1.Artificial intelligence and anti-cancer drugs' response.
Xinrui LONG ; Kai SUN ; Sicen LAI ; Yuancheng LIU ; Juan SU ; Wangqing CHEN ; Ruhan LIU ; Xiaoyu HE ; Shuang ZHAO ; Kai HUANG
Acta Pharmaceutica Sinica B 2025;15(7):3355-3371
Drug resistance is one of the key factors affecting the effectiveness of cancer treatment methods, including chemotherapy, radiotherapy, and immunotherapy. Its occurrence is related to factors such as mRNA expression and methylation within cancer cells. If drug resistance in patients can be accurately identified early, doctors can devise more effective treatment plans, which is of great significance for improving patients' survival rates and quality of life. Cancer drug resistance prediction based on artificial intelligence (AI) technology has emerged as a current research hotspot, demonstrating promising application prospects in guiding clinical individualized and precise medication for cancer patients. This review aims to comprehensively summarize the research progress in utilizing AI algorithms to analyze multi-omics data including genomics, transcriptomics, epigenomics, proteomics, metabolomics, radiomics, and histopathology, for predicting cancer drug resistance. It provides a detailed exposition of the processes involved in data processing and model construction, examines the current challenges faced in this field and future development directions, with the aim of better advancing the progress of precision medicine.
2.COMPERA 2.0 risk stratification in patients with severe aortic stenosis: implication for group 2 pulmonary hypertension.
Zongye CAI ; Xinrui QI ; Dao ZHOU ; Hanyi DAI ; Abuduwufuer YIDILISI ; Ming ZHONG ; Lin DENG ; Yuchao GUO ; Jiaqi FAN ; Qifeng ZHU ; Yuxin HE ; Cheng LI ; Xianbao LIU ; Jian'an WANG
Journal of Zhejiang University. Science. B 2025;26(11):1076-1085
COMPERA 2.0 risk stratification has been demonstrated to be useful in patients with precapillary pulmonary hypertension (PH). However, its suitability for patients at risk for post-capillary PH or PH associated with left heart disease (PH-LHD) is unclear. To investigate the use of COMPERA 2.0 in patients with severe aortic stenosis (SAS) undergoing transcatheter aortic valve replacement (TAVR), who are at risk for post-capillary PH, a total of 327 eligible SAS patients undergoing TAVR at our institution between September 2015 and November 2020 were included in the study. Patients were classified into four strata before and after TAVR using the COMPERA 2.0 risk score. The primary endpoint was all-cause mortality. Survival analysis was performed using Kaplan-Meier curves, log-rank test, and Cox proportional hazards regression model. The study cohort had a median (interquartile range) age of 76 (70‒80) years and a pulmonary arterial systolic pressure of 33 (27‒43) mmHg (1 mmHg=0.133 kPa) before TAVR. The overall mortality was 11.9% during 26 (15‒47) months of follow-up. Before TAVR, cumulative mortality was higher with an increase in the risk stratum level (log-rank, both P<0.001); each increase in the risk stratum level resulted in an increased risk of death (hazard ratio (HR) 2.53, 95% confidential interval (CI) 1.54‒4.18, P<0.001), which was independent of age, sex, estimated glomerular filtration rate (eGFR), hemoglobin, albumin, and valve type (HR 1.76, 95% CI 1.01‒3.07, P=0.047). Similar results were observed at 30 d after TAVR. COMPERA 2.0 can serve as a useful tool for risk stratification in patients with SAS undergoing TAVR, indicating its potential application in the management of PH-LHD. Further validation is needed in patients with confirmed post-capillary PH by right heart catheterization.
