1.Screening of hub genes and pathways of idiopathic non-cirrhotic portal hypertension and prediction of traditional Chinese medicine
Yuepei LIU ; Ying ZONG ; Ping ZHANG ; Ranlian YANG ; Yilei LI
China Modern Doctor 2024;62(2):49-53,61
Objective To with analyzing the gene expression profile of idiopathic non-cirrhotic portal hypertension(INCPH)by bioinformatics methods,we may obtain its key genes and signaling pathways to explore the molecular mechanism of INCPH and predict the potential traditional Chinese medicine.Methods The gene microarray dataset GSE77627 on INCPH was downloaded from gene expression omnibus(GEO)database,the data were normalized and screened for differential genes(DEGs)of INCPH using R language,and all DEGs were analyzed for gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)enrichment using Metascape database,and protein-protein interaction network was constructed by STRING database;meanwhile DEGs with the top 15 Degree values were screened as key genes using CytoHubba plugin.Subsequently,the key genes were mapped to each other with the medical ontology information retrieval platform(coremine medical)to screen potential Chinese herbal medicines for the treatment of INCPH with P<0.05,and the potent components that potential Chinese medicines have were screened from the TCMSP database,imported into Cytoscape software to construct a Chinese medicine correlation network map and predict the key targets.Results A total of 1880 DEGs were screened,including 1061 up-regulated and 819 down-regulated genes.DEGs were analyzed using the protein interaction database STRING and cytoHubba in Cytoscape software to obtain key genes,which were RPS27A,CDC42,EIF4E,MAPK1,PIK3R1,RPS6,RPS9,RPS8,RPL15,RPL27A,RPL24,RPL27,RPL26,RPL12 and MAPK14.The GO and KEGG analysis mainly involved gamete production and AGE-RAGE signaling pathway in INCPH.Conclusion The potential traditional Chinese medicines screened for INCPH are Ginseng Radix et Rhizoma,Salviae Miltiorrhizae Radix et Rhizoma,Scutellariae Radix,etc,which may be a potential source of molecular drugs for the treatment of INCPH.
2.Application of machine learning in predictive analysis of blood usage for liver transplantation surgery
Peng ZONG ; Wenli ZHANG ; Ping LI ; Changfeng SHAO ; Haiyan WANG
Chinese Journal of Blood Transfusion 2024;37(3):319-324
【Objective】 To explore the application of machine learning in scientific and rational blood preparation and predictive analysis for surgical blood usage before liver transplantation surgery. 【Methods】 Clinical basic information including gender, age, clinical diagnosis and surgical methods of 356 liver transplantation patients were collected. The duration (Time) and preoperative laboratory test results of hemoglobin (Hb), hematocrit (Hct), platelet count (Plt), prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (Fib), total bilirubin (TBIL), albumin (ALB), creatinine (Crea) and total protein (TP), as well as the amount of intraoperative blood transfusion were collected. A machine learning model capable of predicting the risk of massive blood transfusion during liver transplantation surgery was established by Python, and was evaluated to select the optimal predictive model. 【Results】 Among the 7 machine learning models constructed, the logistic regression model performed the best (AUROC: 0.90, F1 score: 0.82), with an accuracy of 79.44% and precision of 79.69%, followed by the random forest classifier (AUROC: 0.87, F1 score: 0.83), with an accuracy of 79.44% and precision of 77.94%. 【Conclusion】 Establishing a machine learning prediction model by Python is of significant clinical importance for scientific blood preparation, predicting the risk of massive blood transfusion and ensuring the safety of blood use in liver transplantation surgery.
