1.Epidemiological characteristics and disease burden of liver cancer in Guangdong Province
Ying ZHANG ; Yixuan CHEN ; Rong CAO ; Yue GAO ; Yutong HAN ; Ye WANG ; Ruilin MENG ; Xueyan ZHENG ; Yu LIAO ; Zhuanping ZENG
Journal of Public Health and Preventive Medicine 2026;37(1):68-72
Objective To analyze the epidemiological characteristics and disease burden of liver cancer in Guangdong Province in 2020, and to provide a scientific foundation for the development of regionalized prevention and control strategies for liver cancer. Methods According to the cancer registry data of Guangdong Province, the incidence, mortality and age-standardized rate by Chinese standard population in 2020 were calculated to analyze the epidemiological characteristics of liver cancer. The disability adjusted life years (DALYs), year of life loss (YLL), year of lived with disability (YLD), and cause-eliminated life expectancy were used to assess the disease burden of liver cancer. Results In 2020, the crude incidence rate and the age-standardized incidence rate of liver cancer in Guangdong Province were 27.79/100 000 and 20.84/100 000,respectively, and the crude mortality rate and the age-standardized mortality rate of liver cancer were 25.49/100,000 and 17.64/100 000, respectively. The total DALY and DALY rate of liver cancer in Guangdong Province were 515 311 person-years and 513.83/100 000, respectively. After eliminating the causes of death from liver cancer, the life expectancy in Guangdong Province increased from 84.60 years to 84.99 years. All indicators consistently demonstrated that the burden of liver cancer was higher in males than that in females, and the burden of liver cancer was higher in rural areas than that in urban areas. Conclusion Liver cancer in Guangdong Province exhibits a high incidence, mortality and disease burden level in 2020. There are obvious differences of gender, age and region in cancer burden. It is necessary to strengthen liver cancer screening and diagnosis and treatment in men, the elderly and those in rural areas to reduce the burden of liver cancer gradually in Guangdong Province.
2.Visual quality after different interval spherical lens optometry-guided small-incision lenticule extraction for the correction of low-to-moderate myopia
Hongli* MA ; Xueying* SONG ; Shiyang LI ; Xueyan LIU ; Hong SU ; Xiaoniu ZHANG
International Eye Science 2025;25(9):1413-1419
AIM: To compare the visual quality in patients with low-to-moderate myopia after 0.05 D interval spherical lens optometry-guided small-incision lenticule extraction(SMILE)and conventional 0.25 D interval spherical lens optometry-guided SMILE.METHODS: Retrospective study. A total of 400 cases(400 eyes)with low-to-moderate myopia that underwent SMILE in the ophthalmology department of 989th Hospital of Joint Logistic Support Force from August 2021 to August 2023 were enrolled and the data from the right eyes were collected for analysis. According to the method of optometry test modality, they were divided into 0.05 D group and 0.25 D group, with 200 eyes in each group. The differences were compared between the two groups of patients in intraoperative corneal ablation thickness, uncorrected distance visual acuity(UDVA), high-order corneal aberrations(HOA), spherical aberrations, vertical coma, horizontal coma and trefoil aberrations before and at 1, 3 and 6 mo after surgery. Additionally, the percentage of eyes with residual spherical equivalent(SE)≤±0.25 D, postoperative visual symptoms and scores on the quality of visual(Qov)were compared between the two groups at 6 mo after surgery.RESULTS: The corneal ablation thickness in the 0.05 D group was 92.78±16.56 μm, which was slightly higher than that in the 0.25 D group(83.24±17.33 μm; P<0.001). The UDVA at each postoperative time point in the 0.05 D group was superior to that in the 0.25 D group(all P<0.001). The HOA, spherical aberration, horizontal coma and vertical coma in the two groups at 1, 3 and 6 mo after operation were higher than those before operation(all P<0.05). The spherical aberration in the 0.05 D group at each time point after surgery were higher than those in the 0.25 D group, and vertical coma were lower than those in the 0.25 D group(all P<0.05). At 6 mo postoperatively, the percentage of eyes with residual SE ≤±0.25 D in the 0.05 D group was 97.5%(195 eyes), which was higher than 87.5%(175 eyes)in the 0.25 D group(P<0.05). The most common adverse visual symptoms after SMILE in both groups were hazy vision and glare. The total Qov score in the 0.05 D group was 0.35(0.24, 0.55), which was lower than [0.62(0.32, 0.89)] in the 0.25 D group(P<0.05).CONCLUSION: Compared with conventional 0.25 D interval spherical lens optometry-guided SMILE, the 0.05 D interval spherical lens optometry-guided SMILE for the correction of low-to-moderate myopia has better predictability and can achieve better vision and visual quality.
