1.Analysis of Inhibitory Effect of Berberine Compounds on Acetylcholinesterase and Blood-brain Barrier Permeability
Fulu PAN ; Yang LIU ; Huining LIU ; Shuang YU ; Xueyan LI ; Xinyu WANG ; Dongying QI ; Xiaoyu CHAI ; Qianqian WANG ; Zirong YI ; Yanli PAN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(9):116-124
ObjectiveTo examine the inhibitory effects of berberine compounds, including columbamine, on acetylcholinesterase from the perspectives of drug-target binding affinity and kinetics and explore the blood-brain barrier (BBB) permeability of these compounds in different multi-component backgrounds. MethodThe median inhibitory concentration (IC50) of acetylcholinesterase by berberine compounds including columbamine was measured using the Ellman-modified spectrophotometric method. The binding kinetic parameters (Koff) of these compounds with acetylcholinesterase were determined using the enzyme activity recovery method. A qualitative analysis of the ability of these components to penetrate the BBB and arrive at the brain tissue in diverse multi-component backgrounds (including medicinal herbs and compound formulas) was conducted using ultra performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS). ResultBerberine compounds, including columbamine, exhibited strong inhibition of acetylcholinesterase, with IC50 values in the nanomolar range. Moreover, they displayed better drug-target binding kinetics characteristics (with smaller Koff values) than the positive control of donepezil hydrochloride (P<0.01), indicating a longer inhibition duration of acetylcholinesterase. Berberine components such as columbamine could penetrate the BBB to arrive at brain tissue in the form of a monomer, as well as in the multi-component backgrounds of Coptis and Phellodendri Chinensis Cortex medicinal extracts and the compound formula Huanglian Jiedutang. ConclusionThese berberine compounds such as columbamine exhibit a strong inhibitory effect on acetylcholinesterase and can arrive at brain tissue in multi-component backgrounds. In the level of pharmacological substance, this supports the clinical efficacy of compound Huanglian Jiedutang in improving Alzheimer's disease, providing data support for elucidating the pharmacological basis of compound Huanglian Jiedutang.
2.Analysis on Components Absorbed into Blood and Cerebrospinal Fluid of Schisandrae Chinensis Fructus Based on Sequential Metabolism
Shuang YU ; Yanli PAN ; Huining LIU ; Xueyan LI ; Xinyu WANG ; Dongying QI ; Fulu PAN ; Qianqian WANG ; Xiaoyu CHAI ; Guopeng WANG ; Tao MA ; Yang LIU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(3):114-123
ObjectiveTo identify the prototypical components and metabolites absorbed into blood and cerebrospinal fluid of Schisandrae Chinensis Fructus(SCF) based on sequential metabolism combined with liquid chromatography-mass spectrometry. MethodBlood and cerebrospinal fluid samples of integrated metabolism, intestinal metabolism and hepatic metabolism were collected from male SD rats after gavage and in situ intestinal perfusion administration, and ultra-performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry(UPLC Q-Exactive Orbitrap MS) was used to analyze and compare the differences in the spectra of SCF extract, blank plasma, administered plasma, blank cerebrospinal fluid and administered cerebrospinal fluid with ACQUITY UPLC BEH Shield RP18 column(2.1 mm×100 mm, 1.7 µm), the mobile phase was acetonitrile(A)-0.1% formic acid aqueous solution(B) for gradient elution(0-7 min, 95%B; 7-12 min, 95%-35%B; 12-17 min, 35%-15%B; 17-20 min, 15%-12%B; 20-22 min, 12%-5%B; 22-23 min, 5%B; 23-25 min, 5%-95%B; 25-28 min, 95%B). And heated electrospray ionization(HESI) was used with positive and negative ion modes, the scanning range was m/z 100-1 500. The prototypical constituents and their metabolites absorbed into blood and cerebrospinal fluid of SCF were identified according to the retention time, characteristic fragments, molecular formulae and the information of reference substances. ResultA total of 42 chemical components were identified in the extract of SCF, including lignans, flavonoids, amino acids, tannins, and others, of which lignans were the main ones. A total of 27 prototypical components and 14 metabolites were identified in plasma samples from different sites. A total of 15 prototypical components and 9 metabolites were identified in cerebrospinal fluid. The main metabolic reactions involved in the formation of metabolites were mainly demethylation, methylation, demethoxylation and hydroxylation. ConclusionThrough the systematic identification of the prototypical components and metabolites of SCF in rats, it provides data support for further better exploring the material basis of SCF in the treatment of central nervous system diseases.
