Adult ; Aged ; Alopecia ; chemically induced ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Bone Neoplasms ; drug therapy ; pathology ; secondary ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; pathology ; secondary ; Cisplatin ; adverse effects ; therapeutic use ; Humans ; Leukopenia ; chemically induced ; Liver Neoplasms ; drug therapy ; pathology ; secondary ; Lung Neoplasms ; drug therapy ; pathology ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Staging ; Organoplatinum Compounds ; administration & dosage ; Paclitaxel ; administration & dosage ; Remission Induction ; Survival Rate ; Taxoids ; adverse effects ; therapeutic use ; Young Adult

Objective To explore the impact of preoperative neoadjuvant chemotherapy on the expressions of multi-drug resistance genes in patients with cervical cancer and its relationship with the effect of chemotherapy. Methods Ninety-eight cervical cancer patients with TP regimen selected to perform preoperative chemotherapy were enrolled in the Affiliated Hospital of Guiyang Medical College between January 2010 and June 2014. Immunohistochemisty (En vision method) was used to determine the expressions of P-gP, GST-π and TopoII of the same patients before and after neoadjuvant chemotherapy and explore the relationship with the effect of chemotherapy. Results The positive expression rates of P-gp and GST-π were 71.43% and 64.29% before chemotherapy and 80.61%and 74.49%after chemotherapy, respectively. The former two had significant differences (P<0.01). The positive expression rates of TopoII was 48.98%before chemotherapy and 28.57%after chemotherapy , respectively, showing significant differences (P < 0.01). The expressions of P-gp, GST-π and TopoⅡ gene were not affected by the clinical and pathological features of cervical cancer (P > 0.05). Before neoadjuvant chemotherapy, the positive expression of GST-π in the ineffective group was statistically higher than that in the effective group (P<0.05). The positive expressions of P-gp and Topo II showed no statistical significance between the effective group and the ineffective group (P > 0.05). There was significant correlation in the expressions of P-gp, GST-π and TopoⅡ(P < 0.05) before and after neoadjuvant chemotherapy. Conclusions The expression of P-gp, GST-πand TopoⅡgene may not be affected by the clinical and pathological features of cervical cancer, but may change expressions of multi-drug resistance genes in cervical cancer by neoadjuvant chemotherapy. Monitoring their expression has a guiding significance for drug selection, prognostic judgment, and the following treatment regimen decision. The GST-π, expression level can be used as a biological parameter to predict the effect of TP regimen neoadjuvant chemotherapy.

Objective To investigate the effects and mechanism of prone ventilation in rats with lipopolysaccharide(LPS)-induced extra pulmonary acute lung injury(ALI). Methods Thirty-two male Sprague-Dawley(SD)rats were randomly divided into four groups:control group,ALI group,supine position group(ALIS group)and prone position group(ALIP group). The ALI animal model was reproduced by intra-peritoneal injection of LPS 6 mg/kg,and 2 mL/kg sterile saline was intra-peritoneally injected in control group. After 24 hours,the ALIS group and ALIP group were mechanically ventilated for 4 hours in supine and prone positions respectively. Arterial partial pressure of oxygen(PaO2),carbon dioxide partial pressure(PaCO2),wet to dry weight ratio of lung(W/D) were observed,and the levels of tumor necrosis factor-α(TNF-α),interleukins(IL-6,IL-10)in bronchoalveolar lavage fluid(BALF)were measured. The degrees of histopathological changes of lung were investigated and assessed under light microscope. Results Compared with control group,PaO2 was significantly lower in ALI,ALIS and ALIP groups〔mmHg(1 mmHg=0.133 kPa):68±7,82±8,93±7 vs. 116±7〕,and the PaCO2 in ALI and ALIS groups was obviously higher(mmHg:53±6,51±5 vs. 43±7,both P<0.05);lung W/D ratio as well as levels of TNF-α, IL-6 and IL-10 in BALF were significantly higher in ALI,ALIS and ALIP groups〔lung W/D ratio:5.11±0.32, 4.71±0.38,4.53±0.45 vs. 4.48±0.15,TNF-α(ng/L):548±82,431±64,347±53 vs. 162±16,IL-6(ng/L):772±119,587±178,490±139 vs. 127±16,IL-10(ng/L):211±43,295±36,352±59 vs. 104±31,all P<0.05〕. Compared with ALI group,PaO2 in ALIS and ALIP groups was significantly higher,and in ALIP group,PaCO2 was lower,lung W/D ratio,TNF-α and IL-6 in BALF were obviously lower,while IL-10 in BALF was obviously higher(all P<0.05). Compared with ALIS group,the changes in ALIP group were more significant(all P<0.05). Compared with ALIS group,under light microscope,it was shown that the hyper-inflated areas were less,normal and collapsed areas were greater on the ventral side,and the collapsed area was less and the normal ventilation area was greater on the dorsal side in ALIP group(all P<0.05). Conclusion In rats with LPS-induced extra pulmonary ALI,the prone ventilation can improve gas exchange,promote uniform distribution of ventilation,decrease pulmonary edema and in the mean time attenuate inflammatory response.

