1.Hand-brain perception and movement training based on mirror neuron theory promote the recovery of upper limb function after a stroke
Meihong ZHU ; Hongjing BAO ; Linlin CHEN ; Yeping ZHENG ; Meifang SHI ; Ming ZENG ; Chenjie HU ; Huihong ZHAO ; Ya SUN
Chinese Journal of Physical Medicine and Rehabilitation 2024;46(10):887-892
Objective:To explore the effect of combining hand-brain perception training with hand-brain motor training based on mirror neuron theory on the recovery of upper limb function after a stroke.Methods:A group of 105 stroke survivors with upper limb dysfunction were randomly divided into a hand-brain perception (HP) group, a hand-brain motor (HM) group, and a combination (C) group, each of 35. In addition to conventional rehabilitation treatment (including exercise therapy, occupational therapy and physical factor therapy), the HP and HM groups were given hand-brain perception training and hand-brain motor training respectively, while group C was provided with both. Before the intervention and after 4 weeks, the upper limb motor functioning of all of the participants was assessed using the simplified version of the Fugl-Meyer upper limb motor function scale (FMA-UE). Sensory functioning was quantified using the tactile Semmes Weinstein monofilament examination (SWME), and the modified Barthel index (MBI) was used to quantify the participants′ ability in the activities of daily living.Results:After the intervention the average FMA-UE, MBI and SWME scores of all three groups had improved significantly, with group C′s average FMA-UE and MBI scores significantly better than the other two groups′ averages. The average SWME score of group C was then significantly better than that of group HM.Conclusions:Hand-brain perception combined with hand-brain motor training based on mirror neuron theory can further promote the recovery of upper limb sensory and motor functioning of stroke survivors., Such therapy is worthy of clinical promotion and application.
2.The influence of knocking down the expression of low-density lipoprotein receptor associated proteins on the vascular abnormalities in hepatocellular carcinoma and its mechanisms
Qiang WU ; Linlin ZHAN ; Yu WANG ; Yuchao HE ; Lu CHEN ; Ziye CHEN ; Guangtao LI ; Dongming LIU ; Xu BAO ; Xiaomeng LIU ; Hua GUO ; Tianqiang SONG
Chinese Journal of Oncology 2024;46(5):399-408
Objectives:To investigate the effect of the expression of low-density lipoprotein receptor associated protein (LDLR) on the vascular abnormalities in hepatocellular carcinoma (HCC) and its mechanisms.Methods:Based on the information of Oncomine Cancer GeneChip database, we analyzed the correlation between the expression level of LDLR and the expression level of carcinoembryonic antigen (CEA) and CD31 in hepatocellular carcinoma tissues. Lentiviral transfection of short hairpin RNA target genes was used to construct LDLR-knockdown MHCC-97H and HLE hepatocellular carcinoma cells. The differential genes and their expression level changes in LDLR-knockdown hepatocellular carcinoma cells were detected by transcriptome sequencing, real-time fluorescence quantitative polymerase chain reaction, and protein immunoblotting. The gene-related signaling pathways that involve LDLR were clarified by enrichment analysis. The effect of LDLR on CEA was assessed by the detection of CEA content in conditioned medium of hepatocellular carcinoma cells. Angiogenesis assay was used to detect the effect of LDLR on the angiogenic capacity of human umbilical vein endothelial cells, as well as the role of CEA in the regulation of angiogenesis by LDLR. Immunohistochemical staining was used to detect the expression levels of LDLR in 176 hepatocellular carcinoma tissues, and CEA and CD31 in 146 hepatocellular carcinoma tissues, and analyze the correlations between the expression levels of LDLR, CEA, and CD31 in the tissues, serum CEA, and alanine transaminase (ALT).Results:Oncomine database analysis showed that the expressions of LDLR and CEA in the tissues of hepatocellular