3.Incidence of postoperative complications in Chinese patients with gastric or colorectal cancer based on a national, multicenter, prospective, cohort study
Shuqin ZHANG ; Zhouqiao WU ; Bowen HUO ; Huining XU ; Kang ZHAO ; Changqing JING ; Fenglin LIU ; Jiang YU ; Zhengrong LI ; Jian ZHANG ; Lu ZANG ; Hankun HAO ; Chaohui ZHENG ; Yong LI ; Lin FAN ; Hua HUANG ; Pin LIANG ; Bin WU ; Jiaming ZHU ; Zhaojian NIU ; Linghua ZHU ; Wu SONG ; Jun YOU ; Su YAN ; Ziyu LI
Chinese Journal of Gastrointestinal Surgery 2024;27(3):247-260
Objective:To investigate the incidence of postoperative complications in Chinese patients with gastric or colorectal cancer, and to evaluate the risk factors for postoperative complications.Methods:This was a national, multicenter, prospective, registry-based, cohort study of data obtained from the database of the Prevalence of Abdominal Complications After Gastro- enterological Surgery (PACAGE) study sponsored by the China Gastrointestinal Cancer Surgical Union. The PACAGE database prospectively collected general demographic characteristics, protocols for perioperative treatment, and variables associated with postoperative complications in patients treated for gastric or colorectal cancer in 20 medical centers from December 2018 to December 2020. The patients were grouped according to the presence or absence of postoperative complications. Postoperative complications were categorized and graded in accordance with the expert consensus on postoperative complications in gastrointestinal oncology surgery and Clavien-Dindo grading criteria. The incidence of postoperative complications of different grades are presented as bar charts. Independent risk factors for occurrence of postoperative complications were identified by multifactorial unconditional logistic regression.Results:The study cohort comprised 3926 patients with gastric or colorectal cancer, 657 (16.7%) of whom had a total of 876 postoperative complications. Serious complications (Grade III and above) occurred in 4.0% of patients (156/3926). The rate of Grade V complications was 0.2% (7/3926). The cohort included 2271 patients with gastric cancer with a postoperative complication rate of 18.1% (412/2271) and serious complication rate of 4.7% (106/2271); and 1655 with colorectal cancer, with a postoperative complication rate of 14.8% (245/1655) and serious complication rate of 3.0% (50/1655). The incidences of anastomotic leakage in patients with gastric and colorectal cancer were 3.3% (74/2271) and 3.4% (56/1655), respectively. Abdominal infection was the most frequently occurring complication, accounting for 28.7% (164/572) and 39.5% (120/304) of postoperative complications in patients with gastric and colorectal cancer, respectively. The most frequently occurring grade of postoperative complication was Grade II, accounting for 65.4% (374/572) and 56.6% (172/304) of complications in patients with gastric and colorectal cancers, respectively. Multifactorial analysis identified (1) the following independent risk factors for postoperative complications in patients in the gastric cancer group: preoperative comorbidities (OR=2.54, 95%CI: 1.51-4.28, P<0.001), neoadjuvant therapy (OR=1.42, 95%CI:1.06-1.89, P=0.020), high American Society of Anesthesiologists (ASA) scores (ASA score 2 points:OR=1.60, 95% CI: 1.23-2.07, P<0.001, ASA score ≥3 points:OR=0.43, 95% CI: 0.25-0.73, P=0.002), operative time >180 minutes (OR=1.81, 95% CI: 1.42-2.31, P<0.001), intraoperative bleeding >50 mL (OR=1.29,95%CI: 1.01-1.63, P=0.038), and distal gastrectomy compared with total gastrectomy (OR=0.65,95%CI: 0.51-0.83, P<0.001); and (2) the following independent risk factors for postoperative complications in patients in the colorectal cancer group: female (OR=0.60, 95%CI: 0.44-0.80, P<0.001), preoperative comorbidities (OR=2.73, 95%CI: 1.25-5.99, P=0.030), neoadjuvant therapy (OR=1.83, 95%CI:1.23-2.72, P=0.008), laparoscopic surgery (OR=0.47, 95%CI: 0.30-0.72, P=0.022), and abdominoperineal resection compared with low anterior resection (OR=2.74, 95%CI: 1.71-4.41, P<0.001). Conclusion:Postoperative complications associated with various types of infection were the most frequent complications in patients with gastric or colorectal cancer. Although the risk factors for postoperative complications differed between patients with gastric cancer and those with colorectal cancer, the presence of preoperative comorbidities, administration of neoadjuvant therapy, and extent of surgical resection, were the commonest factors associated with postoperative complications in patients of both categories.
