1.Attenuation of esophageal precancerous lesions in mice by Banxia Xiexin Decoction through gut microbiota modulation
Man JIN ; Wenfei ZHU ; Zhaoling WANG ; Kuai YU ; Jianping WU ; Junfeng ZHANG
Digital Chinese Medicine 2026;9(1):114-129
Objective:
To investigate the microbial mechanisms of Banxia Xiexin Decoction (半夏泻心汤, BXXXD) in the treatment of esophageal precancerous lesions.
Methods:
A total of 30 specific pathogen-free (SPF) grade female C57BL/6J mice were randomly assigned to a control group (n = 6) and a 4-nitroquinoline 1-oxide (4-NQO)-exposed group (n = 24). Esophageal precancerous lesions were induced by providing the 4-NQO-exposed group with 4-NQO in drinking water (100 μg/mL) for 17 consecutive weeks, whereas control group received sterile drinking water. After model establishment, the mice in 4-NQO-exposed group were further randomized into model group and three BXXXD-treated groups: low-dose (BXXXD-L, 3.7 g/kg), medium-dose (BXXXD-M, 7.4 g/kg), and high-dose (BXXXD-H, 14.8 g/kg) groups (n = 6 per group). During the subsequent intervention period, mice in control and model groups were gavaged with sterile water, while mice in BXXXD groups were gavaged once daily with the corresponding dose of BXXXD aqueous extract for 4 weeks. Histopathological changes in esophageal tissues were observed by hematoxylin and eosin (HE) staining. The fecal and esophageal microbiota were profiled via 16S rDNA high-throughput sequencing to evaluate bacterial diversity, community structure, and co-occurrence networks. BXXXD chemical fingerprints were analyzed using ultra-high-performance liquid chromatography coupled with quadrupole QExactive Orbitrap mass spectrometry (UHPLC-QE-MS). Serum short-chain fatty acids (SCFA) level was quantified by targeted metabolomics using gas chromatography-mass spectrometry (GC-MS). Transcriptomic analysis of esophageal tissues was performed to assess gene expression profiles.
Results:
Compared with model group, BXXXD-M group exhibited reduced mucosal hyperplasia and more orderly epithelial cell arrangement, with superior therapeutic effects in comparison with both BXXXD-L and BXXXD-H groups (P < 0.01). Microbiota analysis revealed that BXXXD increased the abundance of beneficial Enterococcus and reduced pathogenic Escherichia-Shigella in the esophagus. In the gut, BXXXD elevated the relative abundance of beneficial taxa, including Lactobacillus, Dubosiella, Bacteroides, and Faecalibacterium. Targeted metabolomics showed that BXXXD significantly reduced total serum SCFA level (P < 0.01). Transcriptomic analysis indicated that BXXXD downregulated the expression of genes associated with the progression, migration, and invasion of esophageal cancer, which were identified as kallikrein-related peptidase 6 (Klk6), defensin beta 4 (Defb4), family with sequence similarity 3 member B (Fam3b), carboxypeptidase A4 (Cpa4), serum amyloid A1 (Saa1), and chitinase-like 1 (Chil1) (P < 0.05).
Conclusion
BXXXD may reduce the expression levels of esophageal cancer-related genes and improve esophageal precancerous lesions through modulation of the gut microbiota and metabolites.
