1.Change Law in Material Basis of Rhei Radix et Rhizoma During Nine-time Repeating Steaming and Sun-drying Processing Based on Characteristic Chromatogram and Chemometrics
Xuan AO ; Taotao LIU ; Miao YU ; Lan WANG ; Xiaojie YIN ; Jingyu ZUO ; Li LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(15):191-198
ObjectiveTo characterize the changes in the overall chemical profile and key index components during nine-time repeating steaming and sun-drying processing of Rhei Radix et Rhizoma, and to reveal the change law of its material basis. MethodsHigh performance liquid chromatography(HPLC) was used to analyze the changes in the overall chemical profile of Rhei Radix et Rhizoma decoction pieces, and the contents of 15 main active components such as chrysophanol-8-O-β-D-glucoside, chrysophanol and gallic acid in the process of nine-time repeating steaming and sun-drying were determined. Combined with chemometrics, the contents and quantity ratio relationships of the glycosides, aglycones and tannins during the processing of Rhei Radix et Rhizoma were analyzed, and the partial least squares-discriminant analysis(PLS-DA) and cluster analysis of the main components in different steaming times were conducted, the statistically significant differential markers were selected with the variable importance in the projection(VIP) value>1. ResultsIn the nine-time repeating steaming and sun-drying process of Rhei Radix et Rhizoma, there were certain regularity in the number and peak area of characteristic peaks and the steaming and sun-drying times, the anthraquinone glycosides and aglycones could be roughly divided into three stages, including rapid change stage, fluctuation change stage and stable stage, and the total amount of tannins showed a decreasing trend. However, the ratios between the three components mentioned above tended to stabilize after five rounds of steaming and sun-drying. The results of PLS-DA and cluster heatmap showed that the content of each component in Rhei Radix et Rhizoma fluctuated greatly during the 1-4 steaming and sun-drying processes, while the content of each component was relatively close during the 5-9 steaming and sun-drying processes. After screening, it was found that chrysophanol, emodin, chrysophanol-8-O-β-D-glucoside, rhein, physcion and emodin-8-O-β-D-glucoside could be used as the index components for distinguishing the processed products of Rhei Radix et Rhizoma with different steaming and sun-drying times. ConclusionThe changes in the properties and efficacy of Rhei Radix et Rhizoma caused by the processing of nine-time repeating steaming and sun-drying are due to the changes in the composition and ratio of various glycosides and complex tannins in this herb, which is also the key to the formation of its characteristic of "purgation with supplement". This study can provide a basis for the research on the processing mechanism of Rhei Radix et Rhizoma and the establishment of processing specifications.
2.External validation of the model for predicting high-grade patterns of stage ⅠA invasive lung adenocarcinoma based on clinical and imaging features
Yu RONG ; Nianqiao HAN ; Yanbing HAO ; Jianli HU ; Yajin NIU ; Lan ZHANG ; Yuehua DONG ; Nan ZHANG ; Junfeng LIU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(08):1096-1104
Objective To externally validate a prediction model based on clinical and CT imaging features for the preoperative identification of high-grade patterns (HGP), such as micropapillary and solid subtypes, in early-stage lung adenocarcinoma, in order to guide clinical treatment decisions. Methods This study conducted an external validation of a previously developed prediction model using a cohort of patients with clinical stage ⅠA lung adenocarcinoma from the Fourth Hospital of Hebei Medical University. The model, which incorporated factors including tumor size, density, and lobulation, was assessed for its discrimination, calibration performance, and clinical impact. Results A total of 650 patients (293 males, 357 females; age range: 30-82 years) were included. The validation showed that the model demonstrated good performance in discriminating HGP (area under the curve>0.7). After recalibration, the model's calibration performance was improved. Decision curve analysis (DCA) indicated that at a threshold probability>0.6, the number of HGP patients predicted by the model closely approximated the actual number of cases. Conclusion This study confirms the effectiveness of a clinical and imaging feature-based prediction model for identifying HGP in stage ⅠA lung adenocarcinoma in a clinical setting. Successful application of this model may be significant for determining surgical strategies and improving patients' prognosis. Despite certain limitations, these findings provide new directions for future research.
