1.Influence of Gene Mutation on the Effectiveness of Arsenic-Containing Herbal Compound Formula in Treatment of Myelodysplastic Syndromes of Different TCM Patterns
Zichun WANG ; Zhuo CHEN ; Dexiu WANG ; Haiyan XIAO ; Weiyi LIU ; Ruibai LI ; Chi LIU ; Fengmei WANG ; Shanshan ZHANG ; Mingjing WANG ; Liu LI ; Xiaoqing GUO ; Hongzhi WANG ; Xudong TANG
Journal of Traditional Chinese Medicine 2025;66(14):1463-1472
ObjectiveTo observe the effect of gene mutation on the effectiveness of arsenic-containing Chinese herbal compound formulas in the treatment of myelodysplastic syndromes (MDS) of different traditional Chinese medicine (TCM) patterns, so as to provide the basis for the clinical application. MethodsClinical data of 442 MDS patients who were treated with arsenic-containing herbal compound formulas were retrospectively collected, including the baseline demographic and clinical characteristics of the patients. Based on the TCM four examinations, the patients were divided into the spleen-kidney deficiency group as well as the qi-yin deficiency group, and according to the results of the next-generation sequencing (NGS) test, they were divided into the group with and without gene mutation respectively. The influence of gene mutation on the clinical effectiveness of patients with different TCM patterns was analyzed, the baseline demographic and clinical characteristics of the patients with different outcomes of the two TCM patterns were compared, and multivariate Logistic regression analysis was conducted on the influencing factors of the effective rate of MDS patients with gene mutation. ResultsA total of 190 cases were included in the spleen-kidney deficiency group (119 cases with gene mutation) and 43 cases in the qi-yin deficiency group (23 cases with gene mutation). No statistically significant differences were noted in effectiveness assessment, total effective rate, and total response rate between the spleen-kidney deficiency group and the qi-yin deficiency group (P>0.05). In the spleen-kidney deficiency group, the total effective rate of MDS with gene mutation was 65.55% (78/119), which was lower than 80.28% (57/71) of MDS without gene mutation, with statistical significance (P = 0.033), while no statistical differences in effectiveness assessment and total response rate were noted (P>0.05). In the qi-yin deficiency group, no statistical differences were observed in effectiveness assessment, total effective rate, and total response rate of the patients in with or without gene mutation (P>0.05). In the spleen-kidney deficiency group with gene mutation, the rate of complex karyotype (P = 0.031) and the mutation rate of CBL gene (P = 0.032) in the ineffective population were higher than those in the effective population, while the mutation rate of DDX41 gene in the effective population was higher than that in the ineffective population (P = 0.033). No statistically significant differences were found in other gene mutations, age, gender distribution, number of gene mutations, bone marrow hyperplasia degree, blast cell range, reticular fiber tissue proliferation or not, and prognosis of chromosomal abnormalities between the effective and ineffective populations (P>0.05). In the qi-yin deficiency group with gene mutation, no statistically significant differences were found in various items between populations with different outcomes (P>0.05). Multivariate Logistic regression analysis showed that complex karyotype, CBL mutation, and DDX41 mutation were independently associated with the effective rate of MDS with spleen-kidney deficiency and gene mutation (P<0.05). DDX41 mutation was an independent protective factor in the spleen-kidney deficiency group (OR>1), while complex karyotype and CBL mutation were independent risk factors (OR<1). ConclusionThe arsenic-containing TCM compound formulas exhibited better effectiveness in MDS with spleen-kidney deficiency pattern without mutation; and in MDS with spleen-kidney deficiency pattern without complex karyotypes, CBL mutation, and with DDX41 mutations. Furthermore, DDX41 mutation was an independent protective factor in the spleen-kidney deficiency group, while complex karyotype and CBL mutation were independent risk factors. In MDS with qi-yin deficiency pattern, gene mutation-related factors showed no significant impact on the effectiveness of arsenic-containing TCM compound formulas.
2.Development and multicenter validation of machine learning models for predicting postoperative pulmonary complications after neurosurgery.
