1.Study on medication adherence factors among patients with severe mental disorders in Zhuhai city based on XGBoost model
Zhongshu YE ; Yongyong TENG ; Jingju QUAN ; Yajun SUN ; Jiaju HUANG ; Yixuan WU ; Changlin HAN ; Guangchuan ZHANG
Sichuan Mental Health 2026;39(1):36-43
BackgroundLow medication compliance among patients with severe mental disorders increases the disease burden on both the patients' families and the society. Medication adherence is influenced by numerous factors. Traditional methods such as Logistic regression struggle to quantify the importance of these factors. By introducing Extreme Gradient Boosting (XGBoost) combined with Shapley Additive Explanations (SHAP), enables the quantification of the relative contribution weights of each factor, providing support for identifying the core influencing factors. ObjectiveTo explore the influencing factors of medication adherence among patients with severe mental disorders in Zhuhai, aiming to provide references for optimizing patient management strategies. MethodsExtract the data of patients with severe mental disorders who were registered on the mental health system platform in Zhuhai City from January 1, 2023 to March 31, 2025. A total of 9 329 patients were finally included for analysis. Influencing factors were screened using univariate analysis and multivariate logistic regression analysis, and an XGBoost model combined with the SHAP algorithm was constructed to quantify the importance of each influencing factor. ResultsAmong 9 329 patients, 8 446 demonstrated medication adherence, yielding an adherence rate of 90.53%. Multivariable analysis identified several risk factors significantly associated with medication non-adherence, being unmarried (OR=1.237, 95% CI: 1.019–1.502) or divorced (OR=1.389, 95% CI: 1.038–1.832), a diagnosis of mental retardation with psychiatric disorders (OR=3.025, 95% CI: 2.402–3.796) or paranoid psychosis (OR=5.117, 95% CI: 3.086–8.299), a disease duration of 2–4 years (OR=1.355, 95% CI: 1.085–1.696), 4–6 years (OR=2.143, 95% CI: 1.671–2.747), or >6 years (OR=1.681, 95% CI: 1.365–2.079), lack of guardian subsidies (OR=1.412, 95% CI: 1.099–1.801), absence of a disability certificate (OR=1.900, 95% CI: 1.588–2.282), not being enrolled in care and support groups (OR=1.384, 95% CI: 1.183–1.617) or community services (OR=1.313, 95% CI: 1.042–1.645), and not cohabiting with a guardian (OR=1.257, 95% CI: 1.048–1.501). Conversely, the enrollment in special outpatient disease programs (OR=0.716, 95% CI: 0.609–0.842) and a family history of mental illness (OR=0.713, 95% CI: 0.503–0.982) were identified as protective factors. The XGBoost model exhibited robust predictive performance, with a sensitivity of 0.433, specificity of 0.944, accuracy of 0.891, Area Under the Curve (AUC) of 0.837, and F1 value of 0.449. Feature importance ranking indicated that the top three factors were disease duration, diagnosis, and the acquisition of disability certificates. ConclusionPolicy-based support (acquisition of disability certificates, special outpatient disease enrollment) and clinical disease characteristics (disease duration, diagnosis type) are key factors affecting medication adherence among patients with severe mental disorders in Zhuhai City. [Funded by Zhuhai Medical Research Project (number, 2220009000281)]
2.Change in the number of peripheral blood regulatory T cells in patients with chronic kidney disease and its correlation with vascular calcification
Di ZHANG ; Hui WU ; Jing CHEN ; Liyu LIN ; Shaomin GONG ; Xiaoyan ZHANG ; Xiaoqiang DING ; Han ZHANG
Chinese Journal of Clinical Medicine 2026;33(2):285-292
Objective To explore the number of peripheral blood regulatory T cells (Treg) in patients with chronic kidney disease (CKD) and its correlation with vascular calcification. Methods This was a single-center, cross-sectional, and observational study. Non-dialysis patients with CKD treated at Zhongshan Hospital, Fudan University from March 2021 to March 2022 were enrolled. Abdominal aortic calcification (AAC) was assessed using lateral abdominal X-ray. Number of Treg and cytokine levels were measured by flow cytometry. Logistic regression analysis was performed to evaluate the related factors for AAC in CKD patients. Results A total of 83 patients were included, aged 17–86 years, with 57 males (68.7%). The distribution of CKD stages was as follows: stage G1 in 7 patients (8.4%), stage G2 in 17 patients (20.5%), stage G3 in 21 patients (25.3%), stage G4 in 19 patients (22.9%), and stage G5 in 19 patients (22.9%). No AAC was observed in patients with stages G1 and G2, while the prevalence of AAC in patients with stages G3, G4, and G5 was 23.8%, 21.1%, and 26.3%, respectively. Compared with stage G1 patients, those with stages G3–5 showed decreased number of peripheral blood Treg and elevated levels of interleukin (IL)-6 and IL-17F (P<0.05). The area under the receiver operating characteristic curve for number of peripheral blood Treg in predicting AAC in CKD patients was 0.766 (95%CI 0.652–0.879, P=0.002). Logistic regression analysis showed that decreased number of Treg was related factor for AAC in CKD patients (OR=0.957, 95%CI 0.922–0.992, P=0.018). Conclusion As CKD progresses, number of peripheral blood Treg significantly decreases, which is correlated with AAC in CKD patients.