3.A Mouse Model and Mechanism Study of Premature Ovarian Insufficiency Induced by Different Concentrations of Cyclophosphamide
Leilei GONG ; Xiaoxia WANG ; Xuewei FENG ; Xinlei LI ; Han ZHAO ; Xueyan ZHANG ; Xin FENG
Laboratory Animal and Comparative Medicine 2025;45(4):403-410
ObjectiveTo observe and compare the effects of different concentrations of cyclophosphamide (CTX) in inducing premature ovarian insufficiency (POI) model in mice and investigate the mechanism of injury. MethodsThirty-two 6~8-week-old female C57BL/6J mice were randomly divided into four groups (n=8 per group) using a weight-based block randomization method. The POI model was established via a single intraperitoneal injection of 75 mg/kg cyclophosphamide (CTX), 120 mg/kg CTX, 120 mg/kg CTX + 12 mg/kg Busulfan, or an equivalent volume of normal saline (control). Ovarian coefficients, serum estradiol (E2) and follicle-stimulating hormone (FSH) levels were measured. Western blotting was performed to assess changes in ovarian expression levels of NAD-dependent deacetylase sirtuin-5 (SIRT5) and forkhead box O3a (FOXO3a) under different modeling conditions. After determining the optimal CTX concentration for modeling, an additional forty 6~8-week-old femal C57BL/6J mice were randomly divided into five groups (n=8 per group) using a weight-based block randomization method: saline control, 120 mg/kg CTX sampling at 1, 2, 7, or 14 days after modeling. Western blotting was used to evaluate temporal changes of ovarian SIRT5 and FOXO3a protein expression. ResultsCompared with the saline control, all concentrations of CTX (75 mg/kg CTX, 120 mg/kg CTX) and 120 mg/kg CTX + 12 mg/kg Busulfan induced POI injury in mice. The 120 mg/kg CTX group exhibited smaller changes in ovarian coefficients (P<0.001) and E2 levels (P<0.05), whereas the 120 mg/kg CTX + 12 mg/kg Busulfan group showed rough and reduced luster fur, sluggish response and was in the worst state. Compared with the saline control group, FOXO3a expression was significantly down-regulated (P<0.05), while SIRT5 remained unchanged in the 75 mg/kg CTX group (P>0.05). In contrast, both SIRT5 (P<0.05) and FOXO3a (P<0.05) were significantly down-regulated in the 120 mg/kg CTX group. Further analysis revealed that on day 2 and 7 after 120 mg/kg CTX modeling, the expressions of SIRT5 (P<0.01) and FOXO3a (P<0.001) were significantly down-regulated, with the largest decrease observed on day 7 (SIRT5, P<0.000 1; FOXO3a, P<0.000 1). ConclusionOvarian injury in the POI model induced by 120 mg/kg CTX is milder than that in the POI model induced by 75 mg/kg CTX. Moreover, the expression changes of SIRT5 and FOXO3a are most significant on day 7 after modeling induced by 120 mg/kg CTX, which may be related to the inhibition of the SIRT5-FOXO3a signaling pathway.