Humans
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Aortic Valve Stenosis/complications*
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Aged
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Hypertension, Pulmonary/mortality*
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Male
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Female
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Transcatheter Aortic Valve Replacement
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Aged, 80 and over
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Risk Assessment/methods*
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Proportional Hazards Models
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Kaplan-Meier Estimate
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Retrospective Studies
3.Overview of the outbreak of varicella in Zhejiang Province from 2019 to 2022 and analysis of associated factors for breakthrough cases
Xuan DENG ; Xinrui LIU ; Yang ZHOU ; Lingzhi SHEN ; Rui YAN ; Xuewen TANG ; Yao ZHU ; Xiaoping XU ; Hanqing HE
Chinese Journal of Preventive Medicine 2024;58(3):315-324
Objective:To evaluate the epidemiological characteristics and explore the associated factors of breakthrough cases (BC) from Public Health Emergency Events (PHEEs) of varicella in Zhejiang Province from 2019 to 2022.Methods:Data on cases were obtained from the China Information System for Disease Control and Prevention and the PHEEs Reporting Information Database of Varicella in Zhejiang Province. History records were matched through the Zhejiang Provincial Immunization Information System. Descriptive analysis and multiple logistic regression model with a bidirectional stepwise selection method were performed to explore associated factors for BC during 2019-2022.Results:A total of 144 276 varicella cases were reported from 2019 to 2022, with the annual reported incidence of 47.35-82.80 cases per 100 000 population. Among these cases, 109 172 were non-breakthrough cases (NBC, accounting for 75.67%), 34 517 were BC (23.92%), and the rest 587 cases had unclear vaccination history on varicella (0.41%). A total of 214 PHEEs of varicella were reported, of which 99.07% occurred in school settings. The proportion of PHEEs that occurred in high school increased significantly as time went on ( χ2trend=5.742, P=0.017). Multiple logistic regression model which focused on "BC vs. NBC (as the reference)" indicated that the year of onset ( OR=1.585, 95% CI:1.343-1.878), the month of onset (taking January as the reference, OR=2.311-15.652), city (taking Hangzhou as the reference, Jiaxing OR=2.370, Jinhua OR=2.197, Lishui OR=0.134), age ( OR=0.887, 95% CI: 0.826-0.944), PHEEs setting (taking "primary school and below" as the reference, "high school and above" OR=0.516, 95% CI: 0.305-0.897), and the number of rashes ( OR=0.569, 95% CI: 0.458-0.703) were associated factors. Multiple logistic regression model which focused on "two-dose BC vs. one-dose BC (as the reference)" showed that the age of initial vaccination ( OR=0.045, 95% CI: 0.014-0.107), the time interval from onset to the last dose ( OR=0.037, 95% CI: 0.011-0.087) and the age of onset ( OR=20.724, 95% CI: 8.383-72.485) were associated factors. Conclusion:During 2019-2022, the reported high-risk group of varicella in Zhejiang Province has shifted to adolescents and young adults. Although vaccination could not completely prevent the onset of VZV, it could relieve clinical symptoms and delay the age of onset.
4.Overview of the outbreak of varicella in Zhejiang Province from 2019 to 2022 and analysis of associated factors for breakthrough cases
Xuan DENG ; Xinrui LIU ; Yang ZHOU ; Lingzhi SHEN ; Rui YAN ; Xuewen TANG ; Yao ZHU ; Xiaoping XU ; Hanqing HE
Chinese Journal of Preventive Medicine 2024;58(3):315-324
Objective:To evaluate the epidemiological characteristics and explore the associated factors of breakthrough cases (BC) from Public Health Emergency Events (PHEEs) of varicella in Zhejiang Province from 2019 to 2022.Methods:Data on cases were obtained from the China Information System for Disease Control and Prevention and the PHEEs Reporting Information Database of Varicella in Zhejiang Province. History records were matched through the Zhejiang Provincial Immunization Information System. Descriptive analysis and multiple logistic regression model with a bidirectional stepwise selection method were performed to explore associated factors for BC during 2019-2022.Results:A total of 144 276 varicella cases were reported from 2019 to 2022, with the annual reported incidence of 47.35-82.80 cases per 100 000 population. Among these cases, 109 172 were non-breakthrough cases (NBC, accounting for 75.67%), 34 517 were BC (23.92%), and the rest 587 cases had unclear vaccination history on varicella (0.41%). A total of 214 PHEEs of varicella were reported, of which 99.07% occurred in school settings. The proportion of PHEEs that occurred in high school increased significantly as time went on ( χ2trend=5.742, P=0.017). Multiple logistic regression model which focused on "BC vs. NBC (as the reference)" indicated that the year of onset ( OR=1.585, 95% CI:1.343-1.878), the month of onset (taking January as the reference, OR=2.311-15.652), city (taking Hangzhou as the reference, Jiaxing OR=2.370, Jinhua OR=2.197, Lishui OR=0.134), age ( OR=0.887, 95% CI: 0.826-0.944), PHEEs setting (taking "primary school and below" as the reference, "high school and above" OR=0.516, 95% CI: 0.305-0.897), and the number of rashes ( OR=0.569, 95% CI: 0.458-0.703) were associated factors. Multiple logistic regression model which focused on "two-dose BC vs. one-dose BC (as the reference)" showed that the age of initial vaccination ( OR=0.045, 95% CI: 0.014-0.107), the time interval from onset to the last dose ( OR=0.037, 95% CI: 0.011-0.087) and the age of onset ( OR=20.724, 95% CI: 8.383-72.485) were associated factors. Conclusion:During 2019-2022, the reported high-risk group of varicella in Zhejiang Province has shifted to adolescents and young adults. Although vaccination could not completely prevent the onset of VZV, it could relieve clinical symptoms and delay the age of onset.
