1.Effects of subanesthetic dose of esketamine on postoperative anxiety and recovery in patients undergoing laparo-scopic cholecystectomy
Zhangzhen ZHONG ; Xian ZHENG ; Ting XU ; Jie WANG ; Hui CAO ; Xinggen ZHOU ; Hui LI ; Jiacheng ZHAO ; Hui LIU ; Chao ZHANG
China Pharmacy 2026;37(2):204-209
OBJECTIVE To investigate the effects of subanesthetic dose of esketamine on postoperative anxiety and recovery in patients undergoing laparoscopic cholecystectomy. METHODS A total of 200 patients scheduled for laparoscopic cholecystectomy at Suzhou Ninth Hospital Affiliated to Soochow University from January 2023 to December 2024 were randomly assigned to control group (n=100) and observation group (n=100). One minute before the initiation of anesthesia, patients in the control group received intravenous injections of Propofol emulsion injection, Sufentanil citrate injection, and Succinylcholine chloride injection. On this basis, patients in the observation group received an intravenous injection of Esketamine hydrochloride injection. The anxiety status of patients in both groups was compared, along with their general intraoperative conditions (including sufentanil dosage, duration of pneumoperitoneum, operative time, anesthesia time, and extubation time), postoperative recovery, incidence of adverse reactions, and the need for dezocine rescue analgesia. Heart rate and mean arterial pressure, entropy index (state entropy and response entropy), inflammatory marker levels [interleukin-6 (IL-6) and C-reactive protein (CRP)], numerical rating scale (NRS) for pain intensity were compared between the two groups at different time points. RESULTS No significant differences were found between the two groups in pneumoperitoneum duration, operative time, anesthesia time,extubation time, incidence of postoperative dry mouth, entropy index or length of stay in the post-anesthesia care unit (P>0.05). Compared with the control group, the observation group showed significantly lower postoperative STAI-S scores, reduced intraoperative sufentanil consumption, decreased incidence of postoperative nausea, vomiting, and shivering, the need for dezocine rescue analgesia, as well as lower plasma IL-6 and CRP levels at 24 h after surgery, and NRS (P<0.05). The heart rate and mean arterial pressure of patients in the observation group at the start of surgery, end of surgery, and during extubation were all significantly higher than those in the control group (P<0.05). CONCLUSIONS Subanesthetic dose of esketamine can effectively alleviate postoperative anxiety, reduce intraoperative opioid consumption, suppress postoperative inflammatory response, relieve postoperative pain, and promote recovery in patients undergoing laparoscopic cholecystectomy.
2.Study on the effect and mechanism of Qiwei dongqingye powder against bronchial asthma based on transcriptomics
Jiacheng JIN ; Wenyan CHEN ; Xin LI ; Qing XU ; Hangyu WANG ; Ke ZHANG ; Pinghua SUN ; Jinhui WANG
China Pharmacy 2026;37(5):595-601
OBJECTIVE To investigate the therapeutic effect and mechanism of Qiwei dongqingye powder (QDP) on bronchial asthma in mice. METHODS The mice were divided into blank group (normal saline), model group (normal saline), dexamethasone group (2 mg/kg), and QDP low-, medium-, and high-dose groups (200, 400, 800 mg/kg), with 14 mice in each group. Except for the blank group, mice in all other groups were given ovalbumin via intraperitoneal injection followed by aerosol inhalation to induce a bronchial asthma model. During the modeling process, mice in each group were administered corresponding drug solutions or normal saline intragastrically/intraperitoneally. After the last medication, the number of cells in the bronchoalveolar lavage fluid (BALF) of the mice was observed and counted; the pathological changes of the bronchus and lung tissue were observed; the levels of malondialdehyde (MDA), nitric oxide (NO), total superoxide dismutase (T-SOD), and glutathione peroxidase (GSH-Px) in the lung tissue of the mice were determined, and the level of interleukin-17 (IL-17) in the BALF and serum was determined. Transcriptomics was employed to predict and validate the mechanism of action of QDP against bronchial asthma. RESULTS Compared with the model group, the total cell count, neutrophil count, lymphocyte count, and macrophage counts in the BALF of the QDP high-dose group were all significantly reduced ( P <0.05); the levels of MDA and NO in the lung tissue, and the levels of IL-17 in the BALF and serum were all decreased significantly ( P <0.05); the levels of T-SOD and GSH-Px were significantly increased ( P <0.05); the arrangement of lung tissue cells tended to normalize, with reduced infiltration of inflammatory cells and decreased exfoliation of bronchial simple columnar epithelial cells. The transcriptomic results revealed that the differentially expressed genes were B-cell receptor signaling pathway, nuclear factor κB (NF-κB) signaling pathway, ferroptosis signaling pathway, and others. Further validation revealed that, compared with the model group, the expression levels of NF-κB p65 and chemokine ligand 20, as well as the phosphorylation level of NF-κB inhibitor protein α, were significantly decreased in the lung tissues of the mice in all QDP groups ( P <0.05). Conversely, the protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) were significantly increased ( P <0.05). CONCLUSIONS QDP can effectively alleviate bronchial asthma by inhibiting the NF-κB signaling pathway, activating the Nrf2/HO-1 signaling pathway, regulating oxidative stress, and reducing inflammatory responses.
