1.Comparison of clinical efficacy of evolocumab and probucol after PCI in patients with ultra-high-risk atherosclerotic cardiovascular disease
Yi YUAN ; Na LI ; Haiying SUN ; Jing SUN ; Yongqiang MA ; Yan WU ; Guohong YANG ; Junxiang LIU
China Pharmacy 2026;37(5):645-649
OBJECTIVE To compare the efficacy and safety of evolocumab and probucol in patients with ultra-high-risk atherosclerotic cardiovascular disease (ASCVD) following percutaneous coronary intervention (PCI). METHODS A retrospective analysis was conducted on 156 ultra-high-risk ASCVD patients who underwent PCI in our institution between January 1, 2023 and December 31, 2024. According to the lipid-lowering regimen, the patients were categorized into evolocumab group ( n =86) and probucol group ( n =70). Changes in lipid parameters [total cholesterol (TC), low-density lipoprot ein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, lipoprotein (a), and lipid goal achievement rate ] , inflammatory markers [interleukin-6 (IL-6) and C-reactive protein (CRP) ] , and cardiac function indices (left ventricular ejection fraction, left ventricular end-systolic diameter, left ventricular end-diastolic diameter, and N-terminal pro-B-type natriuretic peptide) were compared between two groups at baseline and after 6 months of treatment. The incidence of adverse clinical events during treatment, including acute myocardial infarction, in-stent restenosis, acute heart failure, cerebral hemorrhage, and stroke, was also evaluated. RESULTS No statistically significant differences were observed between the two groups at baseline ( P >0.05). After 6 months of treatment, both groups demonstrated significant improvements in lipid profiles (except HDL-C) and inflammatory markers compared to those at baseline ( P <0.05). The evolocumab group exhibited greater reductions in TC, LDL-C, IL-6, and CRP, along with a higher lipid target achievement rate, compared with the probucol group ( P <0.05). There were no statistically significant differences in the cardiac function-related indicators before and after treatment between the two groups, nor in the incidence of adverse events during the treatment ( P >0.05). CONCLUSIONS For ultra-high-risk ASCVD patients after PCI, both of the above treatment options are associated with improvements in blood lipid and inflammatory response, with good safety during short-term follow-up. Evolocumab shows superior efficacy in TC, LDL-C and inflammatory markers reduction and lipid target achievement, compared to probucol.
2.Practice and efficacy of refined management on antimicrobial agents in chest specialty hospital
Na ZHU ; Ye LI ; Haihua DING ; Yan YANG ; Rui JIANG ; Shuya XUE ; Xinli WU ; Yunling ZHANG
Chinese Journal of Infection Control 2025;24(11):1634-1640
Objective To explore the application efficacy of refined management on antimicrobial agents in a chest specialty hospital.Methods Multiple measures were implemented through perfecting management systems and processes,as well as conducting knowledge training,such as multi-dimensional specialized prescription reviewing,optimizing information systems,and implementing grid-based management of clinical pharmacist.A refined manage-ment mode for antimicrobial agents in a chest specialty hospital has been established.Antimicrobial management in-dicators for the whole hospital and each clinical specialty in 2023(before management)and 2024(after manage-ment)were analyzed.Results Compared with 2023,antimicrobial use rate among hospitalized patients in 2024 de-creased from 47.48%to 45.92%,and antimicrobial use density(AUD)decreased from 46.28 defined daily doses(DDDs)/(100 person·day)to 39.73 DDDs/(100 person·day).The ratio of antimicrobial cost to total drug cost decreased from 12.71%to 9.51%,and the per capita cost of antimicrobial use decreased from 1 344.18 Yuan to 975.52 Yuan.The use rate of prophylactic antimicrobial agents for class Ⅰ incision surgery increased from 84.48%to 89.52%,and the rationality rate increased from 69.25%to 94.53%.The management indicators of each clinical specialty improved significantly.Conclusion Through adopting a series of refined management measures,antimi-crobial management modes that are suitable for the actual situation of the hospital has been constructed,and obvious efficacy was achieved.Clinical application of antimicrobial agents is more standardized and rational.
