1.Role of endoplasmic reticulum stress-mediated DEAD-box helicase 3 X-linked in a mouse model of concanavalin A-induced immune-mediated liver injury
Zhenzhen PAN ; Ling XU ; Xianru ZHU ; Zihao FAN ; Yaling CAO ; Yinkang MO ; Sai YAN ; Feng REN
Journal of Clinical Hepatology 2026;42(1):134-142
ObjectiveTo investigate the role of DEAD-box helicase 3 X-linked (DDX3X) in immune-mediated liver injury (ILI), and to clarify its mechanism by regulating endoplasmic reticulum stress (ERS)-dependent apoptotic pathway and its association with the clinical progression of hepatitis B. MethodsMice were given injection of concanavalin A (ConA) via the caudal vein to establish a model of ILI, PBS (control group) and different concentrations of ConA were injected into the tail vein of hepatocyte-specific DDX3X-knockout mice (DDX3XΔHep and DDX3X-flox mice (DDX3Xfl/fl), respectively.. The log-rank survival analysis, measurement of the serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and HE staining of liver tissue were performed to assess liver injury, and qRT-PCR and Western Blot were used to measure the mRNA and protein expression levels of glucose-regulated protein 78 (GRP78), CCAAT/enhancer-binding protein homologous protein (CHOP), and DDX3X in liver tissue. Intraperitoneal injection of 4-phenylbutyric acid (4-PBA, 100 mg/kg) was performed to inhibit ERS. Serum samples (n=30) and liver tissue samples (n=6) were collected from healthy controls, chronic hepatitis B (CHB) patients, and hepatitis B virus-associated liver failure (HBV-LF) patients; ELISA was used to measure the serum level of DDX3X, and qRT-PCR/Western Blot was used to analyze the expression of targets in liver tissue. 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 control group of mice, the expression of DDX3X in the liver of mice induced by ConA was significantly increased after liver injury (P<0.05), and hepatocyte-specific DDX3X knockout increased the 72-hour survival rate of mice by 55% (compared with 20% in the DDX3Xfl/fl group), with significant reductions in the serum levels of ALT and AST (P<0.000 1) and the expression levels of the ERS markers GRP78 and CHOP (P<0.05). After ERS was inhibited by 4-PBA, there was alleviation of liver injury (with reductions in ALT and AST, P <0.001) and a reduction in DDX3X expression (P<0.01). The analysis of clinical samples showed that the mRNA and protein expression levels of liver DDX3X in CHB patients and HBV-LF patients were significantly higher than those in healthy controls (all P<0.01), and there was a significant increase in the serum level of DDX3X in HBV-LF patients (P<0.000 1). ConclusionDDX3X exacerbates ILI by regulating the ERS-dependent apoptotic pathway (GRP78/CHOP), and its expression is associated with the progression of hepatitis B. Therefore, it can be used as a potential therapeutic target.
2.Comprehensive evaluation of benign and malignant pulmonary nodules using combined biological testing and imaging assessment in 1 017 patients: A retrospective cohort study
Lei ZHANG ; Zihao LI ; Nan LI ; Jun CHENG ; Feng ZHANG ; Pinghui XIA ; Wang LÜ ; ; Jian HU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(01):60-66
Objective By combining biological detection and imaging evaluation, a clinical prediction model is constructed based on a large cohort to improve the accuracy of distinguishing between benign and malignant pulmonary nodules. Methods A retrospective analysis was conducted on the clinical data of the 32 627 patients with pulmonary nodules who underwent chest CT and testing for 7 types of lung cancer-related serum autoantibodies (7-AABs) at our hospital from January 2020 to April 2024. The univariate and multivariate logistic regression models were performed to screen independent risk factors for benign and malignant pulmonary nodules, based on which a nomogram model was established. The performance of the model was evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). Results A total of 1 017 patients with pulmonary nodules were included in the study. The training set consisted of 712 patients, including 291 males and 421 females, with a mean age of (58±12) years. The validation set included 305 patients, comprising 129 males and 176 females, with a mean age of (58±13) years. Univariate ROC curve analysis indicated that the combination of CT and 7-AABs testing achieved the highest area under the curve (AUC) value (0.794), surpassing the diagnostic efficacy of CT alone (AUC=0.667) or 7-AABs alone (AUC=0.514). Multivariate logistic regression analysis showed that radiological nodule diameter, nodule nature, and CT combined with 7-AABs detection were independent predictors, which were used to construct a nomogram prediction model. The AUC values for this model were 0.826 and 0.862 in the training and validation sets, respectively, demonstrating excellent performance in DCA. Conclusion The combination of 7-AABs with CT significantly enhances the accuracy of distinguishing between benign and malignant pulmonary nodules. The developed predictive model provides strong support for clinical decision-making and contributes to achieving precise diagnosis and treatment of pulmonary nodules.