5.Efficacy of PD-1 inhibitors combined with nab-paclitaxel and cisplatin in the neoadjuvant treatment of locally advanced hypopharyngeal squamous cell carcinoma
Qi FANG ; Pengfei XU ; Fei CAO ; Zheng ZHAO ; Xinrui ZHANG ; Di WU ; Chunyan CHEN ; Zhiming LI ; Fei HAN ; Xuekui LIU
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2024;59(7):750-757
Objective:To assess the efficacy of neoadjuvant treatment with PD-1 (programmed cell death protein 1) inhibitors combined with paclitaxel (albumin-conjugated) and cisplatin (TP regimen) for locally advanced hypopharyngeal squamous cell carcinoma and laryngeal organ function preservation.Methods:Data of 53 patients, including 51 males and 2 females, aged 38-70 years old, who were diagnosed with locally advanced hypopharyngeal squamous carcinoma confirmed by histology and enhanced CT at the Cancer Prevention and Control Center of Sun Yat-sen University during the initial treatment from January 1, 2019 to January 15, 2023, were retrospectively analyzed. All patients received neoadjuvant therapy with PD-1 inhibitors combined with albumin-bound paclitaxel (260 mg/m 2) and cisplatin (60 mg/m 2) for 3 to 4 cycles. The main outcome measures were larynx dysfunction-free survival (LDFS), overall survival (OS), and progression-free survival (PFS). Survival curves were plotted using the Kaplan-Meier method, and Cox multifactorial analysis was further performed if Cox univariate analysis was statistically significant. Results:The overall efficiency was 90.6% (48/53). The 1-year and 2-year LDFS rates were 83.8% (95% CI: 74.0% to 94.8%) and 50.3% (95% CI: 22.1% to 91.6%), the 1-year and 2-year OS rates were 95.2% (95% CI: 88.9% to 100.0%) and 58.2% (95% CI: 25.6% to 81.8%), and the 1-year and 2-year PFS rates were 83.9% (95% CI: 74.2% to 94.9%) and 53.5% (95% CI: 32.1% to 89.1%). Adverse events associated with the neoadjuvant therapy were mainly myelosuppression (45.3%), gastrointestinal reactions (37.7%) and hypothyroidism (20.8%). Conclusion:The neoadjuvant treatment of locally advanced hypopharyngeal squamous cell carcinoma using PD-1 inhibitors combined with paclitaxel and cisplatin can provide with a higher survival rate with a improved laryngeal organ function preservation rate.
6.Research Progress on Signaling Pathways Related to Treatment of Diabetic Cognitive Dysfunction with Traditional Chinese Medicine: A Review
Xinrui LI ; Yuqing WANG ; Ming SU ; Xinru SUN ; Hui ZHANG ; Kangning XIAO ; Shanxin LIU ; Xinjun ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(19):225-232
Diabetic cognitive dysfunction (DCD) is one of the complications of diabetes, which is characterized by impaired brain structure and progressively decreased learning and memory ability. With the increasing incidence of diabetes worldwide, DCD has become a serious medical and social problem. However, its pathophysiological mechanisms are not well understood. The occurrence and development of DCD involve multiple pathological links and mechanisms, and the prevention and treatment require multi-link and multi-target therapeutic measures. At present, there is no specific drug to prevent or improve DCD. Hypoglycemic drugs such as metformin and vigagliptin or anti-dementia drug including Donepezil are commonly used in clinical treatment to delay the occurrence and progression of cognitive dysfunction, but these drugs have a single target and obvious side effects. Traditional Chinese medicine has a long history in the prevention and treatment of diabetes and central cognitive diseases, and it has many unique advantages such as multiple components, multiple targets, side effects, and low price. A large number of studies have confirmed that traditional Chinese medicine has a significant prevention and treatment effect on DCD, which can improve insulin resistance, synaptic dysfunction, inflammation, oxidative stress, endoplasmic reticulum stress, and neuronal apoptosis by regulating phosphatidylin-ositol 3-kinase (PI3K)/protein kinase B (Akt), advanced glycation end products (AGEs)/advanced glycation end products receptor (RAGE)/nuclear transcription factor-κB (NF-κB), NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome, and endoplasmic reticulum stress and nuclear factor E2 related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathways. This article reviewed the effects and related mechanisms of traditional Chinese medicine on DCD in recent years, so as to provide a reference for the prevention and treatment of DCD by traditional Chinese medicine.
7.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.