3.Treatment Principles and Paradigm of Diabetic Microvascular Complications Responding Specifically to Traditional Chinese Medicine
Anzhu WANG ; Xing HANG ; Lili ZHANG ; Xiaorong ZHU ; Dantao PENG ; Ying FAN ; Min ZHANG ; Wenliang LYU ; Guoliang ZHANG ; Xiai WU ; Jia MI ; Jiaxing TIAN ; Wei ZHANG ; Han WANG ; Yuan XU ; .LI PINGPING ; Zhenyu WANG ; Ying ZHANG ; Dongmei SUN ; Yi HE ; Mei MO ; Xiaoxiao ZHANG ; Linhua ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):272-279
To explore the advantages of traditional Chinese medicine (TCM) and integrative TCM-Western medicine approaches in the treatment of diabetic microvascular complications (DMC), refine key pathophysiological insights and treatment principles, and promote academic innovation and strategic research planning in the prevention and treatment of DMC. The 38th session of the Expert Salon on Diseases Responding Specifically to Traditional Chinese Medicine, hosted by the China Association of Chinese Medicine, was held in Beijing, 2024. Experts in TCM, Western medicine, and interdisciplinary fields convened to conduct a systematic discussion on the pathogenesis, diagnostic and treatment challenges, and mechanism research related to DMC, ultimately forming a consensus on key directions. Four major research recommendations were proposed. The first is addressing clinical bottlenecks in the prevention and control of DMC by optimizing TCM-based evidence evaluation systems. The second is refining TCM core pathogenesis across DMC stages and establishing corresponding "disease-pattern-time" framework. The third is innovating mechanism research strategies to facilitate a shift from holistic regulation to targeted intervention in TCM. The fourth is advancing interdisciplinary collaboration to enhance the role of TCM in new drug development, research prioritization, and guideline formulation. TCM and integrative approaches offer distinct advantages in managing DMC. With a focus on the diseases responding specifically to TCM, strengthening evidence-based support and mechanism interpretation and promoting the integration of clinical care and research innovation will provide strong momentum for the modernization of TCM and the advancement of national health strategies.