carcinoma patients with portal vein metastasis were negatively correlated ( r=-0.64, P=0.001), whereas the expressions of CEA and CD31 in these tissues were positively correlated ( r=0.46, P=0.010). The transcriptome sequencing results showed that there were a total of 1 032 differentially expressed genes in the LDLR-knockdown group and the control group of MHCC-97H cells, of which 517 genes were up-regulated and 515 genes were down-regulated. The transcript expression level of CEACAM5 was significantly up-regulated in the cells of the LDLR-knockdown group. The Gene Ontology (GO) function enrichment analysis showed that the differential genes were most obviously enriched in the angiogenesis function. The Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis showed that the relevant pathways involved mainly included the cellular adhesion patch, the extracellular matrix receptor interactions, and the interactions with the extracellular matrix receptors. The CEA content in the conditioned medium of the LDLR-knockdown group was 43.75±8.43, which was higher than that of the control group (1.15±0.14, P<0.001). The results of angiogenesis experiments showed that at 5 h, the number of main junctions, the number of main segments, and the total area of the lattice formed by HUVEC cells cultured with the conditioned medium of MHCC-97H cells in the LDLR-knockdown group were 295.3±26.4, 552.5±63.8, and 2 239 781.0±13 8211.9 square pixels, which were higher than those of the control group (113.3±23.5, 194.8±36.5, and 660 621.0±280 328.3 square pixels, respectively, all P<0.01).The number of vascular major junctions, the number of major segments, and the total area of the lattice formed by HUVEC cells cultured in conditioned medium with HLE cells in the LDLR-knockdown group were 245.3±42.4, 257.5±20.4, and 2 535 754.5±249 094.2 square pixels, respectively, which were all higher than those of the control group (113.3±23.5, 114.3±12.2, and 1 565 456.5±219 259.7 square pixels, respectively, all P<0.01). In the conditioned medium for the control group of MHCC-97H cells,the number of main junctions, the number of main segments, and the total area of the lattice formed by the addition of CEA to cultured HUVEC cells were 178.9±12.0, 286.9±12.3, and 1 966 990.0±126 249.5 spixels, which were higher than those in the control group (119.7±22.1, 202.7±33.7, and 1 421 191.0±189 837.8 square pixels, respectively). The expression of LDLR in hepatocellular carcinoma tissues was not correlated with the expression of CEA, but was negatively correlated with the expression of CD31 ( r=-0.167, P=0.044), the level of serum CEA ( r=-0.061, P=0.032), and the level of serum ALT (r=-0.147, P=0.05). The expression of CEA in hepatocellular carcinoma tissues was positively correlated with the expression of CD31 ( r=0.192, P=0.020). The level of serum CEA was positively correlated with the level of serum ALT ( r=0.164, P=0.029). Conclusion:Knocking down LDLR can promote vascular abnormalities in HCC by releasing CEA.
3.The influence of knocking down the expression of low-density lipoprotein receptor associated proteins on the vascular abnormalities in hepatocellular carcinoma and its mechanisms
Qiang WU ; Linlin ZHAN ; Yu WANG ; Yuchao HE ; Lu CHEN ; Ziye CHEN ; Guangtao LI ; Dongming LIU ; Xu BAO ; Xiaomeng LIU ; Hua GUO ; Tianqiang SONG
Chinese Journal of Oncology 2024;46(5):399-408
Objectives:To investigate the effect of the expression of low-density lipoprotein receptor associated protein (LDLR) on the vascular abnormalities in hepatocellular carcinoma (HCC) and its mechanisms.Methods:Based on the information of Oncomine Cancer GeneChip database, we analyzed the correlation between the expression level of LDLR and the expression level of carcinoembryonic antigen (CEA) and CD31 in hepatocellular carcinoma tissues. Lentiviral transfection of short hairpin RNA target genes was used to construct LDLR-knockdown MHCC-97H and HLE hepatocellular carcinoma cells. The differential genes and their expression level changes in