3.Automatic acquisition and analytic procedure of acupuncture manipulation based on optical navigation.
Changshuai ZHANG ; Zihao FENG ; Weichao CHANG ; Weigang MA ; Yongjian WU ; Haiming LI ; Xingfang PAN ; Haiyan REN ; Yangyang LIU ; Zhaoshui HE ; Wenjun TAN
Chinese Acupuncture & Moxibustion 2025;45(10):1383-1390
This paper presents an automatic acquisition and analytic procedure of acupuncture manipulation based on optical navigation, aiming at solving the shortcomings of existing acquisition methods of acupuncture manipulation. An acquisition holder installed at the handle tail of filiform needle was designed to display the movement trajectory of the needle during acupuncture delivery by collecting the movement trajectory of holder. The 3-month old male Bama miniature pig was selected as the experimental subject, and 6 points, "Bojian" "Qiangfeng" "Housanli" "Xiaokua" "Huiyang" (BL35) and "Baihui" (GV20), were selected during acupuncture manipulation. The optical navigation system was used to collect the real-time data, and these data were per-processed and analyzed using mean filtering and Fourier transform. The acupuncture procedure was divided into 3 stages, inserting, lifting-thrusting, and twisting. The results showed that the accuracy was 96.3% at lifting-thrusting stage, and that was 100.0% at twisting stage. The decomposition effect of the entire procedure was satisfactory. This study provides a new approach to the quantitative analysis of acupuncture manipulation. In the future, it needs to further optimize the algorithm and expand the sample size so as to improve the accuracy of this analytic technique.
Acupuncture Therapy/methods*
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Male
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Animals
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Swine
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Acupuncture Points
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Humans
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Swine, Miniature
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Needles
4.A Novel Functional Method of Protector Screening for Zebrafish Lateral Line Hair Cells via the Acoustic Escape Response.
Ling ZHENG ; Qiaosen SHEN ; Tong ZHAO ; Qingsong LIU ; Zihao HUANG ; Feng ZHAO ; Mengqian ZHANG ; Yongdong SONG ; Daogong ZHANG ; Dong LIU ; Fangyi CHEN
Neuroscience Bulletin 2025;41(9):1537-1552
Zebrafish larvae are useful for identifying chemicals against lateral line (LL) hair cell (HC) damage and this type of chemical screen mainly focuses on searching for protectors against cell death. To expand the candidate pool of HC protectors, a self-built acoustic escape response (AER)-detecting system was developed to apply both low-frequency near-field sound transmission and AER image acquisition/processing modules. The device quickly confirmed the changed LL HC functions caused by most known ototoxins, protectors, and neural transmission modifiers, or knockdown of LL HC-expressing genes. With ten devices wired in tandem, five 'hit' chemicals were identified from 124 cyclin-dependent kinase inhibitors to partially restore cisplatin-damaged AER in less than a day. AS2863619, ribociclib, and SU9516 among the hits, protected the HCs in the mouse cochlea. Therefore, using free-swimming larval zebrafish, the self-made AER-detecting device can efficiently identify compounds that are protective against HC damage, including cell death and loss-of-function.
Animals
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Zebrafish
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Hair Cells, Auditory/physiology*
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Lateral Line System/cytology*
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Escape Reaction/physiology*
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Larva
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Mice
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Cisplatin/toxicity*
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Drug Evaluation, Preclinical/methods*
5.The lysine methyltransferase SMYD2 facilitates neointimal hyperplasia by regulating the HDAC3-SRF axis.