4.Comparison of the efficacy of saline irrigation following mesh basket lithotripsy and mesh basket combined with balloon lithotripsy for choledocholithiasis
Jun MI ; Zhenjuan LI ; Shanshan XU ; Sai MA ; Hao ZHANG ; Jiaxin LI ; Runzhao QUAN ; Manman LU ; Xueyan WANG ; Hui DING ; Xiuqi WANG ; Xiuling LI
Chinese Journal of Digestive Endoscopy 2025;42(7):539-544
Objective:To compare the efficacy of saline irrigation following mesh basket lithotripsy and mesh basket combined with balloon lithotripsy for choledocholithiasis.Methods:Data of 76 patients who received endoscopic retrograde cholangiopancreatography (ERCP) for choledocholithiasis in Henan Provincial People's Hospital from May 2021 to May 2023 were retrospectively analyzed. Among them, 30 patients underwent saline irrigation of the biliary tract after mesh basket lithotripsy (the saline group), while 46 patients underwent mesh basket combined with balloon lithotripsy (the balloon group). The procedure success rate, operation time, procedure cost, and incidence of postoperative complications were compared.Results:The stone extraction success rates were 100.0% in both groups. The operation time in the saline group was shorter than that in the balloon group [20.0 (16.0, 27.5) min VS 29.0 (22.0, 33.3) min, Z=-2.88 , P=0.004]. The procedure cost in the saline group was lower than that in the balloon group [13 466.5 (13 318.0, 13 784.0) yuan VS 16 209.0 (15 989.0, 16 327.8) yuan, Z=-6.37 , P<0.001]. There was no significant difference in the incidence of postoperative fever, cholangitis or pancreatitis between the two groups ( P>0.05). Conclusion:Compared with mesh basket combined with balloon lithotripsy, saline irrigation of the biliary tract after mesh basket lithotripsy can shorten the operation time, reduce the procedure cost, and maintain a high procedure success rate for treating choledocholithiasis.
5.Safety and efficacy of PED Shield in intracranial unruptured saccular aneurysms
Runze GE ; Xin FENG ; Xueyan DENG ; Zehui XIE ; Can LI ; Shuyin LIANG ; Shixing SU ; Xin ZHANG ; Xifeng LI ; Chuanzhi DUAN
Chinese Journal of Neuromedicine 2025;24(7):649-655
Objective:To investigate the safety and efficacy of Pipeline embolization device (PED) Shield in intracranial unruptured saccular aneurysms.Methods:This is a retrospective cohort study; 124 patients with intracranial unruptured saccular aneurysms treated with PED Shield at Department of Cerebrovascular Surgery, Neurosurgery Center, Zhujiang Hospital, Southern Medical University from July 2023 to October 2024 were enrolled. Intraoperative device-related complications and occurrence of hemorrhagic and ischemic complications within 30 days of the procedure were recorded. The clinical results and imaging results (degrees of stent patency and aneurysm occlusion rate) 6 months after follow-up were statistically analyzed. Modified Rankin scale (mRS) score>2 was defined as poor prognosis in clinical follow-up, and grade D according to O'Kelly Marotta (OKM) classification was considered as complete aneurysm occlusion in imaging follow-up.Results:Eighty-seven females and 37 males, aged (56.44±12.17) years (ranging from 27 to 80 years) were enrolled, with a maximum aneurysm diameter of 5.12 (3.73, 7.24) mm. Among the 124 patients, incidence of intraoperative instrument-related complications was 6.5% (8/124); and within 30 days of the procedure, incidence of ischemic complications was 4.8% (6/124) and that of hemorrhagic complications was 1.6% (2/124). Eighty-four patients had a 6-month clinical follow-up, with 1 patient (1.2%) having poor prognosis. Eighty-four patients (67.7%) completed a 6-month imaging follow-up: complete occlusion rate of aneurysms was 82.1% (69/84), incidence of in-stent stenosis (stenosis degree ≥25%) was 4.8% (4/84), and no symptomatic in-stent stenosis was found.Conclusion:Result of this study shows that PED Shield may be an effective and safe clinical option for intracranial unruptured saccular aneurysms.