Ming XU ; Wenhao ZHU ; Siyu HOU ; Hongzhi XU ; Jingwen XIA ; Liyu LIN ; Hao FU ; Mingyu YOU ; Jiafeng WANG ; Zhi XIE ; Xiaohong WEN ; Yingwei WANG
Chinese Medical Journal 2025;138(17):2170-2179
BACKGROUND:
Postoperative pulmonary complications (PPCs) are major adverse events in neurosurgical patients. This study aimed to develop and validate machine learning models predicting PPCs after neurosurgery.
METHODS:
PPCs were defined according to the European Perioperative Clinical Outcome standards as occurring within 7 postoperative days. Data of cases meeting inclusion/exclusion criteria were extracted from the anesthesia information management system to create three datasets: The development (data of Huashan Hospital, Fudan University from 2018 to 2020), temporal validation (data of Huashan Hospital, Fudan University in 2021) and external validation (data of other three hospitals in 2023) datasets. Machine learning models of six algorithms were trained using either 35 retrievable and plausible features or the 11 features selected by Lasso regression. Temporal validation was conducted for all models and the 11-feature models were also externally validated. Independent risk factors were identified and feature importance in top models was analyzed.
RESULTS:
PPCs occurred in 712 of 7533 (9.5%), 258 of 2824 (9.1%), and 207 of 2300 (9.0%) patients in the development, temporal validation and external validation datasets, respectively. During cross-validation training, all models except Bayes demonstrated good discrimination with an area under the receiver operating characteristic curve (AUC) of 0.840. In temporal validation of full-feature models, deep neural network (DNN) performed the best with an AUC of 0.835 (95% confidence interval [CI]: 0.805-0.858) and a Brier score of 0.069, followed by Logistic regression (LR), random forest and XGBoost. The 11-feature models performed comparable to full-feature models with very close but statistically significantly lower AUCs, with the top models of DNN and LR in temporal and external validations. An 11-feature nomogram was drawn based on the LR algorithm and it outperformed the minimally modified Assess respiratory RIsk in Surgical patients in CATalonia (ARISCAT) and Laparoscopic Surgery Video Educational Guidelines (LAS VEGAS) scores with a higher AUC (LR: 0.824, ARISCAT: 0.672, LAS: 0.663). Independent risk factors based on multivariate LR mostly overlapped with Lasso-selected features, but lacked consistency with the important features using the Shapley additive explanation (SHAP) method of the LR model.
CONCLUSIONS:
The developed models, especially the DNN model and the nomogram, had good discrimination and calibration, and could be used for predicting PPCs in neurosurgical patients. The establishment of machine learning models and the ascertainment of risk factors might assist clinical decision support for improving surgical outcomes.
TRIAL REGISTRATION
ChiCTR 2100047474; https://www.chictr.org.cn/showproj.html?proj=128279 .
Adult
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Aged
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Female
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Humans
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Male
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Middle Aged
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Algorithms
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Lung Diseases/etiology*
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Machine Learning
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Neurosurgical Procedures/adverse effects*
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Postoperative Complications/diagnosis*
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Risk Factors
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ROC Curve
3.Pan-cancer characterization of matrix metalloproteinase 12 and its value as a serum marker
Min Jia ; Qingmei Deng ; Huifen Wang ; Xiaofeng Wan ; Hongzhi Wang ; Wulin Yang
Acta Universitatis Medicinalis Anhui 2025;60(5):945-954
Objective :
To characterize MMP12 as a pan-cancer marker and assess its screening value as a tumor serum marker.
Methods :
Bioinformatics tools such as GEPIA2,GSCA,cBioPortal,and GeneMANIA were used to analyze the pan-cancer features of MMP12 in TCGA datasets,including encompassing differential gene expression analysis,prognostic analysis,DNA methylation analysis,gene structural variation analysis and immune microenvironment analysis.Furthermore,serum samples we collected from patients with lung adenocarcinoma,breast invasive carcinoma,esophageal squamous cell carcinoma,stomach adenocarcinoma,liver hepatocellular carcinoma,and healthy individuals.ELISA was used to detect MMP12 expression in serum,and the screening performance was evaluated using the area under the ROC curve.Additionally,we followed up 28 ESCC patients and compared serum MMP12 levels between 19 patients with disease progression and 9 patients with stable disease.
