1.Machine and deep learning-based clinical characteristics and laboratory markers for the prediction of sarcopenia.
He ZHANG ; Mengting YIN ; Qianhui LIU ; Fei DING ; Lisha HOU ; Yiping DENG ; Tao CUI ; Yixian HAN ; Weiguang PANG ; Wenbin YE ; Jirong YUE ; Yong HE
Chinese Medical Journal 2023;136(8):967-973
BACKGROUND:
Sarcopenia is an age-related progressive skeletal muscle disorder involving the loss of muscle mass or strength and physiological function. Efficient and precise AI algorithms may play a significant role in the diagnosis of sarcopenia. In this study, we aimed to develop a machine learning model for sarcopenia diagnosis using clinical characteristics and laboratory indicators of aging cohorts.
METHODS:
We developed models of sarcopenia using the baseline data from the West China Health and Aging Trend (WCHAT) study. For external validation, we used the Xiamen Aging Trend (XMAT) cohort. We compared the support vector machine (SVM), random forest (RF), eXtreme Gradient Boosting (XGB), and Wide and Deep (W&D) models. The area under the receiver operating curve (AUC) and accuracy (ACC) were used to evaluate the diagnostic efficiency of the models.
RESULTS:
The WCHAT cohort, which included a total of 4057 participants for the training and testing datasets, and the XMAT cohort, which consisted of 553 participants for the external validation dataset, were enrolled in this study. Among the four models, W&D had the best performance (AUC = 0.916 ± 0.006, ACC = 0.882 ± 0.006), followed by SVM (AUC =0.907 ± 0.004, ACC = 0.877 ± 0.006), XGB (AUC = 0.877 ± 0.005, ACC = 0.868 ± 0.005), and RF (AUC = 0.843 ± 0.031, ACC = 0.836 ± 0.024) in the training dataset. Meanwhile, in the testing dataset, the diagnostic efficiency of the models from large to small was W&D (AUC = 0.881, ACC = 0.862), XGB (AUC = 0.858, ACC = 0.861), RF (AUC = 0.843, ACC = 0.836), and SVM (AUC = 0.829, ACC = 0.857). In the external validation dataset, the performance of W&D (AUC = 0.970, ACC = 0.911) was the best among the four models, followed by RF (AUC = 0.830, ACC = 0.769), SVM (AUC = 0.766, ACC = 0.738), and XGB (AUC = 0.722, ACC = 0.749).
CONCLUSIONS:
The W&D model not only had excellent diagnostic performance for sarcopenia but also showed good economic efficiency and timeliness. It could be widely used in primary health care institutions or developing areas with an aging population.
TRIAL REGISTRATION
Chictr.org, ChiCTR 1800018895.
Humans
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Aged
;
Sarcopenia/diagnosis*
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Deep Learning
;
Aging
;
Algorithms
;
Biomarkers
2.EGFR-TKI Combined with Pemetrexed versus EGFR-TKI Monotherapy in Advanced EGFR-mutated NSCLC: A Prospective, Randomized, Exploratory Study
Weiguang GU ; Hua ZHANG ; Yiyu LU ; Minjing LI ; Shuang YANG ; Jianmiao LIANG ; Zhijian YE ; Zhihua LI ; Minhong HE ; Xiaoliang SHI ; Fei WANG ; Dong YOU ; Weiquan GU ; Weineng FENG
Cancer Research and Treatment 2023;55(3):841-850
Purpose:
We aimed to evaluate whether the addition of pemetrexed is effective in improving progression-free survival (PFS) in epidermal growth factor receptor (EGFR)–mutated patients with or without concomitant alterations.
Materials and Methods:
This multicenter clinical trial was conducted in China from June 15, 2018, to May 31, 2019. A total of 92 non–small cell lung cancer (NSCLC) patients harboring EGFR-sensitive mutations were included and divided into concomitant and non-concomitant groups. Patients in each group were randomly treated with EGFR–tyrosine kinase inhibitor (TKI) monotherapy or EGFR-TKI combined with pemetrexed in a ratio of 1:1. PFS was recorded as the primary endpoint.