6.Comparison of image quality between gradient and spin-echo and compressed sensing sequences for single breath-hold magnetic resonance cholangiopancreatography
Yanan LI ; Ganglian FAN ; Xing LI ; Yannan CHENG ; Huan WANG ; Xueyan ZHANG ; Zhangrui LIANG ; Jianxin GUO
Journal of Xi'an Jiaotong University(Medical Sciences) 2025;46(1):125-131
Objective To compare image quality and clinical usefulness between single breath-hold three-dimensional magnetic resonance cholangiopancreatography with compressed sensing(3D BH-CS-MRCP)and with gradient and spin-echo(3D BH-GRASE-MRCP)and conventional three-dimensional breath-triggered magnetic resonance cholangiopancreatography(3D RT-MRCP).Methods A retrospective analysis was performed in 48 patients(26 males and 22 females,mean age of 53.14±15.19 years),who underwent 3D BH-GRASE-MRCP,3D BH-CS-MRCP and 3D RT-MRCP from September to December 2023.Pancreaticobiliary duct visibility,motion artifacts,background suppression,and overall image quality were scored on a 5-point scale by two radiologists.The relative contrast ratio of three bile duct segmentations(common bile duct,left and right intrahepatic bile ducts)were calculated,and the acquisition time of the three sequences was recorded.Friedman test with a post-hoc test was performed to compare image acquisition time,qualitative and quantitative results.Results The acquisition time was significantly shorter in the two breath-hold groups than for conventional 3D RT-MRCP(P<0.001).There were no significant differences in overall image quality,motion artifacts,common bile duct and primary branch of intrahepatic bile duct among the three groups.The relative contrast ratio,intrahepatic biliary secondary branch visibility and background suppression score of 3D RT-MRCP and BH-CS-MRCP were significantly higher than those of BH-GRASE-MRCP(P<0.01).The pancreatic duct(proximal,middle,distal)visibility score of 3D RT-MRCP was significantly better than that of BH-GRASE-MRCP(P=0.002,0.043,0.001),but the gallbladder and gallbladder duct visibility score of BH-GRASE-MRCP was higher than that of 3D RT-MRCP(P=0.036).There was no significant difference between 3D RT-MRCP and BH-CS-MRCP scores except for the middle and distal pancreatic duct visibility.Conclusion Breath-hold 3D MRCP with GRASE and CS can give us feasible options for pancreaticobiliary diagnosis,which significantly shortens the acquisition time without reducing the overall image quality.Compared with BH-GRASE-MRCP,BH-CS-MRCP has better consistency in pancreaticobiliary duct visibility and background suppression.
7.Analysis of the intervention effects of skill training for parents with autism child on toddlers with autism spectrum disorder
Qinyi YE ; Bingrui ZHOU ; Ying ZHANG ; Chunchun HU ; Yingzhi GU ; Xueyan LI ; Huiping LI ; Qiong XU ; Feiyong JIA ; Lan ZHANG ; Xiu XU
Chinese Journal of Pediatrics 2025;63(5):491-497
Objective:To explore the intervention effects of the skill training for parents with autism child (STPAC) on toddlers with autism spectrum disorder (ASD).Methods:A multicenter non-randomized concurrent controlled study design was conducted. Thirty children with ASD aged 15-30 months, first diagnosed at the Children′s Hospital of Fudan University, the First Hospital of Jilin University, and Chengdu Women′s and Children′s Central Hospital from 2019 to 2020, were enrolled in the STPAC group. Thirty children with ASD who visited the same hospitals during the same period but refused the STPAC intervention were selected as the control group. The STPAC group received an 8-week intervention (3 h/week) followed by quarterly follow-ups for 1 year, while the control group voluntarily chose community-based routine interventions. The Griffiths development scales-Chinese (GDS-C) was used to assess the developmental levels, and the communication and symbolic behavior scales developmental profile infant-toddler checklist (CSBS-DP-ITC) was completed by the primary caregivers to evaluate social, language and symbolic behavior. The independent samples t-tests or Mann-Whitney U tests, etc.was used for inter-group comparison. The paired t-tests or Wilcoxon signed-rank tests, etc. was used for inter-group pre-post intervention comparison. Results:The STPAC group included 30 children (22 males and 8 females, aged (23.9±2.2) months), and the control group included 30 children (20 males and 10 females, aged (24.2±2.6) months). Before the intervention, there were no statistically differences in GDS-C development quotient (DQ) and CSBS-DP-ITC scores between groups (all P>0.05). After 1-year intervention, GDS-C DQ in personal-social, hearing-language, hand-eye coordination, performance domains of STPAC group and GDS-C DQ in personal-social, hearing-language domains of control group were all increased (all P<0.01). After 1-year intervention, CSBS-DP-ITC scores of both groups were all improved in socia, language, symbolic behavior, and total scores (all P<0.001). GDS-C DQ changes before and after 1 year of intervention in hearing-language, hand-eye coordination, performance domains of the STPAC group were all higher the those of control group (34(15, 48 vs. 10(-4, 39), 11±20 vs. -1±19, 23±25 vs. 8±22, all P<0.05). CSBS-DP-ITC scores changes before and after 1 year of intervention in social and total scores of the STPAC group were both higher the those of control group (10(5, 30) vs. 3(1, 7), 26±17 vs. 11±8, both P<0.001). Conclusion:Compared with the community routine interventions, the STPAC better improves the language, hand-eye coordination, visual-spatial, social communication, and play skills in ASD toddlers.