4.Bidirectional association between metabolic associated fatty liver disease and the risk of atherosclerotic cardiovascular disease
Yanan ZHAO ; Qi QI ; Xinyu WU ; Quanle HAN ; Jing YANG ; Boheng ZHANG ; Xuyang LI ; Lei LI ; Yun ZHANG ; Shouling WU ; Kangbo LI
Journal of Clinical Hepatology 2026;42(4):856-865
ObjectiveTo investigate the association between metabolic associated fatty liver disease (MAFLD) and the risk of atherosclerotic cardiovascular disease (ASCVD), and to provide data support for the prevention and treatment of such metabolic-associated diseases in clinical practice. MethodsAn observation cohort was established for the workers of Kailuan who underwent physical examination for the first time from June 2006 to October 2007 and had complete liver assessment data, without the history of malignant tumor, MAFLD or ASCVD. According to the presence or absence of MAFLD, the patients were divided into non-MAFLD group with 67 565 patients and MAFLD group with 29 004 patients, and according to the presence or absence of ASCVD, the patients were divided into non-ASCVD group with 69 141 patients and ASCVD group with 481 patients. The group t-test or the Wilcoxon rank-sum test was used for comparison of continuous data between the two groups. The
5.Meconium containing intestinal structures: a histological study using human fetuses
Jun ZHANG ; Zhe-Wu JIN ; Feng HAN ; Ye XU ; Gen MURAKAMI ; Masahito YAMAMOTO ; Shogo HAYASHI
Anatomy & Cell Biology 2026;59(1):105-114
Meconium is changed from defoliated intestinal villi with apoptosis. A meconium corpuscle is a limited architecture in the meconium at the light microscopic level. In histological and immunohistochemical sections of the abdomen from 40 fetuses at 20–31 weeks of gestation, we found 12 fetuses with meconium and examined the architecture.A solid or loose meconium was seen depending on sites. The solid meconium in the colon and rectum contained numerous spherical or rugby ball-like corpuscles comprising of a core with tightly-packed atrophied cells and a laminar fibrous sheath.The solid meconium surrounded and incorporated villi that maintained the original architecture. The loose meconium was seen not only in the stomach and duodenum but also, depending on specimens, in the colon and rectum. It was composed of a large mucosal fold, a single small villus and/or fragmented epithelia. Notably, these mucosal tissues still contained chromogranin-positive gastrointestinal cells and cytokeratin-positive epithelia. A large ring-like meconium was composed of the entirely circular mucosa or epithelia that seemed to be detached along the muscularis mucosae or the basal lamina.A sheath-like fibrous structure in meconium seemed to originate from the lamina propria and basal lamina of villi. A defoliation of villi with apoptosis seemed difficult to explain a detachment of the entirely circular mucosa or epithelia in large fetuses examined. The latter event might require a specific mechanism such as an in utero intussusception in which a proximal side of the colon was invaginated into the distal lumen.
6.Thrombus Migration After Tenecteplase Versus Alteplase in Acute Large Vessel Occlusion
Lu WANG ; Fuxia YANG ; Xiao WU ; Lulan LI ; Xueqiao JIAO ; Fangfang ZHANG ; Fengyuan CHE ; Hongxing HAN ; Weidong LIU ; Peifu WANG ; Xuesong LI ; Junfeng SHI ; Jia LIU ; Xunming JI ; Xiuhai GUO
Journal of Stroke 2026;28(2):283-292
Background:
and Purpose In patients with large vessel occlusion (LVO), intravenous thrombolysis (IVT) frequently alters thrombus location; however, the clinical impact of this phenomenon remains unclear. We aimed to compare post-IVT thrombus dynamics between tenecteplase and alteplase and to evaluate the association between thrombus dynamics and 3-month outcomes.
Methods:
This retrospective study analyzed prospectively collected, multicenter data from consecutive patients with LVO who underwent bridging therapy between January 2022 and December 2024. Thrombus dynamics were classified as resolution, migration, or stability. Analyses incorporated propensity score matching with weighting to balance baseline characteristics.
Results:
Of the 806 initially included patients, 746 were included after matching (373 treated with tenecteplase and 373 treated with alteplase). The incidence of thrombus migration was significantly higher in the tenecteplase group than in the alteplase group (19.3% vs. 11.3%; odds ratio [OR]: 1.92; 95% confidence interval [CI] 1.27–2.91). The advantage of tenecteplase over alteplase was restricted to patients with an IVT-to-puncture time of <60 minutes (18.6% vs. 6.2%; p=0.001) and was no longer significant when the interval ≥60 minutes (19.7% vs. 15.0%; p=0.204; pinteraction=0.043). Additionally, thrombus migration was associated with a better functional outcome (OR: 1.62; 95% CI 1.04–2.53). Finally, tenecteplase was associated with improved functional independence compared with alteplase (OR: 1.43; 95% CI 1.04–1.95).
Conclusions
Tenecteplase demonstrated superior efficacy in inducing thrombus migration compared with alteplase, particularly within 60 minutes of IVT administration. Thrombus migration independently predicted improved functional independence. These findings support the preferential use of tenecteplase for bridging therapy in patients with LVO.
