1.Correlation between gross tumor volume and prognosis of patients with esophageal cancer receiving radiotherapy
Zhetao MI ; Qi LI ; Yaqin ZHENG ; Dan GUO
Cancer Research and Clinic 2024;36(10):757-761
Objective:To explore the correlation between gross tumor volume (GTV) and prognosis of patients with esophageal cancer undergoing radiotherapy.Methods:A retrospective cohort study was conducted. The clinical data of 130 newly diagnosed esophageal squamous cell carcinoma patients who received radiotherapy at Shanxi Province Cancer Hospital from February 2016 to June 2018 were analyzed. All patients underwent conformal intensity-modulated radiotherapy (IMRT) for esophageal lesions. Pinnacle planning system was used to calculate GTV, and GTV classification was performed: GTV ≤ 30 cm 3 was classified as grade Ⅰ, GTV > 30 cm 3 and ≤ 60 cm 3 was classified as grade Ⅱ, and GTV > 60 cm 3 was classified as grade Ⅲ. Kaplan-Meier method was used to analyze the progression free survival (PFS) and overall survival (OS) of patients, and the multivariate Cox proportional hazards model was used to analyze the independent influencing factors of poor PFS and OS. Results:The median age of 130 patients [ M ( Q1, Q3)] was 59 years old (56 years old, 69 years old), with 90 males and 40 females; Karnofsky performance scores were all ≥ 70 points; tumors were located in the neck in 10 cases, upper chest in 34 cases, middle chest in 55 cases, and lower chest in 31 cases; clinical staging for esophageal carcinoma treated with non-surgical methods: 3 cases in stage Ⅰ, 37 cases in stage Ⅱ, 79 cases in stage Ⅲ, and 11 cases in stage Ⅳ; 25 cases were classified as GTV grade Ⅰ, 62 cases as GTV grade Ⅱ, and 43 cases as GTV grade Ⅲ. The 1-year PFS rate of 130 patients was 55%, the 2-year PFS rate was 19%, and the median PFS time was 14 months; the 1-year OS rate was 76%, the 2-year OS rate was 32%, and the median OS time was 20 months. PFS and OS of patients in stages Ⅰ+Ⅱ, Ⅲ and Ⅳ deteriorated sequentially, and the differences between the three groups were statistically significant (both P < 0.001); the PFS and OS of patients with GTV grades Ⅰ, Ⅱ and Ⅲ deteriorated sequentially, and the differences in PFS and OS between the three groups were statistically significant (both P < 0.001); there were no statistically significant differences in PFS and OS among patients of different genders, ages, and tumor locations (all P > 0.05). The results of multivariate Cox regression analysis showed that high clinical staging (stage Ⅳ vs. stage Ⅰ, HR = 8.34, 95% CI: 3.88-17.94, P < 0.001) and high GTV grading (grade Ⅱ vs. grade Ⅰ: HR = 6.81, 95% CI: 3.39-13.67, P < 0.001; grade Ⅲ vs. grade Ⅰ: HR = 23.97, 95% CI: 10.81-53.14, P < 0.001) were independent risk factors for poor PFS; high clinical staging (stage Ⅳ vs. stage Ⅰ: HR = 9.94, 95% CI: 4.50-21.97, P < 0.001) and high GTV grading (grade Ⅱ vs. grade Ⅰ: HR = 13.55, 95% CI: 5.58-32.91, P < 0.001; grade Ⅲ vs. grade Ⅰ: HR = 35.01, 95% CI: 13.57-90.34, P < 0.001) were independent risk factors for poor OS. Conclusions:GTV is associated with the prognosis of patients with esophageal cancer undergoing radiotherapy.