3.Effect of Tongbian Decoction (通便汤) on the VAPB-PTPIP51 Complex and Autophagy of Interstitial Cells of Cajal in the Colon of Slow Transit Constipation Model Rats
Chuyue WANG ; Jiacheng LI ; Yingqi YANG ; Sicheng SHEN ; Zhiyang CHEN ; Zhizhong XU ; Bensheng WU ; Meiyao CHEN ; Ziwei XIONG ; Jinhui GU ; Xiaopeng WANG
Journal of Traditional Chinese Medicine 2026;67(9):985-993
ObjectiveTo explore the possible mechanism of Tongbian Decoction (通便汤, TD) in treating slow transit constipation (STC). MethodsTwenty-four SD rats were randomly divided into normal group, model group, TD group, and mosapride group, with 6 rats per group. Except for the normal group, STC models were established by intragastric administration of loperamide hydrochloride combined with normal saline. On the day following successful model establishment, rats in the TD group received 18.63 g·kg⁻¹ of TD by gavage, while those in the mosapride group received 1.605 mg·d⁻¹ of mosapride, and those in the normal group and the model group received 10 ml·kg⁻¹ of normal saline by gavage. All treatments were administered once daily for 7 consecutive days. Twenty-four hours after the last administration, fecal pellet number and fecal water content were measured. After intragastric administration of a 10% activated charcoal suspension, the small intestinal transit rate was calculated 30 minutes later. Serum levels of gastrin (GAS) and motilin (MTL) were measured by ELISA. Colonic histopathology was observed by HE staining, and mucus secretion by Alcian blue-periodic acid-Schiff (AB-PAS) staining. Ultrastructure of colon tissue was examined using transmission electron microscopy. Protein expression levels of C-kit, stem cell factor (SCF), autophagy-related protein 5 (ATG5), Beclin1, vesicle-associated membrane protein B (VAPB), and protein tyrosine phosphatase interacting protein 51 (VAPB-PTPIP51) were measured by Western Blot, and the mRNA levels were detected by real-time PCR. Immunohistochemistry was used to detect SCF, C-kit, Beclin1, and ATG5 expression. The calcium content in colon tissue was determined by ELISA. ResultsCompared to the normal group, rats in the model group showed significantly reduced fecal pellet number, fecal water content, small intestinal transit rate, and serum GAS and MTL levels (P<0.01); the number of goblet cells decreased, and the mucosal and muscular layers of the colon became thinner; mRNA and protein expression levels of ATG5 and Beclin1 in colon tissue significantly increased, while calcium content decreased (P<0.05 or P<0.01); and electron microscopy revealed vacuolar degeneration and increased autophagosomes in colonic cells. Compared to the model group, both TD group and mosapride group showed increased fecal pellet number, fecal water content, small intestinal transit rate, serum GAS and MTL levels, and colonic calcium content, along with decreased Beclin1 and ATG5 protein levels (P<0.05 or P<0.01); the mucosal thickness and goblet cell number increased significantly, and autophagosomes decreased; in the TD group, ATG5 and Beclin1 mRNA levels decreased; in the mosapride group, SCF, VAPB, and PTPIP51 mRNA levels increased, while Beclin1 mRNA decreased (P<0.05 or P<0.01). Compared to the mosapride group, the TD group showed higher fecal pellet number, fecal water content, serum GAS levels, colonic calcium content, and C-kit expression, along with lower ATG5 and Beclin1 levels (P<0.05 or P<0.01). ConclusionTD may improve constipation symptoms by upregulating the VAPB-PTPIP51 complex during mitochondria-endoplasmic reticulum interactions, reducing autophagy of interstitial cells of Cajal, and promoting intestinal motility.
