1.Correlation of mitochondrial genetic differentiation and spatial variables of Oncomelania hupensis robertsoni in Yunnan Province
Yuanyuan ZHANG ; Jing SONG ; Yuwan HAO ; Zaogai YANG ; Xinping SHI ; Siqi NING ; Hongqiong WANG ; Chunhong DU ; Jihua ZHOU ; Zongya ZHANG ; Kai LI ; Shizhu LI ; Yi DONG
Chinese Journal of Schistosomiasis Control 2026;38(1):54-59
Objective Objective To analyze the potential spatial factors affecting the genetic differentiation of Oncomelania hupensis robertsoni in Yunnan Province. Methods A total of 13 administrative villages were selected from schistosomiasis-endemic areas of Yunnan Province as O. hupensis snail sampling sites. At least 200 snails were collected in each site, and the spatial variable data of each site were recorded, including longitude, latitude and altitude. Thirty active and Schistosoma japonicum uninfected O. hupensis snails were selected from each sampling site by means of the crawling method and the cercarial shedding method. Genomic DNA was extracted from O. hupensis snails. Following PCR amplification, purification of PCR amplification products and sequencing, the gene sequences of O. hupensis snail samples were spliced and edited using the DNAstar software and the NCBI database to yield the complete mitochondrial sequences of O. hupensis snails at each sampling site, and the mitochondrial genetic distance matrix of O. hupensis robertsoni was calculated at each sampling site. The geographical coordinates of each sampling site were marked using the software ArcGIS 10.2, and the straight-line geographical distance between each sampling site was calculated. The altitude difference, longitude difference and latitude difference between each sampling site were calculated using the Excel software, and the correlation between the mitochondrial genetic distance matrix of O. hupensis robertsoni and each spatial variable matrix was examined by using the Mantel test at 13 sampling sites in Yunnan Province. Results Among the 13 O. hupensis snail sampling sites in Yunnan Province, the largest mitochondrial genetic distance of O. hupensis robertsoni snail populations was seen between Anding Village, Nanjian Yi Autonomous County and Caizhuang Village, Midu County (26.244 2), and the largest geographical distance was seen between Dongyuan Village, Gucheng District and Cangling Village, Chuxiong County (272.64 km). The highest altitude difference was seen between Anding Village, Nanjian Yi Autonomous County and Dongyuan Village, Gucheng District (1 086.10 m), and the largest longitude difference was found between Qiandian Village, Eryuan County and Cangling Village, Chuxiong County (1.86°), while the largest latitude difference was measured between Leqiu Village, Nanjian Yi Autonomous County and Dongyuan Village, Gucheng District (1.81°). In addition, the mitochondrial genetic distance of O. hupensis robertsoni snail populations was positively correlated with altitude at 13 snail sampling sites in Yunnan Province (r = 0.542 8, P < 0.001), and showed no significant correlations with geographical distance (r = 0.093 4, P > 0.05), longitude (r = −0.199 5, P > 0.05) or latitude (r = 0.205 7, P > 0.05). Conclusion Altitude may be a potential spatial factor affecting the genetic differentiation of O. hupensis robertsoni in Yunnan Province.
2.Analysis on factors affecting blood transfusion volume of obstetric patients in a tertiary hospital in Beijing
Lihui FU ; Chunya MA ; Yuanyuan LUO ; Xiaozhen GUAN ; Shengfei TAI ; Hongmei SHI ; Yang YU
Chinese Journal of Blood Transfusion 2026;39(8):1018-1025
Objective: To explore the influencing factors of blood transfusion volume in obstetric patients based on the national health development strategy, and to provide evidence for clinical transfusion management and maternal and infant safety. Methods: A total of 1 203 obstetric patients who received blood transfusion in a tertiary hospital in Beijing from 2013 to 2023 were enrolled retrospectively. Seventeen indicators including age, body mass index (BMI), hemoglobin and prothrombin time were selected as research variables. Descriptive analysis was conducted firstly. Scatter plot matrix was used to analyze the correlation between continuous variables and transfusion volume, and box plots were used to analyze the relationship between categorical variables and transfusion volume. Linear regression, logistic regression and random forest models were established for empirical analysis, and ROC curves and AUC values were compared to evaluate model performance. Results: Descriptive analysis showed that the distribution of obstetric blood transfusion volume was right-skewed, and multiple indicators were significantly correlated with transfusion volume. Linear regression indicated that 9 variables such as age, BMI and hemoglobin had linear correlation with transfusion volume. Logistic regression confirmed that 7 variables including BMI and hemoglobin were statistically correlated with the probability of massive blood transfusion. Random forest model screened the core influencing factors, which were ranked by importance: hemoglobin, prothrombin time, hematocrit, BMI, activated partial thromboplastin time, platelet count and age. The AUC values of logistic regression and random forest were 0.78 and 0.81 respectively, and the latter had better predictive performance. Conclusion: Prenatal anemia, coagulation disorders, advanced age, obesity, gestational hypertension, placental abnormalities and organ damage can increase the risk of massive blood transfusion in obstetric patients. The random forest model has better analytical and predictive ability in this study. The results can provide reference for accurate blood transfusion and risk prediction in obstetrics.
