1.Early Diagnosis of Bipolar Disorder Coming Soon: Application of an Oxidative Stress Injury Biomarker (BIOS) Model.
Zhiang NIU ; Xiaohui WU ; Yuncheng ZHU ; Lu YANG ; Yifan SHI ; Yun WANG ; Hong QIU ; Wenjie GU ; Yina WU ; Xiangyun LONG ; Zheng LU ; Shaohua HU ; Zhijian YAO ; Haichen YANG ; Tiebang LIU ; Yong XIA ; Zhiyu CHEN ; Jun CHEN ; Yiru FANG
Neuroscience Bulletin 2022;38(9):979-991
Early distinction of bipolar disorder (BD) from major depressive disorder (MDD) is difficult since no tools are available to estimate the risk of BD. In this study, we aimed to develop and validate a model of oxidative stress injury for predicting BD. Data were collected from 1252 BD and 1359 MDD patients, including 64 MDD patients identified as converting to BD from 2009 through 2018. 30 variables from a randomly-selected subsample of 1827 (70%) patients were used to develop the model, including age, sex, oxidative stress markers (uric acid, bilirubin, albumin, and prealbumin), sex hormones, cytokines, thyroid and liver function, and glycolipid metabolism. Univariate analyses and the Least Absolute Shrinkage and Selection Operator were applied for data dimension reduction and variable selection. Multivariable logistic regression was used to construct a model for predicting bipolar disorder by oxidative stress biomarkers (BIOS) on a nomogram. Internal validation was assessed in the remaining 784 patients (30%), and independent external validation was done with data from 3797 matched patients from five other hospitals in China. 10 predictors, mainly oxidative stress markers, were shown on the nomogram. The BIOS model showed good discrimination in the training sample, with an AUC of 75.1% (95% CI: 72.9%-77.3%), sensitivity of 0.66, and specificity of 0.73. The discrimination was good both in internal validation (AUC 72.1%, 68.6%-75.6%) and external validation (AUC 65.7%, 63.9%-67.5%). In this study, we developed a nomogram centered on oxidative stress injury, which could help in the individualized prediction of BD. For better real-world practice, a set of measurements, especially on oxidative stress markers, should be emphasized using big data in psychiatry.
Biomarkers/metabolism*
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Bipolar Disorder/metabolism*
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Depressive Disorder, Major/diagnosis*
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Early Diagnosis
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Humans
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Oxidative Stress
2. Hypothalamic-Pituitary-End-Organ Axes: Hormone Function in Female Patients with Major Depressive Disorder
Yuncheng ZHU ; Yuncheng ZHU ; Xiaohui WU ; Rubai ZHOU ; Zhiang NIU ; Yiru FANG ; Oliver SIE ; Fang WANG ; Yiru FANG ; Yiru FANG
Neuroscience Bulletin 2021;37(8):1176-1187
Classic hypothalamic-pituitary-end-organ feedback loops – the hypothalamic-pituitary-adrenal axis (HPAA), hypothalamic-pituitary-thyroidal axis (HPTA), and hypothalamic-pituitary-gonadal axis (HPGA) – are associated with the neuroendocrine and immune systems in major depressive disorder (MDD). Female patients with MDD present with evident neuroendocrine and immunological changes. Glucocorticoid, thyroid hormone, and reproductive steroid levels fluctuate with menstrual cycles, which might lead to glucocorticoid receptor resistance, impairment of triiodothyronine conversion, and sex hormone secretion disorders. In this review, we summarize the independent and interactive functions of these three axes in female MDD patients. The similar molecular structure of steroids implies an interrelationship between the hypothalamic-pituitary-end-organ axes and the competitive inhibitory effects at the receptor level, especially when considering the HPAA and HPGA.
3.Clinicopathological analysis of lung metastatic tumor
Ning LOU ; Yiru NIU ; Fan YANG ; Zhaohui LU
Chinese Journal of Pathology 2021;50(9):1039-1044
Objective:To investigate the clinicopathological features and differential diagnosis of metastatic tumors in the lung.Methods:The clinicopathological data of 226 metastatic tumors in the lung were collected at Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, from January 2014 to December 2018, and the pathomorphological characteristics were analyzed.Results:There were 84 males and 142 females, with an age range from 13 to 77 years. There were 122 patients with multiple pulmonary nodules and 104 patients with solitary pulmonary nodule. The tumors of the highest frequencies were colorectal cancer ( n=59), followed by trophoblast tumor ( n=44), kidney cancer ( n=31), breast cancer ( n=20), cervix cancer ( n=14), and urinary urothelium cancer ( n=8). The time from the diagnosis of primary tumors to metastasis and the status of surgical treatment varied by tumor origin. The morphology of metastatic lung tumors overlapped with that of the primary tumors to some extent. The relative specific morphological characteristics and the presence of carcinoma in situ surrounding the tumors should be carefully searched for to confirm the tumor origin. The metastatic tumors of the lung had morphological characteristics, immunohistochemical TTF1 (-) and tumor of various sources, while the primary tumor differentiation had relatively specific antibodies: colorectal cancer CK20 (+), CDX2 (+), CK7 (-); malignant trophoblastic tumor, HCG (+); renal clear cell carcinoma CD10 (+), vimentin (+), CK7 (-); breast cancer, GATA3 and ER (+); cervical cancer, p16 (+); urothelial carcinoma, CK20, p63 and GATA3 (+). Conclusions:There is overlap between pulmonary metastatic tumor and primary tumor in morphology. Therefore, the diagnosis should be made by combining clinical history, pathological morphology and immunophenotypic characteristics.
