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The cisplatin-based concurrent chemoradiotherapy (CCRT) has been accepted as a standard treatment for most locally advanced cervical cancer. Compared with radiation therapy alone, CCRT can increase tumor control and survival rates, whereas it also can increase the incidence of acute hematological toxicity, which results in the treatment interruption or delay, and may even affect clinical efficacy and prognosis of patients. Therefore, how to reduce the incidence and severity of acute hematological toxicity induced by CCRT is a hot spot of clinical research. Previous studies have demonstrated that the occurrence of hematological toxicity is associated with the volume and dose of irradiated pelvic bone marrow. With the development of modern radiotherapy technology, precise radiotherapy technologies, such as intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT), not only guaranteed the enough dose for tumor, but also realized the protection of normal tissues. This article will focus on the feasibility of bone marrow sparing during CCRT for cervical cancer, and summarize the research progress in recent years.
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Aim To establish subcutaneous and orthotopic transplantation models of human lung cancer in nude mice, and compare the anti-cancer effects of digoxin between the two models. Methods After subcutaneous inoculation of H460 tissues in nude mice, the tumor volume was measured; HE staining and immunohistochemistry were performed; H460-Luc cell suspension was injected into the lung of nude mice toestablish orthotopic tumor model, the in vivo imaging and fluorescence values were recorded, and the tumor lesions in other organs were observed after dissection. Results Compared with control group, the gemcitabine group had a significant anti-tumor effect (P 0.05). HE staining showed that the cell density in each treatment group decreased, and necrosis and/or fibrous hyperplasia were obvious. Immunohistochemistry indicated that the protein expression of p-p38, p-ERK and Nur77 in each treatment group significantly increased in the subcutaneous transplantation model; in the orthotopic transplantation model, the gemcitabine, the middle (P < 0.05) and low dose of digoxin group could inhibit the tumor growth, while the high dose of digoxin group accelerated the development of tumor (P < 0.05). Conclusion Digoxin is more sensitive to orthotopic transplanted tumor than subcutaneous transplanted tumor, anddigoxin may inhibit the tumor growth by up-regulating the expression of p-p38, pERK and Nur77.
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Objective: To investigate the prevalence, harm and risk factors of hyperuricemia (HUA) among middle-aged and elderly residents in Tianning District of Changzhou City, Jiangsu Province. Methods: From January to May 2018, a total of 6110 residents aged over fifty years were randomly selected from two communities in Tianning District of Changzhou City, Jiangsu Province, and then arranged to take part in a questionnaire and physical examination. Their fasting venous blood were extracted for detection of serum uric acid, creatinine, urea nitrogen, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG). The prevalence of HUA in all the subjects and the clinical features of HUA patients were investigated, the factors affecting HUA were analyzed with monofactorial independent-samples t test and multivariate logistic regression analysis, and the relationship of bad habits and comorbidities to HUA was analyzed with monofactorial independent-samples t test. Results: Rejecting the subjects with incomplete data, 5848 subjects were involved in present investigation, among them 993 were HUA patients (17.0%). Compared with those with normal uric acid, the proportion of males [50.5%(501/993) vs. 45.4%(2206/4855), P=0.004] was higher, the average age [(67.9 ±9.4) vs. (66.6 ± 8.7), P<0.0001] was elder, smoking [26.1%(259/993) vs. 22.7%(1104/4855), P=0.023), alcohol drinking [24.4%(242/993) vs. 18.4%(891/4855), P<0.0001], and with hypertension [65.3%(648/993) vs. 53.3%(2587/4855), P<0.0001] and proteinuria [11.1%(110/993) vs. 7.4%(358/4855), P<0.0001] were higher in HUA residents. The LDL-C [(2.89 ± 0.80) vs. (2.95 ± 0.76) mmol/L, P=0.041), HDL-C [(1.09 ± 0.26) mmol/L vs. (1.18 ± 0.28) mmol/L, P<0.0001], and GFR [(68.4 ± 18.7) ml/(min·1.73 m2) vs. (76.3 ± 17.4) ml/(min·1.73 m2), P<0.0001] were significantly lower, while the BMI [(26.3 ± 3.3) kg/m2 vs. (25.2 ± 3.4) kg/m2, P<0.0001] and TG [(2.06 ± 1.65) mmol/L vs. (1.57 ± 1.11) mmol/L, P<0.0001] were significantly higher in residents with HUA than those with normal uric acid. The serum uric acid levels increased gradually with age increasing in 50-60 years, 60-70 years, 70-80 years and ≧80 years elder groups [(296.4 ± 97.0), (300.4 ±91.1), (304.8 ±93.5) and (334.3 ± 110.2) μmol/L, respectively], and the same was in the prevalence of HUA (15.0%, 15.8%, 17.7% and 26.2%, respectively) with statistically significance (P<0.0001). The results of univariate analysis showed that age, male, smoking, alcohol drinking, hypertension, BMI, TG, proteinuria