Objective:To explore the relationship between the type of mutation and clinical features, prognosis, and clinical characteristics of chronic granulomatous disease (CGD) caused by compound heterozygous mutations in the NCF2 gene in children. Methods:The clinical data of 1 case of neonatal CGD caused by compound heterozygous mutations of NCF2 gene at Tianjin Children′s Hospital in August 2019 was analyzed, and domestic and international literatures were searched to summarize the clinical characteristics, gene mutation type and prognosis of CGD caused by NCF2 mutation. Results:The diagnosis of CGD was confirmed by the presence of compound heterozygous mutations c. 196_197insA (p.Arg66Glnfs23X) and c. 1180T>G (p.Tyr394Asp) in the NCF2 gene, accompanied with the clinical manifestations of fever, cough, multiple clumps and nodules in the chest CT at 25 days after birth, and the neutrophil respiratory burst test stimulation index(SI) 23.This new mutation was not reported in the Human Genetic Mutation Database.The child had a residual portion of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and was followed up until the age of 9 months with an antifungal drug without recurrent infection.A total of 101 cases of CGD patients with NCF2 gene mutation were reported in domestic and international databases.Totally, 33 cases had SI results, with 22 cases below 3, 11 cases above 3, and 8 cases of missense mutations. Conclusions:c. 196_197insA and c. 1180T>G are new mutations in NCF2 gene that can lead to CGD.CGD patients containing missense mutations in the NCF2 gene may have more residual NADPH oxidase activity.

Objective: To investigate the genotypes and prognosis of infants with definitive diagnosis of inherited metabolic diseases during neonatal screening in Zhejiang Province from 2009 to 2021, so as to provide insights into the management of birth defects. Methods: The medical records of infants with definitive diagnosis of inherited metabolic diseases by tandem mass spectrometry during neonatal screening in Zhejiang Province from 2009 to 2021 were collected from the database created by Zhejiang Provincial Center for Neonatal Disease Screening. The prevalence, genotypes and prognosis of inherited metabolic diseases were analyzed. Results: A total of 1 038 infants were definitively diagnosed with inherited metabolic diseases in Zhejiang Province from 2009 to 2021, with an overall incidence rate of 1/4 535. There were 400 infants with amino acid metabolic disorders (AAD), 342 infants with fatty acid oxidation metabolic disorders and 296 infants with organic acid metabolic disorders (OAD), with incidence of 1/11 767, 1/13 763 and 1\15 902, respectively. There were 32 types of diseases, including 13 types of AAD, 8 types of FAOD and 11 types of OAD identified, and phenylketonuria and tetrahydrobiopterin deficiency (PKU/BH4D), primary carnitine deficiency (PCD) and methylmalonic academia (MMA) were detected as the most common forms of AAD, FAOD and OAD, with incidence of 1/20 827, 1/24 262 and 1\49 030, respectively. A total of 789 infants received genetic testing (76.01%), and genetic testing was performed among 70.00% of infants with AAD, 83.04% of infants with FAOD and 76.01% of infants with OAD. The c.728G >A (p.R243Q) variant was the most common mutation in infants with PKU (29.17%), c.1400C>G (p.S467C) variant was the most common mutation in infants with PCD (33.46%), c.609G>A (p.W203X) variant was the most common mutation in infants with combined MMA (40.00%), and c.1663G>A (p.A555T) variant was the most common mutation in infants with MMA (17.86%). Among the 997 infants (96.05%) with successful follow-up, 973 infants (93.74%) had normal intelligence and physical developments, and 41 infants died (3.95%), including 9 deaths due to AAD, 15 deaths due to FAOD and 17 deaths due to OAD. Conclusions The incidence of PKU, PCD and MMA was high among infants with inherited metabolic diseases in Zhejiang Province from 2009 to 2021, with c.728G>A (p.R243Q), c.1400C>G (p.S467C) and c.609G>A (p.W203X) variants as common gene mutations, respectively. Most infants with inherited metabolic diseases had a favorable prognosis; however, the mortality of OAD was relatively high.

This article introduces an overview of management system for conflict of interest of the European Pharmacopoeia Commission (EPC) and the United States Pharmacopoeia Convention (USP). The EPC and USP have standardized the management system for conflict of interest in drug standard work in multiple management documents, such as the Guide for the Work, Code of Practice for the Work, Form for Declaration of Interests and Confidentiality Undertaking of the EPC, bylaws, Rules and Procedures of the Council of Experts, Code of Ethics, Standards of Conduct of the USP, in order to ensure the transparency and fairness of drug standard development, improve the credibility and rigor of drug standards. This article introduces the management system for conflict of interest of the EPC and USP, providing reference for the improvement of relevant management systems of the Chinese Pharmacopoeia Commission.