4.Opportunities and challenges of clinical research on psychiatry in the information age
Yiru FANG ; Zhiang NIU ; Daihui PENG ; Jun CHEN
Chinese Journal of Psychiatry 2021;54(1):3-8
The rapid development of technology in the information age has brought profound changes to healthcare. In particular, the close integration of artificial intelligence technology and medical services has demonstrated potential application value in disease diagnosis, treatment and clinical research.Psychiatry strives to keep pace with the times and of information technology. Artificial intelligence has made multi-faceted explorations in psychiatric clinical research. The process is not only full of opportunities and challenges, but also insightful dawn.Meanwhile, the application of information technology in psychiatric clinical research also has inevitable limitations.Psychiatric clinical research needs to pay attention to real data in the real world. On the basis of standardization and safety, it should be expected that artificial intelligence technology and real data in psychiatric clinical diagnosis and treatment should be combined to strengthen evidence-based studies, update clinical diagnosis and treatment guidelines, and promote a tool for translational application.From the perspective of scientific development, these tools will eventually help psychiatrists benefit the majority of patients with mental illness and promote the vigorous development of psychiatry.
5.Opportunities and challenges of clinical research on psychiatry in the information age
Yiru FANG ; Zhiang NIU ; Daihui PENG ; Jun CHEN
Chinese Journal of Psychiatry 2021;54(1):3-8
The rapid development of technology in the information age has brought profound changes to healthcare. In particular, the close integration of artificial intelligence technology and medical services has demonstrated potential application value in disease diagnosis, treatment and clinical research.Psychiatry strives to keep pace with the times and of information technology. Artificial intelligence has made multi-faceted explorations in psychiatric clinical research. The process is not only full of opportunities and challenges, but also insightful dawn.Meanwhile, the application of information technology in psychiatric clinical research also has inevitable limitations.Psychiatric clinical research needs to pay attention to real data in the real world. On the basis of standardization and safety, it should be expected that artificial intelligence technology and real data in psychiatric clinical diagnosis and treatment should be combined to strengthen evidence-based studies, update clinical diagnosis and treatment guidelines, and promote a tool for translational application.From the perspective of scientific development, these tools will eventually help psychiatrists benefit the majority of patients with mental illness and promote the vigorous development of psychiatry.
6.Clinicopathological features and prognosis of synchronous bilateral breast cancers
Yiru NIU ; Huanwen WU ; Zhiyong LIANG
Chinese Journal of Pathology 2020;49(5):435-440
Objective:To study the clinicopathologic characteristics and relevant factors affecting prognosis of patients with synchronous bilateral breast cancer.Methods:The clinical data, pathologic characteristics and immunohistochemical expression characteristics of 151 patients with synchronous bilateral breast cancers diagnosed in Peking Union Medical College Hospital from 2008 to 2018 were collected and analyzed. The factors affecting the prognosis were analyzed by Log rank test, Kaplan-Meier survival analysis, Cox regression and other methods.Results:Synchronous bilateral breast cancer cases accounted for 1.2% (151/12 239) of all breast cancer patients in the same period, and 14.6% (22/151) had a family history. The patients′ age range was 22-88 years, mainly female, with a mean survival of 42.5 months. There were 106 patients with synchronous bilateral invasive breast cancers, 6 patients with synchronous bilateral breast cancer in situ, and 39 patients with unilateral invasive breast cancer and unilateral breast cancer in situ. In synchronous bilateral invasive breast cancers, the histological type was mainly non-specific type (84.9%, 180/212), the histological grade was mainly Grade 2 (60.8%,129/212), the TNM stage was mainly stage Ⅰ (50.5%, 107/212), the tumor size was mainly T1 (68.9%, 146/212), and the regional lymph node was mainly N0 (61.8%, 131/212). The molecular subtypes were mainly Luminal A-like (38.1%, 75/197) and Luminal B-like (43.7%, 86/197); ER (78.2%, 154/197) and PR (72.1%,142/197)were mainly positive, and HER2 was mainly negative (91.9%, 181/197). There were 85 (80.2%) patients and 75 (70.8%) patients with the same histological type and histological grade on both sides, respectively. The concordance of tumor size T stage and the regional lymph nodes N stage were 58.5% (62/106) and 55.7% (59/106), respectively. The concordance of molecular subtype was 54.9% (50/91), and the concordance of ER, PR, HER2 and Ki-67 were 83.5% (76/91), 76.9% (70/91), 89.0% (81/91) and 59.3% (54/91), respectively. The expression of ER and PR in synchronous bilateral invasive breast cancer was significantly correlated with prognosis ( P<0.05). Conclusions:Among patients with synchronous bilateral breast cancers, bilateral invasive breast cancer is the most common, the prognosis is the worst, and the pathologic characteristics of bilateral breast cancer tend to be consistent. The expression of ER and PR in synchronous bilateral invasive breast cancer is significantly correlated with prognosis, that is, best for bilateral ER-positive patients, worst for bilateral ER-negative patients, and intermediate for unilateral ER-positive patients, thus suggesting the importance of ER and PR detection in synchronous bilateral invasive breast cancers.