2.Intra-articular injection of different concentrations of silicon-based bioceramics in treatment of knee osteoarthritis in rats
Jingwen GUO ; Qingwei WANG ; Zijun HE ; Zihang HU ; Zhi CHEN ; Rong ZHU ; Yuming WANG ; Wenfei LIU ; Qinglu LUO
Chinese Journal of Tissue Engineering Research 2026;30(2):288-295
BACKGROUND:Currently,treatment method for knee osteoarthritis includes oral medicine,joint cavity drug injection,and physiotherapy,but the curative effect is limited.Existing studies have confirmed that silicon-based bioceramics can promote cartilage and subchondral bone repair and vascular regeneration.OBJECTIVE:To explore the effect of different concentrations of silicon-based bioceramics injected into the knee joint cavity in the treatment of knee osteoarthritis in rats.METHODS:Silicon-based bioceramics-calcium silicate was prepared.Twenty-five SD rats were randomly divided into five groups,with five rats in each group.The healthy group did not receive any intervention,and the modeling group,low-dose calcium silicate group,high-dose calcium silicate group,and saline group used anterior cruciate ligament transection to establish bilateral knee osteoarthritis models.Four weeks after modeling,0.05 mL of 50 and 100 mg/mL calcium silicate solution were injected into the knee joint cavity in the low-dose calcium silicate group and high-dose calcium silicate group,respectively,and 0.05 mL of saline was injected into the knee joint cavity in the saline group,once a week for 4 consecutive weeks.In the fifth week of administration,bilateral knee joint Micro-CT detection,knee joint cartilage hematoxylin-eosin staining,and modified Mankin score were performed.RESULTS AND CONCLUSION:(1)Micro-CT quantitative analysis showed that compared with the healthy group,the volume fraction and number of trabeculae of the medial tibial plateau in the modeling group decreased(P<0.05),and the separation of trabeculae increased(P<0.05).Compared with the modeling group,the volume fraction and number of trabeculae of the medial tibial plateau in the low-dose calcium silicate group and the saline group increased(P<0.05),and the separation of trabeculae decreased(P<0.05).(2)Hematoxylin-eosin staining showed that the cartilage surface of the healthy group and the low-dose calcium silicate group was relatively smooth and flat,the chondrocytes were evenly distributed,without clustered chondrocytes,the tide line was complete,and the staining was uniform;the cartilage surface of the high-dose calcium silicate group was slightly uneven,the middle and deep cells were disordered,with a small number of clustered chondrocytes,the tide line was discontinuous,and the staining was uneven;the cartilage surface of the saline group and the modeling group was obviously rough,the cells were disordered,with a large number of clustered chondrocytes,the tide line disappeared,and the staining was uneven.The modified Mankin score of the healthy group was lower than that of the high-dose calcium silicate group,the saline group,and the modeling group(P<0.05).The modified Mankin score of the high-dose calcium silicate group and the low-dose calcium silicate group was lower than that of the saline group and the modeling group(P<0.05).(3)The results show that calcium silicate knee joint injection has a certain effect in the treatment of knee osteoarthritis.Compared with 100 mg/mL calcium silicate solution,50 mg/mL calcium silicate solution can promote the recovery of subchondral bone and cartilage.
3.Intra-articular injection of different concentrations of silicon-based bioceramics in treatment of knee osteoarthritis in rats
Jingwen GUO ; Qingwei WANG ; Zijun HE ; Zihang HU ; Zhi CHEN ; Rong ZHU ; Yuming WANG ; Wenfei LIU ; Qinglu LUO
Chinese Journal of Tissue Engineering Research 2026;30(2):288-295
BACKGROUND:Currently,treatment method for knee osteoarthritis includes oral medicine,joint cavity drug injection,and physiotherapy,but the curative effect is limited.Existing studies have confirmed that silicon-based bioceramics can promote cartilage and subchondral bone repair and vascular regeneration.OBJECTIVE:To explore the effect of different concentrations of silicon-based bioceramics injected into the knee joint cavity in the treatment of knee osteoarthritis in rats.METHODS:Silicon-based bioceramics-calcium silicate was prepared.Twenty-five SD rats were randomly divided into five groups,with five rats in each group.The healthy group did not receive any intervention,and the modeling group,low-dose calcium silicate group,high-dose calcium silicate group,and saline group used anterior cruciate ligament transection to establish bilateral knee osteoarthritis models.Four weeks after modeling,0.05 mL of 50 and 100 mg/mL calcium silicate solution were injected into the knee joint cavity in the low-dose calcium silicate group and high-dose calcium silicate group,respectively,and 0.05 mL of saline was injected into the knee joint cavity in the saline group,once a week for 4 consecutive weeks.In the fifth week of administration,bilateral knee joint Micro-CT detection,knee joint cartilage hematoxylin-eosin staining,and modified Mankin score were performed.RESULTS AND CONCLUSION:(1)Micro-CT quantitative analysis showed that compared with the healthy group,the volume fraction and number of trabeculae of the medial tibial plateau in the modeling group decreased(P<0.05),and the separation of trabeculae increased(P<0.05).Compared with the modeling group,the volume fraction and number of trabeculae of the medial tibial plateau in the low-dose calcium silicate group and the saline group increased(P<0.05),and the separation of trabeculae decreased(P<0.05).(2)Hematoxylin-eosin staining showed that the cartilage surface of the healthy group and the low-dose calcium silicate group was relatively smooth and flat,the chondrocytes were evenly distributed,without clustered chondrocytes,the tide line was complete,and the staining was uniform;the cartilage surface of the high-dose calcium silicate group was slightly uneven,the middle and deep cells were disordered,with a small number of clustered chondrocytes,the tide line was discontinuous,and the staining was uneven;the cartilage surface of the saline group and the modeling group was obviously rough,the cells were disordered,with a large number of clustered chondrocytes,the tide line disappeared,and the staining was uneven.The modified Mankin score of the healthy group was lower than that of the high-dose calcium silicate group,the saline group,and the modeling group(P<0.05).The modified Mankin score of the high-dose calcium silicate group and the low-dose calcium silicate group was lower than that of the saline group and the modeling group(P<0.05).(3)The results show that calcium silicate knee joint injection has a certain effect in the treatment of knee osteoarthritis.Compared with 100 mg/mL calcium silicate solution,50 mg/mL calcium silicate solution can promote the recovery of subchondral bone and cartilage.