4.Effects of antibacterial absorbable suture closure in the repair of small range of bone defect wounds due to deep sternal wound infection after median thoracotomy
Hanhua LI ; Bing XIONG ; Zu'an LIU ; Zhifeng HUANG ; Chuanwei SUN ; Hongmin LUO ; Lianghua MA ; Huining BIAN ; Shaoyi ZHENG ; Wen LAI
Chinese Journal of Burns 2024;40(5):461-467
Objective:To investigate the effects of antibacterial absorbable suture closure in the repair of small range of bone defect wounds due to deep sternal wound infection after median thoracotomy.Methods:This study was a retrospective non-randomized clinical controlled study. A total of 32 patients (20 males and 12 females, aged (58±11) years) who met the inclusion criteria and underwent closure with antibacterial absorbable sutures (hereinafter referred to as direct closure surgery) admitted to Guangdong Provincial People's Hospital of Southern Medical University (hereinafter referred to as our hospital) from October 2017 to December 2021 were included in direct closure group. A total of 39 patients (27 males and 12 females, aged (59±11) years) who met the inclusion criteria and received bilateral pectoralis major muscle flap packing repair admitted to our hospital from January 2015 to January 2020, were included in muscle flap packing group. In the two groups, sternal infected wounds were thoroughly debrided during stage Ⅰ surgery, followed by wound repair during stage Ⅱ surgery. The width of sternal cross-section defects after debridement was less than 1 cm for patients in the two groups. For patients in direct closure group, stage Ⅱ wound repair involved intermittent sutures to the anterior sternal plate or full-thickness sternum with a total of 6 or 7 double sternal sutures. Relevant data including the duration of the stage Ⅱ wound repair surgery and the volume of blood loss during surgery, length of hospital stay, and bacterial wound infection of patients in the two groups were recorded. The postoperative complications and wound healing of patients in the two groups were recorded. During follow-up, the wound infection or recurrence of patients in the two groups and the sternal healing of patients in direct closure group were observed.Results:Compared with those in muscle flap packing group, the duration of stage Ⅱ wound repair surgery and length of hospital stay of patients in direct closure group were significantly shorter (with t values of 13.61 and 6.25, respectively, P<0.05), and there was no statistically significant difference in intraoperative blood loss volume of the stage Ⅱ wound repair surgery between the two groups ( P>0.05). The main bacterial infection in the two groups was Staphylococcus. In direct closure group, one patient had exudation in the wound two weeks post-operation, however the wound healed well after two weeks of conservative dressing changes; the wounds of the other patients healed well. In muscle flap packing group, 5 patients had postoperative complications, of which one patient died, and the wounds of 4 patients healed after dressing change or reoperation; the wounds of the other patients healed well. There was no statistically significant difference in complication incidence of patients between the two groups ( P>0.05). During the follow-up of 22-45 months, there was no re-infection or recurrence in the wound of patients in direct closure group and surviving patients in muscle flap packing group, the sternum of patients in the direct closure group achieved anatomical union. Conclusions:Direct closure surgery can not only effectively repair sternal cross-sectional defects with width below 1 cm due to deep sternal wound infections after median thoracotomy, but can also significantly shorten the operation time and duration of hospitalization.
