1.On-site rapid detection of multiple pesticide residues in tea leaves by lateral flow immunoassay
Gao JUNXIA ; Zhang TIANYI ; Fang YIHUA ; Zhao YING ; Yang MEI ; Zhao LI ; Li YE ; Huang JUN ; Zhu GUONIAN ; Guo YIRONG
Journal of Pharmaceutical Analysis 2024;14(2):276-283
The application of pesticides(mostly insecticides and fungicides)during the tea-planting process will undoubtedly increase the dietary risk associated with drinking tea.Thus,it is necessary to ascertain whether pesticide residues in tea products exceed the maximum residue limits.However,the complex matrices present in tea samples comprise a major challenge in the analytical detection of pesticide residues.In this study,nine types of lateral flow immunochromatographic strips(LFICSs)were developed to detect the pesticides of interest(fenpropathrin,chlorpyrifos,imidacloprid,thiamethoxam,acet-amiprid,carbendazim,chlorothalonil,pyraclostrobin,and iprodione).To reduce the interference of tea substrates on the assay sensitivity,the pretreatment conditions for tea samples,including the extraction solvent,extraction time,and purification agent,were optimized for the simultaneous detection of these pesticides.The entire testing procedure(including pretreatment and detection)could be completed within 30 min.The detected results of authentic tea samples were confirmed by ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS),which suggest that the LFICS coupled with sample rapid pretreatment can be used for on-site rapid screening of the target pesticide in tea products prior to their market release.
2.Association between short-term exposure to atmospheric fine particulate matter and ozone and inflammatory indicators in peripheral blood of patients with pneumonia
Lulu SONG ; Qi YU ; Nannan LIU ; Yuhui GAO ; Zeyu NIU ; Yan ZHANG ; Huiqiu ZHENG ; Jiayu TIAN ; Junxia LIU ; Lifang ZHAO ; Zhihong ZHANG
Shanghai Journal of Preventive Medicine 2024;36(6):551-558
ObjectiveTo explore the association between short-term exposure to atmospheric fine particulate matter (PM2.5) and ozone (O3) and systemic inflammatory indicators in patients with pneumonia, and to identify the susceptible populations. MethodsFrom September 2018 to April 2020, data of 1 480 patients admitted for pneumonia was collected from a tertiary hospital in Taiyuan City. Generalized additive models (GAMs) were used to explore the associations between PM2.5 and O3 exposure and inflammatory indicators of patients with pneumonia; and to explore the susceptibility factors and susceptible populations to PM2.5 and O3 exposures through stratified analyses. ResultsThe short-term exposure to PM2.5 was associated with changes in peripheral blood C-reation protein (CRP), erythrocyte sedimentation (ESR), easinophil (EOS), neutrophil (NEU) and neutrophil-lymphocyte ratio (NLR) in patients with pneumonia, and there were different degrees of hysteresis effects, with the effect values reaching a maximum at lag03, lag03, lag0, lag03, lag03, respectively, which were 4.13% (95%CI: 0.43%‒7.84%), 3.10% (95%CI: 0.24%‒5.97%), 5.27% (95%CI: 3.12%‒7.42%), 1.85% (95%CI: 0.36%‒3.34%), and 2.53% (95%CI: 0.53%‒4.74%) for every 10 μg·m-3 of PM2.5. The changes in O3 concentration were associated with the elevation of peripheral blood PCT and ESR in patients with pneumonia, and their effect values all reached the maximum at lag01 d, every 1 μg·m-3 of O3 elevation increased by 0.38% (95%CI: 0.04%‒0.73%) and 0.47% (95%CI: 0.19%‒0.76%), respectively. Stratified analyses showed that the associations of PM2.5 with peripheral blood CRP, ESR, NEU, and NLR in pneumonia patients were more significant in males, the elderly, and those with onset in the cold season; the associations of O3 with peripheral blood PCT and ESR in pneumonia patients were more significant in the elderly and those with onset in the warm season, and the peripheral blood CRP and PCT in female patients with pneumonia were more susceptible to the changes of O3. ConclusionShort-term exposure to atmospheric PM2.5 and O3 are positively associated with changes in inflammatory indicators in patients with pneumonia, and the effects of PM2.5 on patients with pneumonia are more extensive than those of O3, with a longer lag effect. In addition, elderly patients with pneumonia are more sensitive to air pollution, male patients with pneumonia are more sensitive to PM2.5, and female patients with pneumonia are more sensitive to O3. Cold and warm seasons can exacerbate the effects of PM2.5 and O3 on inflammatory indicators in patients with pneumonia, respectively, and the patients must be protected well.