4.Effect of Tongbian Decoction (通便汤) on the VAPB-PTPIP51 Complex and Autophagy of Interstitial Cells of Cajal in the Colon of Slow Transit Constipation Model Rats
Chuyue WANG ; Jiacheng LI ; Yingqi YANG ; Sicheng SHEN ; Zhiyang CHEN ; Zhizhong XU ; Bensheng WU ; Meiyao CHEN ; Ziwei XIONG ; Jinhui GU ; Xiaopeng WANG
Journal of Traditional Chinese Medicine 2026;67(9):985-993
ObjectiveTo explore the possible mechanism of Tongbian Decoction (通便汤, TD) in treating slow transit constipation (STC). MethodsTwenty-four SD rats were randomly divided into normal group, model group, TD group, and mosapride group, with 6 rats per group. Except for the normal group, STC models were established by intragastric administration of loperamide hydrochloride combined with normal saline. On the day following successful model establishment, rats in the TD group received 18.63 g·kg⁻¹ of TD by gavage, while those in the mosapride group received 1.605 mg·d⁻¹ of mosapride, and those in the normal group and the model group received 10 ml·kg⁻¹ of normal saline by gavage. All treatments were administered once daily for 7 consecutive days. Twenty-four hours after the last administration, fecal pellet number and fecal water content were measured. After intragastric administration of a 10% activated charcoal suspension, the small intestinal transit rate was calculated 30 minutes later. Serum levels of gastrin (GAS) and motilin (MTL) were measured by ELISA. Colonic histopathology was observed by HE staining, and mucus secretion by Alcian blue-periodic acid-Schiff (AB-PAS) staining. Ultrastructure of colon tissue was examined using transmission electron microscopy. Protein expression levels of C-kit, stem cell factor (SCF), autophagy-related protein 5 (ATG5), Beclin1, vesicle-associated membrane protein B (VAPB), and protein tyrosine phosphatase interacting protein 51 (VAPB-PTPIP51) were measured by Western Blot, and the mRNA levels were detected by real-time PCR. Immunohistochemistry was used to detect SCF, C-kit, Beclin1, and ATG5 expression. The calcium content in colon tissue was determined by ELISA. ResultsCompared to the normal group, rats in the model group showed significantly reduced fecal pellet number, fecal water content, small intestinal transit rate, and serum GAS and MTL levels (P<0.01); the number of goblet cells decreased, and the mucosal and muscular layers of the colon became thinner; mRNA and protein expression levels of ATG5 and Beclin1 in colon tissue significantly increased, while calcium content decreased (P<0.05 or P<0.01); and electron microscopy revealed vacuolar degeneration and increased autophagosomes in colonic cells. Compared to the model group, both TD group and mosapride group showed increased fecal pellet number, fecal water content, small intestinal transit rate, serum GAS and MTL levels, and colonic calcium content, along with decreased Beclin1 and ATG5 protein levels (P<0.05 or P<0.01); the mucosal thickness and goblet cell number increased significantly, and autophagosomes decreased; in the TD group, ATG5 and Beclin1 mRNA levels decreased; in the mosapride group, SCF, VAPB, and PTPIP51 mRNA levels increased, while Beclin1 mRNA decreased (P<0.05 or P<0.01). Compared to the mosapride group, the TD group showed higher fecal pellet number, fecal water content, serum GAS levels, colonic calcium content, and C-kit expression, along with lower ATG5 and Beclin1 levels (P<0.05 or P<0.01). ConclusionTD may improve constipation symptoms by upregulating the VAPB-PTPIP51 complex during mitochondria-endoplasmic reticulum interactions, reducing autophagy of interstitial cells of Cajal, and promoting intestinal motility.