5.Incidence of postoperative complications in Chinese patients with gastric or colorectal cancer based on a national, multicenter, prospective, cohort study
Shuqin ZHANG ; Zhouqiao WU ; Bowen HUO ; Huining XU ; Kang ZHAO ; Changqing JING ; Fenglin LIU ; Jiang YU ; Zhengrong LI ; Jian ZHANG ; Lu ZANG ; Hankun HAO ; Chaohui ZHENG ; Yong LI ; Lin FAN ; Hua HUANG ; Pin LIANG ; Bin WU ; Jiaming ZHU ; Zhaojian NIU ; Linghua ZHU ; Wu SONG ; Jun YOU ; Su YAN ; Ziyu LI
Chinese Journal of Gastrointestinal Surgery 2024;27(3):247-260
Objective:To investigate the incidence of postoperative complications in Chinese patients with gastric or colorectal cancer, and to evaluate the risk factors for postoperative complications.Methods:This was a national, multicenter, prospective, registry-based, cohort study of data obtained from the database of the Prevalence of Abdominal Complications After Gastro- enterological Surgery (PACAGE) study sponsored by the China Gastrointestinal Cancer Surgical Union. The PACAGE database prospectively collected general demographic characteristics, protocols for perioperative treatment, and variables associated with postoperative complications in patients treated for gastric or colorectal cancer in 20 medical centers from December 2018 to December 2020. The patients were grouped according to the presence or absence of postoperative complications. Postoperative complications were categorized and graded in accordance with the expert consensus on postoperative complications in gastrointestinal oncology surgery and Clavien-Dindo grading criteria. The incidence of postoperative complications of different grades are presented as bar charts. Independent risk factors for occurrence of postoperative complications were identified by multifactorial unconditional logistic regression.Results:The study cohort comprised 3926 patients with gastric or colorectal cancer, 657 (16.7%) of whom had a total of 876 postoperative complications. Serious complications (Grade III and above) occurred in 4.0% of patients (156/3926). The rate of Grade V complications was 0.2% (7/3926). The cohort included 2271 patients with gastric cancer with a postoperative complication rate of 18.1% (412/2271) and serious complication rate of 4.7% (106/2271); and 1655 with colorectal cancer, with a postoperative complication rate of 14.8% (245/1655) and serious complication rate of 3.0% (50/1655). The incidences of anastomotic leakage in patients with gastric and colorectal cancer were 3.3% (74/2271) and 3.4% (56/1655), respectively. Abdominal infection was the most frequently occurring complication, accounting for 28.7% (164/572) and 39.5% (120/304) of postoperative complications in patients with gastric and colorectal cancer, respectively. The most frequently occurring grade of postoperative complication was Grade II, accounting for 65.4% (374/572) and 56.6% (172/304) of complications in patients with gastric and colorectal cancers, respectively. Multifactorial analysis identified (1) the following independent risk factors for postoperative complications in patients in the gastric cancer group: preoperative comorbidities (OR=2.54, 95%CI: 1.51-4.28, P<0.001), neoadjuvant therapy (OR=1.42, 95%CI:1.06-1.89, P=0.020), high American Society of Anesthesiologists (ASA) scores (ASA score 2 points:OR=1.60, 95% CI: 1.23-2.07, P<0.001, ASA score ≥3 points:OR=0.43, 95% CI: 0.25-0.73, P=0.002), operative time >180 minutes (OR=1.81, 95% CI: 1.42-2.31, P<0.001), intraoperative bleeding >50 mL (OR=1.29,95%CI: 1.01-1.63, P=0.038), and distal gastrectomy compared with total gastrectomy (OR=0.65,95%CI: 0.51-0.83, P<0.001); and (2) the following independent risk factors for postoperative complications in patients in the colorectal cancer group: female (OR=0.60, 95%CI: 0.44-0.80, P<0.001), preoperative comorbidities (OR=2.73, 95%CI: 1.25-5.99, P=0.030), neoadjuvant therapy (OR=1.83, 95%CI:1.23-2.72, P=0.008), laparoscopic surgery (OR=0.47, 95%CI: 0.30-0.72, P=0.022), and abdominoperineal resection compared with low anterior resection (OR=2.74, 95%CI: 1.71-4.41, P<0.001). Conclusion:Postoperative complications associated with various types of infection were the most frequent complications in patients with gastric or colorectal cancer. Although the risk factors for postoperative complications differed between patients with gastric cancer and those with colorectal cancer, the presence of preoperative comorbidities, administration of neoadjuvant therapy, and extent of surgical resection, were the commonest factors associated with postoperative complications in patients of both categories.