8.Prevalence and risk factors of food allergies among children in North China grassland: a cross-sectional study based on Zhangbei County, Hebei Province
Yang LIU ; Yanlei CHEN ; Yaojun PANG ; Ruijuan ZHANG ; Haiyun SHI ; Weiting JIN ; Wenhua MING ; Ye WANG ; Zilu CHENG ; Tingting MA ; Xueyan WANG
Chinese Journal of Preventive Medicine 2025;59(10):1725-1733
Objective:To determine the prevalence of self-reported food allergies among children in the grasslands of North China and to analyze its associated risk factors.Methods:In this study, a cross-sectional epidemiological survey method was used to select children under 14 years old by multi-stage, stratified and random cluster sampling in the grassland ecological area of Zhangbei County, Hebei Province, China from May to July 2018. Face-to-face questionnaires were administered to gather food allergy-related information from the participants. Multivariate logistic regression analysis was used to analyze the risk factors associated with self-reported food allergy.Results:A total of 2 086 children completed the survey. The prevalence of self-reported food allergies was 22.0%(459/2 086). The prevalence of multiple food allergies (≥3 types) was 3.1%(64/2 086) versus 16.3% (341/2 086) for a single food allergy among all children. Mango allergy (6.1%, 127/2 086) was the most common, followed by peach allergy (4.1%, 85/2 086). Children who reported food allergies had a significantly higher prevalence of all 4 atopic disorders (eczema, asthma, allergic rhinitis, and allergic conjunctivitis than those without food allergies(35.73% vs. 20.65%, 5.88% vs. 2.77%, 17.86% vs. 7.38%, 16.78% vs. 10.45%, χ2 =44.663 1, 10.434 3, 45.038 3, 13.728 4, all P<0.001).Significantly associated risk factors of food allergy were found to be pollen allergy ( OR: 2.29; 95% CI: 1.80-2.92) and drug allergy ( OR: 1.53; 95% CI: 1.12-2.09). Conclusions:The prevalence of self-reported food allergies among children in the Zhangbei County area of the North China Grassland was relatively high. Pollen allergy and drug allergy are major risk factors.
9.Observation on the Curative Effect of Lishui Xiaozhong Granules Combined with Conbercept in Treating Diabetic Macular Edema
Xueyan YANG ; Lijun LAN ; Shengguang WU ; Hai ZHU ; Jue ZHANG
Journal of Guangzhou University of Traditional Chinese Medicine 2025;42(5):1133-1139
Objective To investigate the efficacy of Lishui Xiaozhong Granules combined with Conbercept for the treatment of diabetic macular edema(DME).Methods From December 2022 to June 2023,46 patients(46 eyes)with DME of spleen and kidney yang deficiency complicated with blood-stasis obstructing the eye collaterals syndrome admitted to Foshan Hospital of Traditional Chinese Medicine were selected as the study objects.According to the principle of single-blind randomized controlled trial,the patients were randomly divided into treatment group and control group by random number table method,with 23 cases(23 eyes)in each group.The control group was treated with intravitreal injection of Conbercept,and the treatment group was treated with oral use of Lishui Xiaozhong Granules on the basis of treatment for the control group.The course of treatment lasted 3 months and then a follow-up for 6 months was conducted.Before and after treatment,the two groups were observed int the changes of traditional Chinese medicine(TCM)syndrome score,best corrected visual acuity(BCVA,LogMAR),central macular thickness(CMT),mean vessel density(VD)of superficial capillary plexus(SCP)and deep capillary plexus(DCP)in macular area,and the amplitude density and the latency of P1 and N1 wave in the R1 ring of multifocal electroretinogram(mf-ERG).Results(1)After 1,3 and 6 month(s)of treatment,BVCA in the two groups was improved when compared with that at the previous observation time point(P<0.05),and the improvement in the treatment group was superior to that in the control group after 1,3 and 6 month(s)of treatment(P<0.01).(2)After 1,3 and 6 month(s)of treatment,the CMT of the two groups was lowered as compared with that at the previous observation time point(P<0.05),and the decrease in the treatment group was significantly superior to that in the control group(P<0.01).(3)After 6 months of treatment,SCP-VD and DCP-VD in the two groups showed no obvious changes when compared with those before treatment(P>0.05),the differences between the two groups after treatment were no statistically significant,either(P>0.05).