3.Mechanisms of Shuangshen Ningxin Capsules in Modulating NF-κB and MAPK Signaling Pathways to Reduce Cardiac Inflammation and Alleviate Myocardial Ischemia-reperfusion Injury in Rats
Shujuan XU ; Gaojie XIN ; Ce CAO ; Zixin LIU ; Yuanyuan CHEN ; Ran ZHAO ; Lu XING ; Yehao ZHANG ; Yue SHI ; Yanlei MA ; Jianhua FU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(23):83-91
ObjectiveTo investigate the effect and mechanism of Shuangshen Ningxin capsules (SSNX) in regulating the nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways to inhibit inflammation and alleviate myocardial ischemia-reperfusion injury (MIRI) in rats. MethodsThe 45 healthy male Sprague-Dawley (SD) rats were divided into sham operation group, model group, and SSNX capsules group (90 mg·kg-1). The left anterior descending coronary artery was ligated to establish the MIRI model. Cardiac function was evaluated by echocardiography, and microvascular reperfusion was analyzed using contrast echocardiography. Myocardial inflammation and injury were assessed by hematoxylin and eosin (HE) staining, immunohistochemistry, and TdT-mediated dUTP nick end labeling (TUNEL). The expression levels of cardiac inflammatory cytokines, including interleukin-1α (IL-1α), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA). Core differentially expressed genes (DEGs) and enriched pathways were screened by transcriptome sequencing. Real-time quantitative polymerase chain reaction (Real-time PCR) and Western blot were used to verify the mRNA expression of Toll-like receptor 2 (TLR2), chemokine (C-X-C motif) ligand 1 (CXCL1) and prostaglandin-endoperoxide synthase 2 (PTGS2), as well as the protein expression of Caspase-3, cleaved Caspase-3, p-NF-κB/NF-κB, phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2/ERK1/2) and p-p38 MAPK/p38 MAPK. ResultsCompared with the sham operation group, the ejection fraction (EF), fractional shortening (FS), stroke volume (SV) and cardiac output (CO) of the model group were significantly decreased (P<0.01), the peak time of myocardial perfusion was prolonged (P<0.01), hypoxia-inducible factor (HIF)-1α and α-smooth muscle actin (SMA) expression increased (P<0.01), the concentrations of inflammatory factors IL-1α, IL-6, TNF-α, TLR2, CXCL1 and PTGS2 increased (P<0.01), and the expression of cleaved Caspase-3, p-NF-κB/NF-κB, p-ERK1/2/ERK1/2 and p-p38 MAPK/p38 MAPK proteins was significantly increased (P<0.01). SSNX could improve cardiac function (P<0.05, P<0.01), and significantly shorten the peak time of myocardial perfusion (P<0.01). Moreover, it could also down-regulate HIF-1α and a-SMA expression (P<0.05, P<0.01), and reduce the concentrations of IL-1α, IL-6, TNF-α (P<0.01), and the mRNA expression of TLR2, CXCL1 and PTGS2 (P<0.01). Additionally, SSNX inhibited the apoptosis rate (P<0.01) and significantly reduced the expression of Cleaved Caspase-3, p-NF-κB/NF-κB, p-ERK1/2/ERK1/2 and p-p38 MAPK/p38 MAPK proteins (P<0.01). ConclusionSSNX can alleviate cardiac inflammation by regulating the NF-κB and MAPK signaling pathways, thereby effectively preventing and alleviating myocardial reperfusion injury.