5.Diagnosis of An Abbreviated Breast MRI Protocol Based on First Post-Contrast Subtracted for Breast Cancer
Xu HE ; Tingting HUANG ; Jiacheng ZHANG ; Dingsheng HAN ; Fukun SHI ; Qian XU ; Yanru ZHOU ; Lan ZHANG
Chinese Journal of Medical Imaging 2025;33(5):531-536
Purpose To evaluate the diagnostic value of an abbreviated protocol MRI(AP-MRI)based on first post-contrast subtracted(FAST)images for breast cancer detection.Materials and Methods This study included imaging data from 160 female patients with solid breast lesions who underwent breast MRI in the First Affiliated Hospital of Henan University of Chinese Medicine from April 2021 to January 2024.Two AP-MRI protocols were extracted from the full diagnostic protocol(FDP),including:dynamic contrast-enhanced MRI(DCE-MRI)A protocol:FAST and maximum-intensity projection(MIP)images,and DCE-MRI B protocol:FAST+MIP+diffusion-weighted imaging(DWI).Lesions categorized as breast imaging reporting and data system(BI-RADS)1-3 were classified as negative,and those categorized as BI-RADS 4-5 were classified as positive.Pathological findings served as the diagnostic gold standard.Two radiologists independently evaluated the lesions as negative/positive and compared with the gold standard.The sensitivity,specificity and accuracy of the three protocols were compared.Receiver operating characteristic curves were generated for each protocol,and the area under the curve(AUC)was compared.Results The accuracy of the three protocols showed statistically significant differences(Cochran's Qreader1=6.000,P=0.050;Cochran's Qreader2=10.909,P=0.012).The accuracy of the DCE-MRI A protocol was significantly lower than that of the FDP protocol(Z=2.449,Preader1=0.043;Z=2.858,Preader2=0.013).There were no statistically significant differences in sensitivity(Cochran's Qreader1=3.000,P=0.223;Cochran's Qreader2=2.667,P=0.264)or specificity(Cochran's Qreader1=3.000,P=0.223;Cochran's Qreader2=2.800,P=0.247)between the two AP-MRI protocols and the FDP protocol.There were no statistically significant differences in AUC between the DCE-MRI B protocol and the FDP protocol(Z=1.390-1.719,all P>0.05),while the AUC of the DCE-MRI A protocol had lower AUCs than the FDP protocol(Z=1.980,2.441;both P<0.05).Conclusion The AP-MRI protocol combining FAST,MIP and DWI shows diagnostic accuracy comparable to that of the FDP and greatly saves time and cost,suggesting its potential as an alternative imaging strategy for women with dense breasts and as a new diagnostic approach for high-risk populations.
6.Safety and efficacy analysis of TACE combined with donafenib and PD-1 inhibitors in the treatment of unresectable hepatocellular carcinoma
Daqian HAN ; Wenze XU ; Chao LIANG ; Hao LI ; Shuguang JU ; Manzhou WANG ; Jiacheng WANG ; Yang-yang NIU ; Xinwei HAN ; Jianzhuang REN ; Xuhua DUAN
Chinese Journal of Hepatobiliary Surgery 2025;31(7):503-509
Objective:To compare the safety and efficacy of transarterial chemoembolization (TACE) combined with donafenib and programmed death protein 1 (PD-1) inhibitors and TACE combined with donafenib in the treatment of unresectable hepatocellular carcinoma (uHCC).Methods:Clinical data of 148 patients with uHCC treated at the First Affiliated Hospital of Zhengzhou University from December 2021 to December 2022 were retrospectively analyzed, including 127 males and 21 females, aged (56.6±9.9) years. Patients were divided into two groups: the TACE combined with donafenib and PD-1 inhibitors group (TACE+ DP, n=73) and TACE combined with single donafenib (TACE+ D, n=75). The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and the occurrence of treatment-related adverse events (TRAEs) of the two groups of patients were observed. Kaplan-Meier analysis was used for survival assessment, and the log-rank test was used for comparison. The related factors affecting the prognosis of patients were indentified and analyzed. Results:The median PFS of patients in the TACE+ D group and