4.Construction and Validation of a Predictive Model for Ventilator-associated Pneumonia after Endovascular Treatment in Patients with Hy-pertension Complicating Acute Cerebral Infarction
Xiaohua HE ; Wenfei LIANG ; Jingling ZHU
Journal of Medical Research 2025;54(4):96-101,129
Objective Through the analysis of the clinical characteristics of post-interventional complications of ventilator-associ-ated pneumonia(VAP)in patients with hypertension and acute large vessel occlusive cerebral infarction(AIS-LVO),we aim to develop and validate a risk prediction model.Methods We conducted a retrospective analysis of clinical data from 107 patients hospitalized for hypertension with AIS-LVO at Dongguan Hospital of Guangzhou University of Traditional Chinese Medicine between July 2020 and Au-gust 2023.Patients were categorized into two groups based on their hospitalization:the VAP group,consisting of 64 patients who devel-oped VAP,and the non-VAP group,comprising 43 patients who did not experience VAP.Least absolute shrinkage and selection opera-tor regression(LASSO)analysis was employed to identify potential predictors.Subsequently,a nomogram model was constructed using multifactorial Logistic regression analysis.The model's discriminative ability,calibration,and clinical utility were assessed using the area(AUC)under the receiver operating characteristic(ROC)curve,calibration curves,and decision curve analysis(DCA).Results In 107 patients with hypertension and AIS-LVO who underwent interventional surgery,the incidence of VAP was 59.8%.The results revealed statistically significant differences between the two groups in terms of age,presence of atrial fibrillation,admission national institutes of health stroke scale(NIHSS)score,admission glasgow coma scale(GCS)score,impaired consciousness,swallowing dysfunction,opera-tive time,postoperative 24-hour systemic inflammatory response index(SIRI),duration of mechanical ventilation,length of ICU stay,and the presence of an indwelling gastrostomy tube(P<0.05).Additionally,the incidence of poor functional outcomes was 57.8%in the VAP group compared to 14.0%in the non-VAP group,indicating a worse prognosis for patients in the VAP group.The variables i-dentified through LASSO regression screening were included in a multifactorial Logistic regression analysis.This analysis revealed that the SIRI and the duration of mechanical ventilation were independent risk factors for the development of VAP following intervention in patients with hypertension and AIS-LVO(P<0.05).Conversely,the admission GCS score was identified as a protective factor(P<0.05).These three indicators were utilized to construct a prognostic nomogram model.The model's internal validity was assessed using the Boot-strap method with 1000 resamples,and the calibration curves were found to be in close agreement with the ideal fitted line,exhibiting a mean absolute error of 0.029,indicating good curve accuracy.The Logistic regression model's goodness of fit was evaluated using the Hos-mer and Lemeshow test,which yielded a x2 value of 5.38 and a P-value of 0.716,suggesting a good fit.The AUC of the model was 0.812(95%confidence interval 0.730-0.894),and the DCA indicated that the model has favorable clinical applicability.Conclusion A prediction model based on admission GCS score,postoperative 24-hour SIRI,and duration of mechanical ventilation demonstrates a robust predictive value for the incidence of VAP following intervention in patients with hypertension and acute ischemic stroke with AIS-LVO.