LDLR-knockdown hepatocellular carcinoma cells were detected by transcriptome sequencing, real-time fluorescence quantitative polymerase chain reaction, and protein immunoblotting. The gene-related signaling pathways that involve LDLR were clarified by enrichment analysis. The effect of LDLR on CEA was assessed by the detection of CEA content in conditioned medium of hepatocellular carcinoma cells. Angiogenesis assay was used to detect the effect of LDLR on the angiogenic capacity of human umbilical vein endothelial cells, as well as the role of CEA in the regulation of angiogenesis by LDLR. Immunohistochemical staining was used to detect the expression levels of LDLR in 176 hepatocellular carcinoma tissues, and CEA and CD31 in 146 hepatocellular carcinoma tissues, and analyze the correlations between the expression levels of LDLR, CEA, and CD31 in the tissues, serum CEA, and alanine transaminase (ALT).Results:Oncomine database analysis showed that the expressions of LDLR and CEA in the tissues of hepatocellular carcinoma patients with portal vein metastasis were negatively correlated ( r=-0.64, P=0.001), whereas the expressions of CEA and CD31 in these tissues were positively correlated ( r=0.46, P=0.010). The transcriptome sequencing results showed that there were a total of 1 032 differentially expressed genes in the LDLR-knockdown group and the control group of MHCC-97H cells, of which 517 genes were up-regulated and 515 genes were down-regulated. The transcript expression level of CEACAM5 was significantly up-regulated in the cells of the LDLR-knockdown group. The Gene Ontology (GO) function enrichment analysis showed that the differential genes were most obviously enriched in the angiogenesis function. The Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis showed that the relevant pathways involved mainly included the cellular adhesion patch, the extracellular matrix receptor interactions, and the interactions with the extracellular matrix receptors. The CEA content in the conditioned medium of the LDLR-knockdown group was 43.75±8.43, which was higher than that of the control group (1.15±0.14, P<0.001). The results of angiogenesis experiments showed that at 5 h, the number of main junctions, the number of main segments, and the total area of the lattice formed by HUVEC cells cultured with the conditioned medium of MHCC-97H cells in the LDLR-knockdown group were 295.3±26.4, 552.5±63.8, and 2 239 781.0±13 8211.9 square pixels, which were higher than those of the control group (113.3±23.5, 194.8±36.5, and 660 621.0±280 328.3 square pixels, respectively, all P<0.01).The number of vascular major junctions, the number of major segments, and the total area of the lattice formed by HUVEC cells cultured in conditioned medium with HLE cells in the LDLR-knockdown group were 245.3±42.4, 257.5±20.4, and 2 535 754.5±249 094.2 square pixels, respectively, which were all higher than those of the control group (113.3±23.5, 114.3±12.2, and 1 565 456.5±219 259.7 square pixels, respectively, all P<0.01). In the conditioned medium for the control group of MHCC-97H cells,the number of main junctions, the number of main segments, and the total area of the lattice formed by the addition of CEA to cultured HUVEC cells were 178.9±12.0, 286.9±12.3, and 1 966 990.0±126 249.5 spixels, which were higher than those in the control group (119.7±22.1, 202.7±33.7, and 1 421 191.0±189 837.8 square pixels, respectively). The expression of LDLR in hepatocellular carcinoma tissues was not correlated with the expression of CEA, but was negatively correlated with the expression of CD31 ( r=-0.167, P=0.044), the level of serum CEA ( r=-0.061, P=0.032), and the level of serum ALT (r=-0.147, P=0.05). The expression of CEA in hepatocellular carcinoma tissues was positively correlated with the expression of CD31 ( r=0.192, P=0.020). The level of serum CEA was positively correlated with the level of serum ALT ( r=0.164, P=0.029). Conclusion:Knocking down LDLR can promote vascular abnormalities in HCC by releasing CEA.