Xiaoxuan ZHONG ; Xiang WEI ; Yan XU ; Xuehai ZHU ; Bo HUO ; Xian GUO ; Gaoke FENG ; Zihao ZHANG ; Xin FENG ; Zemin FANG ; Yuxuan LUO ; Xin YI ; Ding-Sheng JIANG
Acta Pharmaceutica Sinica B 2024;14(2):712-728
Coronary restenosis is an important cause of poor long-term prognosis in patients with coronary heart disease. Here, we show that lysine methyltransferase SMYD2 expression in the nucleus is significantly elevated in serum- and PDGF-BB-induced vascular smooth muscle cells (VSMCs), and in tissues of carotid artery injury-induced neointimal hyperplasia. Smyd2 overexpression in VSMCs (Smyd2-vTg) facilitates, but treatment with its specific inhibitor LLY-507 or SMYD2 knockdown significantly inhibits VSMC phenotypic switching and carotid artery injury-induced neointima formation in mice. Transcriptome sequencing revealed that SMYD2 knockdown represses the expression of serum response factor (SRF) target genes and that SRF overexpression largely reverses the inhibitory effect of SMYD2 knockdown on VSMC proliferation. HDAC3 directly interacts with and deacetylates SRF, which enhances SRF transcriptional activity in VSMCs. Moreover, SMYD2 promotes HDAC3 expression via tri-methylation of H3K36 at its promoter. RGFP966, a specific inhibitor of HDAC3, not only counteracts the pro-proliferation effect of SMYD2 overexpression on VSMCs, but also inhibits carotid artery injury-induced neointima formation in mice. HDAC3 partially abolishes the inhibitory effect of SMYD2 knockdown on VSMC proliferation in a deacetylase activity-dependent manner. Our results reveal that the SMYD2-HDAC3-SRF axis constitutes a novel and critical epigenetic mechanism that regulates VSMC phenotypic switching and neointimal hyperplasia.
6.Establishment and evaluation of a RAA-CRISPR-Cas13a method for detecting KPC carbapenemase genes
Yaling CAO ; Yuan TIAN ; Zihao FAN ; Ling XU ; Yao GAO ; Xiangying ZHANG ; Feng REN
Chinese Journal of Laboratory Medicine 2024;47(2):159-164
Objective:To establish a rapid and accurate method for the detection of Klebsiella pneumoniae carbapenemase (KPC) carbapenemase gene based on recombinase aided amplification (RAA)-CRISPR-Cas13a (CRISPR-Cas13a) technology. Methods:Twenty-five clinical isolates of carbapenem-resistant Klebsiella pneumoniae (CRKP) and five carbapenem-sensitive Klebsiella pneumoniae (CSKP) strains preserved in 2020-2021 in Beijing Chuiyangliu Hospital were randomly collected, and the total DNA samples of the strains was extracted. RAA primers specific for KPC DNA and CRISPR RNA (crRNA) were designed to establish a rapid and accurate method for the detection of KPC carbapenemase gene based on RAA-CRISPR-Cas13a technology. The method was evaluated by plasmids and clinical sample strains, and the detection was also performed by Quantitative real-time PCR (qPCR) method to compare the detection rate and consistency of the two methods. Results:The RAA-CRISPR-Cas13a method can detect KPC plasmids and samples with a sensitivity of 1 copy/μl, which is higher than that of qPCR (10 1 copies/μl). Among the 30 clinical strains (including 25 CRKP strains and 5 CSKP strains), 23 strains were detected to carry KPC gene by both RAA-CRISPR-Cas13a method and qPCR method, and 7 strains were not detected with KPC gene. The detection rate of KPC gene in the 25 CRKP strains was 92% (23/25). The positive coincidence rate of the two methods was 100% (23/23). Conclusions:This study combined RAA amplification technology with CRISPR-Cas13a technology to establish a rapid and accurate method for detecting KPC carbapenemase gene. The method is useful for accurate screening of KPC carbapenemase-producing strains. It has a wide application prospect in drug resistance monitoring and infection control.