3.Application of quality monitoring indicators of blood testing in blood banks of Shandong province
Xuemei LI ; Weiwei ZHAI ; Zhongsi YANG ; Shuhong ZHAO ; Yuqing WU ; Qun LIU ; Zhe SONG ; Zhiquan RONG ; Shuli SUN ; Xiaojuan FAN ; Wei ZHANG ; Jinyu HAN ; Lin ZHU ; Xianwu AN ; Hui ZHANG ; Junxia REN ; Xuejing LI ; Chenxi YANG ; Bo ZHOU ; Haiyan HUANG ; Guangcai LIU ; Ping CHEN ; Hui YE ; Mingming QIAO ; Hua SHEN ; Dunzhu GONGJUE ; Yunlong ZHUANG
Chinese Journal of Blood Transfusion 2024;37(3):258-266
【Objective】 To objectively evaluate the quality control level of blood testing process in blood banks through quantitative monitoring and trend analysis, and to promote the homogenization level and standardized management of blood testing laboratories in blood banks. 【Methods】 A quality monitoring indicator system covering the whole process of blood collection and supply, including blood donation service, blood component preparation, blood testing, blood supply and quality control was established. The questionnaire Quality Monitoring Indicators for Blood Collection and Supply Process with clear definition of indicators and calculation formulas was distributed to 17 blood banks in Shandong province. Quality monitoring indicators of each blood bank from January to December 2022 were collected, and 31 indicators in terms of blood testing were analyzed using SPSS25.0 software. 【Results】 The proportion of unqualified serological tests in 17 blood bank laboratories was 55.84% for ALT, 13.63% for HBsAg, 5.08% for anti HCV, 5.62% for anti HIV, 18.18% for anti TP, and 1.65% for other factors (mainly sample quality). The detection unqualified rate and median were (1.23±0.57)% and 1.11%, respectively. The ALT unqualified rate and median were (0.74±0.53)% and 0.60%, respectively. The detection unqualified rate was positively correlated with ALT unqualified rate (r=0.974, P<0.05). The unqualified rate of HBsAg, anti HCV, anti HIV and anti TP was (0.15±0.09)%, (0.05±0.04)%, (0.06±0.03)% and (0.20±0.05)% respectively. The average unqualified rate, average hemolysis rate, average insufficient volume rate and the abnormal hematocrit rate of samples in 17 blood bank laboratories was 0.21‰, 0.08‰, 0.01‰ and 0.02‰ respectively. There were differences in the retest concordance rates of four HBsAg, anti HCV and anti HIV reagents, and three anti TP reagents among 17 blood bank laboratories (P<0.05). The usage rate of ELISA reagents was (114.56±3.30)%, the outage rate of ELISA was (10.23±7.05) ‰, and the out of range rate of ELISA was (0.90±1.17) ‰. There was no correlation between the out of range rate, outrage rate and usage rate (all P>0.05), while the outrage rate was positively correlated with the usage rate (r=0.592, P<0.05). A total of 443 HBV DNA positive samples were detected in all blood banks, with an unqualified rate of 3.78/10 000; 15 HCV RNA positive samples were detected, with an unqualified rate of 0.13/10 000; 5 HIV RNA positive samples were detected, with an unqualified rate of 0.04/10 000. The unqualified rate of NAT was (0.72±0.04)‰, the single NAT reaction rate [(0.39±0.02)‰] was positively correlated with the single HBV DNA reaction rate [ (0.36±0.02) ‰] (r=0.886, P<0.05). There was a difference in the discriminated reactive rate by individual NAT among three blood bank laboratories (C, F, H) (P<0.05). The median resolution rate of 17 blood station laboratories by minipool test was 36.36%, the median rate of invalid batch of NAT was 0.67%, and the median rate of invalid result of NAT was 0.07‰. The consistency rate of ELISA dual reagent detection results was (99.63±0.24)%, and the median length of equipment failure was 14 days. The error rate of blood type testing in blood collection department was 0.14‰. 【Conclusion】 The quality monitoring indicator system for blood testing process in Shandong can monitor potential risks before, during and after the experiment, and has good applicability, feasibility, and effectiveness, and can facilitate the continuous improvement of laboratory quality control level. The application of blood testing quality monitoring indicators will promote the homogenization and standardization of blood quality management in Shandong, and lay the foundation for future comprehensive evaluations of blood banks.