and renal dysfunction were positively correlated with the increase of serum uric acid, while HDL-C were negatively correlated with serum uric acid. The relationship of some comorbidities (overweight, hypertension, diabetes, dyslipidemia and renal dysfunction) and of some bad habits (smoking and alcohol drinking) to HUA was further analyzed, the total number of comorbidities and bad habits was seven. Of the 5848 residents, 415(7.1%), 1215(20.8%), 1775(30.4%), 1507(25.8%), 717(12.3%), 192(3.3%) and 27(0.5%) with zero, one, two, three, four, five and six number comorbidities and bad habits, respectively. With the increase of the number of co-morbidity and bad habits, the levels of serum uric acid increased [(256.6 ± 69.5), (278.8 ± 81.2), (295.9 ± 87.0), (319.3 ± 103.0), (337.8 ± 99.9), (361.0 ± 100.4) and (390.0 ± 106.2) μmol/L, respectively], and the prevalence of HUA (4.6%, 10.3%, 15.7%, 22.2%, 24.6%, 26.0% and 37.0%, respectively) increased too, both with statistically significance (P<0.0001). The effects of renal dysfunction on HUA were further analyzed, the results showed that the incidence of HUA was higher in patients with renal dysfunction than those with normal renal function, no matter whatever combination of risk factors, except for seven residents with renal dysfunction and alcohol drinking, and combined with dyslipidemia and hypertension. The results of multivariate logistic regression analysis showed that age, alcohol drinking, hypertension, overweight, increased TG, and renal dysfunction were the independent risk factors of HUA, while high HDL-C was the protective factor of HUA. Conclusions The prevalence of HUA is 17.0% in the urban residents aged over fifty years in Tanning District of Changzhou City, Jiangsu Province in 2018. Advanced age, alcohol drinking, hypertension, overweight, high serum TG, proteinuria and renal dysfunction are the risk factors for HUA, while high HDL-C is the protective factor of HUA. The serum uric acid and the prevalence of HUA increased significantly as the number of co-morbidity and bad habits increased. Renal dysfunction is important risk factor of HUA.
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This study aimed to establish characteristic chromatogram and content determination method for Chan Taoren formula granules,evaluate the production processes of Chan Taoren formula granules based on the correlation of characteristic chromatogram and the transfer rate of D-amygdalin,and clarify the key control points. The optimized analytical method was carried out on a Waters CORTECS C18 column(4. 6 mm×150 mm,2. 7 μm) with acetonitrile-0. 1% phosphoric acid aqueous solution as the mobile phase at a flow rate of 0. 6 m L·min-1. The detection wavelength was 207 nm,and the column temperature was 20 ℃ ． As compared with the standard decoction of Chan Taoren,there were five characteristic peaks in the decoction pieces,extracts,concentrates,spray-dried powders and formula granules,basically consistent in relative retention time and peak pattern; in addition,the transfer rate of D-amygdalin from Chan Taoren pieces to the formula granules was within the transfer rate range of standard decoction. The average transfer rate of D-amygdalin was 56.65%,72.85%,94.58% and 99.29% respectively in the extraction,concentration,spray drying and granulation processes. Therefore,the factors affecting D-amygdalin in the extraction process were further studied. The results showed that D-amygdalin was easily converted to L-amygdalin in the water extraction process,leading to a low transfer rate of D-amygdalin in this process.D-amygdalin was unstable under alkaline conditions and prone to isomerization. Both liquid to solid ratio and extraction time had significant effects on the extraction rate of D-amygdalin. In this study,the key links in the production process of Chan Taoren formula granules was clarified based on the characteristic chromatogram and the quantity transmission of D-amygdalin,which provided a theoretical basis for production and quality control.
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Amygdalin , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal , Quality Control , WaterABSTRACT
The fingerprint technology could reflect the internal chemical characteristics of Chinese herbal medicine or preparation, which has the characteristics of "wholeness" and "fuzziness". It is suitable for evaluating the quality of intermediate and finished products in the production process of traditional Chinese medicine formula granules. In this paper, the applications of high performance liquid chromatography (HPLC), thin layer chromatography (TLC), gas chromatography (GC) and infrared spectrum (IR) fingerprint technology in the quality control of traditional Chinese medicine formula granules were reviewed, and their advantages and disadvantages were analyzed. The aim of this article is to enhance the combined application of various fingerprint technologies in traditional Chinese medicine formula granules. It could provide technical reference for realizing the stability of production process and improving the overall quality of formula granules.