3.Overexpression of Slc1a2 regulates Glu/GABA balance,inhibits ferroptosis and improves cognitive dysfunction in sleep-deprived mice
Fengying ZHANG ; Yonghong TANG ; Yanqing XIE ; Min LI ; Li JIANG ; Na WU ; Zhao PAN ; Yingfeng TANG ; Ling YUAN ; Yuanyuan HONG ; Hui LIU ; Ping ZHANG
Journal of China Medical University 2025;54(11):967-976
Objective To explore the effect and mechanism of Slc1a2 overexpression on cognitive dysfunction in sleep-deprived mice.Methods A total of 130 mice were divided into five groups:normal sleep(NS),NS+ov-Slc1a2,sleep deprivation(SD),SD+ov-NC,and SD+ov-Slc1a2,with 26 mice in each group.The SD mice model was established using an automatic system based on a rotating rod,and overexpress Slc1a2 adenovirus was injected into the prefrontal cortex(PFC).Immunofluorescence and Western blotting were used to detect the expression of Slc1a2 in the mouse PFC.Electrophysiological tests were used to evaluate non-rapid eye movement(NREM)sleep time,rapid eye movement(REM)sleep time,and wakefulness time in mice.Real-time quantitative PCR was used to detect the expression of glutamate(Glu)and gamma-aminobutyric acid(GABA)metabolic enzymes in the mouse PFC.Whole-cell patch-clamp recording was used to detect the frequency and amplitude of miniature excitatory postsynaptic currents(mEPSC)in mouse PFC.Immunofluorescence was used to detect the proportion of GABA-positive cells in the mouse PFC.The C11-BODIPY fluorescent probe was used to detect lipid reac-tive oxygen species(ROS)levels in mouse PFC.Commercial kits were used to detect Fe2+and malondialdehyde(MDA)levels in the mouse PFC.Cognitive function in mice was evaluated using the open field,novel object recognition,and Y-maze tests.Results Compared with the NS group,the NREM sleep time,REM sleep time,central area stay time,recognition index,and novel wall selection index increased significantly,while wakefulness time decreased significantly in the NS+ov-Slc1a2 group(all P<0.05).The percentage of Slc1a2+GFAP+cells,expression of Slc1a2 protein,expression of Glul,Slc6a1,and Abat mRNA,frequency and amplitude of mEPSC,and proportion of GABA-positive cells in the PFC increased significantly,whereas lipid ROS,Fe2+,and MDA levels decreased significantly(all P<0.05).Compared with the NS group,the NREM sleep time,REM sleep time,central area stay time,recognition index,and novel wall selection index of the SD group and the SD+ov-NC group were significantly decreased,whereas wakefulness time was significantly increased(all P<0.05).The percentage of Slc1a2+GFAP+cells,expression of Slc1a2 protein,expression of Glul,Slc6a1,and Abat mRNA,frequency and amplitude of mEPSC,and proportion of GABA-positive cells in the mouse PFC decreased significantly,whereas lipid ROS,Fe2+,and MDA levels increased significantly(all P<0.05).Compared with the SD and SD+ov-NC groups,the NREM sleep time,REM sleep time,central area stay time,recognition index,and novel wall selection index of the SD+ov-Slc1a2 group increased significantly,whereas the wakeful-ness time decreased significantly(all P<0.05).The percentage of Slc1a2+GFAP+cells,the expression of Slc1a2 protein,the expression of Glul,Slc6a1,and Abat mRNA,the frequency and amplitude of mEPSC,and the proportion of GABA-positive cells in the mouse PFC increased significantly,whereas lipid ROS,Fe2+,and MDA levels decreased significantly(all P<0.05).Conclusion Ectopic overexpres-sion of Slc1a2 in the PFC can improve sleep disorders in SD mice,reduce the damage caused by SD to excitatory synaptic transmission and GABAergic neuron function in the PFC,and alleviate cognitive impairment and anxiety-like behavior in these mice.Its mechanism may be related to the improvement of Glu/GABA metabolic imbalance in the PFC and inhibition of ferroptosis.
