1.Impact of number of positive regional lymph nodes in N1 stage on the prognosis of patients with non-small cell lung cancer: A propensity score matching study
Dandan LIU ; Jiachen WANG ; Lidan CHANG ; Jia CHEN ; Ranran KONG ; Shiyuan LIU ; Minxia ZHU ; Jiantao JIANG ; Shaomin LI ; Zhengshui XU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(01):63-71
Objective To explore the impact of number of positive regional lymph nodes (nPRLN) in N1 stage on the prognosis of non-small cell lung cancer (NSCLC) patients. Methods Patients with TxN1M0 stage NSCLC who underwent lobectomy and mediastinal lymph node dissection from 2010 to 2015 were screened from SEER database (17 Regs, 2022nov sub). The optimal cutoff value of nPRLN was determined using X-tile software, and patients were divided into 2 groups according to the cutoff value: a nPRLN≤optimal cutoff group and a nPRLN>optimal cutoff group. The influence of confounding factors was minimized by propensity score matching (PSM) at a ratio of 1 : 1. Kaplan-Meier curves and Cox proportional hazards models were used to evaluate overall survival (OS) and lung cancer-specific survival (LCSS) of patients. Results A total of 1316 patients with TxN1M0 stage NSCLC were included, including 662 males and 654 females, with a median age of 67 (60, 73) years. The optimal cutoff value of nPRLN was 3, with 1165 patients in the nPRLN≤3 group and 151 patients in the nPRLN>3 group. After PSM, there were 138 patients in each group. Regardless of before or after PSM, OS and LCSS of patients in the nPRLN≤3 group were superior to those in the nPRLN>3 group (P<0.001). N1 stage nPRLN>3 was an independent prognostic risk factor for OS [HR=1.52, 95%CI (1.22, 1.89), P<0.001] and LCSS [HR=1.72, 95%CI (1.36, 2.18), P<0.001]. Conclusion N1 stage nPRLN>3 is an independent prognostic risk factor for NSCLC patients in TxN1M0 stage, which may provide new evidence for future revision of TNM staging N1 stage subclassification.
3.Research progress on health effects of triclosan and triclocarban
Jiaqi LIU ; Min HUANG ; Zichen YANG ; Yi WANG ; Ke ZHAO ; Yuhua ZHOU ; Yuanping WANG ; Na WANG ; Hexing WANG ; Qingwu JIANG
Shanghai Journal of Preventive Medicine 2026;38(3):251-258
Triclosan (TCS) and triclocarban (TCC) are widely used synthetic broad-spectrum antibacterial agents that can enter the human body through the skin, gastrointestinal tract, and other pathways. More and more studies have found that exposure to TCS and TCC can affect human health, but currently, review reports on the health effects of human exposure to TCS and TCC are limited. Therefore, this study reviewed population studies on the relationship between TCS and TCC exposure and health effects by searching the PubMed database, summarized the associated health outcomes, and elucidated the biological mechanisms. A total of 56 studies were retrieved, among which cross-sectional studies (25 studies, 44.64%) and cohort studies (25 studies, 44.64%) accounted for a relatively large proportion, while case-control studies (6 studies, 10.72%) were relatively few. Studies on TCS exposure (48 studies, 85.71%) were far more prevalent than those on TCC exposure (2 studies, 3.57%). The remaining 6 studies involved both TCS and TCC exposure. The research results revealed that TCS exposure was associated with male and female abnormal reproductive functions, fetal growth restriction, abnormal behavior development in children, obesity, gestational diabetes mellitus (GDM), and immune-related diseases. Although the results of different studies show significant differences, they have indicated that exposure to TCS is a potential risk factor for these health problems. Due to the limited number of studies, the evidence for the relationship between TCC exposure and most of the aforementioned health effects is insufficient. Population studies and in vitro and in vivo studies have shown that exposure to TCS and TCC can interfere with the microbial homeostasis, the endocrine system, oxidative stress and immune function of the body, which are potential mechanisms causing adverse health effects. In the future, large-scale prospective cohort studies, as well as in vivo and in vitro studies, are still needed to further clarify the associations between TCS and TCC exposure and health effects, and to deeply explore its mechanism of action. These efforts will provide references for clarifying the human health hazards of TCS and TCC exposure and formulating targeted prevention and control strategies.