Results:
The pancancer feature analysis revealed a significant negative correlation between MMP12 mRNA expression and its promoter DNA methylation(P<0.05),as well as a positive correlation with gene copy number variations(P<0.05).MMP12 mRNA expression was up-regulated in 14 cancer tissues compared to normal tissues next to cancer(P<0.05) and was associated with poor prognosis of cancer patients(P<0.05).Immunocorrelation analysis showed that MMP12 was significantly associated with immunity,infiltration of stromal cells,tumor mutational burden(TMB) and microsatellite instability(MSI)(P<0.05).ROC curve analysis indicated that MMP12 could serve as a potential biomarker for screening lung adenocarcinoma,breast invasive carcinoma,esophageal squamous cell carcinoma,stomach adenocarcinoma,and liver hepatocellular carcinoma.In a 30-month follow-up study of esophageal squamous cell carcinoma patients,the expression of MMP12 was higher in the disease progression group than that in the stable group.
Conclusion
MMP12 serves as a potential prognostic and screening marker of pan-cancer.
4.Optimal concentration of ropivacaine in continuous epidural anesthesia combined with general anesthesia for radical resection of esophageal cancer
Cancer Research and Clinic 2024;36(7):515-518
Objective:To investigate the optimal concentration of ropivacaine in continuous epidural anesthesia combined with general anesthesia for radical resection of esophageal cancer.Methods:A retrospective case series study was conducted. A total of 100 patients with esophageal cancer undergoing radical surgery in Shanxi Province Cancer Hospital from February 2020 to February 2022 were collected. According to the concentration of ropivacaine in continuous epidural anesthesia combined with general anesthesia, all patients with esophageal cancer were divided into 0.25% concentration group and 0.50% concentration group, 50 cases in each group. The vital signs, analgesic effects, time of recovery from anesthesia and satisfaction with anesthesia of the 2 groups at entering the operating room (T 0), 5 minutes after general anesthesia induction (T 1), and time of extubation (T 2) were compared. Results:There were statistically significant differences in the age, gender, body mass of the both groups (all P > 0.05). The heart rate, mean arterial pressure (MAP) at T 1 were lower than those at T 0 and T 2 (all P < 0.05), but there were no significant differences in heart rate and MAP at T 0 and T 2 (all P > 0.05); at T 0, T 1 and T 2, there were no significant differences in HR and MAP between the both groups (all P > 0.05). The static visual analogue scale (VAS) score of patients in the 0.25% concentration group was lower than that in the 0.50% concentration group [(1.24±0.28) scores vs. (2.58±0.41) scores, t = 19.09, P < 0.05], and the dynamic VAS score in the 0.25% concentration group was lower than that in the 0.50% concentration group [(2.86±0.47) scores vs. (4.02±1.16) scores, t = 6.55, P < 0.05]. The recovery time of spontaneous respiration, the extubation time and the time of complete consciousness in the 0.25% concentration group was shorter than those in the 0.50% concentration group (all P < 0.05). The anesthesia satisfaction in the 0.25% concentration group was higher than that in the 0.50% concentration group [94% (47/50) vs.78% (39/50), χ2 = 5.32, P < 0.05]. Conclusions:The optimal concentration of ropivacaine in continuous epidural anesthesia combined with general anesthesia for radical resection of esophageal cancer is 0.25%.
