1.The role and significance of serum B factor in the pathogenesis of systemic lupus erythematosus
Xianming LONG ; Yan GONG ; Jian WU ; Yufan GUO
Journal of Chinese Physician 2015;17(5):703-705,709
Objective To investigate the expression of serum B factor in the peripheral blood of patients with systemic lupus erythematosus (SLE),and explore its role in the pathogenesis.Methods Seventy eight patients with SLE in our hospital and 46 healthy persons were eligible to participate in this study.Rate nphelometyr was used to test serum B factor for 78 patients with SLE and 46 healthy controls.According to systemic lupus erythematosus disease activity index (SLEDAI),participants were divided into steady SLE group (SLEDAI < 5) and active SLE group (SLEDAI ≥5),which was further divided into mild,moderate,and serious subgroups.The differences in serum B factor between SLE patients and healthy controls,including SLE patients with different severity,were all compared.Then we analyzed the differences in serum B factor and other laboratory and clinical indexes between active and steady SLE patients.The correction of serum B factor and other laboratory and clinical indexes were also analyzed.Results Compared to healthy controls,patients with SLE had significantly lower value of serum B factor [(27.13 ± 8.98) mg/dl vs (36.73 ± 5.47) mg/dl,t =7.4,P < 0.01].Compared to steady SLE group,SLE active group had significantly lower level of serum factor B,C3 and C4,and also had significant higher level of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) (all P < 0.05).Moreover,There were significant differences in the lower level of serum B factor between subgroups.Correlation analysis showed that the level of serum B factor was negatively associated with the levels of CRP and SLEDAI scores,whereas serum B factor was positively associated with the levels of C3 and C4 (all P < 0.05).Conclusions Serum B factor is related to SLE.Serum B factor might be involved in the pathogenesis of SLE.Detection of serum B factor is helpful for diagnosis and evaluation of SLE disease activity.
2.Atypical vascular lesions after conservative surgery and radiation of breast cancer: report of a case and review of the literature
Junna CAI ; Song QING ; Yufan CHENG ; Wentao YANG ; Jian WANG
Chinese Journal of Clinical and Experimental Pathology 2010;(1):40-45
Purpose To describe the clinical and pathological features of atypical vascular lesions (AVLs) after conservative surgery and radiation of the breast cancer,and to discuss the association with post-radiation angiosarcoma.Methods The clinical and pathological features in one case of AVLs was evaluated.The literatures were reviewed.Results The patient is a 57-yeAR~-old female who underwent a conservative surgery of the right breast because of a carcinoma.She received standard dose of radiation as adjuvant therapy.Three years later, multiple erythematous plaques developed around the former scar, which radiated to the nipple.Clinically,the plaques were considered as relapses of the carcinoma.However, fine needle aspiration gave negative results.Biopsy of one large plague revealed a circumscribed vascular lesion confined to the superficial dermis.It was composed of thin-walled anastomosing lymphatic vessels lined by attenuated endothelial cells.In focal areas, the vessels extended to the mid-dermis.Immunohistochemically, the endothelial cells were positive for CD31, CD34 and D2-40,with absent of α-SMA positive pericytes.Review of the breast tumor sections showed an invasive micropapillary carcinoma.Conclusions AVLs is a rare vascular lesion related with conservative surgery and post-radiation therapy of the breast.AVLs may represent as a precursor of breast angiosarcoma.Being familiar with the clinicopathologic characteristics of AVLs is important not only for the pathologists but also for the clinicians.
3.Drilling off the Petrosal Apex and Opening the Upper Wall of Meckel’s Cave Are the Key Elements of Good Outcomes in the Treatment of Trigeminal Neuralgia Secondary to Petrous Apex Meningioma
Jie BAI ; Yufan ZHOU ; Gang SONG ; Jian REN ; Xinru XIAO
Journal of Korean Neurosurgical Society 2022;65(3):479-488
Objective:
: The surgical management of trigeminal neuralgia (TN) caused by petrous apex meningioma (PAM) is still a challenge because of the lesion’s deep location and the surrounding complex structures. The authors describe the intradural anterior transpetrosal approach (ATPA) and its effect on the treatment of TN secondary to PAM.