4.Visualization Analysis of Research Progress on Outpatient Services in Geriatric Pharmacy in China by CiteSpace
Qingfang WU ; Xiaoyu LI ; Kexin LIU ; Peng CHEN ; Na SU
Herald of Medicine 2025;44(8):1317-1321
Objective The purpose of this study is to utilize CiteSpace visualization software for literature analysis to investigate published literature concerning geriatric pharmacy outpatient services,create a knowledge graph,and analyze and discuss the developmental process and relevant hotspots of geriatric pharmacy outpatient services in China.Methods Utilizing the China National Knowledge Infrastructure(CNKI)as the source database,a search for literature containing the core phrases"pharmacy outpatient",'pharmacist outpatient","drug outpatient","drug consultation outpatient"and"elderly"was conducted from the inception of the database to March 2024 for data extraction.CiteSpace was employed to generate a visual knowledge graph,analyze,and discuss key nodes such as authors,institutions,and keywords within the realm of geriatric pharmacy outpatient services.Results After screening based on inclusion criteria,a total of 396 articles were included in the study.Scholars such as Ge Weihong,Wu Qiuhui and Liu Yang have made significant contributions to the research field of geriatric pharmacy outpatient services.Drum Tower Hospital affiliated with Nanjing University Medical School,the Sixth People's Hospital affiliated with Shanghai Jiao tong University,Dali University rank as the top three publishing institutions in terms of publication volume.The most frequently occurring keywords in the published literature include"pharmaceutical services","clinical pharmacists","pharmacy clinics","rational drug use"and"pharmacists".Conclusion"Drug safety","survey questionnaires"and"tertiary hospitals"have emerged as prominent and evolving topics within the realm of geriatric pharmacy outpatient services in China in recent years.In general,there remains considerable potential for further development in both the scope and depth of outpatient services for the elderly in the field of pharmacy in China.
5.Study on the consistency of ossification ratio between left and right sides in ultrasound assessment of bone age
Li ZHANG ; Na CHEN ; Mingcui WU ; Ruoyan WANG ; Chao ZHANG ; Xiaoli HU
China Medical Equipment 2025;22(1):68-71
Objective:To study whether the bone age of the left and right limbs in children was consistent when the ossification ratio was measured by ultrasound,and to compare this consistency between ultrasound bone age of left and right limbs,and the bone age that was determined by X-ray. Method:A total of 526 children aged 3 to 18 years,who were treated at the Affiliated Hospital of Guizhou Medical University from October 2022 to November 2023,were retrospectively included. The ossification ratios of the left and right ulna,radius,and femur of these children were measured by using ultrasound to calculate the bone age of ultrasound. Simultaneously,all children underwent X-ray examination on left-hand for bone age within two weeks before and after the ultrasonic examination for bone age. The differences in ossification ratios of the ulna,radius and femur of dual sides in assessing bone age by using ultrasound were compared,and the differences of assessing bone age among left ultrasound,right ultrasound and X-ray were further compared. Results:In the ultrasound test,Ossification rate of the left ulna was 48.0%,Less than 49.5% on the right side,The difference was statistically significant (W=25425.5,P<0.001),the left femoral ossification rate was 77.0%,Higher than 76.0% on the right side,The difference was statistically significant (W=57829,P=0.041). The overall ossification rate of the left ulna,radius,and femur was 184.0%,Below 185.0% on the right side,The difference was statistically significant (W=46314.5,P<0.001). The ultrasound bone age of the left limb was 10.1 years,Below 10.3 years on the right,The difference was statistically significant (W=67958.5,P<0.001). The median X-ray bone age of the included children was 10.2 years between ultrasound bone age and X-ray bone age (P>0.05). Conclusion:There is difference in the bone age between left and right side of limbs in assessing bone age by using ultrasound to detect ossification ratio. Therefore,the left and right sides should be assessed by using ultrasound to assess bone age.