5.Comparative study of CT measurement of adult kidney depth with estimation formula
Liu FENG ; Xiaojie LIU ; Zhigang ZHANG ; Hongzhi WANG
China Modern Doctor 2024;62(29):33-36
Objective To analyze the correlation and consistency between different kidney depth estimation formulas and computed tomography(CT)measurement of kidney depth,discussing the best kidney depth calculation formula for this region.Methods A total of 213 patients who underwent renal dynamic imaging in the First Hospital of Jiaxing from January 2019 to January 2024 were retrospectively included in this study.The abdominal CT image data of the same period were obtained,and the gender,age,height and weight were recorded.The patient's body thickness and kidney depth were measured by CT.Seven calculation formulas(Tonnesen formula,Li Qian formula,Taylor formula,Inoue formula,Xue JJ formula,Li's equation and Ma G's formula)were used to estimate the kidney depth.Paired sample t-test,Pearson correlation analysis and Bland-Altman consistency analysis were performed between the kidney depth calculated by the equation and the kidney depth measured by CT.Results There was a correlation between the estimated values calculated by the calculation formulas and actual CT measurements,and the kidney depth calculated by the seven formulas were lower than the CT measurements.The results of correlation analysis showed that the correlation coefficient between Ma G's formula and CT measurements was better than other formulas,and the correlation coefficients of Tonnesen formula and Inoue formula were consistent.The bias between the kidney depth calculated by Tonnesen formula and the CT measured value is the largest,and the bias between the kidney depth calculated by Ma G's formula and the CT measured value is the smallest.Conclusion The Ma G'S formula introduces body thickness as a key reference variable for calculating kidney depth.Compared to the other six calculation formulas,it has demonstrated higher accuracy and reliability in estimating kidney depth,thereby having a broader applicability in clinical practice.
6.Automatic segmentation of identified vertebral bones from CT images using CA-SegResNet
Zhongqi ZHU ; Xiaolong GAO ; Yinghao LI ; Guang YANG ; Liguo HAO ; Hongzhi WANG
Chinese Journal of Medical Physics 2024;41(11):1349-1356
A three-dimensional(3D)medical image segmentation network(CA-SegResNet)which incorporates a 3D coordinate attention mechanism is proposed to address the issue of segmenting identified vertebral bones from spinal computed tomography(CT)images.The network extracts image features through a deep residual convolutional neural network and fuses the feature maps from each encoder layer with the input of the corresponding decoder layer.Subsequently,a 3D coordinate attention module is introduced to capture inter-channel relationships as well as directional and positional information,establishing long-range dependencies across different spatial directions,thereby enabling precise segmentation of the identified vertebral bones.For the segmentation tasks involving the identified cervical vertebra(the 7th cervical vertebra)and the identified thoracic vertebra(the 12th thoracic vertebra)across 105 cases,CA-SegResNet achieves average Dice similarity coefficients(DSC)of 0.934 5 and 0.918 9 on the test set,with average Hausdorff distances(HD)of 7 and 8 mm.Compared with U-Net results,the average DSC is improved by 0.014 5 and 0.0463,while average HD is reduced by 176 and 388 mm.The results demonstrate that the network can realize the precise segmentation of identified vertebral bones from CT images.
7.Predictive value of gated myocardial perfusion imaging for all-cause mortality risk in patients with familial hypercholesterolemia
Jian JIAO ; Luya WANG ; Wei DONG ; Tiantian MOU ; Ying ZHANG ; Zhi CHANG ; Xiaofen XIE ; Junqi LI ; Hongzhi MI
Chinese Journal of Nuclear Medicine and Molecular Imaging 2024;44(5):297-302
Objective:To evaluate the predictive value of stress+ rest gated myocardial perfusion imaging (G-MPI) in assessing all-cause mortality risk in patients with familial hypercholesterolemia (FH).Methods:From June 2010 to March 2022, 72 patients (39 males, 33 females; age (21.1±12.3) years) who diagnosed with FH clinically and genetically and underwent stress+ rest G-MPI in Beijing Anzhen Hospital, Capital Medical University were retrospectively followed up. Image analysis was performed using the 17-segment 5-point method to obtain left ventricular myocardial perfusion and functional parameters. Patients were followed for all-cause mortality events, and predictors associated with the risk of all-cause mortality were analyzed using Cox regression. The efficiencies of predictors were evaluated by ROC curve analysis, and the Kaplan-Meier method and log-rank test were used to compare the differences in the incidence of all-cause mortality in different groups of patients with FH. Independent-sample t test or Mann-Whitney U test was used to analyze the data. Results:The follow-up time of 72 patients was 7(4, 10) years, and all-cause death occurred in 16(22.2%) patients during the follow-up period. There were statistically significant differences in total cholesterol (TC), low density lipoprotein cholesterol (LDLC), summed stress score (SSS), summed rest score (SRS), summed difference score (SDS), stress end-systolic volume (SESV), stress ejection fraction (SEF), rest end-diastolic volume (REDV), rest end-systolic volume (RESV) and rest ejection fraction (REF) between the death group and the survival group ( t values: from -2.65 to 4.47, z values: from -3.43 to -1.98, all P<0.05). Cox regression analysis showed that SDS (hazard ratio ( HR)=1.337, 95% CI: 1.114-1.604, P=0.002), SESV ( HR=1.019, 95% CI: 1.008-1.030, P<0.001) and LDLC ( HR=1.355, 95% CI: 1.049-1.749, P=0.020) were independent predictors associated with the risk of all-cause mortality in patients with FH. The optimal cut-off value of SESV for predicting mortality in patients with FH determined by ROC curve analysis was 35.5 ml, with the AUC of 0.701 (95% CI: 0.517-0.885). The incidence of all-cause mortality in the group with SESV≥35.5 ml was significantly higher than that in the group with SESV<35.5 ml (28.6% vs 6.9%; χ2=5.15, P=0.023). Conclusion:Stress+ rest G-MPI is an important imaging method for all-cause mortality risk assessment in patients with FH, and SDS, SESV and LDLC are important factors in predicting mortality in patients with FH.