Methods:
: A retrospective analysis of 15 patients with TN secondary to PAM who underwent surgery via the intradural ATPA was conducted. The key techniques, which included drilling off the petrosal apex (PA) and opening the upper wall of Meckel’s cave (MC), are described in detail.
Results:
: Total removal of the tumor and complete pain relief (Barrow Neurological Institute I) were achieved in all 15 patients without significant morbidity. Five patients developed new facial numbness postoperatively, which disappeared within three months after surgery. The postoperative magnetic resonance imaging showed temporal lobe swelling in three patients, but no clinical symptoms. One patient had cerebrospinal fluid leakage and was managed with bed rest and temporary lumbar drainage. One patient had an intracranial infection and was treated with antibiotics. By the last follow up, no patients had pain relapse or/and tumor recurrence. It is worth noting that the vascular compression at the root of the trigeminal nerve was found in one patient during the operation.
Conclusion
: Our experience suggests that drilling off the PA and opening the upper wall of the MC are key elements for a good outcome of the treatment of TN secondary to PAM. The intradural ATPA has the advantages for both tumor resection and pain relief.
4.Efficacy and safety of Tofacitinib in treating the elderly rheumatoid arthritis
Keqin ZENG ; Erye ZHOU ; Tian REN ; Yufeng YIN ; Michun HE ; Xianming LONG ; Mingjun WANG ; Yufan GUO ; Jian WU
Chinese Journal of Geriatrics 2023;42(1):40-45
Objective:To observe the efficacy and safety of Tofacitinib in treating elderly rheumatoid arthritis(RA), in order to provide clinical evidence.Methods:In the randomized control trial, a total of 90 elderly RA patients admitted to the Department of Rheumatology of the First Affiliated Hospital of Soochow University from January 2019 to January 2021 were selected and divided into Methotrexate group(MTX group, MTX 10mg, qw, n=45)and Tofacitinib group(TOF group, oral 5mg, bid, n=45). The efficacy and safety of the two groups were evaluated at week 12.The primary endpoint was the proportion of patients meeting the American College of Rheumatology 50%(ACR50)improvement response criteria at week 12.Secondary endpoints included ACR20/70 improvement response, proportion of patients who met treat-to-target(T2T)criteria, including Disease Activity Score in 28 joints using erythrocyte sedimentation rate(DAS28-ESR), Disease Activity Score in 28 joints using C-reactive protein level(DAS28-CRP), clinical disease activity index(CDAI), and simplified disease activity index(SDAI), and patient-reported outcomes(PROs)which included changes compared to baseline in pain visual analog scale(VAS)and Health Assessment Questionnaire Disability Index(HAQ-DI)score, at week 12.Safety outcomes including drug-related adverse events, serious adverse events, dropping out due to adverse events, and deaths were assessed throughout.Results:Five patients in each group withdrew from the trial due to adverse events, and the number of patients who finally completed the observation was 40 in each group.At week 12, the ACR50 response rate was higher in TOF group than in MTX group[35%(14/40) vs.12.5%(5/40), χ2=5.591, P=0.018)], achieving the primary endpoint.When comparing TOF vs.MTX group, the ACR20 response rate[55%(22/40) vs.25%(10/40), χ2=7.500, P=0.006]and ACR70 response rate[25%(10/40) vs.7.5%(3/40), χ2=4.501, P=0.034], and proportions of indexes of disease remission including DAS28-ESR<2.6[25%(11/40) vs.7.5%(3/40), χ2=4.501, P=0.034], or DAS28-CRP<2.6[27.5%(11/40) vs.7.5%(3/40), χ2=5.541, P=0.019], or CDAI≤2.8[30%(12/40) vs.10%(4/40), χ2=5.000, P=0.025], or SDAI≤3.3[27.5%(11/40) vs.7.5%(3/40), χ2=5.541, P=0.019], and the proportions of patients with low disease activity including DAS28-ESR≤3.2[32.5%(14/40) vs.12.5%(5/40), χ2=5.591, P=0.018], or DAS28-CRP≤3.2[32.5%(14/40) vs.12.5%(5/40), χ2=5.591, P=0.018], or CDAI≤10[37.5%(15/40) vs.17.5%(7/40), χ2=4.013, P=0.045], or SDAI≤11[37.5%(15/40) vs.15%(6/40), χ2=5.230, P=0.022], as well as changes compared to baseline data in pain VAS[(26.51±8.32)scores vs.(14.16±4.39)scores, t=8.371, P<0.001]and in HAQ-DI score(0.65±0.24 vs.0.32±0.06, t=9.387, P<0.001)were all better in the TOF group than in the MTX group at week 12.During the 12-week observation period, the number of patients with infection and hyperlipidemia was higher in TOF group than in MTX group, while the number of patients with abnormal blood cell count and liver function was lower than that in MTX group, but the differences were not statistically significant(all P<0.05). Conclusions:Tofacitinib has good efficacy and safety in the elderly RA.In patients over 70 years of age who are at high risk of infection, tofacitinib should be used with caution.