6.Effects of Bushen Shengjing Tiaohe Qixue Prescription in Regulating Wnt/β-catenin Signaling Pathway on Diminished Ovarian Reserve Rats
Jun WANG ; Na TANG ; Chaoyang YE ; Ling LI ; Tongqing GAO ; Jiamei HUANG ; Qiang DENG ; Fengying WU ; Zhichun JIN
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(4):100-106
Objective To investigate the effects of Bushen Shengjing Tiaohe Qixue Prescription on rats with diminished ovarian reserve(DOR)based on Wnt/β-catenin signaling pathway.Methods Totally 60 8-week-old SD female rats were randomly divided into control group,model group,estradiol valerate group and TCM low-,medium-and high-dosage groups,with 10 rats in each group.Except for the control group,the rats in the other groups were given a single intraperitoneal injection of cyclophosphamide 75 mg/kg to replicate the DOR rat model.From the next day of modeling,the corresponding drugs was administered for medication groups by gavage for 3 weeks.The general conditions of the rats were observed,ELISA was used to detect the contents of serum follicle-stimulating hormone(FSH),luteinizing hormone(LH),estradiol(E2),anti-mullerian hormone(AMH)and inhibin B(INHB),HE staining was used to observe the morphologic changes in ovarian tissue,Western blot was used to detect GSK3β,β-catenin,CyclinD1 and c-MYC protein expressions in ovarian tissues,immunohistochemical staining was used to observe β-catenin expression in ovarian tissue,RT-qPCR was used to detect Wnt1,Wnt2,Wnt4,GSK3β,β-catenin,CyclinD1 and c-MYC mRNA expression in ovarian tissue,transmission electron microscopy was used to observe ultrapathologic structure of ovarian granulosa cells.Results Compared with the control group,the rats in the model group had reduced intake of food and water,slow or even reduced body mass gain,and disturbed estrous cycle,the serum contents of FSH and LH increased(P<0.01),the contents of E2,AMH and INHB decreased(P<0.01);the number of follicles of all levels in ovarian tissue was reduced,and there was increased number of atretic follicles with disturbed arrangement of the granulosa cells;the expression of GSK3β protein in ovarian tissue increased(P<0.01),the expression of β-catenin,CyclinD1 and c-MYC protein decreased(P<0.05,P<0.01),and β-catenin positive expression decreased(P<0.01),the expression of Wnt1,Wnt2,Wnt4,β-catenin,CyclinD1 and c-MYC mRNA in ovarian tissue decreased(P<0.01),GSK3β mRNA expression was increased(P<0,01);organelles such as mitochondria and nuclei of ovarian granulosa cells were highly swollen and partially lysed.Compared with the model group,the rats in the administered group all had different degrees of body mass increase,partial restoration of the motility cycle,serum FSH and LH contents decreased,and serum E2,AMH and INHB contents increased(P<0.01,P<0.05);the number of follicles at all levels in ovarian tissue increased to varying degrees,and the atretic follicles were reduced;the expression of GSK3β protein in ovarian tissue decreased,β-catenin,CyclinD1 and c-MYC protein expressions increased,β-catenin positive expression increased,the expression of Wnt1,Wnt2,Wnt4,β-catenin,CyclinD1 and c-MYC mRNA in ovarian tissue increased,and GSK3β mRNA expression decreased,with statistical significance in estradiol valerate group and TCM high-dosage group(P<0.05,P<0.01);mitochondria,endoplasmic reticulum and other organelles of ovarian granulosa cells were mildly to moderately swollen.Conclusion Bushen Shengjing Tiaohe Qixue Prescription can improve ovarian function and regulate serum sex hormone levels in DOR model rats,and its mechanism might be related to the activation of Wnt/β-catenin signaling pathway.
7.Characteristics and factors affecting treatment in hospitalized patients with abnormal uterine bleeding in sub-plateau region
Dan-feng DU ; Ru-juan WANG ; Rong-qun CHA ; Ping JIANG ; Li-qin WANG ; Xi CHEN ; Li-na YANG ; Zhi-yong WU
Fudan University Journal of Medical Sciences 2025;52(3):408-415,423
Objective To investigate the clinical characteristics of women with abnormal uterine bleeding(AUB)in sub-plateau regions and analyze the factors affecting their treatment methods.Methods AUB patients who were hospitalized from Jan 1,2018 to Dec 31,2022,in a sub-plateau region(Yongping County People's Hospital of Yunnan Province)with an average altitude of 1 620 meters were selected.The general clinical characteristics of the patients were summarized,and patients were classified into two categories(with or without uterine structural lesion)and nine subtypes(PALM-COEIN)according to the FIGO recommended etiological classification guidelines.Then the patients were divided into groups based on the presence or absence of uterine structural lesions,ethnic group(Han and minority),conservative drug treatment and surgical treatment groups,blood