8.Study of Ctsk knockout regulating type H blood vessel formation and tooth extraction socket healing in mice
Wuyang ZHANG ; Dengke LI ; Yiming WANG ; Yuan LI ; Yuzhe CHEN ; Xueni ZHENG ; Hongzhi ZHOU ; Kaijin HU ; Yang XUE
Journal of Practical Stomatology 2024;40(3):330-336
Objective:To study the effects of cathepsin K(CTSK)on the healing process of tooth extraction socket and type H blood vessel angiogenesis in mice.Methods:Ctsk knockout(Ctsk-/-)mice were generated by CRISPR/Cas9 technology,and genotype sequen-cing,general observation,Micro-CT and immunohistochemistry were performed to confirm successful knockout of Ctsk.Then 8 week-old WT and Ctsk-/-mice were used to establish the tooth extraction modle by extracting the left maxillary first molars,and the mice were sac-rificed at the day 7,10,14,21,28 and 35 respectively(n=3)after tooth extraction.Then samples were subjected to stereo microscope and Micro-CT examination.Immunofluorescence staining was used to study the effect of Ctsk knockout on type H blood vessel angiogene-sis.Results:Ctsk knockout did not affect the soft tissue healing of tooth extraction socket,but significantly promoted the bone healing process,and Ctsk deficency significantly enhanced type H blood vessel angiogenesis in the tooth extraction socket.Conclusion:Ctsk knockout can enhance type H vessel angiogenesis,and promote bone healing process of tooth extraction socket in mice.
9.Single-centre diagnosis, treatment and prognostic analysis of abdominal aortic endograft infection
Xuebin WANG ; Bin LIU ; Zhe ZHANG ; Hongzhi YU ; Zhiwen ZHANG ; Lishan LIAN ; Xiang GAO ; Hai FENG ; Xueming CHEN
International Journal of Surgery 2024;51(11):759-765
Objective:To summarise and analyse the experience in the diagnosis and management of abdominal aortic endograft infection in recent years.Methods:Retrospectively summarised and analysed the general data, clinical presentation, laboratory and imaging findings, causative organisms and treatment choices of 14 patients with abdominal aortic endograft infection treated in Beijing Friendship Hospital, Capital Medical University, from January 2018 to June 2024, and analysed the prognosis of the patients and the risk factors associated with prognosis.Results:Positive bacterial cultures were 10 out of 14 patients. One non-operatively treated patient died of infectious toxic shock. Thirteen surgically treated patients underwent axillary-bifemoral artery bypass, removal of the infected stent, and closure of the aortic stump. Four of the 13 cases had combined aortoenteric fistula, 3 cases underwent one-stage enterocutaneous fistula repair, 1 case only fistula drainage, 3 cases of gastrojejunal anastomosis, all of them underwent gastric or jejunal nutrient tube implantation. Two of the 13 patients had combined the infection foci spread to the renal artery openings. To save the kidney, intraoperative left kidney autologous renal transplantation was performed in 1 case, and autologous saphenous vein reconstruction from celiac trunk artery-left renal artery and superior mesenteric artery-right renal artery was performed in the other case. All 14 patients were retrospectively summarised and followed up in August 2024, with 5 deaths in the early postoperative period (< 3 months), 3 deaths in the mid- to long-term period (≥3 months), and 5 survivors, with a median follow-up time of 2 years (1-5 years) for surviving patients. Among the 13 operated patients, 4 cases were combined with aortoenteric fistula, and 3 cases died in the early postoperative period; 4 cases of abdominal aortic infection foci involving renal artery openings, 2 cases of early postoperative death; 4 cases with pleural effusion, 4 cases died in the early postoperative period; 2 cases of combined creatinine elevation, 2 cases of early postoperative death; 2 cases of postoperative infection of artificial blood vessels.Conclusions:Abdominal aortic endograft infection are aggressive. The risk of early death is increased in patients who are elderly, in poor general condition, with aortoenteric fistula or with pre-existing cardiac, pulmonary, hepatic and renal insufficiency, but surgery based on adequate anti-infective therapy remains an effective means of saving the patient′s life.