2.Effect of Toll-like receptor 4 on liver regeneration during acetaminophen-induced liver injury in mice
Mingyue CHEN ; Xiuliang ZHENG ; Yaqin QIAO ; Haitao SHEN ; Yan LU
Journal of Clinical Hepatology 2023;39(5):1110-1118
Objective To investigate whether Toll-like receptor 4 (TLR4) inhibition affects liver regeneration during acetaminophen (APAP)-induced liver injury in mice, as well as the mechanism of TLR4 involved in liver regeneration. Methods A total of 78 male CD-1 mice were divided into nine groups using a random number table, i.e., three control groups (normal control group, solvent control group, inhibitor control group) with 6 mice in each group and six experimental groups (APAP 24-hour group, TAK-242+APAP 24-hour group, APAP 48-hour group, TAK-242+APAP 48-hour group, APAP 72-hour group, TAK-242+APAP 72-hour group) with 10 mice in each group. The mice in the experimental groups were given a single dose of intraperitoneally injected APAP (300 mg/kg), and TAK-242 was intraperitoneally injected at a dose of 3 mg/kg at 3 hours before APAP administration. Serum and liver tissue samples were collected at different time points. The biochemical method was used to measure the serum level of alanine aminotransferase (ALT); HE staining was used to observe liver pathological changes; RT-PCR, Western blot, and immunohistochemistry were used to measure the expression levels of Cyclin D1, PCNA, Ki-67, STAT3, and p-STAT3. The t -test was used for comparison of normally distributed continuous data between two groups; a one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t -test was used for further comparison between two groups. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups, and the Kruskal-Wallis H test was used for comparison between multiple groups and further comparison between two groups. Results Compared with the normal control group, the APAP 24-hour and 48-hour groups had a significantly higher serum level of ALT (both P < 0.05), and the TAK-242+APAP 24-hour and 48-hour groups had a significantly higher serum level of ALT than the APAP group at the same time point (both P < 0.05). HE staining showed typical central lobular necrosis in the liver of APAP-treated mice, and the TAK-242+APAP 24-hour and 48-hour groups had a significantly larger necrotic area than the APAP group at the same time point (both P < 0.05). RT-PCR, Western blot, and immunohistochemistry showed that the TAK-242+APAP 24-hour, 48-hour, and 72-hour groups had significantly lower mRNA and protein expression levels of Cyclin D1 than the APAP group at the same time point (all P < 0.05); the TAK-242+APAP 24-hour, 48-hour, and 72-hour groups had a significantly lower mRNA expression level of PCNA than the APAP group at the same time point (all P < 0.05), and the TAK-242+APAP 24-hour and 48-hour groups had a significantly lower protein expression level of PCNA than the APAP group at the same time point (all P < 0.05); the TAK-242+APAP 24-hour and 72-hour groups had a significantly lower mRNA expression level of Ki-67 than the APAP group at the same time point (all P < 0.05), and the TAK-242+APAP 24-hour, 48-hour, and 72-hour groups had a significantly lower protein expression level of Ki-67 than the APAP group at the same time point (all P < 0.05). In addition, the TAK-242+APAP 24-hour and 48-hour groups had a significantly lower phosphorylation level of STAT3 than the APAP group at the same time point (both P < 0.05). Conclusion TLR4 may promote liver regeneration by increasing the phosphorylation level of STAT3 during APAP-induced liver injury in mice.
3.Application of flat-sided culture tubes during prenatal diagnosis.
Tiansheng LIU ; Hongqian HUANG ; Jiangyu SU ; Wangshang QIN ; Dongmei FEI ; Luping OUYANG ; Minpan HUANG ; Jinwu YU ; Yaqin LEI ; Shan OU ; Weijia SUN ; Qingming QIU ; Qian ZHENG
Chinese Journal of Medical Genetics 2023;40(10):1306-1311
OBJECTIVE:
To assess the value of using flat-sided culture tubes for preparing chromosomes through chorionic villi (CV) and amniotic fluid (AF) cell cultures during prenatal diagnosis.
METHODS:
From February to March 2020, 157 CV samples and 147 AF samples subjected to prenatal diagnosis at the Maternal and Child Health Care Hospital of Guangxi Zhuang Autonomous Region were selected as the study subjects. For each sample, one flat-sided tube and one flask culture were set up by following the standard protocols. The methods were evaluated by comparing the cell growth, experimental process, quality of chromosome preparation and costs.