7.The Relationship Between Neuroimmunity and Bipolar Disorder: Mechanism and Translational Application.
Zhiang NIU ; Lu YANG ; Xiaohui WU ; Yuncheng ZHU ; Jun CHEN ; Yiru FANG
Neuroscience Bulletin 2019;35(4):595-607
Neuroimmune system may be involved in the pathological process of bipolar disorder (BD), but the essential association is not fully understood. Accumulating evidence has shown that BD involves the activation of immune cells and the release of inflammatory substances in the central nerve system (CNS). Meanwhile, neuroimmune responses also interact with other hypothesis of the etiology of BD that are widely recognized, such as neurotransmitter systems, neuroendocrine systems, neurotrophic factors, and oxidative stress. Simultaneously, related genes and immune changes in peripheral blood vary with it. Overall, neuroimmunity may play an important role in the pathogenesis of BD, and the inflammatory cytokines, especially interleukin-6 and tumor necrosis factor-alpha, have potential value for the clinical diagnosis and prognosis of BD, as well as predicting the therapeutic effects of drugs. Large-scale studies are needed to extend the evidence on neuroimmunity in BD, and to examine its clinical value for applications such as early prediction and treatment.
8.The residual physical symptoms in Chinese patients with major depressive disorder after acute treatment phase: a cross-sectional survey among eleven mental health centers
Xu ZHANG ; Wei FENG ; Gang WANG ; Yongdong HU ; Yajuan NIU ; Jian HU ; Xueyi WANG ; Chengge GAO ; Ning ZHANG ; Yiru FANG ; Jizhong HUANG ; Tiebang LIU ; Fujun JIA ; Wenyuan WU
Chinese Journal of Psychiatry 2019;52(1):76-81
Objective To investigate the prevalence and characters of residual physical symptoms in Chinese depressive patients after acute treatment and the influence on the quality of life and social function.Methods In the multi-centers cross-sectional study,1 503 adult depressive outpatients,from 11 hospitals,who had been treated by antidepressants for 8-12 weeks with significant improvement of at least 50% by Self-rating Visual Analog Scale were involved.The group with residual physical symptoms could be differentiated by Brief 16-Item Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16) >5,while the QIDS-SR16 of remission group was ≤5.The QIDS-SR16,Patient Health Questionnaire-15 (PHQ-15),Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) and Sheehan Disability Scale (SDS) were used to assess the depressive symptoms,physical symptoms and social function.Results 49.8% (748/1 503) patients had residual physical symptoms (PHQ-15>4).The most common physical symptoms (PHQ-15≥1) were feeling tired or having low energy (56.3%,846/1 503),trouble sleeping (50.6%,760/1 503),headache(43.6%,655 / 1 503),constipation,loose stools or diarrhea(41.3%,620/1 503),feeling heart pound or race (37.6%,565/1 503),dizziness (34.0%,511/ 1 503),nausea,gas or indigestion (33.6%,505/1 503),etc.The 75.7% (555/733) of the physical symptoms (PHQ-15>4) in residual group was significantly higher than the 25.1% (193/770;x2=385.38,P<0.01) in remission group.The differences on social function (t=2.77-10.47) and life quality (t=3.04-11.41) between two groups were significant (P<0.01).Generalized linear regression analysis showed that gender (female),present history of first episode were related to better social function,and the factors related to both social function and quality of life included residual depressive symptoms,residual physical symptoms of different severity,comorbid medical conditions,age,duration of antidepressant treatment for this episode.Conclusion The rate of residual physical symptoms is higher in patients with major depression who responded to acute phase treatment.The more severe the residual physical symptoms,the worse the quality of life and social function.It suggests that physical symptoms be focused in order to achieve clinical recovery.