4.Preliminary study on occupational internal exposure to 131I among nuclear medicine workers in a hospital in Nanjing
Jiayi MA ; Zihao ZHANG ; Yuanyuan ZHOU ; Qun CHEN ; Xiaoyong YANG ; Jin WANG ; Xiaodong SHI
Chinese Journal of Radiological Medicine and Protection 2025;45(10):1009-1014
Objective:To investigate the basic situation of occupational internal exposure to 131I among staff in the nuclear medicine department. Methods:Direct in- vitro measurements of thyroid doses from internal exposure were conducted for six months on 36 staff members of a hospital′s nuclear medicine department in Nanjing using the ORTEC Detective-100 portable high-purity germanium (HPGe) spectrometer. The cumulative effective doses were estimated, and the distribution of internal doses and their relationship with job type and external doses were analyzed. Results:During the monitoring period, a total of 203 monitorings were made. Of the monitoring result, 85.7% were below the recording level. Of the result exceeding the recording level, 12.8% were below the investigation level, while 1.5% exceeded the investigation level. The highest personal internal dose during the monitoring period was 2.54 mSv, the lowest was 0.015 mSv, and the median was 0.094 mSv.Conclusions:During the monitoring period, 14.3% of the monitored staff had result above the recorded levels. In the working environment of radionuclide treatment, there is no significant difference in the internal dose received between doctors, nurses, technicians, or other relevant personnel.
5.Regional molecular transmission characteristics of newly reported HIV-infected students aged ≥18 years in Nanjing City from 2016 to 2022
Hongjie SHI ; Sainan WANG ; Xin LI ; Sushu WU ; Rong WU ; Xin YUAN ; Jingwen WANG ; Xiaoyong SHENG ; Yuanyuan XU ; Zhengping ZHU
Chinese Journal of Preventive Medicine 2025;59(1):82-89
To analyze the transmission characteristics of newly reported HIV-infected students aged ≥18 years in Nanjing City from 2016 to 2022 and provide evidence for AIDS publicity and intervention among young students. The pol region sequences of newly reported HIV-infected students and non-student HIV-infected individuals in Nanjing City from 2016 to 2022 were collected, and the BLAST tool was used to search the published global non-Nanjing reported HIV infection sequences in the LANL HIV database. The basic molecular transmission network and regional molecular transmission network were constructed using the HIV-TRACE in a pairwise genetic distance threshold of 1.0%. 332 sequences of infected students aged≥18 years in Nanjing City, 1 904 sequences of non-student-infected individuals in Nanjing City and 1 698 non-Nanjing-infected individuals were obtained. Among the 332 infected students, the main route of infection was homosexual (96.39%), and the subtypes were CRF01_AE (37.95%), CRF07_BC (37.65%) and CRF105_0107 (10.24%). There were 890 sequences in the regional molecular transmission network, of which 21.80% were infected students in Nanjing City, 39.89% were non-student-infected individuals in Nanjing City, and 38.31% were non-Nanjing-infected individuals. In the CRF105_0107 transmission cluster, non-student-infected individuals from Nanjing accounted for 66.95% (81/121), while in the CRF07_BC transmission cluster, non-Nanjing-infected individuals accounted for 56.66% (200/353). There were 1 644 edges connected to infected students within the regional molecular transmission network, with local transmission accounting for 64.72% and regional transmission accounting for 35.28%. Regional transmission was mainly in Guangdong Province (19.83%) and other cities in Jiangsu Province (4.50%). The HIV-1 subtypes of newly reported HIV-infected students aged≥18 years in Nanjing City are mainly CRF01_AE, CRF07_BC and CRF105_0107, with local transmission as the main transmission characteristics. There is transmission between students and non-students.