5.Construction and Validation of a Predictive Model for Ventilator-associated Pneumonia after Endovascular Treatment in Patients with Hy-pertension Complicating Acute Cerebral Infarction
Xiaohua HE ; Wenfei LIANG ; Jingling ZHU
Journal of Medical Research 2025;54(4):96-101,129
Objective Through the analysis of the clinical characteristics of post-interventional complications of ventilator-associ-ated pneumonia(VAP)in patients with hypertension and acute large vessel occlusive cerebral infarction(AIS-LVO),we aim to develop and validate a risk prediction model.Methods We conducted a retrospective analysis of clinical data from 107 patients hospitalized for hypertension with AIS-LVO at Dongguan Hospital of Guangzhou University of Traditional Chinese Medicine between July 2020 and Au-gust 2023.Patients were categorized into two groups based on their hospitalization:the VAP group,consisting of 64 patients who devel-oped VAP,and the non-VAP group,comprising 43 patients who did not experience VAP.Least absolute shrinkage and selection opera-tor regression(LASSO)analysis was employed to identify potential predictors.Subsequently,a nomogram model was constructed using multifactorial Logistic regression analysis.The model's discriminative ability,calibration,and clinical utility were assessed using the area(AUC)under the receiver operating characteristic(ROC)curve,calibration curves,and decision curve analysis(DCA).Results In 107 patients with hypertension and AIS-LVO who underwent interventional surgery,the incidence of VAP was 59.8%.The results revealed statistically significant differences between the two groups in terms of age,presence of atrial fibrillation,admission national institutes of health stroke scale(NIHSS)score,admission glasgow coma scale(GCS)score,impaired consciousness,swallowing dysfunction,opera-tive time,postoperative 24-hour systemic inflammatory response index(SIRI),duration of mechanical ventilation,length of ICU stay,and the presence of an indwelling gastrostomy tube(P<0.05).Additionally,the incidence of poor functional outcomes was 57.8%in the VAP group compared to 14.0%in the non-VAP group,indicating a worse prognosis for patients in the VAP group.The variables i-dentified through LASSO regression screening were included in a multifactorial Logistic regression analysis.This analysis revealed that the SIRI and the duration of mechanical ventilation were independent risk factors for the development of VAP following intervention in patients with hypertension and AIS-LVO(P<0.05).Conversely,the admission GCS score was identified as a protective factor(P<0.05).These three indicators were utilized to construct a prognostic nomogram model.The model's internal validity was assessed using the Boot-strap method with 1000 resamples,and the calibration curves were found to be in close agreement with the ideal fitted line,exhibiting a mean absolute error of 0.029,indicating good curve accuracy.The Logistic regression model's goodness of fit was evaluated using the Hos-mer and Lemeshow test,which yielded a x2 value of 5.38 and a P-value of 0.716,suggesting a good fit.The AUC of the model was 0.812(95%confidence interval 0.730-0.894),and the DCA indicated that the model has favorable clinical applicability.Conclusion A prediction model based on admission GCS score,postoperative 24-hour SIRI,and duration of mechanical ventilation demonstrates a robust predictive value for the incidence of VAP following intervention in patients with hypertension and acute ischemic stroke with AIS-LVO.