3.Hyperoside Alleviates LPS-induced Inflammation in Zebrafish Model via TLR4/MyD88/NF-κB Pathway
Qing LAN ; Anna WANG ; Feifei ZHOU ; Keqian LIU ; Zhao LI ; Wenjing YU ; Shuyao TANG ; Ping LI ; Shaowu CHENG ; Sisi DENG ; Zhenyan SONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(22):63-72
ObjectiveTo investigate the intervention effects and mechanisms of the flavonoid hyperoside (Hyp) on lipopolysaccharide (LPS)-induced inflammation in the zebrafish model. MethodsZebrafish larvae were either microinjected with 0.5 g·L-1 LPS or immersed in 1 g·L-1 LPS for the modeling of inflammation. The larvae were then treated with Hyp at 25, 50, and 100 mg·L-1 through immersion for four consecutive days. The inflammatory phenotypes were assessed by analyzing the mortality rate, malformation rate, body length, and yolk sac area ratio. Behavioral tests were conducted to evaluate the inflammatory stress responses, and macrophage migration was observed by fluorescence microscopy. Additionally, the mRNA levels of inflammation-related genes, including interleukin-1β (IL-1β), interleukin-6 (IL-6), chemokine C-C motif ligand 2 (CCL2), chemokine C-X3-C motif receptor 1 (CX3CR1), chemokine C-C motif receptor 2 (CCR2), and genes associated with the Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-kappa B (NF-κB) signaling pathway, were measured by Real-time quantitative polymerase chain reaction(Real-time PCR). ResultsCompared with the pure water injection group, the model group exhibited increased mortality, malformation rates and yolk sac area ratio (P0.01), reduced body length (P0.01), increased total swimming distance and high-speed swimming duration (P0.01), and up-regulated mRNA levels of TLR4, MyD88, NF-κB, IL-1β, IL-6, CCL2, CX3CR1, and CCR2 (P0.01). Hyp at low, medium and high doses, as well as aspirin, reduced the mortality and malformation rates (P0.05,P0.01), increased the body length (P0.05,P0.01), decreased the yolk sac area ratio (P0.01), reduced the high-speed swimming duration (P0.01), and down-regulated the mRNA levels of TLR4, MyD88, NF-κB, IL-1β, IL-6, CCL2, CX3CR1, and CCR2 (P0.05,P0.01) compared with the model group. ConclusionHyp may modulate the TLR4/MyD88/NF-κB pathway to ameliorate inflammatory phenotypes and alleviate stress conditions in zebrafish, thereby exerting the anti-inflammatory effect.
4.Traditional Chinese Medicine Syndrome Classification and Characteristics of Cough Variant Asthma Based on Factor Analysis and Cluster Analysis
Mingxia YU ; Ruiheng LAN ; Jiaqi LI ; Yanyan WANG ; Hongsheng CUI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(22):106-115
ObjectiveTo analyze the correlation between the clinical symptoms, signs, syndrome characteristics and laboratory indicators of cough variant asthma (CVA) and deepen the understanding of the treatment of this disease based on the theory of "Fu Feng". MethodsAn observational study was conducted. A total of 207 CVA patients who visited the respiratory department of the Third Affiliated Hospital of Beijing University of Chinese Medicine from September 2022 to November 2023 were included. The information from the four diagnostic methods and the laboratory test results of patients were collected. Factor analysis was conducted on the information obtained through the four diagnostic methods in TCM, and the nature and location of CVA were extracted. Sample cluster analysis (Q clustering) and the K-means method were used for data clustering analysis to determine the syndrome types of CVA and analyze the syndrome characteristics and differences in laboratory indicators among different syndrome types. ResultsThe main symptom of CVA patients was cough, accompanied by symptoms such as itchy throat, foreign body sensation in the throat, dry throat, shortness of breath, dry mouth, chest tightness, hoarseness, bitter mouth, poor appetite, and skin itching. Factor analysis showed that the disease was located in the lung, involving the liver, spleen, and kidney. The pathological factors involved Yin deficiency, Yang deficiency, wind factor, dampness factor, Yin factor, and Qi stagnation. Cluster analysis revealed four syndrome types: Fengfu Yinshang syndrome, Shixie Neiyun syndrome, Tanyin Zufei syndrome, and Ganhuo Fanfei syndrome. Fengfu Yinshang syndrome accounted for the highest proportion, followed by Tanyin Zufei syndrome. There were no significant differences in eosinophil count and percentage, fractional nasal nitric oxide (FnNO) level, and pulmonary function indexes among the four syndromes. The levels of serum total IgE and fractional exhaled nitric oxide (FeNO) in patients with Fengfu Yinshang syndrome were significantly higher than those in patients with Shixie Neiyun syndrome and Tanyin Zufeisyndrome. ConclusionCough is the main symptom of CVA, accompanied by pharyngeal itching, foreign body sensation in the throat, dry throat, shortness of breath, dry mouth, and allergic manifestations. The disease involves the lung, liver, spleen, and kidneys. The essence of the pathogenesis lies in a latent dormant pathogen and a disorder of the pivot mechanism. The four common syndrome types are Fengfu Yinshang syndrome, Shixie Neiyun syndrome, Tanyin Zufei syndrome, and Ganhuo Fanfei syndrome. The TCM syndrome types are correlated with laboratory indexes. The serum total IgE and FeNO of patients with Fengfu Yinshang syndrome are worse.