the TACE+ DP group were 7.2 months (95% CI: 5.7-8.3 months) and 10.5months (95% CI: 8.9-11.3 months), respectively. The median OS was 13.2 months (95% CI: 12.3-13.7 months) and 16.9 months (95% CI: 15.1-19.8 months), respectively. All these differences were statistically significant ( χ2=17.81, 26.92, respectively, both P<0.001). The ORR and DCR of TACE+ DP group were both higher than those in TACE+ D group [53.4% (39/73) vs 36.0% (27/75), χ2=4.55, P=0.031; and 90.4% (66/73) vs 77.3% (58/75), χ2=4.66, P=0.044]. No grade 4 or above adverse events occurred in either the TACE+ DP or the TACE+ D group. The most common treatment-related adverse events in TACE+ D and TACE+ DP group were hand-foot syndrome [46.7% (35/75) vs 49.3% (36/73)], hypertension [26.7% (20/75) vs 30.1% (22/73)], fatigue [22.7% (17/75) vs 24.7% (18/73)], diarrhea [26.7% (20/75) vs 28.8% (21/73)], and thrombocytopenia [25.3% (19/75) vs 28.8% (21/73)]. There was no significant difference in the incidence and severity of TRAEs between the groups ( χ2=0.08, P=0.774). TACE+ DP treatment was a favorable prognostic factor for PFS ( HR=0.33, 95% CI: 0.22-0.49, P<0.001) and OS ( HR=0.19, 95% CI: 0.11-0.33, P<0.001) of patients. Conclusion:Compared to TACE combined with donafenib, TACE combined with donafenib and PD-1 inhibitors, with good efficacy and safety, significantly improved the treatment response and survival in patients with uHCC.
7.Research Progress on Imaging Features and Prognosis of Histopathological Subtypes of Hepatocellular Carcinoma
Jiameng SI ; Lan ZHANG ; Xu HE ; Junjie SHU ; Jiacheng ZHANG ; Pinxiong LI
Chinese Journal of Medical Imaging 2025;33(3):267-273
Hepatocellular carcinoma(HCC)is categorized into two major classes based on the heterogeneity of histological phenotypes:proliferative HCC and non-proliferative HCC.These classes exhibit distinct clinical,molecular and imaging characteristics.Within these two major categories,there exist multiple pathological subtypes,each demonstrating unique molecular and histological features that manifest differently in imaging findings.Additionally,the prognosis of these HCC pathological subtypes diverges from that of not-otherwise-specified HCC,and current clinical guidelines for their treatment remain unclear.This article aims to summarize the imaging manifestations and prognosis of the histopathological subtypes of HCC,so as to enhance identification and judgement of HCC subtypes,and to provide a theoretical basis for selecting appropriate therapeutic strategies.
8.Research Progress on Prognosis Prediction of Hepatocellular Carcinoma Based on MRI Features
Yihao YAN ; Lan ZHANG ; Qian XU ; Jiameng SI ; Fukun SHI ; Junjie SHU ; Jiacheng ZHANG ; Xu HE
Chinese Journal of Medical Imaging 2025;33(3):274-279
In clinical practice,the diagnosis of hepatocellular carcinoma primarily relies on imaging findings.For cases with atypical imaging features or insufficient diagnostic specificity,pathological analysis remains essential.With the advancement of precision medicine,research focus has expanded from pure diagnostic evaluation to therapeutic efficacy prediction.Imaging-based prognostic biomarkers have emerged as a key research frontier in hepatocellular carcinoma management.Although accurate diagnosis remains paramount,current investigations increasingly prioritize the identification of biomarkers for treatment response prediction and outcome stratification.Recent studies demonstrate that radiological characteristics not only reflect tumor heterogeneity but also carry prognostic implications for hepatocellular carcinoma.These imaging biomarkers enable non-invasive outcome prediction and provide objective evidence to optimize therapeutic decision-making.This comprehensive review summarizes MRI-derived imaging features associated with hepatocellular carcinoma prognosis,aiming to guide personalized treatment strategies and ultimately improve survival outcomes for hepatocellular carcinoma patients.