7.Analysis of Clinical and Phenomics Characteristics of Patients with Phlegm-Stasis Binding Syndrome and Its Accompanied Patterns in Stable Angina Pectoris of Coronary Heart Disease
Chongchai LI ; Han LI ; Zheng LI ; Zeng LI ; Yushi ZHOU ; Yuhan AO ; Shuang XU ; Xue WANG ; Yaoyao SUN ; Dongning WU ; Hongcai SHANG ; Mingxue ZHANG
Journal of Traditional Chinese Medicine 2026;67(14):1514-1522
ObjectiveTo explore the clinical and phenomics characteristics of patients with phlegm-stasis binding syndrome and its accompanied patterns in stable angina pectoris (SAP) of coronary heart disease (CHD). MethodsA multicenter cross-sectional study design was adopted. A total of 300 patients with SAP of CHD were enrolled and classified into 120 cases of phlegm-stasis binding syndrome, 125 cases of qi deficiency-accompanied syndrome, 38 cases of qi stagnation-accompanied syndrome, and 17 cases of toxin accumulation-accompanied syndrome according to traditional Chinese medicine (TCM) patterns. Data of patients with different TCM patterns were collected, including general condition, TCM symptoms, blood lipids, coagulation function, immune indicators, and serum metabolomics. Metabolic pathway enrichment analysis was used to compare differences in phenomics characteristics among groups. Metabolites with variable importance in projection (VIP) ≥1 and fold change (FC) ≥2 were considered as representative differential metabolites. ResultsPatients in each TCM pattern type were most commonly in the 60-75 years age group, with a relatively high proportion of males. Regarding TCM symptoms, patients with phlegm-stasis binding syndrome most commonly presented with wiry-choppy or wiry-slippery pulse, chest pain, and chest tightness; in patients with qi deficiency-accompanied syndrome, fatigue, chest pain, and weak pulse were most common; in patients with qi stagnation-accompanied sydnrome, wiry-choppy or wiry-slippery pulse, chest pain, and symptoms that increase or decrease with emotional changes, belching, or flatulence were most common; in patients with toxin accumulation-accompanied syndrome, bitter taste in the mouth, chest tightness, irritability, restlessness or manic delirium, and dry and hard stools or foul-smelling diarrhea were most common. Comparisons among the different TCM patterns showed statistically significant differences in coagulation parameters (P<0.05), whereas no statistically significant difference was found in blood lipid levels and immune indicators (P>0.05).Metabolomics analysis suggested that disorders of glycerophosphate metabolism and valine, leucine, and isoleucine metabolism are characteristic features of phlegm-stasis binding syndrome and its accompanied patterns. The representative differential metabolites between phlegm-stasis binding syndrome and qi deficiency-accompanied syndrome were 7,8-dihydrobiopterin (FC = 3.58) and oxypurinol (FC = 124.50). Those between phlegm-stasis binding syndrome and qi stagnation-accompanied syndrome were cytidine 5′-diphosphocholine (FC = 2.62) and D-mannosamine (FC = 2.99). Those between phlegm-stasis binding syndrome and toxin accumulation-accompanied syndrome were anserine (FC = 7.83) and canrenone (FC = 8.94). ConclusionThere are certain differences in the clinical characteristics and phenomics characteristics among patients with SAP due to CHD exhibiting phlegm-stasis binding syndrome and its accompanied patterns. The phenomics characteristics mainly involve biological alterations such as lipid metabolism disorders, amino acid metabolism abnormalities, and multiple immune indicators activation, which may provide a reference for precise differentiation and treatment of SAP of CHD in TCM clinical practice.