RESULTS:
The success rates for the culturing of CV and AF samples by the flat-sided culture tube method were 97.45% (153/157) and 97.96% (144/147), respectively. By contrast, the success rates for the conventional flask method were 98.72% (155/157) for CV and 98.64% (145/147) for AF samples. No significant difference was found between the two methods (P > 0.05). The average harvest time required by the flat-sided culture tube method was 8.45 days for CV and 9.43 days for AF cultures, whilst the average harvest time for conventional flask method was 9.05 days and 9.54 days, respectively. The flat-sided culture tube method for CV had required significantly shorter average harvest time than the conventional method (P < 0.001). No statistical significant difference was found in the average harvest time for AF by the two methods (P > 0.05). The conventional culturing method had required three containers with two sample transfers. By contrast, the flat-sided culture tube method was carried out in one tube without any sample transfer. The average total amount of medium used was 3.91 mL for each flat-sided culture tube and 6.26 mL for each conventional flask.
CONCLUSION
The flat-sided culture tube method can provide a simple, cost-effective and error-reducing procedure for the CV and AF samples culture during prenatal diagnosis.
Child
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Female
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Pregnancy
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Humans
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China
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Prenatal Diagnosis
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Chorionic Villi Sampling
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Amniotic Fluid
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Cell Proliferation
4.Role of Toll⁃like receptor 4 in the early stage of acetaminophen⁃induced acute liver inj ury in mice
Xiuliang Zheng ; Mingyue Chen ; Yaqin Qiao ; Haitao Shen ; Yan Lu
Acta Universitatis Medicinalis Anhui 2023;58(11):1904-1910
Objective :
To used Toll⁃like receptor 4( TLR4) inhibitor ( TAK⁃242) investigate the role of TLR4 in the early stage of acetaminophen (APAP) Ⅳinduced acute liver injury in mice.
Methods :
Fifty⁃eight male institute of cancer research( ICR) mice were randomly divided into control group ( normal control group , solvent control group , inhibitor control group) and experimental group (APAP 4 ⁃ hour group , APAP + TAK⁃242 4 ⁃ hour group , APAP 12 ⁃ hour group , APAP + TAK⁃242 12 ⁃ hour group) . Mice in the experimental group were given a single dose of APAP (300 mg/kg) and TAK⁃242 (3 mg/kg) were given intraperitoneal injection 3 ⁃ hour before APAP injection. The serum alanine aminotransferase (ALT) level and liver index of mice in each group were compared ;
HE staining showed pathological changes of liver tissue;the level of high mobility group box⁃1 (HMGB1) was determined by immunohistochemistry;the levels of TLR4 , HMGB1 and nuclear factor kappa B(NF⁃κB) protein were detected by Western blot;the levels of monocyte chemoattractant protein⁃1( MCP⁃1) , interleukin( IL) Ⅳ1β , tumor necrosis factor⁃α ( TNF⁃α ) and IL⁃6 genes were determined by real⁃time fluorescence quantitative PCR ( RT⁃qPCR) . The content of IL⁃6 in liver tissue was determined by enzyme linked immunosorbent assay (ELISA) .
Results :
HE staining showed liver tissue of mice obvious swelling and congestion of in APAP group at 4 ⁃hour and typical lobular central necrosis in APAP group at 12 ⁃ hour;the degree of liver necrosis in APAP + TAK⁃242 groups at 4 ⁃ hour and 12⁃ hour was less than that in APAP group at the same time point. Compared with the normal control group , serum ALT level , liver index , TLR4 , HMGB1 , NF⁃κB protein content , MCP⁃1 , IL⁃1β , TNF⁃α , IL⁃6 gene levels and IL⁃6 content in liver tissue of APAP 4 ⁃ hour group increased ; serum ALT level , liver index , HMGB1 protein content and IL⁃6 content in liver tissue increased in APAP 12 ⁃ hour group. Compared with APAP 4 ⁃ hour group , serum ALT level , liver index , TLR4 , HMGB1 , NF⁃κB protein content , MCP⁃1 , IL⁃1β , TNF⁃α , IL⁃6 gene level and IL⁃6 content in liver tissue decreased in APAP + TAK⁃242 4 ⁃ hour group. Compared with APAP 12 ⁃hour group , the levels of TLR4 , HMGB1 protein and MCP⁃1 , IL⁃1β , TNF⁃α genes in APAP + TAK⁃242 12 ⁃ hour group decreased.