5.Changes of serum lipid profiles and the correlation analysis in clinic-pathological features of pancreatic cancer patients
Jian YANG ; Zhiyao FAN ; Yongzheng LI ; Shujie LIU ; Yufan MENG ; Jianwei XU ; Lei WANG ; Hanxiang ZHAN
Chinese Journal of Surgery 2022;60(7):680-687
Objective:To examine the characteristics of blood lipid profile and the correlation with clinic-pathological features of pancreatic cancer patients.Methods:The clinical and pathological data of 265 pancreatic cancer patients who received radical surgical treatment at Department of General Surgery,Qilu Hospital,Shandong University from January 2013 to September 2020 were collected and analyzed retrospectively. Among the 265 pancreatic cancer patients,there were 170 males and 95 females,with age of (61.0±9.6)years(range:28 to 86 years). General information,lipid indicators and clinic-pathological information were collected from electronic medical record system,and follow-up information gained by telephone. According to level of serum lipid in pancreatic cancer patients,265 patients were divided into dyslipidemia group( n=115) and normal lipid group( n=150). Pearson χ 2,Student′s t tests, variance analysis or univariate Logistic regression was used to analyze the correlation between dyslipidemia and clinico-pathological characteristics of pancreatic cancer,respectively. Kaplan-Meier survival curve was used to assessed the influence of dyslipidemia on prognosis of pancreatic cancer patients. Results:In 265 pancreatic cancer patients,115(43.4%)of them had dyslipidemias,and the most common form was increase of triglyceride(TG)(72.2%). In pancreatic cancer with dyslipidemias group,patients with body mass index ≥25 kg/m 2 had higher proportion than normal lipid group(36.1%(26/72) vs. 21.2%(21/99),χ2=4.643, P=0.031); The proportion of carcinoma located at head of pancreas(83.5%(96/115) vs. 40.7%(61/150),χ2=49.412, P<0.01), staging of T1/T2(79.1%(91/115) vs. 60.7%(91/150),χ2=10.316, P<0.01) and lymphatic metastasis(36.5%(42/115) vs. 22.7%(34/150),χ2=6.007, P<0.01) were higher. In patients of pancreatic cancer, dyslipidemias were closely associated with tumor location( OR=10.529, P<0.01)and body mass index( OR=3.671, P=0.008). Serum lipid profile results showed that TG,total cholesterol and high-density lipoprotein(HDL) disorders were associated with tumor location( P<0.05). TG disorder had association with body mass index( P<0.05), and HDL disorder had association with tumor stage( P<0.05). Moreover, the result of survival analysis showed that dyslipidemia was not a factor to impact the prognosis of pancreatic cancer patients underwent surgery( P>0.05). Conclusions:In pancreatic cancer patients,TG disorder was the most common type of dyslipidemia. Dyslipidemia has closely association with clinicopathologic features,including tumor location,body mass index,tumor stage. However,dyslipidemia had little effect on prognosis of pancreatic cancer patients.