3.Therapeutic effect of transplantation of bone marrow mesenchymal stem cells co-cultured with bone marrow M2 macrophages on a rat model of liver cirrhosis
Xinrui ZHENG ; Yannan XU ; Danyang WANG ; Feifei XING ; Mengyao ZONG ; Shihao ZHANG ; Junyi ZHAN ; Wei LIU ; Gaofeng CHEN ; Jiamei CHEN ; Ping LIU ; Yongping MU
Journal of Clinical Hepatology 2024;40(1):96-103
ObjectiveTo investigate the effect of transplantation of bone marrow mesenchymal stem cells (BMSCs) co-cultured with bone marrow-derived M2 macrophages (M2-BMDMs), named as BMSCM2, on a rat model of liver cirrhosis induced by carbon tetrachloride (CCl4)/2-acetaminofluorene (2-AAF). MethodsRat BMDMs were isolated and polarized into M2 phenotype, and rat BMSCs were isolated and co-cultured with M2-BMDMs at the third generation to obtain BMSCM2. The rats were given subcutaneous injection of CCl4 for 6 weeks to establish a model of liver cirrhosis, and then they were randomly divided into model group (M group), BMSC group, and BMSCM2 group, with 6 rats in each group. A normal group (N group) with 6 rats was also established. Since week 7, the model rats were given 2-AAF by gavage in addition to the subcutaneous injection of CCl4. Samples were collected at the end of week 10 to observe liver function, liver histopathology, and hydroxyproline (Hyp) content in liver tissue, as well as changes in the markers for hepatic stellate cells, hepatic progenitor cells, cholangiocytes, and hepatocytes. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the N group, the M group had significant increases in the activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (P<0.01); compared with the M group, the BMSC and BMSCM2 groups had significant reductions in ALT and AST (P<0.01), and the BMSCM2 group had significantly better activities than the BMSC group (P<0.05). Compared with the N group, the M group had significant increases in Hyp content and the mRNA and protein expression levels of alpha-smooth muscle actin (α-SMA) in the liver (P<0.01); compared with the M group, the BMSC and BMSCM2 groups had significant reductions in Hyp content and the expression of α-SMA (P<0.05), and the BMSCM2 group had a significantly lower level of α-SMA than the BMSC group (P<0.01). Compared with the N group, the M group had significant increases in the mRNA expression levels of the hepatic progenitor cell markers EpCam and Sox9 and the cholangiocyte markers CK7 and CK19 (P<0.01) and significant reductions in the expression levels of the hepatocyte markers HNF-4α and Alb (P<0.01); compared with the M group, the BMSC and BMSCM2 groups had significant reductions in the mRNA expression levels of EpCam, Sox9, CK7, and CK19 (P<0.05) and significant increases in the mRNA expression levels of HNF-4α and Alb (P<0.05), and compared with the BMSC group, the BMSCM2 group had significant reductions in the mRNA expression levels of EpCam and CK19 (P<0.05) and significant increase in the expression level of HNF-4α (P<0.05). ConclusionM2-BMDMs can enhance the therapeutic effect of BMSCs on CCl4/2-AAF-induced liver cirrhosis in rats, which provides new ideas for further improving the therapeutic effect of BMSCs on liver cirrhosis.
4.Sarcopenia index as a predictor of in-hospital adverse events in patients with acute myocardial infarction after emergency PCI
Cheng-Si LI ; Zhang-Yu WANG ; Shao-Qing CAO ; Yu-Qin WANG ; Jiang-Ping YE ; Ye-Hong LIU ; Tian-Hui JIN ; Gang-Jun ZONG
Medical Journal of Chinese People's Liberation Army 2024;49(4):408-415
Objective To investigate the association between the serum creatinine/cystatin C ratio(SCr/Cys C)as a Sarcopenia index(SI)and the incidence of in-hospital adverse events in patients with acute myocardial infarction(AMI)undergoing emergency percutaneous coronary intervention(PCI).Additionally,we evaluate the predictive efficacy of the SI in predicting major adverse cardiovascular events(MACEs)during hospitalization.Methods A total of 306 patients with AMI who underwent emergency PCI in the 904th Hospital of PLA Joint Logistics Support Force from January 2020 to March 2023 were consecutively included in this retrospective analysis.Patients were divided into two groups based on the occurrence of MACEs during hospitalization:MACEs group(n=43)and non-MACEs group(n=263).Clinical characteristics and pre-PCI laboratory test results were collected.Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for MACEs.The predictive performance of SI was assessed using receiver operating characteristic(ROC)curve analysis.Results The incidence of in-hospital MACEs in AMI patients was 14.1%.The results of the independent samples t-test showed that the SI level in MACEs group was significantly lower than that in non-MACEs group,with a statistically significant difference(P<0.001).The results of the multivariate logistic regression analysis suggested that new-onset atrial fibrillation,Killip class 2-4,SI,and TG were independent risk factors for in-hospital adverse events after emergency PCI.The ROC curve results showed that the predictive value of SI(AUC=0.741,95%CI 0.666-0.816)using the SCr/Cys C ratio was superior to that of single Cys C(AUC=0.658,95%CI 0.570-0.746)for predicting post-PCI MACEs,with a statistically significant difference(P<0.05),and the optimal cutoff value for SI was 78.14.After stratifying SI based on the cutoff value,the results of the independent samples t-test showed that compared to the higher SI group,the lower SI group had a higher occurrence of specific adverse events such as heart failure(P<0.001),malignant arrhythmias(P=0.009),and strokes(P=0.003),with statistically significant differences.Conclusions The results highlight SI as an independent risk factor for MACEs during hospitalization after emergency PCI in AMI patients.Furthermore,SI has proven to be an effective prognostic index for patient outcomes.