6.Low contrast dose and low flow rate one-stop craniocervical CT angiography-cerebral CT perfusion for detecting carotid atherosclerosis
Yuanyuan CUI ; Rongrong FAN ; Qinling JIANG ; Xiaolei SHI ; An SUN ; Chenshi ZHANG ; Weimin YUAN ; Shiyuan LIU ; Yi XIAO
Chinese Journal of Medical Imaging Technology 2025;41(7):1144-1149
Objective To explore the value of low contrast dose and low flow rate one-stop craniocervical CT angiography(CT A)-cerebral CT perfusion(CTP)for detecting carotid atherosclerosis(CAS).Methods Totally 117 CAS patients were prospectively enrolled and divided into group A(n=19),B(n=52),C(n=46),and low contrast dose and low flow rate one-stop craniocervical CTA-brain CTP scanning,low contrast dose and low flow rate craniocervical CT A scanning,as well as conventional craniocervical CT A scanning were performed,respectively.Virtual monoenergetic images(VMI)of 40,50 and 60 keV were reconstructed in group A and B.The subjective and objective evaluations of image quality were compared among 3 groups.Results Subjective scores of image quality and diagnostic confidence of 40 and 50 keV VMI,and the diagnostic confidence of 60 keV VMI in group A and B were not significant different compared with those in group C(all P>0.05).Signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)of each segment of craniocervical blood vessels at 40 and 50 keV VMI in group A and B were all higher than those in group C(all P<0.05).CNR of cavernous sinus segment of internal carotid artery(C5 segment),horizontal segment of middle cerebral artery(MCA)(A1 segment),lateral sulcus segment of MCA(M2 segment)and basilar artery(BA)segment in group A at 60 keV VMI were all higher than those in group C(all P<0.05).SNR of C5 segment,A1 segment and BA segment,as well as CNR of BA segment of 60 keV VMI in group B were all higher than those in group C(all P<0.05).Conclusion Low contrast dose and low flow rate one-stop craniocervical was feasible for detecting CAS.
7.Investigations into the mechanisms underlying the regulatory effect of EPHA2 on keratinocyte proliferation and differentiation via ERK pathway in psoriasis
Xingyu JIANG ; Zengyang YU ; Rui MA ; Rongcan SHI ; Dawei HUANG ; Yuanyuan WANG ; Jiangluyi CAI ; Yuling SHI
Chinese Journal of Dermatology 2025;58(11):1042-1052
Objective:To investigate the expression of ephrin type-A receptor 2 (EPHA2) in psoriatic lesions and its effect on the proliferation and differentiation of normal human epidermal keratinocytes (NHEKs) .Methods:The GDS4602 dataset from the Gene Expression Omnibus (GEO) database was analyzed to determine EPHA2 gene expression changes in psoriatic lesions. Skin tissue samples were collected from 3 psoriasis patients and 3 healthy controls, and EPHA2 expression was determined in the skin tissues by immunofluorescence staining. Twelve female BALB/c mice were randomly divided into 3 groups (4 mice in each group) : a normal control group (receiving no treatment), an imiquimod group (topically treated with 62.5 mg of imiquimod 5% cream), and an imiquimod + ALWⅡ-41-27 group (topically treated with 62.5 mg of imiquimod 5% cream, followed by intraperitoneal injections of the EPHA2 inhibitor ALWⅡ-41-27 at a dose of 20 mg·kg -1·d -1) ; after 6 days of treatment, dorsal skin samples were harvested for hematoxylin-eosin (HE) staining, immunofluorescence staining was performed to determine the expression of EPHA2 and phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2), and real-time fluorescence-based quantitative PCR (qPCR) was conducted to determine the mRNA expression of the nuclear proliferation antigen Ki67, involucrin (Ivl), loricrin (Lor), and keratin 10 (Krt10). In vitro cultured NHEKs were divided into a control group (receiving no treatment), an M5 group (treated with 10 ng/ml M5 cytokines [including interleukin-17A, interleukin-22, interleukin-1α, oncostatin M and tumor necrosis factor-α]), an ALWⅡ-41-27 group (treated with 1 μmol/L ALWⅡ-41-27), and an M5 + ALWⅡ-41-27 group (treated with 10 ng/ml M5 and 1 μmol/L ALWⅡ-41-27) ; after 24 hours of treatment, the 5-ethynyl-2′-deoxyuridine (EdU) assay was performed to assess cellular proliferative activity, Western blot analysis to determine the expression of EPHA2, ERK and their phosphorylated proteins, and qPCR to determine the mRNA expression of KI67, IVL, LOR, and KRT10. One-way analysis of variance, Dunnett's T3 test, two-independent-sample t test, and paired t test were used for statistical analysis. Results:GEO database analysis revealed upregulated EPHA2 expression in psoriatic lesions compared with normal skin tissues from healthy controls ( t = 21.07, P < 0.001). Immunofluorescence staining showed increased EPHA2 expression in skin tissues from psoriasis patients and mouse models of psoriasis compared with those from healthy controls and normal control mice, respectively (both P < 0.01). In the animal experiments, the imiquimod group showed thicker epidermis, increased Ki67 mRNA expression, decreased mRNA expression of Ivl, Lor, and Krt10, and elevated p-ERK1/2 expression compared with the normal control group and imiquimod + ALWⅡ-41-27 group (all P < 0.05). In the cell experiments, the M5 group showed an increased proportion of EdU-positive cells (35.61% ± 1.18% vs. 24.83% ± 0.60% and 12.49% ± 1.52%, t = 8.12, 12.00, P = 0.015, 0.001, respectively), increased KI67 mRNA expression, and decreased mRNA expression of IVL, LOR, and KRT10 compared with the control group and M5 + ALWⅡ-41-27 group (all P < 0.05) ; Western blot analysis revealed that the expression levels of EPHA2, p-EPHA2, and p-ERK1/2 in NHEKs were significantly higher in the M5 group than in the control group and M5 + ALWⅡ-41-27 group (all P < 0.05), but there was no significant difference in the ERK1/2 protein expression among groups ( P > 0.05) . Conclusion:EPHA2 expression was upregulated in psoriatic lesions, which may promote keratinocyte proliferation and inhibit its differentiation, possibly via the ERK pathway.
8.Application of f-wave to QRS complex amplitude ratio in PICC tip positioning for patients with atrial fibrillation
Lihua SHI ; Rongrong YANG ; Lihong LIAO ; Jing GUO ; Qiu SUN ; Yuanyuan GONG ; Jiabao YE ; Jianfang ZHANG
Chinese Journal of Nursing 2025;60(13):1553-1557
Objective To evaluate the clinical utility of the f-wave to QRS complex amplitude ratio(f/R ratio)in intracardiac electrogram(IC-ECG)-guided positioning of peripherally inserted central catheter(PICC)tips in patients with atrial fibrillation(AF),providing evidence to enhance clinical practice.Methods This study employed a conve-nience sampling method to enroll eligible AF patients admitted to a tertiary hospital in Suzhou from July 2023 to July 2024.During PICC placement,IC-ECG was utilized to monitor f-wave and QRS complex amplitude variations.Following successful catheterization,the f/R ratio was measured,and chest X-ray was performed to confirm the catheter tip position.The accuracy of PICC tip positioning across different f/R ratio ranges was analyzed,and the incidence of arrhythmias was recorded.A receiver operating characteristic curve was constructed to assess the diag-nostic performance of the f/R ratio in PICC tip localization.Results A total of 68 AF patients were included,with f/R ratios ranging from 20.63%to 91.24%.PICC tip positioning accuracy varied significantly across different f/R ratio ranges(P=0.006).The area under the ROC curve(AUC)for f/R ratio in PICC tip positioning was 0.784(P=0.009),with a maximum Youden index of 0.567,an optimal diagnostic threshold of 40.00%,a sensitivity of 81.7%,a speci-ficity of 75.0%,a positive predictive value of 96.1%,and a negative predictive value of 35.3%.No arrhythmias other than AF occurred during the procedure.Conclusion The f/R ratio provides reliable and safe guidance for PICC tip positioning in AF patients.An f/R ratio ≥40%is associated with higher accuracy in identifying the optimal catheter tip position.