6.Changes of serum lipid profiles and the correlation analysis in clinic-pathological features of pancreatic cancer patients
Jian YANG ; Zhiyao FAN ; Yongzheng LI ; Shujie LIU ; Yufan MENG ; Jianwei XU ; Lei WANG ; Hanxiang ZHAN
Chinese Journal of Surgery 2022;60(7):680-687
Objective:To examine the characteristics of blood lipid profile and the correlation with clinic-pathological features of pancreatic cancer patients.Methods:The clinical and pathological data of 265 pancreatic cancer patients who received radical surgical treatment at Department of General Surgery,Qilu Hospital,Shandong University from January 2013 to September 2020 were collected and analyzed retrospectively. Among the 265 pancreatic cancer patients,there were 170 males and 95 females,with age of (61.0±9.6)years(range:28 to 86 years). General information,lipid indicators and clinic-pathological information were collected from electronic medical record system,and follow-up information gained by telephone. According to level of serum lipid in pancreatic cancer patients,265 patients were divided into dyslipidemia group( n=115) and normal lipid group( n=150). Pearson χ 2,Student′s t tests, variance analysis or univariate Logistic regression was used to analyze the correlation between dyslipidemia and clinico-pathological characteristics of pancreatic cancer,respectively. Kaplan-Meier survival curve was used to assessed the influence of dyslipidemia on prognosis of pancreatic cancer patients. Results:In 265 pancreatic cancer patients,115(43.4%)of them had dyslipidemias,and the most common form was increase of triglyceride(TG)(72.2%). In pancreatic cancer with dyslipidemias group,patients with body mass index ≥25 kg/m 2 had higher proportion than normal lipid group(36.1%(26/72) vs. 21.2%(21/99),χ2=4.643, P=0.031); The proportion of carcinoma located at head of pancreas(83.5%(96/115) vs. 40.7%(61/150),χ2=49.412, P<0.01), staging of T1/T2(79.1%(91/115) vs. 60.7%(91/150),χ2=10.316, P<0.01) and lymphatic metastasis(36.5%(42/115) vs. 22.7%(34/150),χ2=6.007, P<0.01) were higher. In patients of pancreatic cancer, dyslipidemias were closely associated with tumor location( OR=10.529, P<0.01)and body mass index( OR=3.671, P=0.008). Serum lipid profile results showed that TG,total cholesterol and high-density lipoprotein(HDL) disorders were associated with tumor location( P<0.05). TG disorder had association with body mass index( P<0.05), and HDL disorder had association with tumor stage( P<0.05). Moreover, the result of survival analysis showed that dyslipidemia was not a factor to impact the prognosis of pancreatic cancer patients underwent surgery( P>0.05). Conclusions:In pancreatic cancer patients,TG disorder was the most common type of dyslipidemia. Dyslipidemia has closely association with clinicopathologic features,including tumor location,body mass index,tumor stage. However,dyslipidemia had little effect on prognosis of pancreatic cancer patients.
7.Multi-task learning for automated classification of hypertensive heart disease and hypertrophic cardiomyopathy using native T1 mapping
Honglin ZHU ; Yufan QIAN ; Xiao CHANG ; Yan ZHOU ; Jian MA ; Rong SUN ; Shengdong NIE ; Lianming WU
International Journal of Biomedical Engineering 2024;47(4):342-348
Objective:To automatically classify hypertensive heart disease (HHD) and hypertrophic cardiomyopathy (HCM) based on mul-titask learning algorithm using native T1 mapping images.Methods:A total of 203 patients admitted to Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University from January 2017 to December 2021 were enrolled, including 53 patients with HHD, 121 patients with HCM, and 29 patients with normal control (NC). Native T1 mapping images of all enrolled patients were acquired using MRI and processed by a multi-task learning algorithm. The classification performance of each model was validated using ten-fold crossover, confusion matrix, and receiver operator characteristic (ROC) curves. The Resnet 50 model based on the original images was established as a control.Results:The ten-fold crossover validation results showed that the MTL-1 024, MTL-64, and MTL-all models showed better performance in terms of area under the curve (AUC), accuracy, sensitivity, and specificity compared to the Resnet 50 model. In the classification task, the MTL-64 model showed the best performance in terms of AUC (0.942 1), while the MTL-all model reached the highest value in terms of accuracy (0.852 2). In the segmentation task, the MTL-64 model achieved the best results with the Dice coefficient (0.879 7). The confusion matrix plot showed that the MTL model outperforms the Resnet 50 model based on the original image in terms of overall performance. The ROC graphs of all MTL models were significantly higher than the original image input Resnet 50 model.Conclusions:Multi-task learning-based native T1 mapping images are effective for automatic classification of HHD and HCM.