9.Risk Factors for Early Recurrence of Solitary Hepatocellular Carcinoma After Radiofrequency Ablation Based on Gd-EOB-DTPA-Enhanced MRI
Qian XU ; Lan ZHANG ; Tingting HUANG ; Yu GAO ; Xiaoyang ZHAI ; Jiacheng ZHANG ; Xu HE ; Fukun SHI
Chinese Journal of Medical Imaging 2025;33(3):238-244,259
Purpose To investigate the independent risk factors for early recurrence of solitary hepatocellular carcinoma after radiofrequency ablation based on gadoxetic acid disodium(Gd-EOB-DTPA)-enhanced MRI combined with clinical features.Materials and Methods Clinical and imaging data of hepatocellular carcinoma patients who underwent radiofrequency ablation at the First Affiliated Hospital of Henan University of Chinese Medicine from January 2019 to June 2022 were retrospectively collected.All patients underwent preoperative Gd-EOB-DTPA-enhanced MRI and were followed up for up to two years post-surgery.Univariate and multivariate Cox proportional hazards regression were performed to identify independent risk factors for recurrence after radiofrequency ablation.Results A total of 58 patients were finally included,including early recurrence group(n=22)and non-early recurrence group(n=36).Multivariate Cox regression analysis revealed that preoperative alpha-fetoprotein(AFP)levels(HR=1.103,95%CI 1.008-1.206,P=0.033),arterial-phase irregular margin enhancement(HR=4.647,95%CI 1.527-14.110,P=0.007),peritumoral arterial-phase enhancement(HR=11.575,95%CI 3.575-37.478,P=0.001)and peritumoral hepatobiliary phase hypointensity(HR=5.058,95%CI 1.129-22.668,P=0.034)were independent risk factors for early recurrence.The area under the curve for AFP combined with arterial-phase irregular margin enhancement,peritumoral arterial-phase enhancement and peritumoral hepatobiliary phase hypointensity were 0.896,0.842 and 0.860,with accuracy rates of 81.0%,84.5%and 82.8%,respectively.Conclusion Preoperative serum AFP levels,arterial-phase irregular margin enhancement,peritumoral arterial-phase enhancement and peritumoral hepatobiliary phase hypointensity are independent risk factors for early recurrence after radiofrequency ablation in hepatocellular carcinoma patients.The combination of AFP and any of these MRI features significantly improves predictive efficacy.
10.Risk Factors for Early Recurrence of Solitary Hepatocellular Carcinoma After Radiofrequency Ablation Based on Gd-EOB-DTPA-Enhanced MRI
Qian XU ; Lan ZHANG ; Tingting HUANG ; Yu GAO ; Xiaoyang ZHAI ; Jiacheng ZHANG ; Xu HE ; Fukun SHI
Chinese Journal of Medical Imaging 2025;33(3):238-244,259
Purpose To investigate the independent risk factors for early recurrence of solitary hepatocellular carcinoma after radiofrequency ablation based on gadoxetic acid disodium(Gd-EOB-DTPA)-enhanced MRI combined with clinical features.Materials and Methods Clinical and imaging data of hepatocellular carcinoma patients who underwent radiofrequency ablation at the First Affiliated Hospital of Henan University of Chinese Medicine from January 2019 to June 2022 were retrospectively collected.All patients underwent preoperative Gd-EOB-DTPA-enhanced MRI and were followed up for up to two years post-surgery.Univariate and multivariate Cox proportional hazards regression were performed to identify independent risk factors for recurrence after radiofrequency ablation.Results A total of 58 patients were finally included,including early recurrence group(n=22)and non-early recurrence group(n=36).Multivariate Cox regression analysis revealed that preoperative alpha-fetoprotein(AFP)levels(HR=1.103,95%CI 1.008-1.206,P=0.033),arterial-phase irregular margin enhancement(HR=4.647,95%CI 1.527-14.110,P=0.007),peritumoral arterial-phase enhancement(HR=11.575,95%CI 3.575-37.478,P=0.001)and peritumoral hepatobiliary phase hypointensity(HR=5.058,95%CI 1.129-22.668,P=0.034)were independent risk factors for early recurrence.The area under the curve for AFP combined with arterial-phase irregular margin enhancement,peritumoral arterial-phase enhancement and peritumoral hepatobiliary phase hypointensity were 0.896,0.842 and 0.860,with accuracy rates of 81.0%,84.5%and 82.8%,respectively.Conclusion Preoperative serum AFP levels,arterial-phase irregular margin enhancement,peritumoral arterial-phase enhancement and peritumoral hepatobiliary phase hypointensity are independent risk factors for early recurrence after radiofrequency ablation in hepatocellular carcinoma patients.The combination of AFP and any of these MRI features significantly improves predictive efficacy.

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