8.Analysis of Clinical and Phenomics Characteristics of Patients with Phlegm-Stasis Binding Syndrome and Its Accompanied Patterns in Stable Angina Pectoris of Coronary Heart Disease
Chongchai LI ; Han LI ; Zheng LI ; Zeng LI ; Yushi ZHOU ; Yuhan AO ; Shuang XU ; Xue WANG ; Yaoyao SUN ; Dongning WU ; Hongcai SHANG ; Mingxue ZHANG
Journal of Traditional Chinese Medicine 2026;67(14):1514-1522
ObjectiveTo explore the clinical and phenomics characteristics of patients with phlegm-stasis binding syndrome and its accompanied patterns in stable angina pectoris (SAP) of coronary heart disease (CHD). MethodsA multicenter cross-sectional study design was adopted. A total of 300 patients with SAP of CHD were enrolled and classified into 120 cases of phlegm-stasis binding syndrome, 125 cases of qi deficiency-accompanied syndrome, 38 cases of qi stagnation-accompanied syndrome, and 17 cases of toxin accumulation-accompanied syndrome according to traditional Chinese medicine (TCM) patterns. Data of patients with different TCM patterns were collected, including general condition, TCM symptoms, blood lipids, coagulation function, immune indicators, and serum metabolomics. Metabolic pathway enrichment analysis was used to compare differences in phenomics characteristics among groups. Metabolites with variable importance in projection (VIP) ≥1 and fold change (FC) ≥2 were considered as representative differential metabolites. ResultsPatients in each TCM pattern type were most commonly in the 60-75 years age group, with a relatively high proportion of males. Regarding TCM symptoms, patients with phlegm-stasis binding syndrome most commonly presented with wiry-choppy or wiry-slippery pulse, chest pain, and chest tightness; in patients with qi deficiency-accompanied syndrome, fatigue, chest pain, and weak pulse were most common; in patients with qi stagnation-accompanied sydnrome, wiry-choppy or wiry-slippery pulse, chest pain, and symptoms that increase or decrease with emotional changes, belching, or flatulence were most common; in patients with toxin accumulation-accompanied syndrome, bitter taste in the mouth, chest tightness, irritability, restlessness or manic delirium, and dry and hard stools or foul-smelling diarrhea were most common. Comparisons among the different TCM patterns showed statistically significant differences in coagulation parameters (P<0.05), whereas no statistically significant difference was found in blood lipid levels and immune indicators (P>0.05).Metabolomics analysis suggested that disorders of glycerophosphate metabolism and valine, leucine, and isoleucine metabolism are characteristic features of phlegm-stasis binding syndrome and its accompanied patterns. The representative differential metabolites between phlegm-stasis binding syndrome and qi deficiency-accompanied syndrome were 7,8-dihydrobiopterin (FC = 3.58) and oxypurinol (FC = 124.50). Those between phlegm-stasis binding syndrome and qi stagnation-accompanied syndrome were cytidine 5′-diphosphocholine (FC = 2.62) and D-mannosamine (FC = 2.99). Those between phlegm-stasis binding syndrome and toxin accumulation-accompanied syndrome were anserine (FC = 7.83) and canrenone (FC = 8.94). ConclusionThere are certain differences in the clinical characteristics and phenomics characteristics among patients with SAP due to CHD exhibiting phlegm-stasis binding syndrome and its accompanied patterns. The phenomics characteristics mainly involve biological alterations such as lipid metabolism disorders, amino acid metabolism abnormalities, and multiple immune indicators activation, which may provide a reference for precise differentiation and treatment of SAP of CHD in TCM clinical practice.
9.Clinical efficacy of valve-in-valve transcatheter mitral valve replacement for degenerated mitral surgical bioprostheses
Shixiong WU ; Xu HAN ; Zhikun ZHENG ; Yongkai ZHANG ; Jing XU ; Chen HUANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(08):1252-1257
Objective To evaluate the clinical efficacy of valve-in-valve transcatheter mitral valve replacement for the management of degenerated bioprosthetic mitral valves. Methods This study retrospectively analyzed the clinical data of patients who underwent transcatheter mitral valve replacement due to degenerated bioprosthetic mitral valves at the First Affiliated Hospital of Zhengzhou University from 2020 to 2023. The analysis included baseline characteristics, surgical details, perioperative complications, and hemodynamic changes during the early postoperative period and subsequent follow-up. Results A total of 31 patients were included in the study, comprising 7 males and 24 females, with an average age of (66.57±9.32) years. The average duration since the initial surgical placement of the bioprosthetic valves was (9.92±3.71) years. The procedures included 7 patients utilizing the transfemoral venous-atrial septal approach and 24 patients employing the transapical approach. All patients exhibited significant improvement in cardiac function postoperatively, with a reduction in the number of patients classified as New York Heart Association (NYHA) grade Ⅲ or Ⅳ and those with moderate to severe tricuspid valve regurgitation. Echocardiographic assessments revealed a decrease in peak flow velocity across the mitral valve and a reduction in the average transvalvular pressure gradient, while left ventricular ejection fraction remained unchanged. One patient experienced a recurrent stroke and died on the fifth postoperative day; however, the remaining patients were discharged uneventfully, without complications such as cardiac death, left ventricular outflow tract obstruction, or pacemaker implantation. During a median follow-up period of 12 months, no adverse events were reported, and hemodynamic stability was maintained. Conclusion Valve-in-valve transcatheter mitral valve replacement is a safe and effective option for patients with degenerated bioprosthetic mitral valves, demonstrating favorable hemodynamic outcomes and satisfactory short-term clinical results.