4.Application of quality control indicator system in blood banks of Shandong
Qun LIU ; Yuqing WU ; Xuemei LI ; Zhongsi YANG ; Zhe SONG ; Zhiquan RONG ; Shuhong ZHAO ; Lin ZHU ; Xiaojuan FAN ; Shuli SUN ; Wei ZHANG ; Jinyu HAN ; Xuejing LI ; Bo ZHOU ; Chenxi YANG ; Haiyan HUANG ; Guangcai LIU ; Kai CHEN ; Xianwu AN ; Hui ZHANG ; Junxia REN ; Hui YE ; Mingming QIAO ; Hua SHEN ; Dunzhu GONGJUE ; Yunlong ZHUANG
Chinese Journal of Blood Transfusion 2024;37(3):267-274
【Objective】 To establish an effective quality monitoring indicator system for blood quality control in blood banks, in order to analyze the quality control indicators for blood collection and supply, and evaluate blood quality control process, thus promoting continuous improvement and standardizing management of blood quality control in blood banks. 【Methods】 A quality monitoring indicator system covering the whole process of blood collection and supply, including blood donation services, component preparation, blood testing, blood supply and quality control was established. The Questionnaire of Quality Monitoring Indicators for Blood Collection and Supply Process was distributed to 17 blood banks in Shandong, which clarified the definition and calculation formula of indicators. The quality monitoring indicator data from January to December 2022 in each blood bank were collected, and 20 quality control indicators data were analyzed by SPSS25.0 software. 【Results】 The average pass rate of key equipment monitoring, environment monitoring, key material monitoring, and blood testing item monitoring of 17 blood banks were 99.47%, 99.51%, 99.95% and 98.99%, respectively. Significant difference was noticed in the pass rate of environment monitoring among blood banks of varied scales(P<0.05), and the Pearson correlation coefficient (r) between the total number of blood quality testing items and the total amount of blood component preparation was 0.645 (P<0.05). The average discarding rates of blood testing or non-blood testing were 1.14% and 3.36% respectively, showing significant difference among blood banks of varied scales (P<0.05). The average discarding rate of lipemic blood was 3.07%, which had a positive correlation with the discarding rate of non testing (r=0.981 3, P<0.05). There was a statistically significant difference in the discarding rate of lipemic blood between blood banks with lipemic blood control measures and those without (P<0.05). The average discarding rate of abnormal color, non-standard volume, blood bag damage, hemolysis, blood protein precipitation and blood clotting were 0.20%, 0.14%, 0.06%, 0.06%, 0.02% and 0.02% respectively, showing statistically significant differences among large, medium and small blood banks(P<0.05).The average discarding rates of expired blood, other factors, confidential unit exclusion and unqualified samples were 0.02%, 0.05%, 0.003% and 0.004%, respectively. The discarding rate of blood with air bubbles was 0.015%, while that of blood with foreign body and unqualified label were 0. 【Conclusion】 The quality control indicator system of blood banks in Shandong can monitor weak points in process management, with good applicability, feasibility, and effectiveness. It is conducive to evaluate different blood banks, continuously improve the quality control level of blood collection and supply, promote the homogenization and standardization of blood quality management, and lay the foundation for comprehensive evaluation of blood banks in Shandong.