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Chromatography, High Pressure Liquid , Chromatography, Thin Layer , Drugs, Chinese Herbal , Reference Standards , Medicine, Chinese Traditional , Quality ControlABSTRACT
OBJECTIVE Alcohol is mainly metabolized through liver and excreted by kidney in the body. Kidney damage has been considered as the secondary to liver injury and kidney dysfunction is common in hospitalized patients with severe alcoholic hepatitis. Both acute and chronic alcoholism accumulation can compromise kidney function, although alcoholic kidney disease has drawn much more attention recently,the methodology for establishing the in vivo and in vitro alcoholic renal fibrosis models are still lacking,and the underlying mechanisms are to be determined. METHODS and RESULTS Mice were feed with a liquid diet containing alcohol for 4 weeks, 8 weeks and 12 weeks respectively, results of Masson′s Trichrome staining showed that kidney fibrosis peaked in 8-week model group, which consistent with the results of albumin assay,Western blot,immunostaining and real-time PCR of collagen I and α-SMA.In vitro study also confirmed that ethanol upregulated the level of fibrotic index-es,including collagen I and α-SMA,in tubular epithelial cells(HK2 cells).Additionally,both in vivo and in vitro studies showed that Smad7 was decreased and Smad3 was highly activated. Then we further detected the underlying mechanisms by which alcohol induced the imbalance of Smad7 and Smad3. Results of Genome-wide methylation sequencing found DNA methylation of Smad7 in the alcoholic fibrosis kidney,which may be mainly mediated by DNA methyltransferase 1(DNMT1),because knock-down of DNMT1,but not DNMT2 and 3,largely restored Smad7 level in ethanol-treated HK2 cells.Con-sequently, we found that NADPH Oxidases (nox)-mediated oxidative stress is the major force upregu-lating DNMT1,since knockdown of Nox2 and 4 could both decrease DNMT1 while rebalancing Smad7/Smad3 axis, and thereby relieved ethanol-induced fibrotic response in HK2 cells. More importantly, intraperitoneal injection of apocynin,an inhibitor of NADPH oxidoreductase,attenuated renal fibrosis in alcoholic kidney fibrosis mouse model. CONCLUSION By establishing the novel in vivo and in vitro models,we found that through activating oxidative stress-induced DNA methylation of Smad7,alcohol induces renal fibrosis by breaking the balance between Smad7 and Smad3.Elimination of Nox-mediated oxidative stress may be a potential therapy for treatment of long-term alcohol abuse-induced kidney fibrosis.
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Objective To investigate the expression and variation of MIP 1β,MIP-2,and IL-12p70 in mice with bloodstream infection caused by 4 kinds of bacteria.Methods CD-1 (ICR) mouse models of bloodstream infection with Staphylococcus aureus (S.aureus),Enterococcus f aecalis (E.f aecalis),Escherichia coli (E.coli),and K lebsiella pneumoniae (K.pneumoniae) were established.After mice in each trial group and PBS control group were infected by bacteria for 0.5h,1h,3h,6h,12h,24h,and 48h,concentrations of MIP-1β,MIP-2,and IL-12p70 were detected by Luminex liquid suspension chip system.Results Concentrations of MIP-1β increased significantly 1h after bacteria was in blood,S.aureus,E.faecalis,E.coli,K.pneumoniae,and control groups were (134.5 ± 18.3),(61.5 ± 15.4),(3 354.0 ±809.0),(6 888.4 ± 1 100.2),and (28.9 ± 4.6) pg/mL respectively;the peak values of IL-12p70 were (389.3 ± 118.1),(127.6 ± 10.0),(42.2 ± 3.5),(62.8 ± 8.4),and (4.8 ± 0.3) pg/mL respectively.Concentrations of MIP-1β and MIP-2 in E.coli and K.pneumoniae groups were significantly higher than other trial groups and control group (all P＜0.01),while concentrations of IL-12p70 in S.aureus and E.faecalis groups were both significantly higher than E.coli,K.pneumoniae,and control groups (all P＜0.01).Conclusion Concentrations of MIP-1β and MIP-2 in E.coli and K.pneumoniae groups were both significantly higher than those in S.aureus and E.faecalis groups,while concentrations of IL-12p70 in S.aureus and E.faecalis groups were both significantly higher than those in E.coli and K.pneumoniae groups.The combination detection of multiple cytokines or chemokines are valuable in predicting gram-positive or gram-negative bacterial infection,and can provide basis for treatment of early infection.
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<p><b>OBJECTIVE</b>To explore novel pathogenic mutation in the mitochondrial DNA gene in diabetic pedigree.</p><p><b>METHODS</b>Twenty-eight suspected mitochondrial DNA diabetic families were recruited. The gene fragment was produced by PCR, and mutation was detected by direct sequencing.</p><p><b>RESULTS</b>In one pedigree, the proband and her mother were found carrying the most common nt3243 A --> G mutation and another 16S rRNA 3205C --> T mutation. But only 3205C --> T was found in her affected brother. All the two patients were deaf and developed diabetes in early age, characterized by impaired beta cell function and low body mass index (BMI). The proband had relatively higher lactic acid concentration than normal individuals. A novel ND1 gene 3434 A --> G(TAT --> TGT) mutation was explored in another proband with deafness and her affected family members.</p><p><b>CONCLUSION</b>16SrRNA 3205C --> T mutation was found in a mitochondrial diabetes mellitus pedigree, implying its potential pathogenic role in diabetes. Another novel ND1 3434 A --> G mutation was found in another diabetic pedigree. Because this mutation causes amino acid change (Tyr --> Cys) and is co-segregated with diabetes, it may be diabetogenic.</p>