5.Long-term efficacy of oblique lateral interbody fusion combined with vertebral screw fixation for the treatment of lumbar specific infection
Wen-Hui ZHANG ; Yang-Yang DOU ; Feng-Guang YANG ; Zong-Ru HE ; Yu-Ping YANG ; Li-Zhen FAN ; Qing-Hao CHENG ; Jie LIU ; Hui-Ping TAI
China Journal of Orthopaedics and Traumatology 2024;37(9):893-898
Objective To explore medium and long term efficacy of oblique lateral interbody fusion(OLIF)in treating lumbar specific infection.Methods From October 2017 to January 2021,24 patients with lumbar specific infection were treated by OLIF combined with vertebral screw internal fixation,including 15 males and 9 females,aged from 27 to 61 years old with an average of(43.0±15.0)years old;the courses of disease ranged from 6 to 24 months with an average of(14.0±7.0)months;7 patients with L2-L3,12 patients with L3-L4 and 5 patients with L4-L5;19 patients with tuberculosis infection and 5 patients with brucella infection.The amount of intraoperative blood loss,operative time and complications were recorded,and erythro-cyte sedimentation rate(ESR),C-reactive protein(CRP),visual analogue scale(VAS),Japanese Orthopaedic Association(JOA)score and American Spinal Injury Association(ASIA)rating were compared before and one month after opertaion.Re-sults All patients were followed up from 9 to 24 months with an average of(13.0±6.0)months.Operative time was(132.5±21.4)min,and intraoperative blood loss was(227.3±43.1)ml.ESR and CRP were decreased from(82.34±18.62)mmol·h-1 and(53.08±21.84)mg·L-1 before operation to(33.52±17.31)mmol·h-1 and(15.48±8.36)mg·L-1 at one month after opera-tion,respectively(P<0.05).VAS was decreased from(7.52±1.36)before opertaion to(1.74±0.87)at one month after opera-tion(P<0.05).JOA was increased from(17.86±3.95)before operation to(24.72±3.19)at one month after operation(P<0.05).Four patients had neurological symptoms before operation,and were classified to grade D according to ASIA classifica-tion,who were recovered to grade E at 1 month after operation.One patient was suffered from psoas major muscle injury after operation,and returned to normal at 3 weeks.One patient was suffered from abdominal distension and difficulty in defecation,and relieved after gastrointestinal decompression and enema.No complications such as abdominal organ injury and poor wound healing occurred in all patients.Conclusion OLIF combined with vertebral screw internal fixation is a new minimally invasive surgical method for the treatment of lumbar specific infection,especially the lesion located on the middle lumbar vertebra.It has advantages of less trauma,short operation time,less blood loss,convenient operation,complete removal of the lesion,safety and effectiveness,and has good medium-and long-term efficacy for lumbar specific infection.
6.Protective Effect of Endogenous ω-3 Polyunsaturated Fatty Acid Against Cisplatin-Induced Myelosuppression
Qi-Hua XU ; Zong-Meng ZHANG ; Chao-Feng XING ; Han-Si CHEN ; Ke-Xin ZHENG ; Yun-Ping MU ; Zi-Jian ZHAO ; Fang-Hong LI
Journal of Experimental Hematology 2024;32(5):1601-1607
Objective:To investigate the protective effect of endogenous ω-3 polyunsaturated fatty acid(PUFA)against cisplatin-induced myelosuppression and the mechanism of reducing apoptosis in bone marrow nucleated cells using mfat-1 transgenic mice.Methods:The experimental animals were divided into 4 groups:wild-type mice normal control group,mfat-1 transgenic mice normal control group,wild-type mice model group and mfat-1 transgenic mice model group.The mice in the model group were injected intraperitoneally with 7.5 mg/kg cisplatin on day 0 and day 7 to construct a myelosuppression model,while the mice in the normal control group were injected intraperitoneally with an equal amount of saline,and their status was observed and their body weight was measured daily.Peripheral blood was taken after 14 day for routine blood analysis,and the content and proportion of PUFA in peripheral blood were detected using gas chromatography.Bone marrow nucleated cells in the femur of mice were counted.The histopathological changes in bone marrow were observed by histopathological staining.The apoptosis of nucleated cells and the expression level changes of apoptosis-related genes in the bone marrow of mice were detected by flow cytometry and fluorescence quantitative PCR.Results:Compared with wild-type mice,mfat-1 transgenic mice showed significantly increased levels of ω-3 PUFA in peripheral blood and greater tolerance to cisplatin.Peripheral blood analysis showed that endogenous ω-3 PUFA promoted the recovery of leukocytes,erythrocytes,platelets and haemoglobin in peripheral blood of myelosuppressed mice.The results of HE staining showed that endogenous ω-3 PUFA significantly improved the structural damage of bone marrow tissue induced by cisplatin.Flow cytometry and PCR showed that,compared with wild-type mice model group,the apoptosis rate of bone marrow nucleated cells in mfat-1 transgenic mice was significantly reduced(P<0.001),and the expression of anti-apoptotic genes Bcl-2 mRNA was significantly increased(P<0.01),while the expressions of pro-apoptotic genes Bax and Bak mRNA were significantly reduced(P<0.001,P<0.05).Conclusion:Endogenous ω-3 PUFA can reduce cisplatin-induced apoptosis in bone marrow nucleated cells,increase the number of peripheral blood cells and exert a protective effect against cisplatin-induced myelosuppression by regulating the expression of apoptosis-related genes.