6.Comparison of the validity of different self-rated tools for identifying (Hypo-) manic episodes mixed features: based on Date from the Second Phase of the National Bipolar Mania Clinical Pathway Survey
Zuowei WANG ; Yuncheng ZHU ; Chuangxin WU ; Guiyun XU ; Miao PAN ; Zhiyu CHEN ; Xiaohong LI ; Wenfei LI ; Zhian JIAO ; Mingli LI ; Yong ZHANG ; Jingxu CHEN ; Xiuzhe CHEN ; Na LI ; Jing SUN ; Jian ZHANG ; Shaohua HU ; Haishan WU ; Zhaoyu GAN ; Yan QIN ; Yumei WANG ; Yantao MA ; Xiaoping WANG ; Yiru FANG
Chinese Journal of Psychiatry 2024;57(7):426-432
Objective:A nationwide multi-center and large sample survey was conducted to compare the validity of the Mini International Neuropsychiatric Interview (Hypo-) Manic Episode with Mixed Features-DSM-5 Module (MINI-M) questionnaire and the Clinically Useful Depression Outcome Scale Supplemented with Questions for the DSM-5 Mixed Features Specifier (CUDOS-M) depression subscale in identifying mixed features in patients experiencing (hypo-) manic episodes.Methods:Using a convenience sampling method, 366 patients with bipolar disorder experiencing acute (hypo-) manic episodes who met the inclusion and exclusion criteria were recruited. The diagnosis of "with mixed features" was based on the DSM-5 criteria for mixed features. The predictive validity of the MINI-M questionnaire and the CUDOS-M depression subscale to screen mixed features was analyzed using the receiver operating characteristic (ROC) curve. Additionally, the difference in area under the ROC curve (AUC) between the two instruments was compared.Results:The AUC for the MINI-M questionnaire and the CUDOS-M depression subscale in screening mixed features were 0.79 (95 %CI=0.75-0.84) and 0.81 (95 %CI=0.77-0.86), respectively. There was no statistically significant difference in AUC between the two measurements ( Z=-1.19, P>0.05). Among patients with acute (hypo-) manic episodes, 45.9% (168/366) presented with mixed features according to the DSM-5 criteria, while the corresponding figures were 43.7% (160/366) using the MINI-M questionnaire (total score≥3) and 42.1% (154/366) using the CUDOS-M depression subscale (total score≥20). Screening results were comparable among the three measures. Conclusion:Mixed features are common among patients experiencing acute (hypo-) manic episodes. The MINI-M questionnaire and the CUDOS-M depression subscale demonstrate equivalent validity in identifying mixed features.
7.Research on the pathogenesis of humans infected with zoonotic influenza viruses
ZHU Wenfei ; YANG Lei ; WANG Dayan
China Tropical Medicine 2024;24(1):16-
Influenza viruses can infect humans, lead to epidemics within populations, and even cause global pandemics. During the non-pandemic period, there is a continuous threat as avian or swine influenza viruses cross the species barrier to infect humans, resulting in zoonotic influenza infections. For the purpose of pandemic preparation and control, it is crucial to strengthen surveillance, scientific research, and risk assessment of these zoonotic influenza viruses. Here, we focus on the latest zoonotic influenza viruses that have recently garnered significant attention, providing an overview of their latest epidemiological trends and research progress, thereby facilitating scientific risk assessment.
8.Comparison of the validity of different self-rated tools for identifying (Hypo-) manic episodes mixed features: based on Date from the Second Phase of the National Bipolar Mania Clinical Pathway Survey
Zuowei WANG ; Yuncheng ZHU ; Chuangxin WU ; Guiyun XU ; Miao PAN ; Zhiyu CHEN ; Xiaohong LI ; Wenfei LI ; Zhian JIAO ; Mingli LI ; Yong ZHANG ; Jingxu CHEN ; Xiuzhe CHEN ; Na LI ; Jing SUN ; Jian ZHANG ; Shaohua HU ; Haishan WU ; Zhaoyu GAN ; Yan QIN ; Yumei WANG ; Yantao MA ; Xiaoping WANG ; Yiru FANG
Chinese Journal of Psychiatry 2024;57(7):426-432
Objective:A nationwide multi-center and large sample survey was conducted to compare the validity of the Mini International Neuropsychiatric Interview (Hypo-) Manic Episode with Mixed Features-DSM-5 Module (MINI-M) questionnaire and the Clinically Useful Depression Outcome Scale Supplemented with Questions for the DSM-5 Mixed Features Specifier (CUDOS-M) depression subscale in identifying mixed features in patients experiencing (hypo-) manic episodes.Methods:Using a convenience sampling method, 366 patients with bipolar disorder experiencing acute (hypo-) manic episodes who met the inclusion and exclusion criteria were recruited. The diagnosis of "with mixed features" was based on the DSM-5 criteria for mixed features. The predictive validity of the MINI-M questionnaire and the CUDOS-M depression subscale to screen mixed features was analyzed using the receiver operating characteristic (ROC) curve. Additionally, the difference in area under the ROC curve (AUC) between the two instruments was compared.Results:The AUC for the MINI-M questionnaire and the CUDOS-M depression subscale in screening mixed features were 0.79 (95 %CI=0.75-0.84) and 0.81 (95 %CI=0.77-0.86), respectively. There was no statistically significant difference in AUC between the two measurements ( Z=-1.19, P>0.05). Among patients with acute (hypo-) manic episodes, 45.9% (168/366) presented with mixed features according to the DSM-5 criteria, while the corresponding figures were 43.7% (160/366) using the MINI-M questionnaire (total score≥3) and 42.1% (154/366) using the CUDOS-M depression subscale (total score≥20). Screening results were comparable among the three measures. Conclusion:Mixed features are common among patients experiencing acute (hypo-) manic episodes. The MINI-M questionnaire and the CUDOS-M depression subscale demonstrate equivalent validity in identifying mixed features.