5.Quality monitoring indicator system in blood banks of Shandong: applied in blood donation services, component preparation and blood supply process
Yuqing WU ; Hong ZHOU ; Zhijie ZHANG ; Zhiquan RONG ; Xuemei LI ; Zhe SONG ; Shuhong ZHAO ; Zhongsi YANG ; Qun LIU ; Lin ZHU ; Xiaojuan FAN ; Shuli SUN ; Wei ZHANG ; Jinyu HAN ; Haiyan HUANG ; Guangcai LIU ; Ping CHEN ; Xianwu AN ; Hui ZHANG ; Junxia REN ; Xuejing LI ; Chenxi YANG ; Bo ZHOU ; Hui YE ; Mingming QIAO ; Hua SHEN ; Dunzhu GONGJUE ; Yunlong ZHUANG
Chinese Journal of Blood Transfusion 2024;37(3):275-282
【Objective】 To establish an effective quality indicator monitoring system, scientifically and objectively evaluate the quality management level of blood banks, and achieve continuous improvement of quality management in blood bank. 【Methods】 A quality monitoring indicator system that covers the whole process of blood collection and supply was established, the questionnaire of Quality Monitoring Indicators for Blood Collection and Supply Process with clear definition of indicators and calculation formulas was distributed to 17 blood banks in Shandong. Statistical analysis of 21 quality monitoring indicators in terms of blood donation service (10 indicators), blood component preparation (7 indicators ), and blood supply (4 indicators) from each blood bank from January to December 2022 were conducted using SPSS25.0 software The differences in quality monitoring indicators of blood banks of different scales were analyzed. 【Results】 The average values of quality monitoring indicators for blood donation service process of 17 blood banks were as follows: 44.66% (2 233/5 000) of regular donors proportion, 0.22% (11/50) of adverse reactions incidence, 0.46% (23/5 000) of non-standard whole blood collection rate, 0.052% (13/25 000) of missed HBsAg screening rate, 99.42% (4 971/5 000) of first, puncture successful rate, 86.49% (173/200) of double platelet collection rate, 66.50% (133/200) of 400 mL whole blood collection rate, 99.25% (397/400) of donor satisfaction rate, 82.68% (2 067/2 500) of use rate of whole blood collection bags with bypass system with sample tube, and 1 case of occupational exposure in blood collection.There was a strong positive correlation between the proportion of regular blood donors and the collection rate of 400 mL whole blood (P<0.05). The platelet collection rate, incidence of adverse reactions to blood donation, and non-standard whole blood collection rate in large blood banks were significantly lower than those in medium and small blood banks (P<0.05). The average quality monitoring indicators for blood component preparation process of 17 blood banks were as follows: the leakage rate of blood component preparation bags was 0.03% (3/10 000), the discarding rate of lipemic blood was 3.05% (61/2 000), the discarding rate of hemolysis blood was 0.13%(13/10 000). 0.06 case had labeling errors, 8 bags had blood catheter leaks, 2.76 bags had blood puncture/connection leaks, and 0.59 cases had non-conforming consumables. The discarding rate of hemolysis blood of large blood banks was significantly lower than that of medium and small blood banks (P<0.05), and the discarding rate of lipemic blood of large and medium blood banks was significantly lower than that of small blood banks (P<0.05). The average values of quality monitoring indicators for blood supply process of 17 blood banks were as follows: the discarding rate of expired blood was 0.023% (23/100 000), the leakage rate during storage and distribution was of 0.009%(9/100 000), the discarding rate of returned blood was 0.106% (53/50 000), the service satisfaction of hospitals was 99.16% (2 479/2 500). The leakage rate of blood components during storage and distribution was statistically different with that of blood component preparation bags between different blood banks (P<0.05). There were statistically significant differences in the proportion of regular blood donors, incidence of adverse reactions, non-standard whole blood collection rate, 400 mL whole blood collection rate, double platelet collection rate, the blood bag leakage rate during preparation process, the blood components leakage rate during storage and distribution as well as the discarding rate of lipemic blood, hemolysis blood, expired blood and returned blood among large, medium and small blood banks (all P<0.05). 【Conclusion】 The establishment of a quality monitoring indicator system for blood donation services, blood component preparation and blood supply processes in Shandong has good applicability, feasibility and effectiveness. It can objectively evaluate the quality management level, facilitate the continuous improvement of the quality management system, promote the homogenization of blood management in the province and lay the foundation for future comprehensive evaluation of blood banks.