transfusion and non-blood transfusion groups.Binary Logistic regression analysis was used to identify factors affecting treatment methods.Results A total of 481 AUB patients enrolled,and the delayed consultation rate was as high as 80.46%,and the proportion of overweight and obese patients was 49.90%,which was higher than the average level among Chinese women.The main cause was AUB-O(AUB-ovulatory dysfunction),accounting for 78.59%of cases,the proportion of patients with delayed medical treatment was higher than those without delayed medical treatment(82.17%vs.74.47%).Patients who received blood transfusion were significantly younger,had lower hemoglobin(HGB)levels,fewer pregnancies,and lower BMI compared to those in the non-blood transfusion group(P<0.05).Univariate analysis showed that the surgical treatment group had older age,longer onset time,higher HGB levels,more pregnancies and deliveries,higher BMI,a higher proportion of Han ethnicity patients,lower rates of non-blood transfusion,higher rates of hypertension,and more uterine structural lesions compared to the conservative drug treatment group.Multivariate regression analysis revealed that blood transfusion treatment reduced the probability of surgical treatment.Age and uterine structural lesions were risk factors for requiring surgical treatment,for each additional year of age,the risk of undergoing surgical treatment increased by 10%.The risk of requiring surgical treatment for patients with uterine structural lesions was 2.987 times higher than for those without.Conclusion AUB patients in this sub-plateau regions have a high rate of delayed consultation and a high proportion of overweight and obesity,with AUB-O being the primary cause.Older age and the presence of uterine structural lesions were risk factors for requiring surgical treatment.
8.Characteristics and factors affecting treatment in hospitalized patients with abnormal uterine bleeding in sub-plateau region
Dan-feng DU ; Ru-juan WANG ; Rong-qun CHA ; Ping JIANG ; Li-qin WANG ; Xi CHEN ; Li-na YANG ; Zhi-yong WU
Fudan University Journal of Medical Sciences 2025;52(3):408-415,423
Objective To investigate the clinical characteristics of women with abnormal uterine bleeding(AUB)in sub-plateau regions and analyze the factors affecting their treatment methods.Methods AUB patients who were hospitalized from Jan 1,2018 to Dec 31,2022,in a sub-plateau region(Yongping County People's Hospital of Yunnan Province)with an average altitude of 1 620 meters were selected.The general clinical characteristics of the patients were summarized,and patients were classified into two categories(with or without uterine structural lesion)and nine subtypes(PALM-COEIN)according to the FIGO recommended etiological classification guidelines.Then the patients were divided into groups based on the presence or absence of uterine structural lesions,ethnic group(Han and minority),conservative drug treatment and surgical treatment groups,blood transfusion and non-blood transfusion groups.Binary Logistic regression analysis was used to identify factors affecting treatment methods.Results A total of 481 AUB patients enrolled,and the delayed consultation rate was as high as 80.46%,and the proportion of overweight and obese patients was 49.90%,which was higher than the average level among Chinese women.The main cause was AUB-O(AUB-ovulatory dysfunction),accounting for 78.59%of cases,the proportion of patients with delayed medical treatment was higher than those without delayed medical treatment(82.17%vs.74.47%).Patients who received blood transfusion were significantly younger,had lower hemoglobin(HGB)levels,fewer pregnancies,and lower BMI compared to those in the non-blood transfusion group(P<0.05).Univariate analysis showed that the surgical treatment group had older age,longer onset time,higher HGB levels,more pregnancies and deliveries,higher BMI,a higher proportion of Han ethnicity patients,lower rates of non-blood transfusion,higher rates of hypertension,and more uterine structural lesions compared to the conservative drug treatment group.Multivariate regression analysis revealed that blood transfusion treatment reduced the probability of surgical treatment.Age and uterine structural lesions were risk factors for requiring surgical treatment,for each additional year of age,the risk of undergoing surgical treatment increased by 10%.The risk of requiring surgical treatment for patients with uterine structural lesions was 2.987 times higher than for those without.Conclusion AUB patients in this sub-plateau regions have a high rate of delayed consultation and a high proportion of overweight and obesity,with AUB-O being the primary cause.Older age and the presence of uterine structural lesions were risk factors for requiring surgical treatment.