Conclusion
nhibition of TLR4 may inhibit TLR4/HMGB1 pathway to reduce the inflammatory response in the early stage of acetaminophen⁃induced acute liver injury in mice.
5.Exploring Mechanism of Pomegranate Peel on Non-alcoholic Steatohepatitis Based on Network Pharmacology and Experimental Verification
SUN Yi ; HUANG Xinyu ; QU Yaqin ; ZHENG Guohua ; TIAN Xianxiang ; QIU Zhenpeng
Chinese Journal of Modern Applied Pharmacy 2023;40(17):2384-2392
OBJECTIVE To explore the mechanism of pomegranate peel in improving non-alcoholic steatohepatitis (NASH) based on network pharmacology and cell experiments verification. METHODS Using the Traditional Chinese Medicine System Pharmacology Database(TCMSP) to obtain the active components of pomegranate peel and their corresponding targets. NASH-related disease targets were obtained from five disease databases, including the Human Gene Database(GeneCards), etc. To screen the targets of pomegranate peel and NASH and obtain the common targets through Venn diagrams. The protein-protein interaction network of pomegranate peel-NASH was constructed using the protein interaction database(STRING), and the “pomegranate peel-component-target-NASH” network was established with Cytoscape 3.7.1. Gene ontology(GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis were performed using Metascape software. Finally, the effect of the main active components in pomegranate peel on NASH was observed with human hepatoma cells(HepG2). RESULTS There were 7 active ingredients in pomegranate peel, 191 target genes, 1 818 NASH targets, and 98 intersection targets. Topological analysis showed that the core components of pomegranate peel in the treatment of NASH were quercetin, kaempferol, and luteolin, and the core targets were protein kinase B(Akt1), interleukin-1β(IL-1β), interleukin-6(IL-6), tumor necrosis factor(TNF). KEGG pathway analysis predicted that pomegranate peel treatment of NASH mainly involved phosphatidylinositol-3-kinase(PI3K)/Akt, nuclear factor kappa B(NF-κB), and other signaling pathways. The results of in vitro cell experiments showed that the expression levels of phosphorylated protein kinase B(p-Akt), IL-6 and other proteins were elevated in the model group compared with the control group(P<0.05). Compared with the model group, the active ingredients of pomegranate peel could significantly reduce the expression level of p-Akt and IL-6(P<0.05), as well as the mRNA expression level of IL-6 and TNF-α(P<0.05). CONCLUSION Pomegranate peel can exert anti-NASH effects through multiple components, multiple targets, and multiple pathways. The mechanism may be related to the active components quercetin, kaempferol, and luteolin in pomegranate peel affecting core targets such as Akt1 and regulating PI3K/Akt, NF-κB, and other signaling pathways, thereby inhibiting the expression of related inflammatory factors.
6. Development history of tumor radiotherapy in Shanxi province
Jianzhong CAO ; Yaqin ZHENG ; Jianting LIU ; Shengmin LAN ; Chuantai HE ; Hegao WANG ; Jiangang ZHANG ; Fumao MA ; Yuanchao CUI ; Shuping ZHANG ; Yueming XING
Cancer Research and Clinic 2019;31(11):764-765
Tumor radiotherapy is established on the basis of clinical oncology, radio-physics and radiobiology, and has become one of the three major therapeutic methods for malignant tumors. With the pace of socialist construction in China, the subject of radiotherapy in Shanxi province has developed from scratch and from small to large for more than 60 years. Remarkable achievements have been made in the establishment of departments, the updating of technical equipment, the increase of employees and clinical scientific research. This article reviews and summarizes the development history of tumor radiotherapy in Shanxi province.