7.Research progress on effect of unfolded protein response in heat stroke
Yu-Liang PENG ; Jiu-She KOU ; You WU ; Zong-Ping FANG ; Xi-Jing ZHANG
Medical Journal of Chinese People's Liberation Army 2023;48(12):1486-1491
Heat stroke(HS)is a serious life-threatening disease caused by heat injury and characterized by a core body temperature>40℃with central nervous system dysfunction and multi-organ failure.The main pathophysiological manifestations of HS are the thermal acute phase response and thermoregulatory imbalance.Proteins are particularly sensitive to heat,and the thermal environment can cause massive protein denaturation,resulting in the deposition of unfolded and misfolded proteins in the cytoplasm,causing cellular dysfunction and even death.The unfolded protein response(UPR),mainly divided into the endoplasmic reticulum UPR and the mitochondrial UPR,is an important physiological process that helps proteins to fold correctly or degrade irretrievably denatured proteins.This paper summarizes the regulatory mechanisms of UPR,the relationship between UPR and severe diseases,as well as the relationship between HS and UPR to provide new ideas for the treatment of HS.
8.Prediction of Pulmonary Disease Progression in Patients with COVID-19 Based on CT Radiomics
Zhu-ping SU ; Hai-bao WANG ; Si-wei WANG ; Ruo-mei LI ; Qing-hong CHENG ; Zong-gen GAO ; Dong-feng LIU ; Meng-qi ZHANG
Journal of Sun Yat-sen University(Medical Sciences) 2023;44(2):286-294
ObjectivesBased on the changes of lung lesions in patients with COVID-19 at different stages, a nomogram model describing CT image features was established by radiomics method to explore its efficacy in predicting the progression of the disease. MethodsThis retrospective study enrolled 136 patients with COVID-19 pneumonia who received at least two CTs including three cohorts (training cohort and validation cohort 1 and 2). Patients in the training cohort were divided into three groups according to time between onset of fever symptoms and the first CT. The clinical manifestations and CT features of each group were analyzed and compared. A nomogram to predict disease progression was constructed according to the CT features of the patients, and its performance was evaluated. ResultsThe training cohort consisted of 41 patients.A nomogram was generated to predict disease progression based on three CT features: irregular strip shadow, air bronchial sign, and the proportion of lesions with irregular shape ≥50%. AUC(95%CI)=0.906(0.817,0.995).The C index of the training cohort was 0.906, and the C index of the internal verification was 0.892. AUC(95%CI)of the validation cohort 1 (34 cases) =0.889(0.793,0.984);AUC(95%CI)of the validation cohort 2 (61 cases)=0.876(0.706,1.000).The calibration curves show that the predicted values of the nomogram are in good agreement with the observed values. ConclusionThe nomogram model based on CT radiomics can predict the outcome of lung lesions in patients with high sensitivity and specificity.According to the changes of CT image characteristics of patients with COVID-19, lung lesions will be improved when the proportion of irregular cable shadow, air bronchogram and irregular lesions is greater than 50%.
9.Treatment Outcomes in COVID-19 Patients with Brucellosis: Case Series in Heilongjiang and Systematic Review of Literature.