6.Efficacy of autologous fat grafting in the treatment of 40 cases of stable linear scleroderma: a retrospective analysis
Junxia WANG ; Weinan GUO ; Hui CHEN ; Junfeng HAO ; Bing LI ; Jingyi WEI ; Tao ZHAO
Chinese Journal of Dermatology 2023;56(8):762-765
Objective:To investigate the efficacy of autologous fat grafting in the treatment of stable linear scleroderma.Methods:A retrospective analysis was performed on 40 patients with stable linear scleroderma who received autologous fat grafting from October 2017 to November 2020 in the Department of Dermatology, Xijing Hospital, Air Force Medical University. There were 22 males and 18 females, aged 12 - 36 (18.2 ± 4.82) years. Skin lesions involved the forehead in 16 cases, the perioral area in 4, the lower jaw in 2, the cheek in 9, the trunk in 5, and the lower limb in 4, and the size of depressed skin defects was 3 - 24 cm 3. The patients′ subjective satisfaction rate, the decrease in the size of depressed skin defects, and the incidence of adverse reactions after autologous fat grafting were analyzed during the follow-up. Results:Six months after the grafting, 40 patients were followed up and evaluated, and the size of depressed skin defects markedly decreased. The satisfaction rate for appearance improvement after the first grafting was 60% (24/40) ; 35 patients received the second grafting, with a satisfaction rate of 88.6% (31/35) ; 17 received the third grafting, with a satisfaction rate of 94.1% (16/17) ; the total satisfaction rate was 87.5% (35/40). After the grafting, local skin unevenness was observed in the grafting area in 3 patients, and in the liposuction area in 2. The incidence rate of postoperative adverse reactions was 12.5% (5/40) .Conclusion:Autologous fat grafting was markedly effective in the treatment of stable linear scleroderma.
7.Evaluation of therapeutic markers and mechanism of Shuganjieyu capsule in treatment of depression
Yu ZHAO ; Yaojun LI ; Dan WANG ; Xinzhe DU ; Yao GAO ; Junxia LI ; Sha LIU ; Yong XU
Chinese Journal of Behavioral Medicine and Brain Science 2022;31(3):235-240
Objective:To compare the expression levels of candidate genes before and after Shuganjieyu capsule treatment, to analyze their correlation with depression symptoms and cognitive function, and to find and clarify the biomarkers related to the efficacy of Shuganjieyu capsule.Methods:Among 27 patients with mild to moderate depression (MMD), 24 items Hamilton depression rating scale (HAMD-24) was used to assess the severity of depression, Chinese revised Wechsler adult intelligence scale(WAIS-RC) and Chinese revised Wechsler memory scale(WMS) were used to assess cognitive function, and qRT-PCR was used to detect the expression levels of candidate genes in peripheral blood of patients with depression before and after treatment with Shuganjieyu capsule.SPSS 25.0 software was used for statistical analysis, paired t-test, non-parametric test, Spearman correlation analysis and receiver operating characteristic curve were used for data statistics. Results:The symptoms of MMD patients were relieved after Shuganjieyu capsule treatment(HAMD scores: baseline 14.00(9.75, 18.25), 8-week 4.00(2.00, 7.25), Z=-4.462, P<0.01), and the verbal intelligence quotient(VIQ) of WMS was puomoved (VIQ scores: baseline (123.00±10.24), 8-week (128.00±6.77), t=4.372, P<0.01). The level of gene expression brain derived neurotrophic factor(BDNF) (baseline 1.68(0.92, 2.63), 8-week 2.30(1.47, 4.34), Z=-2.781, P=0.005), glial cell derived neurotrophic factor(GDNF) (baseline 0.74(0.31, 1.15), 8-week 0.97(0.50, 1.71), Z=-2.159, P=0.031), 5-hydroxytryptamine receptor 2A(HTR2A) (baseline 0.60(0.39, 1.60), 8-week 0.98(0.44, 2.29), Z=-1.994, P=0.046) and glutamate ionotropic receptor AMPA type subunit 1(GRIA1) (baseline 1.19(0.66, 2.40), 8-week 1.76(0.86, 4.13), Z=-2.756, P=0.006) was up-regulated after treatment.The change rate of BDNF expression were correlated with the score of HAMD-24 ( r=-0.35, P=0.038) and performance intelligence quotient of WMS ( r=0.40, P=0.022). Conclusions:BDNF may be used as a therapeutic marker of Shuganjieyu capsule in the treatment of clinical symptoms and cognitive function of MMD patients, which is used to evaluate the efficacy of antidepressants.
