1.Mechanism of action of 2-acylglycerol O-acyltransferase 2 in metabolic associated fatty liver disease and related targeted therapies
Jingjing HE ; Xinyi ZHANG ; Na DING ; Yanan HAO ; Ya ZHENG ; Rui JI
Journal of Clinical Hepatology 2026;42(7):1677-1682
Metabolic associated fatty liver disease (MAFLD) has become one of the most prevalent chronic liver diseases worldwide, with the core pathological feature of pathological accumulation of triglycerides in hepatocytes, and as a key rate-limiting enzyme for triglyceride synthesis in the liver, 2-acylglycerol O-acyltransferase 2 (DGAT2) plays a central role in this process. Cell and animal model studies have confirmed that inhibition of DGAT2 can effectively alleviate hepatic steatosis and delay disease progression, and subsequent clinical trials have also shown the potential clinical application value in the treatment of MAFLD. This article systematically reviews the mechanism of action of DGAT2 in the development and progression of MAFLD and comprehensively summarizes the therapeutic strategies targeting DGAT2, including the advances in both monotherapy and drug combinations, in order to provide new ideas for individualized treatment of MAFLD patients.
2.Value of Golgi protein 73 in assessing liver fibrosis degree and prognosis of patients with resectable hepatocellular carcinoma
Wanying HUO ; Hua HE ; Xinyi YU ; Maiman HE ; Jing JIANG
Journal of Clinical Hepatology 2026;42(8):1878-1887
ObjectiveTo assess the performance of preoperative serum Golgi protein 73 (GP73) in diagnosing liver fibrosis degree in patients with resectable hepatocellular carcinoma (HCC), to investigate its value in predicting postoperative survival, and to provide a basis for risk stratification and individualized decision-making in this population. MethodsA total of 631 patients with HCC who underwent liver resection at The First Hospital of Jilin University from March 1, 2009 to December 31, 2022 were enrolled. The demographic, pathological, and serological features of the patients were collected, and the serum level of GP73 was measured before surgery. Scheuer score determined by liver biopsy was used as the gold standard for diagnosing liver fibrosis; the Spearman correlation analysis was used to investigate the correlation between GP73 and liver fibrosis; the receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC) were used to assess the value of serum GP73 and compound serological markers in the diagnosis of liver fibrosis, and the Delong test was used for comparison of AUC. With all-cause mortality as the outcome, X-Tile 3.6.1 software was used to determine the optimal cut-off value of GP73; the univariate and multivariate Cox regression analyses were used to identify independent influencing factors for prognosis, and a nomogram model was constructed. Ten-fold cross-validation was used for internal validation; index of concordance (C-index), integrated discrimination improvement (IDI) index, and net reclassification improvement (NRI) index were calculated; calibration curve and decision curve analysis were used to assess the predictive performance of the model. ResultsThe serum level of GP73 was positively correlated with Scheuer liver fibrosis stage (rs=0.255, P<0.001). Serum GP73 had a significantly higher AUC than gamma-glutamyl transferase-to-platelet ratio (0.704 vs 0.634, Z=2.00, P=0.046) and S index (0.704 vs 0.637, Z=1.98, P=0.048) in the diagnosis of significant liver fibrosis, with no significant difference compared with aspartate aminotransferase-to-platelet ratio index (AUC=0.722) and fibrosis-4 index (AUC=0.695) (both P>0.05). During a median follow-up time of 48.66 months, 239 patients (37.9%) died. GP73 had an optimal cut-off value of 65 ng/mL in predicting postoperative mortality in patients with resectable HCC, and high GP73 expression (≥65 ng/mL) alone achieved a C-index of 0.617 for predicting the prognosis of HCC patients, which was better than the C-index of 0.551 for Barcelona Clinic Liver Cancer (BCLC) stage (P<0.001). The multivariate Cox regression analysis showed that serum GP73 (hazard ratio [HR]=2.56, 95% confidence interval [CI]: 1.86 — 3.52, P<0.001), sex (HR=1.58, 95%CI: 1.10 — 