5.Regulation of Sangmei Zhike Granules on Airway Inflammation and CAMP/PKA/CREB Pathway in Cough Variant Asthma Rats with Fengfu Yinshang Syndrome
Mingxia YU ; Hongsheng CUI ; Siyang YU ; Ruiheng LAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(22):116-124
ObjectiveTo observe the regulation effect of Sangmei Zhike granules on airway inflammation and cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA)-cAMP response element binding protein (CREB) pathway in cough variant asthma (CVA) rats with Fengfu Yinshang syndrome. MethodsEight-week-old male rats were randomly divided into a blank group, model group, western medicine group, and traditional Chinese medicine (TCM) group. Except for the blank group, Fengfu Yinshang models of CVA were established in the other groups. On the 16th day of the experiment, the western medicine group was treated with budesonide aerosol inhalation (dosage of 0.5 g·L-1), and the TCM group was given Sangmei Zhike granules by gavage (dosage of 4.19 g·kg-1·d-1), with each group treated once daily for 14 days. On the 30th day of the experiment, lung function parameters were determined. Whole blood inflammatory cell detection, hematoxylin-eosin (HE) staining of lung tissue, and immunohistochemistry were used to detect the expression of CREB, phosphorylated CREB (pCREB), and phosphorylated vasodilator-stimulated phosphoprotein (pVASP) proteins in rat lung tissue, and Reverse transcription quantitative polymerase chain reaction (Real-time PCR) was used to determine the protein expressions of cAMP, CREB, and PKA in rat lung tissue. Western blot (WB) was used to detect the expression of PKA, VASP, p-VASP, CREB, and p-CREB proteins. ResultsCompared with the model group, the average dynamic lung compliance (CDynaverage) in the TCM group increased (P0.05). Compared with the model group, the TCM group showed a decrease in absolute and percentage values of neutrophils (NEUT%), absolute values of lymphocytes (LYMPH), absolute and percentage values of basophils (BASO%), absolute values of monocytes (MONO), absolute and percentage values of eosinophils (EOS%), and white blood cells (WBC) (P0.05). Compared with the western medicine group, the TCM group showed a decrease in MONO, EOS%, and LYMPH% and an increase in MONO% (P0.05). ELISA results showed that compared with the model group, the TCM group had increased interferon-gamma (IFN-γ) and decreased interleukins (IL)-4, IL-5, IL-13, and total serum IgE, while the Western medicine group had increased IFN-γ and decreased IL-5, IL-13, and total serum IgE (P0.05). Compared with the western medicine group, the TCM group had decreased IL-5 (P0.05). HE staining results of rat lung tissue showed that the ciliated epithelium of the D bronchi in the TCM group recovered well. Mucous edema secretion decreased, and a small number of bronchiolar epithelial cells were shed, with reduced infiltration of inflammatory cells and the degree of epithelial injury. Immunohistochemical (IHC) results showed that compared with the model group, positive expressions of CREB, pCREB, and pVASP (brownish-yellow) were significantly increased in the TCM and western medicine groups. Real-time PCR results showed that compared with the model group, the relative expression levels of cAMP, CREB, and PKA in the TCM group were significantly increased (P0.05), and compared with the western medicine group, the TCM group also showed significantly increased relative expression levels of cAMP, CREB, and PKA (P0.05). WB results showed that compared with the model group, the expressions of PKA, VASP, p-VASP, CREB, p-CREB, and p-CREB/CREB proteins were increased in the TCM group, while p-VASP/VASP protein expression decreased (P0.05). Compared with the western medicine group, the TCM group had increased expressions of PKA, VASP, and p-CREB proteins and decreased p-VASP/VASP expression (P0.05). ConclusionSangmei Zhike granules have the effect of improving lung function and inhibiting airway inflammation in rats with CVA due to Fengfu Yinshang syndrome, possibly related to the activation of the cAMP/PKA/CREB pathway.
