 9th family of Van der Woude syndrome (VWS) families and 62 controls with complete dentition. Primers were designed for the MSXl gene. The coding regions of exons 1 and 2 of the MSX1 gene were amplified by PCR. The purified products of exons 1 and 2 of the MSX1 gene were sequenced and analyzed by sequence alignment @*Results@#The ivs2+68 C>T polymorphism in the MSX1 gene was found in the VWS9 members with tooth loss, and the VWS pa⁃tients with IRF6 gene mutations had increased tooth loss@* Conclusion@#Congenital tooth loss in the patients with con⁃genital missing teeth in VWS family 9 may be related to the ivs2 + 68 C> T polymorphism of the MSX1 gene.

Effect of construction orientation on the microstructure and properties of SLM Ti alloy clasps / 口腔疾病防治

Objective@#To investigate the physical properties of Ti-6Al-4V clasps generated by selective laser melting (SLM) with different construction directions and to compare these clasps with cast clasps, which could provide a basis for fabricating SLM clasps with high precision and excellent mechanical properties. @*Methods@# Ti-6Al-4V clasps were fabricated by SLM at 0 degrees (SLM0 group), 45 degrees (SLM45 group) and 90 degrees (SLM90 group) (n = 12). Twelve clasps were cast by the casting method as the control group. Meanwhile, four metal abutments were cast randomly as the abutments of the four groups. X-ray was used to detect cracks in the clasps of each group. The roughness of the clasps was measured by confocal microscopy, the fitness tests between clasps and abutment were processed by stereomicroscopy, and the microstructure of clasps in each group was observed under a metallographic microscope to evaluate the physical properties.@*Results @# There were 0-8 visible cracks in the casting group but no obvious defects in the SLM groups. The maximum surface roughness was observed in the cast group (18.102 ± 3.762) μm, while the minimum roughness was observed in the SLM90 group (5.942 ± 1.486) μm (P < 0.05). There was no statistically significant difference in surface roughness between the SLM0 group [(8.711 ± 2.378) μm] and the SLM45 group [(8.513 ± 1.161) μm]. Fitness was worst in the casting group [(68.445 ± 14.876) μm] and best in the SLM90 group [(33.417 ± 5.880) μm] (P < 0.05). There was no statistically significant difference in fitness between the SLM0 group [(52.917 ± 12.102) μm] and the SLM45 group [(50.889 ± 7.011) μm]. In addition, the growth direction of the β grains was roughly parallel to the build direction, and acicular α grains were present between β grains. SLM was composed of fine grains, while the cast group had large grains.@* Conclusions@# Specimens generated by SLM had finer grains than cast specimens. In addition, SLM90 clasps had the highest fitness and the lowest surface roughness.

FEN1 expression in oral carcinoma-associated fibroblasts and its relationship with PCNA / 口腔疾病防治

Objective@#To research the expression levels of FEN1 and PCNA in carcinoma-associated fibroblasts (CAFs) and analyze their correlation. @*Methods@#Fresh specimens of oral squamous cell carcinoma tissues and normal oral mucosal tissues excised during oral and maxillofacial plastic surgery were collected. Primary oral CAFs and normal fibroblasts (NFs) were obtained by tissue culture, identified by immunocytochemistry and divided into the CAF and NF groups. Western blot and quantitative real-time PCR were used to detect the protein and mRNA expression levels of both FEN1 and PCNA in the oral CAFs and NFs. The correlation between FEN1 and PCNA expression in oral CAFs was analyzed. @*Results@#Oral CAFs and oral NFs were successfully cultured and identified from 12 samples. Both the protein and mRNA expression levels of FEN1 and PCNA were higher in the oral CAFs than NFs, but there were no significant differences (P > 0.05). In the oral CAFs, the linear correlation coefficient between FEN1 and PCNA was 0.677 (P = 0.016) at the mRNA level, indicating a strong positive correlation; however, at the protein level, no correlation was found (P > 0.05). @*Conclusion@# In primary cultured oral CAFs and NFs, there were no significant differences in the FEN1 and PCNA protein and mRNA expression levels. However, in the CAFs, the mRNA levels of FEN1 and PCNA had a strong positive correlation. The relationship and the regulatory mechanism of the two genes require further study.