2.28, P=0.014), vascular invasion (HR=1.69, 95%CI: 1.30 — 2.21, P<0.001), total bilirubin (HR=1.49, 95%CI: 1.16 — 1.93, P=0.002), and maximum tumor diameter (HR=1.07, 95%CI: 1.04 — 1.11, P<0.001) were independent risk factors for all-cause mortality after hepatectomy in patients with HCC. In order to assess whether the addition of GP73 to the other four variables could further improve model performance, the model based on GP73, sex, vascular invasion, total bilirubin, and maximum tumor diameter was defined as the GP73-included model, and the model based on all five variables except GP73 was defined as the GP73-excluded model. The GP73-included model achieved an AUC of 0.704 (95%CI: 0.656 — 0.753) for predicting 5-year survival rate after surgery, and ten-fold cross-validation showed that this model had a mean C-index of 0.716 (95%CI: 0.682 — 0.750), which was higher than the C-index of the GP73-excluded model (C-index=0.682, 95%CI: 0.645 — 0.719, P=0.008) and BCLC stage (C-index=0.551, 95%CI: 0.523 — 0.580, P<0.001). Compared with the GP73-excluded model, the GP73-included model yielded an IDI index of 0.039 (95%CI: 0.016 — 0.069, P<0.001) and an NRI index of 0.259 (95%CI: 0.179 — 0.335, P<0.001), and compared with BCLC stage, the GP73-included model had an IDI index of 0.112 (95%CI: 0.069 — 0.163, P<0.001) and an NRI index of 0.272 (95%CI: 0.169 — 0.380, P<0.001). Calibration curve and decision curve analyses showed that the GP73-included model had good calibration and net clinical benefit. ConclusionGP73 can be used as a serological biomarker for diagnosing liver fibrosis in patients with resectable HCC, and preoperative GP73 level has a certain value in predicting the survival of these patients after hepatectomy. The integrated prognostic model incorporating GP73 can help to optimize postoperative risk stratification, thereby providing a basis for decision-making in precise treatment of HCC.
3.Comparison of the accuracy of an ultrasonic-based jaw tracking device with conventional electronic tracking device
Xinyi GU ; Tingzi HU ; Zidan ZHANG ; Fuming HE ; Jiejun SHI ; Haiping YANG
The Journal of Advanced Prosthodontics 2025;17(1):47-58
PURPOSE:
This study aimed to evaluate the accuracy of the ultrasonic jaw tracking system by comparing with the conventional electronic system in recording condylar movements.
MATERIALS AND METHODS:
Twenty-six subjects with normal occlusion participated in the study. The CADIAX® 4 and Jaw Motion Analyzer (JMA) systems were used to record condylar movement trajectories during mandibular border movements (protrusive/retrusive, lateral, and wide mouth opening), with each movement repeated three times. Both systems used facebows and sensors to locate the condylar axis points and capture movement trajectory data. Paired t-tests were used for normally distributed data, while the Wilcoxon rank-sum test was applied to non-normally distributed data. The level of significance was set at α = .05.
RESULTS:
The maximum condylar displacement in the sagittal plane during mandibular border movements and the sagittal condylar inclination (SCI) values on both the left and right sides showed no significant difference between the two systems (P > .05). The Bennett angle (BA) values on both the left and right sides measured by the JMA system were significantly higher than those measured by the CADIAX® 4 system (P < .05). The comfort levels of the JMA system were significantly higher than the CADIAX® 4 system (P < .05).
CONCLUSION
Through this study, it was found that the accuracy of the ultrasonic jaw tracking system was comparable with the conventional electronic system, except for the Bennett angle measurement. In terms of comfort and ease of use, the ultrasonic jaw tracking system is more favored.
4.Additions and revisions of general chapters of physical and chemical analysis in the Chinese Pharmacopoeia 2025 Edition Volume Ⅳ
XU Xinyi ; WEI Shifeng ; ZHANG Qiming ; HE Langchong ; ZHANG Jun ; MA Shuangcheng
Drug Standards of China 2025;26(1):045-050
Objective: To provide reference for the correct understanding and accurate implementation of the general chapters of physical and chemical analysis in the Chinese Pharmacopoeia 2025 Edition Volume Ⅳ.