Results:
The overall median PFS of this cohort was 10.1 months. There were no significant differences in PFS between patients with and without concomitant and between patients received TKI monotherapy and TKI combined with pemetrexed (p=0.210 and p=0.085, respectively). Stratification analysis indicated that patients received TKI monotherapy had a significantly longer PFS in non-concomitant group than that in concomitant group (p=0.002). In concomitant group, patients received TKI combined with pemetrexed had a significantly longer PFS than patients received TKI monotherapy (p=0.013). Molecular dynamic analysis showed rapidly emerging EGFR T790M in patients received TKI monotherapy. EGFR mutation abundance decreased in patients received TKI combined chemotherapy, which supports better efficacy for a TKI combined chemotherapy as compared to TKI monotherapy. A good correlation between therapeutic efficacy and a change in circulating tumor DNA (ctDNA) status was found in 66% of patients, supporting the guiding role of ctDNA minimal residual disease (MRD) in NSCLC treatment.
Conclusion
EGFR-TKI monotherapy is applicable to EGFR-sensitive patients without concomitant alterations, while a TKI combined chemotherapy is applicable to EGFR-sensitive patients with concomitant alterations. CtDNA MRD may be a potential biomarker for predicting therapeutic efficacy.
3.Mulberry leaf flavonoids activate BAT and induce browning of WAT to improve type 2 diabetes via regulating the AMPK/SIRT1/PGC-1α signaling pathway.
Long CHENG ; Lu SHI ; Changhao HE ; Chen WANG ; Yinglan LV ; Huimin LI ; Yongcheng AN ; Yuhui DUAN ; Hongyu DAI ; Huilin ZHANG ; Yan HUANG ; Wanxin FU ; Weiguang SUN ; Baosheng ZHAO
Chinese Journal of Natural Medicines (English Ed.) 2023;21(11):812-829
Mulberry (Morus alba L.) leaf is a well-established traditional Chinese botanical and culinary resource. It has found widespread application in the management of diabetes. The bioactive constituents of mulberry leaf, specifically mulberry leaf flavonoids (MLFs), exhibit pronounced potential in the amelioration of type 2 diabetes (T2D). This potential is attributed to their ability to safeguard pancreatic β cells, enhance insulin resistance, and inhibit α-glucosidase activity. Our antecedent research findings underscore the substantial therapeutic efficacy of MLFs in treating T2D. However, the precise mechanistic underpinnings of MLF's anti-T2D effects remain the subject of inquiry. Activation of brown/beige adipocytes is a novel and promising strategy for T2D treatment. In the present study, our primary objective was to elucidate the impact of MLFs on adipose tissue browning in db/db mice and 3T3-L1 cells and elucidate its underlying mechanism. The results manifested that MLFs reduced body weight and food intake, alleviated hepatic steatosis, improved insulin sensitivity, and increased lipolysis and thermogenesis in db/db mice. Moreover, MLFs activated brown adipose tissue (BAT) and induced the browning of inguinal white adipose tissue (IWAT) and 3T3-L1 adipocytes by increasing the expressions of brown adipocyte marker genes and proteins such as uncoupling protein 1 (UCP1) and beige adipocyte marker genes such as transmembrane protein 26 (Tmem26), thereby promoting mitochondrial biogenesis. Mechanistically, MLFs facilitated the activation of BAT and the induction of WAT browning to ameliorate T2D primarily through the activation of AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) signaling pathway. These findings highlight the unique capacity of MLF to counteract T2D by enhancing BAT activation and inducing browning of IWAT, thereby ameliorating glucose and lipid metabolism disorders. As such, MLFs emerge as a prospective and innovative browning agent for the treatment of T2D.