8.Expression of peripheral interleukin-35 and its modulatory effect on regulatory T cell functions in patients with alopecia areata
Peng ZHAO ; Xiaowei QIN ; Junxia QIN ; Lili LIANG ; Xinzhong ZHANG ; Jie GAO
Chinese Journal of Dermatology 2022;55(3):224-230
Objective:To investigate changes in the peripheral interleukin-35 (IL-35) level in patients with alopecia areata, and to assess its modulatory effect on regulatory T (Treg) cell activities.Methods:Totally, 81 patients with alopecia areata (alopecia areata group) and 27 healthy volunteers (control group) were enrolled from Shanxi Provincial People′s Hospital between December 2019 and January 2021. Sera and peripheral blood mononuclear cells (PBMCs) were isolated. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the serum IL-35 level, real-time fluorescence-based quantitative PCR to determine the mRNA expression of IL-35 subunits EBI3 and IL-12p35, and flow cytometry to determine the proportion of CD4 + CD25 + CD127 dim/- Treg cells. Sorted Treg cells were stimulated by recombinant human IL-35, ELISA was performed to detect levels of perforin and granzyme B in the culture supernatant, and real-time fluorescence-based quantitative PCR to determine the mRNA expression of EBI3, IL-12p35, and immune checkpoint molecules, such as programmed death protein 1 (PD-1) , T cell immunoglobulin and mucin protein-3 (Tim-3) , cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and lymphocyte activation gene-3 (LAG-3) in Treg cells. IL-35-stimulated or unstimulated Treg cells were co-cultured with autologous PBMCs, and cell counting kit-8 (CCK8) assay was conducted to assess cellular proliferative activity. Measurement data were compared between 2 groups by using t test, comparisons among multiple groups were carried out by using one-way analysis of variance, correlation analysis was carried out by using Pearson correlation analysis, and enumeration data were compared by using chi-square test. Results:Compared with the control group, the alopecia areata group showed significantly decreased IL-35 levels (90.10 ± 11.98 ng/L vs. 100.74 ± 28.71 ng/L, t= 2.71, P= 0.008) , mRNA expression of EBI3 and IL-12p35 in PBMCs (EBI3: 1.06 ± 0.15 vs. 1.25 ± 0.11, t= 6.09, P < 0.001; IL-12p35: 1.00 ± 0.15 vs. 1.38 ± 0.22, t= 10.16, P < 0.001) , and proportions of Treg cells (5.91% ± 1.17% vs. 6.85% ± 1.23%, t= 3.54, P= 0.001) . In the alopecia areata group, the proportion of Treg cells was positively correlated with the serum IL-35 level ( r= 0.25, P= 0.026) , and the mRNA expression of EBI3 and IL-12p35 in PBMCs ( r= 0.31, 0.24, P= 0.004, 0.032, respectively) . Compared with the control group, the unstimulated Treg cells from the alopecia areata group showed significantly decreased supernatant levels of perforin and granzyme B, mRNA expression of EBI3, IL-12p35 and immune checkpoint molecules ( P < 0.05 or 0.001) , as well as weakened inhibitory effect on the proliferative activity of PBMCs ( P= 0.013) . There was no significant difference in the level of perforin or granzyme B between the recombinant human IL-35-stimulated and unstimulated Treg cells from the patients with alopecia areata (both P > 0.05) . However, the mRNA expression of EBI3, IL-12p35 and immune checkpoint molecules was significantly higher in the IL-35-stimulated Treg cells than in the unstimulated Treg cells in the alopecia areata group ( P < 0.05 or 0.001) , and the inhibitory effect on the proliferative activity of PBMCs was also significantly enhanced in the IL-35-stimulated Treg cells compared with the unstimulated Treg cells ( P= 0.037) . Conclusion:The peripheral IL-35 level was significantly decreased in the patients with alopecia areata, which was closely associated with reduced activities of Treg cells, and IL-35 may be involved in the occurrence of alopecia areata.
9.The novel ER stress inducer Sec C triggers apoptosis by sulfating ER cysteine residues and degrading YAP via ER stress in pancreatic cancer cells.