7.Analysis of research hotspots of medical device informatization management based on bibliometrics
Qijun SHAN ; Xie WANG ; Zihao HOU ; Yihang WANG ; Qun CAO ; Shaobo WANG ; Feng ZHANG
China Medical Equipment 2024;21(9):113-117,136
Objective:To analyze the research hotspots and development directions of medical device information management,and to provide reference for the research of medical device information management.Methods:A total of 5434 articles related to information management in the field of medical devices were retrieved from the China National Knowledge Infrastructure(CNKI)database from January 1,2000 to December 31,2023.After screening,1618 valid articles were finally included in the study.Bibliometric methods were used to analyze the publication volume,keywords,journals,and author affiliations,and CiteSpace software was used to visualize the results.Results:The number of literature in the field of medical device information management showed a linear increase from 2000 to 2023,with an average of 70.34 publications per year.The keywords of"medical equipment,""medical consumables,""medical devices,""information systems,"and"management"have the highest centrality.The most representative keywords in cluster analysis are"medical equipment","medical consumables","quality control","management",and"Internet of Things".Conclusion:The research on medical device information management has gone through the initial stage,development stage,integration and integration stage,and the keyword"Internet of Things"has quickly become a research hotspot since its first appearance,and medical device information management has become the main development direction.The medical device management system has effectively improved the service quality and management level of medical institutions with the integration application of various information technologies and management tools and met the growing demand for statistical analysis.
8.Comparison of endoscopic and intrahepatic portosystemic shunt for variceal bleeding combined with portal vein thrombosis
Wei WU ; Zihao CAI ; Chao CHEN ; Ming ZHANG ; Feng ZHANG ; Qin YIN ; Yuzheng ZHUGE ; Jiangqiang XIAO
Chinese Journal of Digestive Endoscopy 2024;41(8):606-613
Objective:To compare the efficacy and safety of transjugular intrahepatic portosystemic shunt (TIPS) and endoscopic treatment for liver cirrhosis with esophageal gastric variceal bleeding (EGVB) and portal vein thrombosis (PVT).Methods:A total of 183 liver cirrhosis patients with EGVB and PVT in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School and the First Affiliated Hospital of Wenzhou Medical University were selected from January 2017 to December 2019, and 66 patients were assigned to the endoscopic group (received endoscopi treatment) and 117 the TIPS group (received TIPS treatment). Propensity score matching was performed according to the 1∶1 ratio, yielding 58 patients in each group for analysis, with a median follow-up time of 36 months in both groups. Postoperative survival, postoperative rebleeding rate, and postoperative hepatic encephalopathy incidence were assessed using Kaplan-Meier survival curves.Results:During the follow-up, the rebleeding rate in the endoscopic group was significantly higher [39.7% (23/58) VS 17.2% (10/58), P=0.005], and the TIPS group had a higher incidence of postoperative hepatic encephalopathy [29.3% (17/58) VS 13.8% (8/58), P=0.048], and no significant difference in survival rate was observed between the two groups [74.1% (43/58) VS 75.9% (44/58), P=0.769]. In the subgroup analysis of mild degree of PVT, there was no significant difference in survival [88.0% (22/25) VS 72.0% (18/25), P=0.164], rebleeding rate [28.0% (7/25) VS 12.0% (3/25), P=0.164], or incidence of hepatic encephalopathy [8.0% (2/25) VS 20.0% (5/25), P=0.202] between the endoscopic group and the TIPS group. In the subgroup analysis of severe degree of PVT, the rebleeding rate in the endoscopic group was significantly higher than that in the TIPS group [48.5% (16/33) VS 21.2% (7/33), P=0.010], while there was no significant difference in the incidence of hepatic encephalopathy [18.2% (6/33) VS 36.4% (12/33), P=0.133], or the survival rate [63.6% (21/33) VS 78.8% (26/33), P=0.154]. Conclusion:For liver cirrhosis patients with mild PVT and EGVB, combining endoscopic therapy with anticoagulation may be superior to TIPS. Conversely, in patients with severe PVT, TIPS may be a more suitable option due to a significantly reduced rebleeding risk without a notable increase in hepatic encephalopathy incidence.