10.Traditional Chinese Medicine Syndrome Element, Evolutionary Patterns of Patients with Hepatitis B Virus-Related Acute on Chronic Liver Failure at Different Stages: A Multi-Center Clinical Study
Simiao YU ; Kewei SUN ; Zhengang ZHANG ; Hanmin LI ; Xiuhui LI ; Hongzhi YANG ; Qin LI ; Lin WANG ; Xiaozhou ZHOU ; Dewen MAO ; Jianchun GUO ; Yunhui ZHUO ; Xianbo WANG ; Xin DENG ; Jiefei WANG ; Wukui CAO ; Shuqin ZHANG ; Mingxiang ZHANG ; Jun LI ; Man GONG ; Chao ZHOU
Journal of Traditional Chinese Medicine 2024;65(12):1262-1268
ObjectiveTo explore the syndrome elements and evolving patterns of patients with hepatitis B virus-related acute on chronic liver failure (HBV-ACLF) at different stages. MethodsClinical information of 1,058 hospitalized HBV-ACLF patients, including 618 in the early stage, 355 in the middle stage, and 85 in the late stage, were collected from 18 clinical centers across 12 regions nationwide from January 1, 2012 to February 28, 2015. The “Hepatitis B-related Chronic and Acute Liver Failure Chinese Medicine Clinical Questionnaire” were designed to investigate the basic information of the patients, like the four diagnostic information (including symptoms, tongue, pulse) of traditional Chinese medicine (TCM), and to count the frequency of the appearance of the four diagnostic information. Factor analysis and cluster analysis were employed to determine and statistically analyze the syndrome elements and patterns of HBV-ACLF patients at different stages. ResultsThere were 76 four diagnostic information from 1058 HBV-ACLF patients, and 53 four diagnostic information with a frequency of occurrence ≥ 5% were used as factor analysis entries, including 36 symptom information, 12 tongue information, and 5 pulse information. Four types of TCM patterns were identified in HBV-ACLF, which were liver-gallbladder damp-heat pattern, qi deficiency and blood stasis pattern, liver-kidney yin deficiency pattern, and spleen-kidney yang-deficiency pattern. In the early stage, heat (39.4%, 359/912) and dampness (27.5%, 251/912) were most common, and the pattern of the disease was dominated by liver-gallbladder damp-heat pattern (74.6%, 461/618); in the middle stage, dampness (30.2%, 187/619) and blood stasis (20.7%, 128/619) were most common, and the patterns of the disease were dominated by liver-gallbladder damp-heat pattern (53.2%, 189/355), and qi deficiency and blood stasis pattern (27.6%, 98/355); and in the late stage, the pattern of the disease was dominated by qi deficiency (26.3%, 40/152) and yin deficiency (20.4%, 31/152), and the patterns were dominated by qi deficiency and blood stasis pattern (36.5%, 31/85), and liver-gallbladder damp-heat pattern (25.9%, 22/85). ConclusionThere are significant differences in the distribution of syndrome elements and patterns at different stages of HBV-ACLF, presenting an overall trend of evolving patterns as "from excess to deficiency, transforming from excess to deficiency", which is damp-heat → blood stasis → qi-blood yin-yang deficiency.


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