9.Analysis of clinical phenotypes of bipolar disorder with mixed states diagnosed using ICD-10 and DSM-5
Yang LI ; Jia ZHOU ; Zuowei WANG ; Yuncheng ZHU ; Guiyun XU ; Miao PAN ; Zhiyu CHEN ; Wenfei LI ; Zhian JIAO ; Mingli LI ; Yong ZHANG ; Jingxu CHEN ; Xiuzhe CHEN ; Na LI ; Jing SUN ; Jian ZHANG ; Shaohua HU ; Haishan WU ; Zhaoyu GAN ; Yan QIN ; Yumei WANG ; Yantao MA ; Xiaoping WANG ; Xiaohong LI ; Yiru FANG
Chinese Journal of Psychiatry 2023;56(4):267-275
Objective:This study investigates the difference in the detection rate and symptomatology between ICD-10 and DSM-5 diagnostic criteria for bipolar disorder with mixed states.Methods:Based on the Phase Ⅰ (2012) and Phase Ⅱ (2021) databases of National Bipolar Mania Pathway Survey (BIPAS), patients with bipolar disorder were included. General demographic data, clinical characteristics, symptomatic phenotypes, and mixed characteristics were retrieved. The detection rates and symptomatic performances of patients with or without mixed states in Phase Ⅰ and Ⅱ were compared using the chi-square test.Results:For patients with mixed states, the detection rate during Phase Ⅱ (2021) using DSM-5 (18.79%, 199/1 059) criteria was significantly higher than that during Phase Ⅰ (2012) using ICD-10 (6.78%, 199/2 934; χ 2=125.05, P<0.001). Whether using ICD-10 or DSM-5 criteria, patients with mixed states had a significantly higher frequency of multiple symptomatic manifestations. Conclusion:The DSM-5 diagnostic criteria generate a high detection rate for bipolar disorder with mixed states. The clinical phenotypes of bipolar disorder with mixed states vary significantly using different diagnostic tools.
10.Analysis of clinical phenotypes of bipolar disorder with mixed states diagnosed using ICD-10 and DSM-5
Yang LI ; Jia ZHOU ; Zuowei WANG ; Yuncheng ZHU ; Guiyun XU ; Miao PAN ; Zhiyu CHEN ; Wenfei LI ; Zhian JIAO ; Mingli LI ; Yong ZHANG ; Jingxu CHEN ; Xiuzhe CHEN ; Na LI ; Jing SUN ; Jian ZHANG ; Shaohua HU ; Haishan WU ; Zhaoyu GAN ; Yan QIN ; Yumei WANG ; Yantao MA ; Xiaoping WANG ; Xiaohong LI ; Yiru FANG
Chinese Journal of Psychiatry 2023;56(4):267-275
Objective:This study investigates the difference in the detection rate and symptomatology between ICD-10 and DSM-5 diagnostic criteria for bipolar disorder with mixed states.Methods:Based on the Phase Ⅰ (2012) and Phase Ⅱ (2021) databases of National Bipolar Mania Pathway Survey (BIPAS), patients with bipolar disorder were included. General demographic data, clinical characteristics, symptomatic phenotypes, and mixed characteristics were retrieved. The detection rates and symptomatic performances of patients with or without mixed states in Phase Ⅰ and Ⅱ were compared using the chi-square test.Results:For patients with mixed states, the detection rate during Phase Ⅱ (2021) using DSM-5 (18.79%, 199/1 059) criteria was significantly higher than that during Phase Ⅰ (2012) using ICD-10 (6.78%, 199/2 934; χ 2=125.05, P<0.001). Whether using ICD-10 or DSM-5 criteria, patients with mixed states had a significantly higher frequency of multiple symptomatic manifestations. Conclusion:The DSM-5 diagnostic criteria generate a high detection rate for bipolar disorder with mixed states. The clinical phenotypes of bipolar disorder with mixed states vary significantly using different diagnostic tools.

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