9.Establishment and application of ultra-fast real-time PCR for Brucella detection
Zhen-na XU ; Zhi-peng WU ; Wei-bin HONG ; Zhi-shen GUAN ; Qi-ming LIN ; Zuan-lan MO ; Yi-fei YE ; Hai-yan XIE ; Min LI ; Yan-qiu ZHU ; Xiao-jun LI ; Xian-peng ZHANG
Chinese Journal of Zoonoses 2025;41(3):278-283
This study was aimed at establishing a method of ultra-fast quantitative PCR for Brucella detection.We used an exogenous recombinant plasmid as the internal reference and targeted the T4SS secretion system,an important Brucella viru-lence factor,to design specific primers and probes.The sensitivity,specificity,and repeatability of this method were evaluated,and a standard curve was constructed.The coincidence rate of detection findings with this method versus quantitative PCR was determined.This method markedly decreased the detection time to only 10 minutes.The standard curve demonstrated a good linear relationship(Y=-3.410 7x+38.357,R2=0.998 5)with a low minimum detection limit of 10 copies/μL.The method exhibited good specificity and did not specifically amplify several common clinical bacteria other than Brucella.The de-tection of three concentrations of positive plasmids yielded coefficients of variation(CVs)of 0.20%to 0.91%,thus demonstra-ting the method's excellent repeatability.Furthermore,140 clinical samples were analyzed concurrently with the fluorescence PCR method,which yielded a 100%compliance rate and consistent results.Our findings indicated that the Brucella ultra-fast quantitative PCR was ultrafast;had high sensitivity,high specificity,and good specificity;and can be used for the clinical de-tection of Brucella and emergency investigation of epidemics.Therefore,this method is valuable for the early diagnosis of Bru-cella.
10.Analysis of risk factors for brucellar spondylitis
Na-na ZHAO ; Mei-gang ZHANG ; Xiang-lei CHEN ; Li ZHAO ; Cui-ping WU
Chinese Journal of Zoonoses 2025;41(3):284-289
The aim of this study was to investigate the risk factors for brucellar spondylitis.Electronic medical record data for patients with brucellosis at Yidu Central Hospital in Weifang City were retrospectively collected from January 2018 to April 2024,including general data,clinical characteristics,and laboratory examinations.The patients were divided into a spinal in-volvement group and a no spinal involvement group.The risk factors for brucellar spondylitis were determined through multi-factorial logistic regression model analysis.Of the 124 patients with brucellosis,59 had brucellar spondylitis,and 65 had bru-cellosis alone.There were more patients with age ≥55 years(x2=17.71),time from onset to diagnosis ≥30 days(x2=26.17),and low back pain(x2=52.71)in the spinal involvement group than in the group without spinal involvement,and the difference was statistically significant(all P<0.001);there were more patients with headaches in the group without spinal in-volvement than in the group with spinal involvement,and the difference was statistically significant(x2=8.34,P<0.05).and there were more patients in the spinal involvement group with neutrophil percent(NEU%)(t=2.94),platelet count(PLT)(t=122.00),blood sedimentation rate(ESR)(Z=-6.74),C-reactive protein(CRP)(Z=-5.74),and interleukin-6(IL-6)(Z=-2.08)were higher in the spine-involved group than in the group without spine-involvement,and the differences were all statistically significant(all P<0.05);Lactate dehydrogenase was significantly lower in the spine-involved group(LDH)than the group without spinal involvement(t=-2.04,P<0.042).A multifactorial logistic regression analysis indicated that a du-ration of out-of-hospital symptoms ≥30 days(OR=6.265,95%CI 1.181-33.241),symptoms of low back pain(OR=14.885,95%CI 3.144-70.472),elevated PLT(OR=1.013,95%CI 1.004-1.023),and elevated ESR(OR=1.053,95%CI 1.008-1.100)were risk factors for brucellar spondylitis(all P<0.05).The optimal cut-off values for ROC analysis were PLT>278.5 ×109/L(sensitivity 89.2%,specificity 59.3%)and ESR>16.5 mm/h(sensitivity 69.2%,specificity of 86.4%);using both PLT and ESR for diagnosis yielded an AUROC of 0.891(95%CI 0.831-0.950),a sensitivity of 86.2%,and a specificity of 84.7%.When patients with brucellosis present with symptoms of low back pain,a time from onset to diagnosis of ≥30 days,and markedly elevated ESR and PLT,lumbar magnetic resonance examination is recommended to rule out brucellar spondylitis,to enable early diagnosis and timely treatment,improve patient prognosis,shorten illness duration,and improve patient quality of life.

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