8.Control of acetic acid metabolism of recombinant Yarrowia lipolytica for efficient succinic acid production.
Chinese Journal of Biotechnology 2018;34(3):389-395
Succinic acid is a high value-added organic acid widely used in food, chemical and pesticide industries. As a new robust non-conventional yeast, Yarrowia lipolytica attracts more and more attention due to its potential for industrial applications. Previously, we obtained a succinic acid-producing strain through gene deletion of succinic acid dehydrogenase subunit encoding gene Ylsdh5, resulting in the strain of PGC01003. However, the recombinant strain produced large amount of acetic acid due to imbalance between glycolysis and TCA cycle which hindered the efficient production of succinic acid. PDH bypass was interfered to decrease the overflow of acetic acid and produce succinic acid under natural pH. Acetic acid was reduced to 4.6 g/L through heterologous expression of acetyl coenzyme A synthase from Salmonella enteric, which was 75.4% of the control strain. Deletion of CoA-transferase gene Ylach1 eliminated acetate formation and improved succinic acid production, and the resulting strain produced as high as 7.0 g/L succinic acid. Our study provides foundation for further construction of efficient cell factory of succinic acid production.
9.Influences of various field-defining methods of Varian accelerator on radiation dosimetry parameters
Yaqin ZHENG ; Tong CUI ; Xuliang ZHENG ; Jianting LIU ; Xiaofen XING
Chinese Journal of Radiological Medicine and Protection 2017;37(9):709-712
Objective To evaluate the influences of various field-defining method of Varian accelerator on radiation dosimetry parameters, and provide theoretical basis for the beam modeling of the treatment planning system ( TPS ) . Methods The percentage depth dose ( PDD ) , the off-axis ratio ( OAR ) and the total scattering factors ( Scp ) of radiation fields were measured in three different conditions, including collimators (JAW), multileaf collimator(MLC) and JAW +MLC. The measured data was analyzed and compared with each other. Results The PDD of central axis was marginally influenced by three field-defining method. In both directions, the MLC-defined field sizes were larger by a maximum of 2. 9 mm ( left-right) or 1. 7 mm ( gun-target) than the JAW-defined ones. In the left-right direction, the width of field penumbra shaped by MLC was larger than the field of the same size as defined by JAW. The result of gun-target direction was to the contrary. In both directions, the field penumbra and size displayed no significant differences as defined by JAW+MLC or JAW. Conclusions The field size, penumbra width, and the total scattering factors were influenced by field-defining method, which indicates that special attention should be paid to the dosimetric parameters of MLC during TPS beam modeling for IMRT planning.
10.Effect of Kidney-reinforcing, Blood-activating and Phlegm-resolving Therapy on Left Ventricular Fibrosis of Spontaneously Hypertensive Rats
Qiong WANG ; Shaoxiang XIAN ; Zhongqi YANG ; Bingqing LYU ; Zheng ZHOU ; Jiao DUAN ; Yaqin TANG
Journal of Guangzhou University of Traditional Chinese Medicine 2017;34(3):397-400
Objective To explore the therapeutic mechanism of kidney-reinforcing,blood-activating and phlegmresolving therapy for left ventricular fibrosis of spontaneously hypertensive rats (SHR).Methods Twenty SHR were randomly assigned to Chinese medicine group and model group.Additionally,ten Wistar-Kyoto(WKY) rats served as normal control group.After 12-week prevention,Masson staining method was used to measure the degree of fibrosis of left ventricular myocardial tissues,reverse transcription-polymerase chain reaction(RT-PCR) was used to detect Smad3 mRNA expression,and Western blotting method was used for the detection of Smad3 protein expression.Results The degree of left ventricular fibrosis myocardial tissue in Chinese medicine group was milder than that in the model group,and Samd3 protein and mRNA expression levels in Chinese medicine group were lower than those in the model group (P < 0.05).Conclusion Kidney-reinforcing,blood-activating and phlegmresolving therapy can improve left ventricular fibrosis in SHR by inhibiting Smad3 expression.


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