6.Effect of mild hypercapnia during the recovery period on the emergence time from total intravenous anesthesia: a randomized controlled trial
Lan LIU ; Xiangde CHEN ; Qingjuan CHEN ; Xiuyi LU ; Lili FANG ; Jinxuan REN ; Yue MING ; Dawei SUN ; Pei CHEN ; Weidong WU ; Lina YU
Korean Journal of Anesthesiology 2025;78(3):215-223
Background:
Intraoperative hypercapnia reduces the time to emergence from volatile anesthetics, but few clinical studies have explored the effect of hypercapnia on the emergence time from intravenous (IV) anesthesia. We investigated the effect of inducing mild hypercapnia during the recovery period on the emergence time after total IV anesthesia (TIVA).
Methods:
Adult patients undergoing transurethral lithotripsy under TIVA were randomly allocated to normocapnia group (end-tidal carbon dioxide [ETCO2] 35–40 mmHg) or mild hypercapnia group (ETCO2 50-55 mmHg) during the recovery period. The primary outcome was the extubation time. The spontaneous breathing-onset time, voluntary eye-opening time, and hemodynamic data were collected. Changes in the cerebral blood flow velocity in the middle cerebral artery were assessed using transcranial Doppler ultrasound.
Results:
In total, 164 patients completed the study. The extubation time was significantly shorter in the mild hypercapnia (13.9 ± 5.9 min, P = 0.024) than in the normocapnia group (16.3 ± 7.6 min). A similar reduction was observed in spontaneous breathing-onset time (P = 0.021) and voluntary eye-opening time (P = 0.008). Multiple linear regression analysis revealed that the adjusted ETCO2 level was a negative predictor of extubation time. Middle cerebral artery blood flow velocity was significantly increased after ETCO2 adjustment for mild hypercapnia, which rapidly returned to baseline, without any adverse reactions, within 20 min after extubation.
Conclusions
Mild hypercapnia during the recovery period significantly reduces the extubation time after TIVA. Increased ETCO2 levels can potentially enhance rapid recovery from IV anesthesia.
7.Clinical and Radiological Outcomes of Transarterial Embolization for Adhesive Capsulitis
Keng-Wei LIANG ; Hsuan Yin LIN ; Kai-Lan HSU ; Fa-Chuan KUAN ; Chia-Yu GEAN ; Chien-Kuo WANG ; Wei-Ren SU ; Bow WANG
Korean Journal of Radiology 2025;26(3):230-238
Objective:
To assess the effect of transarterial embolization (TAE) for adhesive capsulitis (AC) by evaluating clinical outcomes and changes in inflammation using magnetic resonance imaging (MRI).
Materials and Methods:
Patients who had undergone TAE between August 2020 and August 2023 for AC refractory to conservative treatments without any invasive procedures for more than 3 months, and had undergone baseline and 3-month post-AC follow-up contrast-enhanced MRI evaluations, were included. A suspension mixture of 500 mg imipenem/cilastatin in 10 mL of iodinated contrast agent was used for TAE. MRI results were analyzed to assess periarticular capsule/ligament inflammation. Clinical assessments included pain scores using the numeric rating scale (NRS) and functional scores using the quick disabilities of the arm, shoulder, and hand (Quick DASH) questionnaire.
Results:
Twenty-five patients (female:male, 14:11; age, 54.9 ± 7.1 years) were included. Significant reductions in average NRS pain scores as well as improvements in Quick DASH scores and range of motion, including anterior flexion and abduction, were observed at 1, 3, and 6 months after TAE (all P < 0.001). MRI analyses revealed that TAE significantly decreased the grades of axillary recess capsule enhancement, rotator interval (RI) capsule T2 signal intensity, and RI capsule enhancement (all P ≤ 0.004).
Conclusion
TAE may be an effective and safe therapeutic approach for AC refractory to conservative treatments, alleviating pain and supporting functional recovery. The observed MRI findings suggest that the effectiveness of TAE for AC may be attributed to the reduction of inflammation and the elimination of angiogenesis.