9.The residual physical symptoms in Chinese patients with major depressive disorder after acute treatment phase: a cross-sectional survey among eleven mental health centers
Xu ZHANG ; Wei FENG ; Gang WANG ; Yongdong HU ; Yajuan NIU ; Jian HU ; Xueyi WANG ; Chengge GAO ; Ning ZHANG ; Yiru FANG ; Jizhong HUANG ; Tiebang LIU ; Fujun JIA ; Wenyuan WU
Chinese Journal of Psychiatry 2019;52(1):76-81
Objective To investigate the prevalence and characters of residual physical symptoms in Chinese depressive patients after acute treatment and the influence on the quality of life and social function.Methods In the multi-centers cross-sectional study,1 503 adult depressive outpatients,from 11 hospitals,who had been treated by antidepressants for 8-12 weeks with significant improvement of at least 50% by Self-rating Visual Analog Scale were involved.The group with residual physical symptoms could be differentiated by Brief 16-Item Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16) >5,while the QIDS-SR16 of remission group was ≤5.The QIDS-SR16,Patient Health Questionnaire-15 (PHQ-15),Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) and Sheehan Disability Scale (SDS) were used to assess the depressive symptoms,physical symptoms and social function.Results 49.8% (748/1 503) patients had residual physical symptoms (PHQ-15>4).The most common physical symptoms (PHQ-15≥1) were feeling tired or having low energy (56.3%,846/1 503),trouble sleeping (50.6%,760/1 503),headache(43.6%,655 / 1 503),constipation,loose stools or diarrhea(41.3%,620/1 503),feeling heart pound or race (37.6%,565/1 503),dizziness (34.0%,511/ 1 503),nausea,gas or indigestion (33.6%,505/1 503),etc.The 75.7% (555/733) of the physical symptoms (PHQ-15>4) in residual group was significantly higher than the 25.1% (193/770;x2=385.38,P<0.01) in remission group.The differences on social function (t=2.77-10.47) and life quality (t=3.04-11.41) between two groups were significant (P<0.01).Generalized linear regression analysis showed that gender (female),present history of first episode were related to better social function,and the factors related to both social function and quality of life included residual depressive symptoms,residual physical symptoms of different severity,comorbid medical conditions,age,duration of antidepressant treatment for this episode.Conclusion The rate of residual physical symptoms is higher in patients with major depression who responded to acute phase treatment.The more severe the residual physical symptoms,the worse the quality of life and social function.It suggests that physical symptoms be focused in order to achieve clinical recovery.
10.A national survey of residual symptoms in Chinese depressive patients after acute phase treatment
Le XIAO ; Lei FENG ; Xuequan ZHU ; Gang WANG ; Wenyuan WU ; Yongdong HU ; Yajuan NIU ; Jian HU ; Xueyi WANG ; Chengge GAO ; Ning ZHANG ; Yiru FANG ; Jizhong HUANG ; Tiebang LIU ; Fujun JIA
Chinese Journal of Psychiatry 2017;50(3):175-181
Objective To assess the type and prevalence of residual symptoms in Chinese depressive patients after acute phase treatment and the impact on the quality of life and social function. Method It was a nationwide, multi-center survey. A total of 11 sites participated and 1503 outpatients with major depressive disorder who subjectively self-reported a least 50%improvement after 8-12 weeks of antidepressants treatment were included in this study. Brief 16-Item Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16), Patient Health Questionnaire-15 (PHQ-15), Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) and Sheehan Disability Scale (SDS) were used to assess the symptoms and function. Results Altogether 48.8%(733/1503) of patients who self-reported an improvement after acute-phase treatment still presented with residual symptoms (QIDS-SR16>5). The most common residual symptoms (QIDS-SR16≥1) were poor concentration/decision making (82.4%, 604/733), low energy (79.7%, 584/733), loss of interest (75.2%, 551/733), sad mood (72.4%, 531/733) and mid-nocturnal insomnia (72.3%, 530/733). The patients with severe residual symptoms had higher PHQ-15 total score (t=-10.55,P<0.01), lower Q-LES-Q-SF score (t=10.20,P=0.010) and higher SDS score (t=-13.22,P<0.01). Conclusion The great majority of patients who self-report an improvement after acute phase antidepressant treatment may still have residual symptoms. The severity of residual symptoms is associated with significant function impairment and poor life satisfaction.

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