4.Monocytes to high-density lipoprotein cholesterol ratio predicts the early neurological deterioration and outcome in patients with acute anterior circulation ischemic stroke
Jing ZHANG ; Jianhua ZHAO ; Jieyu BAO ; Mengmeng CAI ; Linlin CHAO ; Dongbo LIU
International Journal of Cerebrovascular Diseases 2022;30(10):738-744
Objective:To investigate the monocyte to high-density lipoprotein cholesterol (HDL-C) ratio (MHR) for the predictive value of early neurological deterioration (END) and poor outcome in patients with acute anterior circulation ischemic stroke (AACIS).Methods:Patients with AACIS admitted to Henan Provincial People's Hospital from January 2021 to January 2022 were included retrospectively. END was defined as the National Institutes of Health Stroke Scale (NIHSS) score within 7 d of onset increase ≥2 compred with baseline or the increase of motor function score ≥1. The patients were divided into END group and non-END group according to the presence or absence of END. The patients were also divided into good outcome group (0-2 points) and poor outcome group (3-6 points) according to the modified Rankin Scale score 3 months after onset. Multivariate logistic regression analysis was used to determine the independent risk factors for END and poor outcome, and the predictive value of MHR for END and poor outcome was evaluated by receiver operating characteristic (ROC) curve. Results:A total of 522 patients were enrolled, including 338 male (64.8%), aged 61.99±11.39 years old. One hundred and five patients (20.1%) had END, 123 (23.6%) had poor outcome. Multivariate logistic regression analysis showed that baseline NIHSS score (odds ratio [ OR] 1.075, 95% confidence interval [ CI] 1.017-1.137; P=0.010) and MHR (with the lowest quartile as the reference, the third quartile: OR 2.778, 95% CI 1.255-6.151, P=0.012; the fourth quartile: OR 12.645, 95% CI 5.942-26.912; P<0.001) were the independent risk factors for END; the baseline NIHSS score ( OR 1.075, 95% CI 1.021-1.132; P=0.006), END ( OR 2.306, 95% CI 1.010-6.261; P=0.047) and MHR (with the first quartile as reference, the fourth quartile: OR 2.769, 95% CI 1.167-6.569; P=0.021) were the independent risk factors for poor outcomes. ROC curve analysis showed that area under the curve of MHR for predicting END and poor outcome in patients with AACIS were 0.805 (95% CI 0.750-0.860; P<0.001) and 0.747 (95% CI 0.690-0.803; P<0.001) respectively. The best cutoff value was 0.435, the sensitivity was 73.3% and 64.2%, and the specificity was 79.6% and 78.7% respectively. The area under the curve of MHR for predicting END and poor outcome was higher than that of monocyte and HDL-C alone. Conclusion:MHR can be used as a predictor of END and poor outcome in patients with AACIS, and its predictive value is higher than that of monocytes or HDL-C.
5.A broadly neutralizing human monoclonal antibody against the hemagglutinin of avian influenza virus H7N9.
Jingxin LI ; Li ZHANG ; Linlin BAO ; Yuxiao WANG ; Lin QIU ; Jialei HU ; Rong TANG ; Huiyan YU ; Jun SHAN ; Yan LI ; Chuan QIN ; Fengcai ZHU
Chinese Medical Journal 2022;135(7):799-805
BACKGROUND:
The new emerging avian influenza A H7N9 virus, causing severe human infection with a mortality rate of around 41%. This study aims to provide a novel treatment option for the prevention and control of H7N9.
METHODS:
H7 hemagglutinin (HA)-specific B cells were isolated from peripheral blood plasma cells of the patients previously infected by H7N9 in Jiangsu Province, China. The human monoclonal antibodies (mAbs) were generated by amplification and cloning of these HA-specific B cells. First, all human mAbs were screened for binding activity by enzyme-linked immunosorbent assay. Then, those mAbs, exhibiting potent affinity to recognize H7 HAs were further evaluated by hemagglutination-inhibiting (HAI) and microneutralization in vitro assays. Finally, the lead mAb candidate was selected and tested against the lethal challenge of the H7N9 virus using murine models.
RESULTS:
The mAb 6-137 was able to recognize a panel of H7 HAs with high affinity but not HA of other subtypes, including H1N1 and H3N2. The mAb 6-137 can efficiently inhibit the HA activity in the inactivated H7N9 virus and neutralize 100 tissue culture infectious dose 50 (TCID50) of H7N9 virus (influenza A/Nanjing/1/2013) in vitro, with neutralizing activity as low as 78 ng/mL. In addition, the mAb 6-137 protected the mice against the lethal challenge of H7N9 prophylactically and therapeutically.
CONCLUSION
The mAb 6-137 could be an effective antibody as a prophylactic or therapeutic biological treatment for the H7N9 exposure or infection.