9.Prevalence and risk factors of falls in patients with knee osteoarthritis:a Meta-analysis
Yueyue JIA ; Zhilan YANG ; Yanping ZHAI ; Hongrui SHI ; Huimin ZHAO ; Yuanyuan JIN ; Xingyu LIU ; Zhili YAN ; Ziwei TIAN
Chinese Journal of Nursing 2025;60(10):1177-1183
Objective To clarify the evidence of the frequency and risk factors for falls in knee osteoarthritis(KOA)of adults by meta-analysis.Methods Computerized searches of the CNKI,VIP,Wanfang data,CBM,PubMed,Cochrane Library,Embase,Web of Science were conducted for literature on risk factors for falls in adults with KOA from the inception of the databases to August 2024.After literature screening,data extraction,and quality evaluation,RevMan 5.4 software was used for Meta-analysis.Results A total of 26 articles were involved.Meta-analysis result showed that the rate of falls was 29.0%.Factors associated with increased risk of falls included being female(OR=1.35),decreased lower limb muscle strength(OR=1.72),decreased knee flexion muscle strength(OR=7.05),decreased static posture stability(OR=1.28),opioid use(OR=1.79),antidepressant use(OR=1.69),frequent stair climbing(OR=7.58),combined neurological disease(OR=1.77),history of falls(OR=3.29)and fear of falling(OR=2.54).Conclusion The rate of falls of patients with KOA is high.The adults with KOA who are women,have lower muscle strength of lower limbs and knee flexion muscle strength,poorer static posture stability,use opioids,antidepressant,frequent stair climbing,combined neurological disorders,previous falls in the past year and fear of falls are at higher risk of falls.Healthcare professionals should dynamically assess and detect the risk of falls in the patients with KOA and adopt targeted,individualized interventions to prevent falls.
10.Effect and mechanism of HER2 antibody-drug conjugate combined with anti-PD-1 antibody in mouse bladder cancer models
Shuo HE ; Lu TAO ; Yue WU ; Mengting SHI ; Tiantian ZHANG ; Yuanyuan GUO ; Rui WANG
Journal of Army Medical University 2025;47(14):1623-1631
Objective To investigate the synergistic therapeutic effects of HER2 antibody-drug conjugate(HER2-ADC)combined with anti-PD-1 antibody(anti-PD-1)on HER2-expressing bladder cancer and elucidate its regulatory mechanisms on the tumor immune microenvironment.Methods Orthotopic tumor models were established in 40 female C57BL/6 mice(6~8 weeks old,body mass 18~22 g)using MB49 bladder cancer cells overexpressing human HER2.When tumors reached 100 mm3,the mice were randomized into(n=10)control(intraperitoneal injection of 1.0 mL PBS),anti-PD-1(200 μg per mouse every 3 d),HER2-ADC(2.5 mg/kg once weekly),and combination groups(same regimens as above monotherapy).Tumor volume and body mass were measured every 3 d during 28-day treatment.Tumor growth kinetics and survival rates were analyzed.Post-treatment survival was monitored until natural death to determine median survival time(n=5).At day 28,blood and tumor samples(n=5)were collected to detect myeloid-derived suppressor cells(MDSCs;CD11b?Gr1?)and regulatory T cells(Tregs;CD4?CD25?FOXP3?)with flow cytometry,tumor-infiltrating CD3?T,CD8?T,and FOXP3?T cells with immunohistochemical assasy,and liver/kidney functions[alanine aminotransferase(ALT),aspartate aminotransferase(AST),blood urea nitrogen(BUN),creatinine(CRE)]and tissue damage indicators[lactate dehydrogenase isoenzyme(LDH-L)].Results In 28 d after treatment,the combination group obtained significantly smallest tumor volume than the control group and the 2 monotherapy groups(all P<0.01).The longest median survival was observed in the combination group(65 d,P<0.01),followed by the HER2-ADC group(55 d),anti-PD-1 group(53 d)and control group(41 d).After 28 d of treatment,the combination group exhibited obviously the smallest peripheral proportions of MDSCs/Tregs,most tumor-infiltrating CD3?T/CD8?T cells,and less FOXP3?T cells when compared with the 2 monotherapy groups and control group(all P<0.05).While,the 2 monotherapy groups had smaller MDSCs/Tregs proportions than the control group(P<0.05).No significant differences were observed among the 4 groups in serum ALT,AST,BUN,CRE,or LDH-L levels,and all of them were within normal ranges.Conclusion HER2-ADC combined with anti-PD-1 suppresses the growth of orthotopic bladder tumor,probably through their synergic effects on down-regulating MDSCs/Treg and enhancing CD8?T cell infiltration.

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