8.Protective effects and mechanisms of berberine hydrochloride on intestinal mucosal barrier injury in rats with sepsis
Ying LING ; Qi SHEN ; Jian WANG ; Yufan YUAN ; Peng WANG ; Zelin LI ; Jinlan JIN
Chinese Critical Care Medicine 2024;36(6):597-603
Objective:To investigate the protective effect of berberine hydrochloride on intestinal mucosal barrier damage in sepsis rats and its mechanism.Methods:Forty-eight male SD rats were divided into a control group (Sham group, 6 cases), a sepsis model group (LPS group, 14 cases), a berberine hydrochloride intervention group (Ber group, 14 cases), and a Notch signaling pathway inhibition group (DAPT group, 14 cases) according to random number table method. The DAPT group was intraperitoneally injected with 5 mg/kg Notch signaling pathway inhibition DAPT 2 hours before modeling. The sepsis model was established by intraperitoneal injection of 10 mg/kg lipopolysaccharide (LPS); Sham group was injected with an equal amount of saline (2 mL). The Ber group and DAPT group were treated with gavage of 50 mg/kg berberine hydrochloride 2 hours after modeling; Sham group and LPS group were treated with gavage of an equal amount of saline (2 mL). The temperature, weight, behavior and survival rate of rats were observed at 0, 6, 12 and 24 hours of modeling. After 24 hours of modeling, abdominal aortic blood was collected under anesthesia, and intestinal tissues were obtained after euthanasia. The pathological changes of ileum were observed under light microscope. The ultrastructure of ileum was observed under transmission electron microscope. Enzyme linked immunosorbent assay (ELISA) was used to detect the levels of serum diamine oxidase (DAO), intestinal fatty acid binding protein (iFABP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). Real time-polymerase chain reaction (RT-PCR) and Western blotting were used to detect the mRNA and protein expressions of tight junction proteins (Occludin and Claudin1), Notch1 and their downstream target signals in the ileum tissue.Results:After 24 hours of modeling, compared with the Sham group, the LPS group, Ber group, and DAPT group showed a decrease in weight and an increase in temperature. Among them, the LPS group showed the most significant changes, followed by the DAPT group, and the Ber group showed the least significant changes. The survival rates of the LPS group, Ber group, and DAPT group were all lower than those of the Sham group [42.9% (6/14), 57.1% (8/14), 57.1% (8/14) vs. 100% (6/6)], and six rats were taken from each group for subsequent testing. Macroscopic observation of the intestine showed that the LPS group had the most severe edema in the ileum tissue and abdominal bleeding, with significant improvement in the Ber group and followed by the DAPT group. Under the light microscope, the LPS group showed disordered arrangement of glandular tissue in the ileum mucosa, significantly reduced goblet cells, and extensive infiltration of inflammatory cells, which were significantly improved in the Ber group but less improved in the DAPT group. Under electron microscopy, the LPS group showed extensive shedding of ileal microvilli and severe damage to the tight junction complex structure of intestinal epithelial cells, which was significantly improved in the Ber group but less improved in the DAPT group. The levels of serum DAO, iFABP, TNF-α, IL-6 in the LPS group were significantly higher than those in the Sham group, while the above indicators in the Ber group were significantly lower than those in the LPS group [DAO (μg/L): 4.94±0.44 vs. 6.53±0.49, iFABP (ng/L): 709.67±176.97 vs. 1 417.71±431.44, TNF-α (ng/L): 74.70±8.15 vs. 110.36±3.51, IL-6 (ng/L): 77.34±9.80 vs. 101.65±6.92, all P < 0.01], while the above indicators in the DAPT group were significantly higher than those in the Ber group. The results of RT-PCR and Western blotting showed that the mRNA and protein expressions of Occludin, Claudin1, Notch1, and Hes1 in the ileum tissue of LPS group rats were decreased compared to the Sham group, which were significantly increased in the Ber group compared with the LPS group [mRNA expression: Occludin mRNA (2 -ΔΔCt): 1.61±0.74 vs. 0.30±0.12, Claudin1 mRNA (2 -ΔΔCt): 1.97±0.37 vs. 0.58±0.14, Notch1 mRNA (2 -ΔΔCt): 1.29±0.29 vs. 0.36±0.10, Hes1 mRNA (2 -ΔΔCt): 1.22±0.39 vs. 0.27±0.04; protein expression: Occludin/GAPDH: 1.17±0.14 vs. 0.74±0.04, Claudin1/GAPDH: 1.14±0.06 vs. 0.58±0.10, Notch1/GAPDH: 0.87±0.11 vs. 0.56±0.09, Hes1/GAPDH: 1.02±0.13 vs. 0.62±0.01; all P < 0.05], while those in the DAPT group were significantly lower than those in the Ber group. Conclusion:Early use of berberine hydrochloride can significantly improve intestinal mucosal barrier damage in sepsis rats, and its mechanism may be related to inhibiting inflammatory response and regulating the expression of intestinal mechanical barrier tight junction protein through Notch1 signal.