Clinical effect of prosthesis on type Ⅴ maxillary defects / 口腔疾病防治

Objective @#To investigate the clinical efficacy of prosthesis retained by metal clasp and flexible clasp in the repair of type Ⅴ maxillary defects after tumor resection. @*Methods@#23 maxillary tumor surgical patients were selected in this study and restored with maxillofacial prosthesis. Total 24 prosthesis combined with metal clasp and flexible dentures were followed up for half a year to 2 years. @*Results @#After the application of prosthesis, better maxillofacial appearances are presented in all of the patients, Watian drinking water tests are improved to grade Ⅰ or Ⅱ from grade Ⅳ or Ⅴ in 21 patients, there was significant difference (P < 0.05); Soft diet can be masticated on affected side in 15 patients; The mean speech intelligibility score with and without prosthesis were (83.2 ± 7.3)% and (36.6 ± 5.6)%, there was significant difference (P < 0.05); Favorable hygienic situations of oral cavity and prosthesis are maintained in 18 patients.@*Conclusion @#Prosthesis combined with metal clasp and flexible denture performed favorable clinical efficacy and contributed to improve the living quality and mental health after tumor resection.

Response surface methodology based optimization for degradation of align in Laminaria japónica feedstuff via fermentation by Bacillus in Apostichopus japónicas farming

Background: The alga Laminaria japonica is the most economically important brown seaweed cultured in China, which is used as food and aquatic animal feedstuff. However, the use of L. japonica as a feedstuff in Apostichopus japonicasfarming is not ideal because A. japonicas does not produce enough enzyme activity for degrading the large amount of algin present in L. japonica. In this study, semi solid fermentation of the L. japonica feedstuff employing a Bacillus strain as the microbe was used to as a mean to degrade the algin content in L. japonica feedstuff. Results: The Bacillus strain, Bacillus amyloliquefaciens WB1, was isolated by virtue of its ability to utilize sodium alginate as the sole carbon source. Eight factors affecting growth and algin-degrading capacity of WB1 were investigated. The results of Plackett-Burman design indicated that fermentation time, beef extract, and solvent to solid ratio were the significant parameters. Furthermore, the mutual interaction between the solvent to solid ratio and beef extract concentration was more significant than the other pairs of parameters on algin degradation. Optimal values obtained from Central-Composite Design were 113.94 h for fermentation time, 0.3% (w/v) beef extract and 44.87 (v/w) ratio of solvent to feedstuff. Under optimal conditions, 56.88% of the algin was degraded when a 50-fold scale-up fermentation was carried out, using a 5-L fermenter. Conclusions: This study provides an alternative and economical way to reduce the algin content in L. japonicathrough degradation by WB1, making it a promising potential source of feed for cultured L japonica.

Bioactivity of neolignans from fructus Schizandrae

Fructus Schisandrae sinensis Baill, a traditional Chinese medicine, used as tonic and sedative, has been shown at the beginning of 70's to lower the elevated serum glutamic-pyruvic transaminase (SGPT) levels of patients suffering from chronic viral hepatitis. Durign past 20 years, a series of neolignans have been isolated and identified as effective principles. Pharmacological studies revealed that they increased liver protein and glicogen synthesis, antagonized liver injuries from CCl4 and thioacetamide. The mechanism of SGPT lowering was considered as a hepato-protective and membrane stabilize action, although inhibition of the activity of liver GPT may also be existed. It was found that some principles of Schisandrae have an inducing effect on hepatic microsomal drug-metabolizing enzynme system P-450, thus explained their anti-toxic, anti-carcinogenic and anti-mutagenic effects. A synthetic derivative compound of Schisandrin called DDB has most of the above mentioned actions now used widely in Chine as a hepato-protective drug with high effectiveness in normalizing liver functions and very low side effects. From Schisandrin to synthesized DDB, pointed out a successful way in the development of new drugs from natural products.

Immunomodulating Chinese herbal medicines

Traditional Chinese medicine always pays close attention to the strengthening of the patient"s general resitence against illness, ther are many Chinese herbs used for thousands of years are considered as tonics. Animal experiments and modern clinica; trails have shown that quite a number herbs are immunologically active, and most of the tonics are excellent immunomodulating agents, such as polysaccharides or saponins isolated from Astragalus mongholicus, Acanthopanax senticosus and Panax notoginseng, which stimulated mactophages, promoted antibody formation, actived complement and increased T lymphocyte proliferation. Moreover, some of them were proved to be anti-irradiative and protected animals from liver intoxications. On the other hand, some anti-inflammative or anti-pyretic hervs such as Tripterygium wilfordii, Aconitum and Artemiasiae species were proved to have immunosuppressive principles, some of them were now used clinically for the treatment of rheumatoid arthritis, chronic nephritis, systemic lupus erythematosis and various skin disorders. Pharmacological studies revealed that they have depressant effect on most of the humoral-immunity but not on the cell-mediated immunity. Some of them stimulated adrenal cortex functions and prolonged the survival time of transplanted allograft tissues.