Mice
;
Animals
;
Adipose Tissue, Brown
;
Sirtuin 1/pharmacology*
;
Diabetes Mellitus, Type 2/metabolism*
;
AMP-Activated Protein Kinases/metabolism*
;
Morus/metabolism*
;
Flavonoids/metabolism*
;
Prospective Studies
;
Signal Transduction
;
Adipose Tissue, White
;
Plant Leaves
;
Uncoupling Protein 1/metabolism*
;
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism*
4.Biejiajian Wan Regulates Polarization of Macrophages via HIF-1α/NF-κB Signaling Pathway
Yang LIU ; Chunyu HE ; Tong LI ; Weiguang CHEN ; Yanhao MA ; Ying KUANG ; Songqi HE ; Haitao SUN
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(19):9-16
ObjectiveTo investigate the effect and mechanism of Biejiajian Wan on liver fibrosis by regulating the polarization of macrophages. MethodRaw264.7 cells were cultured in vitro by serum pharmacological method, and the hypoxia model of RAW264.7 cells was established by stimulating RAW264.7 cells with cobalt chloride (CoCl2). The cells were randomly divided into blank group, CoCl2 hypoxia model group (200 mmol·L-1), Biejiajian Wan low-dose group (200 mmol·L-1+0.55 g·kg-1 Fuzheng Quyu capsules), medium-dose group (200 mmol·L-1+1.1 g·kg-1 Biejiajian Wan), and high-dose group (200 mmol·L-1+2.2 g·kg-1 Biejiajian Wan) and Fuzheng Quyu capsule group (200 mmol·L-1+0.56 g·kg-1 Biejiajian Wan). Cell proliferation was detected by cell counting kit-8 (CCK-8), and the gene expression of hypoxia inducible factor-1α (HIF-1α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in macrophages was detected by real time fluorescence quantitative polymerase chain reaction (Real-time PCR). The expression of macrophage polarization-related protein and HIF-1α/nuclear factor-kappa B (NF-κB) signaling pathway-related protein was tested by Western blot, and the distribution and expression of NF-κB signaling pathway-related protein and HIF-1α were determined by cell immunofluorescence. ResultCompared with the conditions in the blank group, the proliferation of RAW264.7 cells was inhibited after CoCl2 stimulation for 24 hours (P<0.05), the mRNA expression of HIF-1α, IL-1β and IL-6 in the model group were increased (P<0.05), the protein expression of HIF-1α and M1 macrophage phenotypic proteins IL-6 and tumor necrosis factor-α (TNF-α) was boosted while that of M2 macrophage phenotypic protein interleukin-10 (IL-10) was reduced (P<0.05), the protein expression of NF-κB p65, phosphorylation (p)-NF-κB p65, phosphorylated NF-κB inhibits protein kinase α/β (p-IKKα/β) and phosphorylated NF-κB inhibits protein α (p-IκBα) was elevated (P<0.05), the nuclear expression of HIF-1α and NF-κB p65 was promoted. Compared with the conditions in the model group, after 24 hours of treatment with corresponding drug-containing serum, each treatment group promoted the proliferation of RAW264.7 cells (P<0.05), the mRNA expression levels of HIF-1α, IL-1β and IL-6 in macrophages were reduced (P<0.05), the protein expression of HIF-1α, IL-6 and TNF-α was decreased, while that of CD163 and IL-10 was increased (P<0.05), the protein expression of NF-κB p65, p-NF-κB p65, p-IKKα/β and p-IκBα was lowered (P<0.05), the nuclear expression of HIF-1α and NF-κB p65 was inhibited. ConclusionBiejiajian Wan could modulate the polarization of macrophages, attenuate the injury of macrophage-associated inflammatory response under hypoxia, and thus delay the progression of liver fibrosis, which might be related to its regulation of HIF-1α/NF-κB signaling pathway.
5.Clinical experience of laparoscopic splenectomy in 62 cases of traumatic spleen rupture
Liang TAO ; Zhijie XIE ; Shufeng GAO ; Qiang HE ; Weiguang ZHOU
Chinese Journal of General Surgery 2019;34(5):428-430
Objective To analyze the safety of laparoscopic splenectomy for traumatic splenic rupture.Methods The clinical data of 62 patients with traumatic splenic rupture treated by laparoscopic splenectomy in our hospital from Jan 2013 to Jan 2018 were retrospectively analyzed.Results All 62 patients successfully underwent laparoscopic surgery except for 1 case who was converted to open surgery.One case suffered from postoperative bleeding.There was no infection,serious pancreatic leakage and other major complications.The total amount of intraoperative bleeding was 1 600 ml on average,the average operation time was 135 min,the average splenectomy time was 55 min,and the average hospital stay was 12.5 d.Conclusion Laparoscopic splenectomy is a safe and reliable minimally invasive operation for traumatic splenic rupture.