9.Application of Molecular Docking in the Studies on Screening and Mechanism of Pharmacodynamic Sub-stances of Traditional Chinese Medicine
Wenjun WANG ; Yi DING ; Fang DOU ; Hang XU ; Yufan JIAN ; Xiaona FENG ; Aidong WEN
China Pharmacist 2018;21(6):1020-1023
Molecular docking is one of the main methods for computer-aided drug design (CADD). In recent years, molecular doc-king is widely used and has made some progress in the screening of pharmacodynamic substance, the target of finding drugs for diseases, and the mechanism exploration for traditional Chinese medicine. In this review, the principle and mechanism of molecular docking, and some commonly used software were introduced. And the application of molecular docking technology was summarized in the studies on the screening and pharmacodynamic mechanisms of traditional Chinese medicine. Finally, the existing problems were discussed, and the fu-ture trend in this field was looked ahead. The study can provide more scientific basis for the clinical research and development of new drugs.
10.Gender and magnetic resonance imaging classification-related differences in clinical and biochemical characteristics of Cushing's disease: a single-centre study.
Yufan CHEN ; Xiaobo MEI ; Fangfang JIAN ; Qinyun MA ; Xiao CHEN ; Liuguan BIAN ; Qingfang SUN
Chinese Medical Journal 2014;127(22):3948-3956
BACKGROUNDCushing's disease (CD) presents a remarkable preponderance in female gender, and a significant minority of patients with CD presented with negative magnetic resonance imaging (MRI) findings. The aim of this study was to evaluate gender-related and MRI classification-related differences in clinical and biochemical characteristics of CD.
METHODSWe retrospectively studied 169 patients with CD, comprising 132 females and 37 males, and 33 patients had no visible adenoma on MRI.
RESULTSWe observed that male and MRI-positive patients presented with high adrenocorticotropic hormone (ACTH) values (P < 0.05). Female patients presented with higher prevalence of hirsutism and hyperpigmentation and lower prevalence of purple striae (P < 0.05). The prevalence of buffalo-hump and hypertension was greater in MRI-negative patients (P < 0.05). In addition, male patients with CD presented at a younger age compared with females (P < 0.05). Patients with fatigue and hypokalaemia presented significantly higher urinary-free cortisol, ACTH and cortisol levels compared with patients without these symptoms (P < 0.05). The prevalence of LH reduction, hyper total cholesterol (TC) and hyper low-density lipoprotein was more frequent in MRI-positive patients (P < 0.05). Hyper-TC levels and PRL reduction were more frequent in males (P < 0.05). T3, T4 and FT3 levels negatively correlated with age at diagnosis (r = -0.310, P < 0.01; r = -0.191, P < 0.05; r = -0.216, P < 0.05). T3, T4, FT3 and FT4 levels significantly negatively correlated with 8-am plasma cortisol levels (r = -0.328, P < 0.01; r = -0.195, P < 0.05; r = -0.333, P < 0.01; r = -0.180, P < 0.05). Females presented higher total protein level (P < 0.01) and lower blood urea nitrogen and serum creatinine levels (P < 0.01), compared with male patients.
CONCLUSIONSCarefulness and caution are required in all patients with CD, because of the complexity of clinical and biochemical characteristics in CD patients of different gender and MRI classification, particularly male patients and MRI-negative patients.
Adolescent ; Adult ; Aged ; Dyslipidemias ; diagnosis ; Female ; Humans ; Hypertension ; diagnosis ; Hypokalemia ; diagnosis ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Pituitary ACTH Hypersecretion ; complications ; diagnosis ; Retrospective Studies ; Sex Factors ; Young Adult