Animals
;
Antibodies, Monoclonal/therapeutic use*
;
Antibodies, Neutralizing/therapeutic use*
;
Antibodies, Viral
;
Hemagglutinins
;
Humans
;
Influenza A Virus, H1N1 Subtype
;
Influenza A Virus, H3N2 Subtype
;
Influenza A Virus, H7N9 Subtype
;
Influenza Vaccines
;
Influenza in Birds
;
Influenza, Human/prevention & control*
;
Mice
6.Study on the construction of the perceived service quality evaluation index system for Internet hospitals
Yurong BAO ; Yue LOU ; Yinghui BAO ; Linlin JIANG ; Cheng CHEN
Chinese Journal of Hospital Administration 2022;38(4):285-289
Objective:To construct an evaluation index system of perceived service quality for Internet hospitals, and to provide references for scientific evaluation and effective management of such hospitals′ service quality.Methods:Thanks to literature review and expert interviews, an index system was initially built based on the Brady and Cronin model.From August to November 2021, Delphi expert consultation method was used in three rounds of correspondence questionnaire survey, and experts were consulted to assess the importance, familiarity and judgment basis of these indexes. The importance of the indexes was expressed by ± s, and the weight value of each index was calculated using analytic hierarchy process fuzzy comprehensive evaluation method and SPSS Au software. Results:The evaluation index system of perceived service quality for such hospitals included 3 level-1 indexes, namely environmental quality, interaction quality and result quality; and 10 level-2 indexes, namely software platform, service support, social factors, attitude, behavior, professional quality, service effect, service efficiency, service cost, satisfaction; and 30 level-3 indexes. Among these indexes, result quality of level-1 indexes scored the highest weight value(0.337); Software platform, professional quality, service support and attitude of level-2 indexes scored a higher weight values, respectively 0.119, 0.119, 0.109 and 0.109. Of level-3 indexes, reputation of Internet hospitals, service attitude of their doctors and doctor-patient communication skills of doctors online scored a higher weight values, respectively 0.102, 0.057 and 0.055.Conclusions:The index system for Internet hospital perceived service quality evaluation built in this study proved scientific, contributing positively to guiding Internet hospitals to improve their quality and safety management.
7.The relationship and optimization suggestions between medical treatment system and medical insurance system from the perspective of system theory, game theory and synergy theory
Yurong BAO ; Liping YING ; Sisi TANG ; Yinghui BAO ; Linlin JIANG ; Shijun ZHU
Chinese Journal of Hospital Administration 2021;37(8):627-630
The positive interaction between medical treatment system and medical insurance system is of great significance to promote the reform of medical and health care system. Due to the complexity of the relationship between them, it is difficult to explain it comprehensively with a single theoretical method. The authors analyzed the relationship between medical treatment system and medical insurance system by applying system theory, game theory and synergy theory, and then put forward policy suggestions to optimize the linkage reform of medical treatment system and medical insurance system, so as to better promote the reform of " three medical linkage" and promote the construction of healthy China. The suggestions included optimizing the allocation of health resources, accelerating the construction of medical insurance legislation and health technical evaluation system, strengthening the construction of multi-level medical insurance system, promoting the inter regional information interconnection between medical care and medical insurance, improving the coordination mechanism, negotiation mechanism, incentive and constraint mechanism between medical care and medical insurance.
8.Correlation between preoperative bile duct dilatation evaluation and prognosis of hilar cholangiocarcinoma
Xin XU ; Jianheng BAO ; Linlin WANG ; Zhonglian LI
Chinese Journal of General Surgery 2021;36(3):165-168
Objective:To evaluate the correlation between the prognosis of patients with hilar cholangiocarcinoma and the degree of bile duct dilatation in MRCP .Methods:The clinical data of 89 patients with hilar cholangiocarcinoma undergoing radical operation at Tianjin Nankai Hospital from Jan 2009 to Dec 2013 were analyzed retrospectively.Results:Tumor size ( P=0.024), Bismuth-Corlette classification ( P=0.048) and tumor stage ( P=0.013) were related factors of biliary dilatation. Tumor differentiation ( P=0.002), R 0 resection ( P=0.002) and biliary dilatation ( P<0.001) were independent predictors of disease-free survival (DFS). Conclusion:The imaging evaluation of the degree of biliary dilatation has a certain predictive value for the prognosis of patients with hilar cholangio-carcinoma.
9.Repurposing carrimycin as an antiviral agent against human coronaviruses, including the currently pandemic SARS-CoV-2.