8.Analysis of the Use of Sacubitril/valsartan in 2 682 Patients During Hospitalization
Xinrui CAO ; Ruobin ZHANG ; Ziqiu LIU ; Simin YAN ; Weihong GE
Herald of Medicine 2024;43(3):457-463
Objective To retrospective analyze the use of inpatients taking sacubitril/valsartan in Nanjing Drum Tower Hospital,and to provide references for rational clinical application.Methods The relevant data of inpatients taking sacubitril/valsartan in our hospital were systematically collected from July 2019 to September 2021,and the rationality of drug use was eval-uated.Results A total of 2 682 cases were collected,and 868 cases(32.36%)of them involved 918 times of irrational drug use.The specific situations of irrational drug use included off-label use(182 times),irrational usage and dosage(389 times),irrational conversation of drugs(251 times),and irrational drug use for special populations(96 times).Conclusion The use of sacubitril/valsartan exists in unreasonable situations in our hospital.Clinical pharmacists should participate in medication man-agement to a certain extent,strengthen the pharmaceutical care of patients,and improve the rational rate of drug use.
9.Correlation with nutritional status and risk factors of depressed mood in patients with decompensated liver cirrhosis
Di ZHU ; Yan LIU ; Shuyue HE ; Tianyu HE ; Xinrui SHI ; Zixu LI ; Tingjuan HUANG ; Junjie REN
Chinese Journal of Clinical Nutrition 2024;32(1):1-7
Objective:To evaluate the nutritional status of patients with decompensated liver cirrhosis and explore the correlation with malnutrition and the risk factors of depressed mood.Methods:190 cirrhotic patients admitted to the Department of Gastroenterology of the First Hospital of Shanxi Medical University from June to September 2023 were selected according to the inclusion and exclusion criteria. Eligible patients were divided into subgroups based on the presence or absence of malnutrition as determined by subjective global assessment (SGA). The Center for Epidemiological Studies Depression (CES-D) scale was used to assess patients' propensity for depressed mood. Relevant clinical data were also collected and analyzed.Results:A total of 185 patients were included, of which 126 were in the non-malnutrition group and 59 malnutrition group. There were significant between-group differences in terms of CES-D results, age, body mass index, platelets, D-dimer, serum sodium, third lumbar skeletal muscle index, grip strength, triceps skinfold thickness, and upper arm muscle circumference (all P<0.05). Correlation analysis showed that grip strength, triceps skinfold thickness, upper arm muscle circumference, serum sodium, and depressed mood tendency status were correlated with the development of cirrhotic malnutrition ( P<0.05). The diagnostic model for malnutrition in cirrhosis using these five indicators showed the area under the curve of 81.9%. Conclusions:Depression is closely related to the development of malnutrition in patients with liver cirrhosis. Independent risk factors for malnutrition in cirrhosis include serum sodium≤135 mmol/L, grip strength, triceps skinfold thickness, lower-than-normal upper arm circumference , and the tendency of depression , which demonstrate the combined contribution to the diagnosis of malnutrition in cirrhosis.
10.Expert opinions on operation rules of Morita therapy outpatient service
Jiangbo LI ; Zucheng WANG ; Yuhua CUI ; Yingzhi LU ; Weijie QU ; Haiyin ZHANG ; Fuqiang MAO ; Fengqing QIE ; Wanghong SHI ; Qinfeng ZHANG ; Lingyi PAN ; Ling ZHANG ; Jianzhong LI ; Guangcheng CUI ; Tongxian CHEN ; Xiuqing MA ; Wei RONG ; Jianjun ZHANG ; Qingfang ZHONG ; Yanchi ZHANG ; Boquan ZHANG ; Xinrui WANG ; Wenyou MA ; Qingtao REN ; Yongfa JING ; Huanzhong LIU ; Zhenjian YU ; Laitian ZHAO ; Tianming HAN ; Xue HAN
Chinese Mental Health Journal 2024;38(1):68-72
Morita therapy has been bom for more than 100 years.Inpatient Morita therapy is highly oper-able and easy to master.It can improve many refractory neuroses through four-stage treatment.But more neuroses are treated in outpatient clinics,and Morita therapy cannot be used in hospitalized patients.Therefore,the formula-tion of expert opinions on outpatient operations is particularly important.This paper is based on domestic and for-eign references,and after many discussions by domestic Morita therapy experts,and then drew up the first version of the expert opinions on operation of outpatient Morita therapy.Meanwhile the operation rule of Morita therapy in three stages of outpatient treatment was formulated:in the etiological analysis stage,under the theoretical guidance of Morita therapy,analyze the pathogenic factors,to improve treatment compliance and reduce resistance;during the operating stage,guide patients to engage in constructive and meaningful actions,realizing the achievement of letting nature take its course principle;in the cultivating character and enriching life stage,pay attention to positive infor-mation,expanding the scope and content of actions,improving the ability to adapt to complex life,and preventing recurrence caused by insufficient abilities.It will lay a foundation for the promotion of Morita therapy in domestic outpatient clinics,so that more patients with neurosis and other psychological diseases could receive characteristic Morita therapy treatment in outpatient clinics.

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