6.Determination and effect of five alkaloids from extracts of Piper longum on rats with experimental myocardial ischemia induced by injection of pituitrin
Bowen YI ; Huining LIU ; Rui ZHENG ; Jiawei REN ; Yang LIU
Journal of Pharmaceutical Practice 2023;41(4):218-221
Objective To determine the content of five alkaloids from extracts of Piper longum and test the pharmacodynamic effect of them on rats with experimental myocardial ischemia induced by injection of pituitrin. Methods The content of five alkaloids was determined simultaneously by HPLC. The experimental myocardial ischemia in rats was induced by injection of pituitrin, and the absolute value of T wave change and change of heart rate before and after model establishment were chosen to be the observation index. The effects of large, medium and small dose groups were evaluated. Results Three batches of samples were analyzed, with the contents of piperine for 56.1%, 49.7%, 51.6%; N-isobutyl-(2E,4E)-octadecatrienamide for 4.5%, 4.2%, 4.3%; guineensine for 0.46%, 0.38%, 0.40%; piplartine for 1.73%, 1.67%, 1.70% and piperamide for 0.55%, 0.46%, 0.49%, respectively. All dose groups from extracts of piper longum had significantly reduced the absolute value of T wave and almost have no effect on the change of heart rate, except the high dose group showed the effect of reducing heart rate at some time . Conclusion The HPLC method was suitable for the simultaneous determination of five alkaloids from extracts of Piper longum. It was shown that extracts of Piper longum had good bioactivity in anti-myocardial ischemia.
7.Analysis on Components Absorbed into Blood of Citri Reticulatae Pericarpium in Rats Based on Sequential Metabolism and UPLC-HRMS
Hongjiao CHEN ; Wei LIU ; Xueyan LI ; Dongying QI ; Shuang YU ; Huining LIU ; Haibo LIU ; Yang LIU
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(9):179-187
ObjectiveTo study the metabolism of chemical components from Citri Reticulatae Pericarpium(CRP)in different parts of rats by sequential metabolism and ultra performance liquid chromatography-high resolution mass spectrometry(UPLC-HRMS). MethodSD male rats were employed as experimental subjects, and blood samples of intestinal metabolism and hepatic metabolism were prepared after administration of CRP ethanol extract by in situ intestinal perfusion, and comprehensive metabolic samples were collected after intragastric administration. UPLC-HRMS was used to analyze the samples with acetonitrile(A)-0.1% formic acid aqueous solution(B)as the mobile phase for gradient elution(0-10 min, 10%-30%A; 10-30 min, 30%-95%A; 30-31 min, 95%-10%A; 31-35 min, 10%A)at a flow rate of 0.35 mL·min-1, using a heated electrospray ionization with positive and negative ion mode scanning in the range of m/z 100-1 500. Under these conditions, the differences in the profiles of CRP ethanol extract, blank plasma and drug-containing plasma under different treatment groups were compared, and the chemical components of each sample were analyzed and identified based on the retention time, accurate relative molecular mass, primary and secondary ion fragments, and the information of reference substances. ResultA total of 44 chemical components were identified in the CRP ethanol extract, including flavone-O-glycosides, flavone-C-glycosides and polymethoxyflavonoids, etc. The results of sequential metabolism showed that 22 chemical components in CRP were detected in the intestinal metabolic sample, 18 chemical components were detected in the hepatic metabolic sample, and 9 identical chemical components(narirutin, hesperidin, meranzin, 5,7,8,3ʹ,4ʹ,5ʹ-hexamethoxy-flavone, isosinensetin, sinensetin, 3,5,6,7,8,3ʹ,4ʹ-heptamethoxyflavone, nobiletin and tangeretin)could be detected in all three metabolic samples, with a total of 22 compounds entering the blood in prototype form. ConclusionThe identified 21 components with well-defined structures entering the blood as prototypes may be potential active components of CRP, and differences in the components at different metabolic parts can provide an experimental basis for elucidating the in vivo biotransformation process of the metabolic components of CRP.