(4)After 1,3 and 6 month(s)of treatment,the amplitude densities of P1 wave and N1 wave in the R1 ring of mf-ERG in the two groups were increased when compared with those at the previous observation time point(P<0.05),and the latency of P1 wave and N1 wave was shortened when compared with that at the previous observation time point(P<0.05),and the treatment group had stronger effect on increasing the amplitude densities and on shortening the latency than the control group(P<0.01).(5)After 6 months of treatment,the scores of TCM syndromes in the treatment group were lowered(P<0.05)while the scores in the control group showed no obvious changes as compared with those before treatment.The intergroup comparison showed that the decrease of TCM syndrome score in the treatment group was significantly superior to that in the control group(P<0.01).Conclusion In the treatment of DME with spleen and kidney yang deficiency complicated with blood-stasis obstructing the eye collaterals syndrome,Lishui Xiaozhong Granules combined with Conbercept have no influence on improving the SCP-VD and DCP-VD,but the combined therapy exerts satisfactory efficacy on increasing BCVA and on improving macular oedema,retinal function in the macular area and systemic symptoms.
10.Clinical Efficacy of Yiqi Wenyang Lishui Formula in Treating Heart Failure with Yang Deficiency and Fluid Retention Syndrome:Changes in Cardiac Function and Remodeling,and Analysis of Risk Factors Affecting Therapeutic Efficacy
Min SHI ; Chuanwei ME ; Bing HE ; Hongli SHI ; Xueyan ZHANG ; Yong SUI ; Yan LI
Journal of Guangzhou University of Traditional Chinese Medicine 2025;42(11):2637-2643
Objective To investigate the effects of Yiqi Wenyang Lishui Formula(derived from Wuling San combined with Astragali Radix and Descurainiae Semen Lepidii Semen)on cardiac function and remodeling in heart failure(HF)patients with yang deficiency and fluid retention syndrome and to analyze risk factors for influencing therapeutic efficacy.Methods A total of 120 HF patients with yang deficiency and fluid retention syndrome admitted to Liaocheng Hospital of Traditional Chinese Medicine from February 2022 to January 2024 were enrolled and randomly divided into observation group(n=60)and control group(n=60)using a random number table.The control group received conventional western therapy,while the observation group received Yiqi Wenyang Lishui Formula additionally.Both groups were treated for 2 months.Changes in cardiac function indicators and remodeling markers were observed.Clinical efficacy was evaluated,and univariate and binary logistic regression analyses were performed to identify independent risk factors affecting treatment outcomes.Results(1)The total effective rate was 81.67%(49/60)in the observation group versus 70.00%(42/60)in the control group.Intergroup comparison(by chi-square test)showed that the efficacy in the observation group was superior to the control group(P<0.05).(2)After treatment,both groups showed significant reductions compared to those before treatment in left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),and N-terminal pro-brain natriuretic peptide(NT-proBNP)(P<0.01).The reduction in LVEDD,LVESD,and serum NT-proBNP levels in the observation group was significantly greater than that in the control group(P<0.05 or P<0.01).(3)Univariate analysis revealed that New York Heart Association(NYHA)functional classification,LVEDD,LVESD,and NT-proBNP levels were significantly associated with the therapeutic efficacy of the Yiqi Wenyang Lishui Formula in heart failure patients with yang deficiency and fluid retention syndrome(P<0.05).(4)Logistic regression identified NYHA classification,LVEDD,LVESD,and NT-proBNP as independent risk factors(P<0.05)in affecting therapeutic effect of Yiqi Wenyang Lishui Formula in treating HF with yang deficency and fluid retention syndrome,increasing the risk of ineffective treatment by 4.12-fold,1.21-fold,1.19-fold,and 1.00-fold,respectively.Conclusion Yiqi Wenyang Lishui Formula effectively improves cardiac function and remodeling in HF patients with yang deficiency and fluid retention syndrome.NYHA classification,LVEDD,LVESD,and NT-proBNP are independent risk factors for influencing efficacy,warranting close monitoring for optimized therapeutic adjustments.


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