Methods: Introduce the main characteristics and content of the additions and revisions of the general chapters of physical and chemical analysis in the Chinese Pharmacopoeia 2025 Edition Volume Ⅳ.
Results: The general chapters of physical and chemical analysis in the Chinese Pharmacopoeia 2025 Edition are more harmonized with the relevant guidelines of the ICH Q series, and the inclusion of advanced and mature instrument analysis technology standards and analysis method standards related to drug safety, efficacy, and quality controllability is further increased.
Conclusion: The general chapters of physical and chemical analysis in the Chinese Pharmacopoeia 2025 Edition have provided a more convenient new bridge for China’s drugs to go international, standardized testing technology support for achieving full process quality control, and better meet the needs of drug research and development, production, quality control, and supervision in China.
5.Research progress on molecular mechanisms of lipid metabolism disorders mediating pulmonary vascular remodeling in pulmonary arterial hypertension
Qi SUN ; Yanming HE ; Jinjing YUAN ; Mengwen SHEN ; Chunlei DING ; Xinyi ZHANG ; Lei ZHAO
Journal of Clinical Medicine in Practice 2025;29(14):142-148
Pulmonary vascular remodeling is the core pathological feature in the onset and pro-gression of pulmonary arterial hypertension(PAH).Currently,there is no well-defined therapeutic strategy that can effectively delay or reverse this process.Despite the widespread clinical application of targeted vasodilator drugs,patients still face a high risk of mortality and adverse cardiovascular e-vents,suggesting an urgent need to explore new pathological mechanisms and therapeutic targets.In recent years,the relationship between dyslipidemia and PAH has garnered increasing attention.This article aimed to review the role of lipid metabolism disorders in pulmonary vascular remodeling in pul-monary arterial hypertension and its underlying mechanism,with the hope of providing new interven-tion targets for the treatment of PAH,thereby improving patient survival rates and quality of life.
6.Risk Factor Evaluation for Venous Thromboembolism during the Perioperative Period in Gynecology and Rationality Analysis of Anticoagulant Drug Use
Xinyi LI ; Yong YUAN ; Qianmei CHEN ; Yan ZHU ; Dafang HE ; Chunlan ZHANG
Journal of Kunming Medical University 2025;46(8):93-99
Objective To evaluate the high-risk factors for venous thromboembolism(venous throm-boembolism,VTE)during the perioperative period in gynecology and analyze the rationality of anticoagulant drug use.Methods Clinical data of 183 gynecological surgical patients treated at Kunming Maternal and Child Health Hospital from January 2023 to December 2024 were collected.Among them,29 diagnosed with postoperative VTE were classified as the VTE group and 154 diagnosed with no postoperative VTE during the same period were classified as the non-thrombosis group.Independent sample t-test,Mann-Whitney U test,or χ2 test were used to analyze high-risk factors for VTE during the perioperative period.Logistic regression analysis was employed to identify risk factors for VTE after the gynecological surgery and a predictive regression model was established.The ROC curve was plotted to evaluate the model's validity.Results Elevated D-dimer levels,open abdominal surgery,and history of thrombosis were independent risk factors for VTE in postoperative gynecological patients(OR>1,P<0.05).The AUC of the regression-based predictive model was higher than that of the Caprini and G-Caprini scores,indicating that this model had the good discriminatory ability its resolution was better than G-Caprini and Caprini risk assessment tools.The identified issues in VTE prophylaxis at the hospital included the insufficient mechanical prevention time limit and delayed initiation of anticoagulant therapy in patients at moderate risk of bleeding.Conclusion This predictive model has certain clinical value for broader application.For issues related to drug therapy such as delayed use of anticoagulant drugs,clinical pharmacists should collaborate with physicians to assess patients'bleeding and thrombosis risks,jointly develop precise anticoagulation regimens.