8.Evaluating the risk assessment method of occupational stress in workplaces
Aohe LIU ; Huining WANG ; Tenglong YAN ; Xiaowen DING ; Baolong LIU ; Jue LI ; Jisheng NIE
China Occupational Medicine 2023;50(6):626-631
{L-End}Objective To study and develop a suitable scale to identify and assess risks of occupational stress in workplaces of enterprises, and to explore the establishment of a workplace occupational stress risk assessment method aimed at guiding enterprises to improve working conditions based on the electronics industry in Beijing City. {L-End}Methods The initial version of the Workplace Occupational Stress Risk Assessment Scale (WOSRAS) was constructed based on literature review and expert evaluation. A total of 1 284 employees from four electronics enterprises in Beijing City were selected as the research subjects using a convenient sampling method. Item analysis and exploratory factor analysis were used to determine the final items of the scale and test its reliability and validity. The method of percentile norms was used to establish risk assessment method for the electronics industry workplace and its stress sources, and the cut-off values of low, medium, high risk was graded by the 50th and 80th percentiles of the total score and the score of each dimension of the risk assessment scale. {L-End}Results i) Based on item analysis and exploratory factor analysis, a WOSRAS consisting of six dimensions and 23 items was constructed, which could explain 63.2% of the total variation of occupational stress. The results of confirmatory factor analysis showed that the root mean square error of approximation and standardized root mean square residual were both <0.080, and the comparative fit index and Tucker-Lewis index were both >0.900. The total criterion validity of the scale was 0.816. The total Cronbach's α coefficient of the scale was 0.835, and the Spearman-Brown coefficient was 0.802. ii) The cut-off values of WOSRAS scores for high, medium and low risk in electronics industry were <53.0, 53.0-60.0 and >60.0,respectively. According to the result, the workplace stress risk levels of the production, research and development, and logistics departments of the electronics industry in Beijing were medium risk, while the management department was low risk. {L-End}Conclusion The WOSRAS constructed in this study has good reliability and validity. The proposed risk assessment method can reflect the actual risk status of enterprises in the electronic industry and is convenient for widespread application.
9.Study on the methods of individual occupational stress examination and assessment for workers in electronic industry
Yanping ZHANG ; Tenglong YAN ; Baolong LIU ; Qingsong CHEN ; Xiaowen DING ; Mingli BI ; Huining WANG ; Jue LI
China Occupational Medicine 2023;50(6):632-639
{L-End}Objective To explore the suitable methods for individual occupational stress examination and evaluation for workers in China based on the electronics industry. {L-End}Methods A total of 1 164 workers from four electronics enterprises in Beijing City were selected as the research subjects using a convenient sampling method. The Occupational Stress Measurement Scale, which was developed based on the Japanese Brief Job Stress Questionnaire, was used to assess the occupational stress of the research subjects, and test the reliability and validity of the scale. Percentile norms and T-score norms were established, and the T-scores of the three dimensions of stress reaction (psychological reaction and physical symptoms), stress factors, and social support were divided into five stages using the normal distribution method with
10.Analysis on occupational stress status of employees and its influencing factors in pharmaceutical enterprises in Beijing City
Jiaojiao SHA ; Huining WANG ; Baolong LIU ; Tenglong YAN ; Xiaowen DING ; Jue LI
China Occupational Medicine 2023;50(6):640-644
{L-End}Objective To analyze the current status of occupational stress and its influencing factors among workers in pharmaceutical enterprises in Beijing City. {L-End}Methods A total of 860 employees from six pharmaceutical enterprises in Beijing City were selected as the research subjects using convenience sampling method. The Chinese version of the New Brief Job Stress Questionnaire was used to evaluate the occupational stress, and multiple linear regression analysis was used to analyze the influencing factors of occupational stress. {L-End}Results The detection rate of high occupational stress was 1.40% (12/860). The results of multiple linear regression analysis showed that the workers with higher education level and longer length of service had a higher risk of high occupational stress (all P<0.01). Workers who were satisfied with their jobs had a lower risk of high occupational stress than those who were unsatisfied with their jobs (P<0.01). Workers who were satisfied with life had a significantly lower risk of high occupational stress than those who were unsatisfied with life (P<0.01). {L-End}Conclusion The detection rate of high occupational stress in workers of pharmaceutical enterprises is relatively low. Occupational stress is mainly affected by individual factors such as education level and length of service, and work and life satisfaction. Improving job and life satisfaction is helpful to reduce occupational stress level.

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