6.CT diagnosis and surgical treatment of adhesive ileus
Hongjie LIU ; Haoran SUN ; Yongyuan LI ; Weiguang HE ; Pei YANG ; Ying ZHOU ; Zonghui GAO ; Chunzhong MA
Chinese Journal of General Surgery 2018;33(1):57-60
Objective To analyze CT findings in adhesive intestinal obstruction caused by different adhesion pattern.Methods Clinical data of 83 adhesive intestinal obstruction cases proved by laparotomy were reviewed.Before surgery two experienced abdominal radiologists randomly double blindly inspected and evaluated the CT findings,as to whether there was intestinal obstruction,the severity of obstruction,the site of obstruction,the adhesion type of obstruction and the diagnosis of strangulated intestinal obstruction,the consensuses were accomplished by discussion.Results The accuracy of diagnosis was 100% for the existence of obstruction,the severity of obstruction and the site of obstruction.There were intra-abdominal hernia caused by intestinal adhesion (44 cases),a cluster of loop (12 cases),bowel twisted angle (8 cases),the intestine and abdominal adhesions (6 cases),intestinal adhesion contracture stenosis (5 cases),adhesive band compression (4 cases),intestinal volvulus caused by adhesion (1 case).The accuracy,sensitivity,specificity,positive predictive value and negative predictive value of CT in diagnosing strangulated intestinal obstruction were 78%,47%,100%,100%,73%,respectively.Conclusion CT can clearly diagnose different adhesion pattern leading to ileus and ensuing strangulation.
7.Establishment of risk warning model for surgical site infection
Wenying HE ; Yuhong DENG ; Xin LIU ; Weiguang LI ; Anhua WU ; Nan REN ; Lijuan XIONG ; Lili DING ; Hui HAN ; Zhong WANG
Chinese Journal of Infection Control 2017;16(6):497-501
Objective To establish a risk warning model for surgical site infection(SSI), provide support for screening high risk population and finding suspected cases.Methods Clinical data of 5 067 patients who underwent abdominal surgery in 6 domestic hospitals from January 2013 to December 2015 were collected retrospectively, all cases were randomly divided into modeling group and validation group according to a 6:4 ratio, warning model was established by employing logistic regression, the area under the receiver operating characteristic curve (AUC) was used to evaluate discriminant ability of evaluation model, the maximum Youden index was as the optimum cut-off point.Results For the warning model of high-risk patients, AUC was 0.823, sensitivity and specificity were 78.81% and 74.33% respectively, positive predictive value and negative predictive value were 19.67% and 97.78% respectively.For the discriminant model of suspected infection cases, AUC was 0.978, sensitivity and specificity were 93.38% and 95.62% respectively, positive predictive value and negative predictive value were 62.95% and 99.45% respectively.Conclusion The early-warning model established in this study has better discrimination ability, which can provide a reference for the development of early warning and discrimination of healthcare-associated infection information system.