7.Potential value of 18F-DPA-714 PET/MR in the diagnosis of autoimmune encephalitis
Xinyi SUN ; Xiaoyu CHEN ; Hangxing CHUNYU ; Yu ZHANG ; Wangxi HAI ; Huanyu MENG ; Qinming ZHOU ; Lu HE ; Sheng CHEN ; Biao LI ; Min ZHANG
Chinese Journal of Nuclear Medicine and Molecular Imaging 2025;45(4):218-223
Objective:To evaluate the potential value of 18×10 3 translocator protein (TSPO) radioligand ( N, N-diethy1-2-(2-(4-(2- 18F-fluoroethoxy) phenyl)-5, 7-dimethylpyrazolo[1, 5-A]pyrimidin-3-yl)acetamide, 18F-DPA-714) PET compared with conventional MR in the detection of autoimmune encephalitis (AE), the correlation with clinical symptoms, and the monitoring of immunotherapy efficacy in patients with AE. Methods:From December 2021 to June 2024, 45 AE patients (17 males, 28 females, age (38.3±17.0) years) diagnosed at Ruijin Hospital, Shanghai Jiao Tong University School of Medicine and 10 healthy volunteers (7 males, 3 females, age (28.7±5.1) years) were enrolled in this prospective study. All participants underwent baseline 18F-DPA-714 PET/MR scans, and 23 of these AE patients underwent further follow-up 18F-DPA-714 PET/MR scans. 18F-DPA-714 PET positivity was defined as having an uptake intensity threshold higher than the mean SUV ratio (SUVR)+ 2 s of the corresponding brain region in healthy controls. MR positivity was defined as abnormal hyperintensity in a specific brain region or multiple brain regions on the T 2 fluid attenuated inversion recovery (FLAIR). The positive detection rates of 18F-DPA-714 PET and MR was analyzed using McNemar χ2 test, and the differences in the uptake intensity (SUVR) of 18F-DPA-714 between symptomatic and non-symptomatic groups, and between remission and non-remission groups after immunotherapy were compared using independent-sample t test or Wilcoxon rank sum test. Spearman rank correlation analysis was used to analyze the correlation between the changing rate of SUVR and the changing of the modified Rankin Scale (mRS) score before and after treatment. Results:The positive detecting rate of 18F-DPA-714 PET for AE was significantly higher than that of MR (73.3%(33/45) vs 35.6%(16/45); χ2=11.56, P=0.001). The cerebellar SUVR of ataxia patients was significantly higher than that of asymptomatic patients (1.22(1.06, 1.33) vs 1.08(0.99, 1.20); Z=-2.14, P=0.034). Follow-up imaging showed that the SUVR of patients in the remission group after immunotherapy was significantly lower than that in the non-remission group ((-15.19±10.17)% vs (14.26±13.36)%; t=5.81, P<0.001). There was a significant correlation between the changing rate of SUVR and the changing of the mRS score before and after treatment ( rs=0.65, P<0.001). Conclusion:Compared with conventional MR, 18F-DPA-714 PET has a higher positive detecting rate for AE, and has the potential to reflect the clinical symptoms of AE and monitor the efficacy of immunotherapy.
8.Molecular characterization of FGFR fusion in a large real-world population and clinical utility of bidirectional fusion.
Xinyi ZHANG ; Jing ZHAO ; Ling MA ; Yitong TIAN ; Jiaguang ZHANG ; Hejian ZHENG ; Junling ZHANG ; Runyu HE ; Luhang JIN ; Jing MA ; Mengli HUANG ; Xiao LI ; Xiaofeng CHEN
Chinese Medical Journal 2025;138(12):1510-1512
9.Comprehensive management of tophaceous wound.