Objective To construct the eukaryotic expression vector for the fusion gene comprising the genes encoding mouse anti-human cross-linked fibrin single-chain fragment variable (scFv) antibody and low-molecular weight single-chain urokinase. Methods The single peptide of recombinant human ipro-urokinase was ligated with the target fusion gene, and the same reading frame was guaranteed. The ligated compound was subsequently incorporated respectively into pcDNA3 and pMJK expression vectors by DNA recombination technique. Results and Conclusion The desired recombinant plasmids pcDNA3 and pMJK3 containing the signal peptide of recombinant human ipro-urokinase gene and the fusion gene were constructed,which lays the foundation for establishing of a cell line that may secrete the fusion protein.

Objective To construct the eukaryotic expression vector for the fusion gene comprising the genes encoding mouse anti-human cross-linked fibrin single-chain fragment variable (scFv) antibody and low-molecular weight single-chain urokinase. Methods The single peptide of recombinant human ipro-urokinase was ligated with the target fusion gene, and the same reading frame was guaranteed. The ligated compound was subsequently incorporated respectively into pcDNA3 and pMJK expression vectors by DNA recombination technique. Results and Conclusion The desired recombinant plasmids pcDNA3 and pMJK3 containing the signal peptide of recombinant human ipro-urokinase gene and the fusion gene were constructed,which lays the foundation for establishing of a cell line that may secrete the fusion protein.

Objective To execute physical performance testing of Mobetron 2000 mobile intraoperative radiotherapy system.Methods Mobetron 2000 mobile intraoperative radiotherapy system had its indexes measured according to TG51 protocol such as percent depth dose (PDD),output dose,beam energy,field flatness and symmetry,X-ray pollution,dose linearity and repeatability.Three-dimensional water phantom was used for verification and acceptance when the measurement was executed,while the calimator end was tangent to the water surface and the nominal ource-skin distance was 50 cm.Results All the indexes of the system met the desired requirements except 12 MeV beam energy.Conclusion The system can be promoted clinically for safe,reliable and efficient treatment.

OBJECTIVEThis study aimed to investigate the effect of trichloroethylene (TCE) intake via drinking water on Th17 cells in mice.

METHODSForty eight six weeks old female BALB/c mice were divided into blank control, vehicle control, 2.5 mg/ml TCE and 5.0 mg/ml TCE groups by random number table (12 mice each group), and exposed to TCE by drinking water. On the 14(th), 28(th), 56(th), 84(th) days, blood were collected and assayed for IL-17, IL-6, and TGF-β concentration in serum through ELISA. Animals were killed and spleen biopsies were taken sterility. The proportion of Th17 cells among CD4(+) T cells and RORγt mRNA expression level in spleen were measured by FCM and real-time PCR.

RESULTSIn 2.5 mg/ml TCE and 5.0 mg/ml TCE group mice, Th17 cells/CD4(+) T cells in spleen were (3.46 ± 0.32)% and (5.45 ± 0.45)% on day 14, (3.47 ± 0.33)% and (4.10 ± 0.39)% on day 84, which were significantly higher than those for solvent control group at the same time point ((2.15 ± 0.20)%, (2.16 ± 0.35)%, respectively) (P < 0.01). RORγt mRNA expression levels were (1.870 ± 0.084) and (1.965 ± 0.060) on 14 day, (1.998 ± 0.079) and (2.028 ± 0.073) on day 56, which were also significantly higher than those for solvent control group at the same time point (1.77 ± 0.04 and 1.75 ± 0.09, respectively) (P < 0.05). IL-17 concentrations in serum were (32.28 ± 5.38) and (34.47 ± 5.02) pg/ml on day 14, and (34.87 ± 5.48) and (41.94 ± 6.19) pg/ml on day 28, which were significantly higher than those for solvent control group at the same time point((21.57 ± 5.23), (22.11 ± 5.11) pg/ml). IL-6 concentration in serum were (43.07 ± 6.71) and (47.86 ± 8.52) pg/ml on day14, (41.32 ± 7.04) and (46.74 ± 9.33) pg/ml on day 56, which were significantly higher than solvent control group at the same time point ((7.56 ± 7.71) and (28.26 ± 7.22) pg/ml). TGF-β concentration were (17.48 ± 3.06) and (18.93 ± 3.12) pg/ml on day 14, which did not show significant difference from solvent control group ((15.25 ± 2.95) pg/ml). Correlation analysis showed that IL-6 in serum were significantly positively correlated with the proportion of Th17 cells among CD4(+) T cells and RORγt expression level in spleen (r = 0.741, 0.765, P < 0.01).

CONCLUSIONTCE might promote the differentiation of Th17 cells and increase IL-17 secretion by inducing IL-6 and up-regulating RORγt expression together with TGF-β.

Animals ; Drinking Water ; chemistry ; Female ; Interleukin-17 ; immunology ; Interleukin-6 ; immunology ; Mice ; Mice, Inbred BALB C ; Nuclear Receptor Subfamily 1, Group F, Member 3 ; immunology ; Th17 Cells ; drug effects ; immunology ; Transforming Growth Factor beta ; immunology ; Trichloroethylene ; toxicity