8.Carvedilol to prevent hepatic decompensation of cirrhosis in patients with clinically significant portal hypertension stratified by new non-invasive model (CHESS2306)
Chuan LIU ; Hong YOU ; Qing-Lei ZENG ; Yu Jun WONG ; Bingqiong WANG ; Ivica GRGUREVIC ; Chenghai LIU ; Hyung Joon YIM ; Wei GOU ; Bingtian DONG ; Shenghong JU ; Yanan GUO ; Qian YU ; Masashi HIROOKA ; Hirayuki ENOMOTO ; Amr Shaaban HANAFY ; Zhujun CAO ; Xiemin DONG ; Jing LV ; Tae Hyung KIM ; Yohei KOIZUMI ; Yoichi HIASA ; Takashi NISHIMURA ; Hiroko IIJIMA ; Chuanjun XU ; Erhei DAI ; Xiaoling LAN ; Changxiang LAI ; Shirong LIU ; Fang WANG ; Ying GUO ; Jiaojian LV ; Liting ZHANG ; Yuqing WANG ; Qing XIE ; Chuxiao SHAO ; Zhensheng LIU ; Federico RAVAIOLI ; Antonio COLECCHIA ; Jie LI ; Gao-Jun TENG ; Xiaolong QI
Clinical and Molecular Hepatology 2025;31(1):105-118
Background:
s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model.
Methods:
Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort.
Results:
In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM).
Conclusions
Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.
9.Effect of mild hypercapnia during the recovery period on the emergence time from total intravenous anesthesia: a randomized controlled trial
Lan LIU ; Xiangde CHEN ; Qingjuan CHEN ; Xiuyi LU ; Lili FANG ; Jinxuan REN ; Yue MING ; Dawei SUN ; Pei CHEN ; Weidong WU ; Lina YU
Korean Journal of Anesthesiology 2025;78(3):215-223
Background:
Intraoperative hypercapnia reduces the time to emergence from volatile anesthetics, but few clinical studies have explored the effect of hypercapnia on the emergence time from intravenous (IV) anesthesia. We investigated the effect of inducing mild hypercapnia during the recovery period on the emergence time after total IV anesthesia (TIVA).
Methods:
Adult patients undergoing transurethral lithotripsy under TIVA were randomly allocated to normocapnia group (end-tidal carbon dioxide [ETCO2] 35–40 mmHg) or mild hypercapnia group (ETCO2 50-55 mmHg) during the recovery period. The primary outcome was the extubation time. The spontaneous breathing-onset time, voluntary eye-opening time, and hemodynamic data were collected. Changes in the cerebral blood flow velocity in the middle cerebral artery were assessed using transcranial Doppler ultrasound.
Results:
In total, 164 patients completed the study. The extubation time was significantly shorter in the mild hypercapnia (13.9 ± 5.9 min, P = 0.024) than in the normocapnia group (16.3 ± 7.6 min). A similar reduction was observed in spontaneous breathing-onset time (P = 0.021) and voluntary eye-opening time (P = 0.008). Multiple linear regression analysis revealed that the adjusted ETCO2 level was a negative predictor of extubation time. Middle cerebral artery blood flow velocity was significantly increased after ETCO2 adjustment for mild hypercapnia, which rapidly returned to baseline, without any adverse reactions, within 20 min after extubation.
Conclusions
Mild hypercapnia during the recovery period significantly reduces the extubation time after TIVA. Increased ETCO2 levels can potentially enhance rapid recovery from IV anesthesia.
10.Carvedilol to prevent hepatic decompensation of cirrhosis in patients with clinically significant portal hypertension stratified by new non-invasive model (CHESS2306)
Chuan LIU ; Hong YOU ; Qing-Lei ZENG ; Yu Jun WONG ; Bingqiong WANG ; Ivica GRGUREVIC ; Chenghai LIU ; Hyung Joon YIM ; Wei GOU ; Bingtian DONG ; Shenghong JU ; Yanan GUO ; Qian YU ; Masashi HIROOKA ; Hirayuki ENOMOTO ; Amr Shaaban HANAFY ; Zhujun CAO ; Xiemin DONG ; Jing LV ; Tae Hyung KIM ; Yohei KOIZUMI ; Yoichi HIASA ; Takashi NISHIMURA ; Hiroko IIJIMA ; Chuanjun XU ; Erhei DAI ; Xiaoling LAN ; Changxiang LAI ; Shirong LIU ; Fang WANG ; Ying GUO ; Jiaojian LV ; Liting ZHANG ; Yuqing WANG ; Qing XIE ; Chuxiao SHAO ; Zhensheng LIU ; Federico RAVAIOLI ; Antonio COLECCHIA ; Jie LI ; Gao-Jun TENG ; Xiaolong QI
Clinical and Molecular Hepatology 2025;31(1):105-118
Background:
s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model.
Methods:
Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort.
Results:
In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM).
Conclusions
Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

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