Guoyu HE ; Shuliang LU ; Xinyi LU ; Yingkai LIU
Journal of Zhejiang University. Medical sciences 2025;54(5):611-619
Tophaceous wound represent a severe complication of end-stage gout, characterized by the deposition of monosodium urate (MSU) crystals leading to localized tissue ischemia, chronic inflammation, and non-healing ulcers. The pathological mechanism involves the formation of MSU crystals under persistent hyperuricemia, inflammatory encapsulation, and mechanical compression of the vascular system due to tophus enlarge-ment, ultimately resulting in chronic non-healing ulcers. This article consolidates current evidence to outline an integrated management strategy for such wounds, combining systemic metabolic control with localized interventions. Effective treatment depends on maintaining serum uric acid levels below 300 μmol/L through urate-lowering agents, including conventional drugs and novel urate transporter 1 inhibitors such as AR882, complemented by anti-inflammatory medications such as nonsteroidal anti-inflammatory drugs and glucocorticoids to alleviate pain and reduce inflammation. Topical agents and advanced dressings are utilized to support healing and manage exudate. Debridement, which encompasses sharp, ultrasonic, and micro-techniques, is essential for removing necrotic tissue and MSU deposits, with efficacy assessed via local uric acid monitoring. Surgical reconstructions, including skin flap grafting and tendon or ligament reconstruction, are indicated for significant tissue loss or functional impairment. Long-term management emphasizes continuous metabolic control, personalized rehabilitation, and lifestyle modification. The comprehensive treatment of tophaceous wounds requires multidisciplinary collaboration to balance local repair and systemic regulation for improved prognosis. Future research directions include gene therapy to regulate purine metabolism and artificial intelligence-assisted personalized treatment plans, to achieve precision medicine for tophaceous wounds.
Humans
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Wound Healing
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Gout/therapy*
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Uric Acid/blood*
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Debridement
10.NK cell-specific knockout of UTX modulates pulmonary metastasis of melanoma in a sex-dependent manner
Pei HUANG ; Hongchen WANG ; He HUANG ; Jiaxin XIE ; Yu WU ; Simin ZHOU ; Xinyi LIAO ; Xiao GUAN
Journal of Army Medical University 2025;47(8):807-815
Objective To explore the role of X chromosome encoded epigenetic regulator UTX in NK cell-mediated anti-tumor activity.Methods Male Ncr1-iCre mice were crossed with female UTXfl/fl mice to generate F1 Ncr1-iCre+UTXfl/-male mice,which were further crossed with female UTXfl/fl mice to obtain male Ncr1-iCre-UTX fl/-control mice(M-Con)and NK-specific deletion of UTX male mice Ncr1-iCre+UTXfl/-(M-KO),as well as female Ncr1-iCre-UTXfl/fl control mice(F-Con)and UTX-deficient female mice Ncr1-iCre+UTXfl/fl(F-KO).UTX-deficient mice were injected with melanoma cell line B16F10 via tail vein to observe pulmonary metastatic tumor nodules.Moreover,flow cytometry was applied to detect the proportion and quantity of pulmonary NK cells(CD3-CD19-NK1.1+),maturation makers KLRG1 and CD11b,activation receptors NKG2D and CD69,and effector molecules,including perforin,granzyme B,CD107a,and IFN-γ.Then pulmonary NK cells were sorted and co-cultured with B16F10 cells,and the apoptosis of the melanoma cells was measured with flow cytometry.Results Compared with the M-Con mice,the M-KO mice presented less number of pulmonary tumor nodules(P<0.05),increased proportion and quantity of NK cells in the tumor microenvironment(P<0.01),though no obvious changes in the ratio of NK maturation makers KLRG1 to CD11b,enhanced expression level of cytotoxic molecule perforin(P<0.01),but no changes in the expression of effector molecule granzyme B,degranulation marker CD107a and cytokine IFN-γ in NK cells.Co-culture of NK cells and B16F10 cells promoted the apoptosis of tumor cells(P<0.05).Compared with the F-Con mice,the F-KO mice had no statistical difference in the number of pulmonary tumor nodules,but larger proportion and number of NK cells(P<0.05),decreased ratio of KLRG1 to CD11b(P<0.01),elevated level of perforin but decreased levels of granzyme B,CD107a and IFN-γ in NK cells(P<0.01).The co-culture of NK cells and B16F10 cells reduced the apoptosis of tumor cells in F-KO female mice(P<0.05).Conclusion NK-specific deletion of UTX regulates pulmonary metastasis of melanoma in a sex-dependent manner.

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