10.Features of HBV RNA level in different stages of the natural history of chronic hepatitis B virus infection and its correlation with HBV DNA and HBsAg
Han GAO ; Juanli WU ; Yushuang ZHANG ; Yiheng ZHANG ; Lei WANG ; Tao LI ; Lixin ZHANG
Journal of Clinical Hepatology 2025;41(4):637-642
ObjectiveTo investigate the features of serum HBV RNA in different stages of the natural history of chronic hepatitis B virus (HBV) infection without antiviral treatment, as well as its correlation with serum HBV DNA and HBsAg. MethodsA total of 306 treatment-naïve patients with chronic HBV infection who attended Department of Infections Diseases and Hepatoloty, the Second Hospital of Shandong University from January 2023 to June 2024 were divided into six groups based on the different stages of natural history, i.e., HBeAg-positive chronic HBV infection group with 29 patients, HBeAg-positive chronic hepatitis B (CHB) group with 107 patients, HBeAg-negative chronic HBV infection group with 18 patients, HBeAg-negative CHB group with 60 patients, HBeAg-positive indeterminate-phase chronic HBV infection group with 7 patients, and HBeAg-negative indeterminate-phase chronic HBV infection group with 85 patients. Real-time isothermal RNA amplification was used to measure serum high-sensitivity HBV RNA. The Kruskal-Wallis H test was used for comparison between multiple groups of continuous data, while the Mann-Whitney U test was used for comparison between two groups. The Spearman method was used to investigate the correlation of HBV RNA with HBV DNA and HBsAg. ResultsThe HBeAg-positive chronic HBV infection group showed the highest level of serum HBV RNA [7.5 (7.4 — 7.9) log10 copies/mL], followed by the HBeAg-positive CHB group [7.4 (6.4 — 7.9) log10 copies/mL], the HBeAg-negative CHB group [4.5 (3.0 — 5.7) log10 copies/mL], and the HBeAg-negative chronic HBV infection group [1.0 (1.0 — 2.0) log10 copies/mL]; the HBeAg-positive indeterminate-phase chronic HBV infection group had a serum HBV RNA level of 3.9 (3.7 — 5.7) log10 copies/mL, and the HBeAg-negative indeterminate-phase chronic HBV infection group had a serum HBV RNA level of 2.0 (1.0 — 3.0) log10 copies/mL; there was a significant difference in serum HBV RNA level between the six groups (H=830.770, P<0.001). There was a significant difference in HBV RNA level between the HBeAg-positive chronic HBV infection group and all the other groups except the HBeAg-positive CHB group (all P<0.001). In the 306 patients with HBV infection, HBV RNA was strongly correlated with HBV DNA (r=0.92, P<0.001) and was moderately correlated with HBsAg (r=0.67, P<0.001). The correlation between serum HBV RNA and HBsAg in HBeAg-positive patients (r=0.61, P<0.001) was stronger than that in HBeAg-negative patients (r=0.31, P<0.001). For the patients with HBeAg-positive chronic HBV infection, the male patients with ALT>30 U/L and the female patients with ALT>19 U/L had a significantly lower serum HBV RNA level than the male patients with ALT≤30 U/L and the female patients with ALT≤19 U/L (P<0.001), and there was no significant difference in serum HBV RNA level between the latter group of patients and the HBeAg-positive CHB group (P>0.05). ConclusionIn patients with chronic HBV infection who do not receive antiviral therapy, there is a difference in serum HBV RNA level in different stages of natural history, and serum HBV RNA level has the strongest correlation with HBV DNA and a relatively weak correlation with HBsAg. In patients with HBeAg-positive chronic HBV infection, serum HBV RNA level in male patients with ALT>30 U/L and female patients with ALT>19 U/L are in the transition stage between HBeAg-positive chronic HBV infection and HBeAg-positive CHB.

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