Junxia WANG ; Minghua CHEN ; Mengyan WANG ; Wenxia ZHAO ; Conghui ZHANG ; Xiujun LIU ; Meilian CAI ; Yuhan QIU ; Tianshu ZHANG ; Huimin ZHOU ; Wuli ZHAO ; Shuyi SI ; Rongguang SHAO
Acta Pharmaceutica Sinica B 2022;12(1):210-227
Pancreatic adenocarcinoma (PAAD) is one of the most lethal malignancies. Although gemcitabine (GEM) is a standard treatment for PAAD, resistance limits its application and therapy. Secoemestrin C (Sec C) is a natural compound from the endophytic fungus Emericella, and its anticancer activity has not been investigated since it was isolated. Our research is the first to indicate that Sec C is a broad-spectrum anticancer agent and could exhibit potently similar anticancer activity both in GEM-resistant and GEM-sensitive PAAD cells. Interestingly, Sec C exerted a rapid growth-inhibiting effect (80% death at 6 h), which might be beneficial for patients who need rapid tumor shrinkage before surgery. Liquid chromatography/mass spectrometry and N-acetyl-l-cysteine (NAC) reverse assays show that Sec C sulfates cysteines to disrupt disulfide-bonds formation in endoplasmic reticulum (ER) proteins to cause protein misfolding, leading to ER stress and disorder of lipid biosynthesis. Microarray data and subsequent assays show that ER stress-mediated ER-associated degradation (ERAD) ubiquitinates and downregulates YAP to enhance ER stress via destruction complex (YAP-Axin-GSK-βTrCP), which also elucidates a unique degrading style for YAP. Potent anticancer activity in GEM-resistant cells and low toxicity make Sec C a promising anti-PAAD candidate.
10.Effect of Karnofsky performance status scale and lactate dehydrogenase as well as their interaction on the therapeutic efficacy of diffuse large B-cell lymphoma
Zhiqiang ZHAO ; Kaihua XIA ; Meng XING ; Junxia WANG ; Qinchuan YU ; Lieyang WANG
Journal of Leukemia & Lymphoma 2022;31(11):675-679
Objective:To explore the factors influencing complete remission in patients with diffuse large B-cell lymphoma (DLBCL), and to explore the effect of the interaction of Karnofsky performance status scale (KPS) scores and the level of lactate dehydrogenases (LDH) on whether patients with DLBCL are completely relieved.Methods:The clinical data of 373 DLBCL patients admitted to Shanxi Province Cancer Hospital from January 2014 to December 2020 were retrospectively analyzed. SPSS 25.0 logistic regression model and Cox proportional risk regression models were used to explore the factors affecting complete remission in patients with DLBCL and to explore whether there was a multiplicative interaction between the factors. For factors with multiplicative interactions, the Matrix package, epiR package, and survival package in R 4.2.0 software were used to analyze whether there was an additive interaction. The relative excess risk of interaction (RERI), attributable proportion due to interaction (AP), and the synergy index (S) were used to evaluate the presence of additive interactions.Results:Elevated β 2 macroglobulin (β 2-MG), KPS scores below 80, and elevated LDH were risk factors for incomplete remission in patients with DLBCL (all P < 0.05). The risk of incomplete remission in patients with elevated β 2-MG, KPS scores below 80 and LDH was 1.971 times ( OR = 1.971, 95% CI 1.161-3.346), 2.056 times ( OR = 2.056, 95% CI 1.057-4.000) and 3.351 times ( OR = 3.351, 95% CI 1.783-6.300) higher than those in patients with normal β 2-MG, KPS scores above 80 and non-elevated LDH, respectively. There was a negative multiplicative interaction between the two risk factors of KPS scores below 80 and elevated LDH ( OR = 0.317, 95% CI 0.126-0.785). The estimated value of RERI, AP and S was -2.07 (95% CI -4.79-0.64),0.50 (95% CI -1.68-0.32),0.50 (95% CI 0.22-1.13), respectively; and there was no additive interaction among them. Conclusions:Elevated β 2-MG, KPS scores below 80, and elevated LDH are risk factors influencing incomplete remission for patients with DLBCL. The combined effect in patients with the combination of elevated LDH and KPS scores below 80 is lower than the single effect of the multiple of the both. There is a negative multiplicative interaction and no additive interaction in DLBCL patients with KPS scores below 80 and elevated LDH level.

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