8.Preliminary study of DWI differential diagnosis in multiple system atrophy,progressive supranuclear palsy and Parkinson's disease
Weiguang HE ; Le ZHANG ; Pei YANG ; Hongjie LIU ; Qi CHEN
Journal of Practical Radiology 2017;33(11):1661-1664,1678
Objective To explore the diffusion-weighted imaging(DWI) values in diagnosis and differential diagnosis in multiple system atrophy (MSA),progressive supranuclear palsy (PSP) and Parkinson's disease (PD).Methods Conventional MRI and DWI were performed in 24 clinically proved MSA patients,35 PD patients,12 PSP patients,and 32 age-matched normal controls (the control group).DWI was performed using a single shot-spin echo-echo planar imaging sequence,and ADC values were measured in the ROIs of different brain regions(including basal ganglia,thalamus,middle cerebellar peduncles and superior cerebellar peduncles).Then one way ANOVA test was used for statistical analysis.Results PSP group had the largest ADC values in putamen,globus pallidus,caudate,andsuperiorcerebellar peduncles[(0.75±0.43) ×10-3 mm2/s,(0.77±0.06)×10 3 mm2/s,(0.77±0.44)×10-3 mm2/s and (1.11±0.22)× 10-3 mm2/s].The ADC values of globus pallidus and caudate had statistically difference comparing with MSA [(0.73±0.04) × 10-3 mm2/s and (0.73±0.40) × 10-3 mm2/s],PD[(0.67±0.11) × 10-3 mm2/s and (0.73±0.04) × 10-3 mm2/s],and control group[(0.71±0.05) × 10-3 mm2/s and (0.72±0.04) × 10-3 mm2/s].MSA group had the largest ADC values in middle cerebellar peduncles[(0.95±0.16) × 10-3 mm2/s],and there was statistically significant difference,comparing with PSP,PD and control group[(0.74±0.49) × 10-3 mm2/s,(0.69±0.50) × 10-3 mm2/s and (0.68±0.31) × 10-3 mm2/s].The ADC values of PD group and control group had no statistically significant difference in putamen,globus pallidus,caudate,thalamus,middle cerebellar peduncles and superior cerebellar peduncles(P>0.05).Conclusion ADC values in the basal ganglia,the middle cerebellar peduncles and superior cerebellar peduncles have very important significance in differential diagnosis in MSA,PSP and PD.
9.Stroke after cardiac surgery
Yanfa HE ; Weiguang HU ; Zili MENG ; Yonghui LIU
International Journal of Cerebrovascular Diseases 2016;24(6):535-539
Stroke is one of the most devastating complications after cardiac surgery,and contributes to both mortality and morbidity.Coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI) are the common procedures for the treatment of coronary artery disease.This article reviews the pathophysiologic mechanisms,risk factors,treatment and prognosis of stroke after CABG and PCI.
10.Effects of drug serum of Jianbuhuqian pills on proliferation and function of osteoblast-like cells in vitro
Yi LUO ; Youzhang DENG ; Benxiang HE ; Weiguang HOU ; Xiaochuan DING ; Xuanwen LIU ; Chun QING
Chinese Journal of Tissue Engineering Research 2016;20(33):4883-4889
BACKGROUND:More recently, the focus has been on searching for a compound Chinese medicine for reinforcing kidney, which cannot only inhibit bone absorption, but also promote osteogenesis to protect against osteoporosis. OBJECTIVE:To explore effects of drug serum of Jianbuhuqian pil s on proliferation and function of osteoblast-like cel s in vitro. METHODS:Twenty-four adult female Sprague-Dawley rats were randomly divided into low-dose, medium-dose, high-dose and normal saline groups, and given intragastric administration of 1.5, 3.0, and 6 g/kg Jianbuhuqian pills and equal volume of normal saline, respectively twice daily for 1 week. At 1 hour after final gavage, rats were decapitated to prepare drug sera used for culturing osteoblast-like cells. At 24, 48 and 72 hours of culture, the cellular morphology was observed, as well as the cell proliferation and alkaline phosphatase activity was detected by MTT assay and alkaline phosphatase staining, respectively. RESULTS AND CONCLUSION:Compared with the normal saline group, the cel density began to increase significantly in three Jianbuhuqian groups at 24 hours after culture, mitotic figures were easy to be observed, cel s were in overlapping growth, much secretions and matrix accumulation appeared, especial y in the high-dose group. The obsorbance values in Jianbuhuqian groups were significantly higher than that in the normal saline group. After 24 hours of culture, the obsorbance values in the medium-dose and high-dose groups were significantly increased compared with the low-dose group, and the values showed significant differences among three Jianbuhuqian groups after 48 and 72-hour culture. In addition, the alkaline phosphatase activity presented overt increase in the Jianbuhuqian groups compared with the normal saline group, and significant differences could be found among Jianbuhuqian groups. To conclude, the drug serum of Jianbuhuqian pil s can promote the activity of osteoblast-like cel s in a time-and concentration-dependent manner.

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