Man Li YANG ; Jing Ya WANG ; Xing Yu ZONG ; Li GUAN ; Hui Zhen LI ; Yi Bai XIONG ; Yu Qin LIU ; Ting LI ; Xin Yu JI ; Xi Yu SHANG ; Hui Fang ZHANG ; Yang GUO ; Zhao Yuan GONG ; Lei ZHANG ; Lin TONG ; Ren Bo CHEN ; Yi Pin FAN ; Jin QIN ; Fang WANG ; Gang LIN ; Nan Nan SHI ; Yan Ping WANG ; Yan MA
Biomedical and Environmental Sciences 2023;36(10):930-939
OBJECTIVE:
Clinical characteristics and outcome in COVID-19 with brucellosis patients has not been well demonstrated, we tried to analyze clinical outcome in local and literature COVID-19 cases with brucellosis before and after recovery.
METHODS:
We retrospectively collected hospitalization data of comorbid patients and prospectively followed up after discharge in Heilongjiang Infectious Disease Hospital from January 15, 2020 to April 29, 2022. Demographics, epidemiological, clinical symptoms, radiological and laboratory data, treatment medicines and outcomes, and follow up were analyzed, and findings of a systematic review were demonstrated.
RESULTS:
A total of four COVID-19 with brucellosis patients were included. One patient had active brucellosis before covid and 3 patients had nonactive brucellosis before brucellosis. The median age was 54.5 years, and all were males (100.0%). Two cases (50.0%) were moderate, and one was mild and asymptomatic, respectively. Three cases (75.0%) had at least one comorbidity (brucellosis excluded). All 4 patients were found in COVID-19 nucleic acid screening. Case C and D had only headache and fever on admission, respectively. Four cases were treated with Traditional Chinese medicine, western medicines for three cases, no adverse reaction occurred during hospitalization. All patients were cured and discharged. Moreover, one case (25.0%) had still active brucellosis without re-positive COVID-19, and other three cases (75.0%) have no symptoms of discomfort except one case fell fatigue and anxious during the follow-up period after recovery. Conducting the literature review, two similar cases have been reported in two case reports, and were both recovered, whereas, no data of follow up after recovery.
CONCLUSION
These cases indicate that COVID-19 patients with brucellosis had favorable outcome before and after recovery. More clinical studies should be conducted to confirm our findings.
Female
;
Humans
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Male
;
Middle Aged
;
Brucellosis
;
COVID-19
;
Retrospective Studies
;
SARS-CoV-2
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Treatment Outcome
;
Case Reports as Topic
10.Efficacy and safety of sacubitril/valsartan after six months in patients with heart failure with reduced ejection fraction and asymptomatic hypotension.
An-Hu WU ; Zong-Wei LIN ; Zhuo-Hao YANG ; Hui ZHANG ; Jia-Yi HU ; Yi WANG ; Rui TANG ; Xin-Yu ZHANG ; Xiao-Ping JI ; Hui-Xia LU
Journal of Geriatric Cardiology 2023;20(12):855-866
BACKGROUND:
It is not clear whether sacubitril/valsartan is beneficial for patients with heart failure (HF) with reduced ejection fraction (HFrEF) and low systolic blood pressure (SBP). This study aimed to investigate the efficacy and tolerability of sacubitril/valsartan in HFrEF patients with SBP < 100 mmHg.
METHODS & RESULTS:
An observational study was conducted on 117 patients, 40.2% of whom had SBP < 100 mmHg without symptomatic hypotension, and 59.8% of whom had SBP ≥ 100 mmHg in an optimized HF follow-up management system. At the 6-month follow-up, 52.4% of patients with SBP < 100 mmHg and 70.0% of those with SBP ≥ 100 mmHg successfully reached the target dosages of sacubitril/valsartan. A reduction in the concentration of N-terminal pro-B-type natriuretic peptide was similar between patients with SBP < 100 mmHg and SBP ≥ 100 mmHg (1627.5 pg/mL and 1340.1 pg/mL, respectively; P = 0.75). The effect of sacubitril/valsartan on left ventricular ejection fraction was observed in both SBP categories, with a 10.8% increase in patients with SBP < 100 mmHg (P < 0.001) and a 14.0% increase in patients with SBP ≥ 100 mmHg (P < 0.001). The effects of sacubitril/valsartan on SBP were statistically significant and inverse across both SBP categories (P = 0.001), with an increase of 7.5 mmHg in patients with SBP < 100 mmHg and a decrease of 11.5 mmHg in patients with SBP ≥ 100 mmHg. No statistically significant differences were observed between the two groups in terms of the occurrence of symptomatic hypotension, deteriorating renal function, hyperkalemia, angioedema, or stroke.
CONCLUSIONS
Within an optimized HF follow-up management system, sacubitril/valsartan exhibited excellent tolerability and prompted left ventricular reverse remodeling in patients with HFrEF who presented asymptomatic hypotension.

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