9.Impact of hospital health literacy environment on patients′ postoperative pain self-management behaviors
Xiang PAN ; Yingge TONG ; Ke NI ; Zihao XUE ; Jing FENG ; Yingqiao LOU ; Danfei JIN ; Yeling WEI ; Miaoling WANG
Chinese Journal of Hospital Administration 2024;40(9):701-707
Objective:To explore the impact of the hospital health literacy environment on patients′ postoperative pain self-management behaviors, aiming to provide insights for hospitals to implement the Comprehensive Pain Management Pilot Work Program in hospitals and to promote self-health management among patients with other diseases or symptoms. Methods:From November to December 2023, a convenience sampling method was used to select postoperative patients from three grade A tertiary general hospitals in Zhejiang Province for an on-site questionnaire survey. The Chinese version of brief health literacy screen (BHLS), short-form health literacy environment scale (SF-HLES) and postoperative pain self-management behavior questionnaire (PPSMB) were used as survey tools to investigate the health literacy level of patients, the health literacy environment of the hospital, and the postoperative pain management behaviors of patients. Two-way ANOVA was used to compare the impact of different dimensions of the hospital health literacy environment on postoperative pain management behaviors among patients with different levels of health literacy. Multiple linear regression analysis was used to explore the relationship between the hospital health literacy environment, individual health literacy, and patients′ postoperative pain self-management behaviors, and to discuss the impact of individual health literacy on patients′ postoperative pain self-management behaviors under different hospital health literacy environments.Results:341 valid questionnaires were collected. The average score of the hospitals′ SF-HLES was (73.62±19.54) points. The average score of the patients′ BHLS was (9.65±2.88) points. The average score of the patients′ PPSMB was (25.99±6.35) points. Two-way ANOVA results showed that the interaction between individual health literacy and the clinical dimension ( F=5.463, P=0.020) and structural dimension ( F=6.470, P=0.011) of the hospital health literacy environment had a statistically significant impact on patients′ postoperative pain self-management behaviors, while the interaction with the interpersonal dimension ( F=0, P=0.984) had no statistically significant impact on pain self-management behaviors. Simple effect analysis indicated that only in the high health literacy environment of the clinical and structural dimensions did the difference in pain self-management behaviors between patients with good health literacy and those with limited health literacy had statistical significance ( P<0.001). Multiple linear regression analysis results showed that for each 1-point increase in the patients′ BHLS score, their PPSMB score increased by 3.74 points ( β1=0.832, P<0.001); for each 1-point increase in the hospital′s SF-HLES score, the patients′ PPSMB score could increase by 0.198 points ( β2=0.610, P<0.001). In a low health literacy environment, individual health literacy did not affect pain self-management behaviors ( P>0.05); however, in a high health literacy environment, for each 1-point increase in the patients′ BHLS score, their PPSMB score correspondingly increased by 4.037 points ( β4=0.317, P<0.001). Conclusions:The positive impact of individual health literacy on pain self-management is contingent upon a high-quality hospital health literacy environment. This suggests that optimizing the hospital health literacy environment is a necessary precondition for implementing the relevant content of the Comprehensive Pain Management Pilot Work Program and can provide a reference for promote self-health management among patients with pain and other diseases or symptoms.
10.Risk factors for intrahepatic venovenous shunt in patients with cirrhosis and its impact on hepatic venous pressure gradient
Liangzi DING ; Zihao CAI ; Jiangqiang XIAO ; Ming ZHANG ; Feng ZHANG ; Yuzheng ZHUGE
Chinese Journal of Hepatology 2024;32(11):984-988
Objective:To evaluate the factors affecting the incidence of intrahepatic venovenous shunt (IVVS) in patients with cirrhosis and its impact on hepatic venous pressure gradient (HVPG).Methods:A retrospective analysis was performed on the data of patients with liver cirrhosis who received HVPG measurement in Nanjing Drum Tower Hospital from April 2013 to March 2022. Univariate and multivariate regression analyses were used to investigate the incidence rate and risk factors of IVVS and its impact on HVPG. The t-test and rank-sum test were used for the measurement data, and the χ2 test was used for the count data. Results:A total of 242 cases with cirrhosis were included in the statistical analysis, including 54 (22.3%) with IVVS and 188 (77.7%) without IVVS. There was a statistically significant difference ( P<0.05) in prothrombin time (PT), HVPG, and splenectomy history between the two groups of patients' baseline data (all P<0.05). The multiple logistic regression analysis results showed that PT was an independent risk factor for the occurrence of IVVS ( P<0.05), and patients combined with IVVS had lower HVPG values [(17.58±5.57) mmHg vs. (11.92±5.38) mmHg, 1 mmHg=0.133 kPa; t=6.623, P<0.001]. Conclusions:Patients with liver cirrhosis have a high incidence rate of IVVS, which is closely associated with a low prothrombin time. Additionally, patients combined with IVVS have low HVPG values, which affect its accuracy.

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