Haiyan YAN ; Jing SUN ; Kun WANG ; Huiqiang WANG ; Shuo WU ; Linlin BAO ; Weiqing HE ; Dong WANG ; Airu ZHU ; Tian ZHANG ; Rongmei GAO ; Biao DONG ; Jianrui LI ; Lu YANG ; Ming ZHONG ; Qi LV ; Feifei QIN ; Zhen ZHUANG ; Xiaofang HUANG ; Xinyi YANG ; Yuhuan LI ; Yongsheng CHE ; Jiandong JIANG
Acta Pharmaceutica Sinica B 2021;11(9):2850-2858
COVID-19 pandemic caused by SARS-CoV-2 infection severely threatens global health and economic development. No effective antiviral drug is currently available to treat COVID-19 and any other human coronavirus infections. We report herein that a macrolide antibiotic, carrimycin, potently inhibited the cytopathic effects (CPE) and reduced the levels of viral protein and RNA in multiple cell types infected by human coronavirus 229E, OC43, and SARS-CoV-2. Time-of-addition and pseudotype virus infection studies indicated that carrimycin inhibited one or multiple post-entry replication events of human coronavirus infection. In support of this notion, metabolic labelling studies showed that carrimycin significantly inhibited the synthesis of viral RNA. Our studies thus strongly suggest that carrimycin is an antiviral agent against a broad-spectrum of human coronaviruses and its therapeutic efficacy to COVID-19 is currently under clinical investigation.
10.A multicenter study on the establishment and validation of autoverification rules for coagulation tests
Linlin QU ; Jun WU ; Wei WU ; Beili WANG ; Xiangyi LIU ; Hong JIANG ; Xunbei HUANG ; Dagan YANG ; Yongzhe LI ; Yandan DU ; Wei GUO ; Dehua SUN ; Yuming WANG ; Wei MA ; Mingqing ZHU ; Xian WANG ; Hong SUI ; Weiling SHOU ; Qiang LI ; Lin CHI ; Shuang LI ; Xiaolu LIU ; Zhuo WANG ; Jun CAO ; Chunxi BAO ; Yongquan XIA ; Hui CAO ; Beiying AN ; Fuyu GUO ; Houmei FENG ; Yan YAN ; Guangri HUANG ; Wei XU
Chinese Journal of Laboratory Medicine 2020;43(8):802-811
Objective:To establish autoverification rules for coagulation tests in multicenter cooperative units, in order to reduce workload for manual review of suspected results and shorten turnaround time (TAT) of test reports, while ensure the accuracy of results.Methods:A total of 14 394 blood samples were collected from fourteen hospitals during December 2019 to March 2020. These samples included: Rules Establishment Group 11 230 cases, including 1 182 cases for Delta check rules; Rules Validation Group 3 164 cases, including 487cases for Delta check; Clinical Application Trial Group 77 269 cases. Samples were analyzed for coagulation tests using Sysmex CS series automatic coagulation analyzers, and the clinical information, instrument parameters, test results, clinical diagnosis, medication history of anticoagulant and other relative results such as HCT, TG, TBIL, DBIL were summarized; on the basis of historical data, the 2.5 and 97.5 percentile of all data arranged from low to high were initially accumulated; on the basis of clinical suggestions, critical values and specific drug use as well as relative guidelines, autoverification rules and limits were established.The rules were then input into middleware, in which Stage I/Stage II validation was done. Positive coincidence, negative coincidence, false negative, false positive, autoverification pass rate, passing accuracy (coincidence of autoverification and manual verification) were calculated. Autoverification rules underwent trial application in coagulation results reports.Results:(1) The autoverification algorisms involve 33 rules regarding PT/INR, APTT, FBG, D-dimer, FDP,Delta check, reaction curve and sample abnormalities; (2)Autoverification Establishment Group showed autoverification pass rate was 68.42% (7 684/11 230), the false negative rate was 0%(0/11230), coincidence of autoverification and manual verification was 98.51%(11 063/11 230), in which positive coincidence and negative coincidence were respectively 30.09% (3 379/11 230) and 68.42%(7 684/11 230); Autoverification Validation Group showed autoverification pass rate was 60.37%(1 910/3 164), the false negative rate was 0%(0/11 230), coincidence of autoverification and manual verification was 97.79%(3 094/3 164), in which positive coincidence and negative coincidence were respectively 37.42%(1 184/3 164) and 60.37%(1 910/3 164); (3) Trialed implementation of these autoverification rules on 77 269 coagulation samples showed that the average TAT shortened by 8.5 min-83.1 min.Conclusions:This study established 33 autoverification rules in coagulation tests. Validation showedthese rules could ensure test quality while shortening TAT and lighten manual workload.

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