4.Association between the non-treatment threshold or upper limit of normal of alanine aminotransferase and liver pathological injury in patients with chronic hepatitis B virus infection and a persistently low level of alanine aminotransferase
Ming SHU ; Suwen JIANG ; Airong HU ; Qin CHEN ; Jialan WANG ; Menghan JIN ; Haojin ZHANG ; Shiqi YANG ; Shiyang FAN
Journal of Clinical Hepatology 2025;41(10):2044-2053
ObjectiveTo investigate the significance of different non-treatment thresholds or upper limits of normal (ULN) of alanine aminotransferase (ALT) in evaluating significant liver pathological injury in patients with chronic hepatitis B virus (HBV) infection, and to provide guidance for clinical diagnosis and treatment. MethodsThis study was conducted among 733 patients with chronic HBV infection who were hospitalized in Ningbo No. 2 Hospital from January 2015 to December 2023 and underwent liver biopsy and histopathological examination, and all patients had a persistent ALT level of ≤40 U/L and positive HBV DNA (>30 IU/mL). According to the treatment threshold or ULN of ALT, the patients were divided into group 1 with 575 patients (≤35 U/L for male patients, ≤25 U/L for female patients), group 2 with 430 patients (≤30 U/L for male patients, ≤19 U/L for female patients), group 3 with 443 patients (≤27 U/L for male patients, ≤24 U/L for female patients), group 4 with 446 patients (≤25 U/L), group 5 with 158 patients (>35 U/L for male patients, >25 U/L for female patients), and group 6 with 145 patients (>30 — ≤35 U/L for male patients, >19 — ≤25 U/L for female patients). Groups 2, 5, and 6 were compared to analyze the severity of liver pathological injury in patients with different ALT levels and the constituent ratio of patients with significant liver pathological injury, and groups 1, 2, 3, and 4 were compared to investigate the value of different ULN or non-treatment thresholds of ALT in determining liver inflammation grade (G), liver fibrosis stage (S), and the treatment indication based on liver pathology. The independent-samples t test was used for comparison of normally distributed continuous data between two groups; a one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t-test or the Tambane’s test was used for further comparison between two groups; the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups, and the Kruskal-Wallis H test was used for comparison between multiple groups and further comparison between two groups; the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups; a Ridit analysis was used for comparison of ranked data. A multivariate Logistic regression analysis (forward stepwise) was performed with whether liver pathology met the treatment indication (≥G2 and/or ≥S2) as the dependent variable and related factors with a significant impact on the dependent variable (P <0.05) as the independent variable. The receiver operating characteristic (ROC) curve was plotted, and the area under the ROC curve (AUC), as well as sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio, was used to assess the diagnostic value of different non-treatment thresholds of ALT. ResultsAmong the 733 patients, 259 (35.33%) had ≥G2 liver inflammation, 211 (28.79%) had ≥S2 liver fibrosis, and 306 (41.75%) had treatment indication (≥G2 and/or ≥S2). There was a significant difference in liver inflammation grade (G0 — G4) between groups 2, 5, and 6 (χ2=22.869, P <0.001), and there were also significant differences in the constituent ratios of patients with ≥G2 or ≥G3 liver inflammation between the three groups (χ2=21.742 and 14.921, P<0.001 and P=0.001). There was a significant difference in liver fibrosis stage (S0 — S4) between groups 2, 5, and 6 (χ2=16.565, P<0.001), and there were also significant differences in the constituent ratios of patients with ≥S2, ≥S3 or S4 liver fibrosis between the three groups (χ2=13.264, 13.050, and 6.260, P=0.001, 0.001, and 0.044). There were significant differences between groups 2, 5, and 6 in the constituent ratios of patients with or without treatment indication based on liver pathology (χ2=20.728, P<0.001). There were significant differences between groups 2, 5, and 6 in the constituent ratio of male patients (χ2=24.836, P<0.05), age (F=5.710, P<0.05), ALT (F=473.193, P<0.05), aspartate aminotransferase (AST) (F=107.774, P<0.05), ALT/AST ratio (F=40.167, P<0.05), γ-glutamyl transpeptidase (GGT) (H=15.463, P<0.05), aspartate aminotransferase-to-platelet ratio index (APRI) (H=63.024, P<0.05), and LIF-5 (5 indicators for liver inflammation and fibrosis) (H=46.397, P<0.05). In groups 1 — 4, compared with the patients without treatment indication, the patients with treatment indication had a significantly lower constituent ratio of patients with positive HBeAg, significantly lower levels of platelet count (PLT) and HBV DNA, and significantly higher age, ALT, AST, GGT, APRI, FIB-4, and LIF-5 (all P<0.05). The Logistic regression analysis showed that age (odds ratio [OR]=1.044, 95% confidence interval [CI]: 1.025 — 1.063, P<0.001), GGT (OR=1.022, 95%CI: 1.007 — 1.038, P=0.003), and HBV DNA (OR=0.839, 95%CI: 0.765 — 0.919, P<0.001) were influencing factors for treatment indication based on liver pathology in group 1; HBeAg (OR=1.978, 95%CI: 1.269 — 3.082, P=0.003), age (OR=1.048, 95%CI: 1.025 — 1.071, P<0.001), GGT (OR=1.016, 95%CI: 1.001 — 1.031, P=0.041), and PLT (OR=0.995, 95%CI: 0.991 — 1.000, P=0.049) were influencing factors in group 2; age (OR=1.040, 95%CI: 1.014 — 1.066, P=0.002), ALT (OR=1.047, 95%CI: 1.005 — 1.092, P=0.029), HBV DNA (OR=0.817, 95%CI: 0.736 — 0.907, P<0.001), and LIF-5 (OR=7.382, 95%CI: 1.151 — 47.330, P=0.035) were influencing factors in group 3; age (OR=1.054, 95%CI: 1.031 — 1.077, P<0.001), ALT (OR=1.061, 95%CI: 1.016 — 1.107, P=0.008), and HBV DNA (OR=0.825, 95%CI: 0.743 — 0.917, P<0.001) were influencing factors in group 4. The diagnostic performance for identifying ≥G2 liver inflammation, ≥S2 liver fibrosis, and treatment indication in groups 1 — 4 had an AUC of >0.7; group 1 showed the lowest sensitivity (28.76%) and the highest specificity, positive predictive value, positive likelihood ratio, and negative likelihood ratio in judging treatment indication; group 2 had the highest sensitivity and negative predictive value and the lowest negative likelihood ratio; groups 3 and 4 had similar diagnostic indicators. ConclusionIn patients with chronic HBV infection and a persistently low ALT level, the severity of liver histopathological injury and the constituent ratio of significant liver histopathological injury decrease with the reduction in ALT level. A higher non-treatment threshold or ULN of ALT can help to identify the patients requiring treatment (with a higher specificity), while a lower non-treatment threshold or ULN of ALT can help to identify the patients who do not require treatment (with a higher sensitivity).
5.Real-world efficacy and safety of azvudine in hospitalized older patients with COVID-19 during the omicron wave in China: A retrospective cohort study.
Yuanchao ZHU ; Fei ZHAO ; Yubing ZHU ; Xingang LI ; Deshi DONG ; Bolin ZHU ; Jianchun LI ; Xin HU ; Zinan ZHAO ; Wenfeng XU ; Yang JV ; Dandan WANG ; Yingming ZHENG ; Yiwen DONG ; Lu LI ; Shilei YANG ; Zhiyuan TENG ; Ling LU ; Jingwei ZHU ; Linzhe DU ; Yunxin LIU ; Lechuan JIA ; Qiujv ZHANG ; Hui MA ; Ana ZHAO ; Hongliu JIANG ; Xin XU ; Jinli WANG ; Xuping QIAN ; Wei ZHANG ; Tingting ZHENG ; Chunxia YANG ; Xuguang CHEN ; Kun LIU ; Huanhuan JIANG ; Dongxiang QU ; Jia SONG ; Hua CHENG ; Wenfang SUN ; Hanqiu ZHAN ; Xiao LI ; Yafeng WANG ; Aixia WANG ; Li LIU ; Lihua YANG ; Nan ZHANG ; Shumin CHEN ; Jingjing MA ; Wei LIU ; Xiaoxiang DU ; Meiqin ZHENG ; Liyan WAN ; Guangqing DU ; Hangmei LIU ; Pengfei JIN
Acta Pharmaceutica Sinica B 2025;15(1):123-132
Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T NANC), time to symptom improvement (T SI), and time of hospital stay (T HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.
6.YOD1 regulates microglial homeostasis by deubiquitinating MYH9 to promote the pathogenesis of Alzheimer's disease.
Jinfeng SUN ; Fan CHEN ; Lingyu SHE ; Yuqing ZENG ; Hao TANG ; Bozhi YE ; Wenhua ZHENG ; Li XIONG ; Liwei LI ; Luyao LI ; Qin YU ; Linjie CHEN ; Wei WANG ; Guang LIANG ; Xia ZHAO
Acta Pharmaceutica Sinica B 2025;15(1):331-348
Alzheimer's disease (AD) is the major form of dementia in the elderly and is closely related to the toxic effects of microglia sustained activation. In AD, sustained microglial activation triggers impaired synaptic pruning, neuroinflammation, neurotoxicity, and cognitive deficits. Accumulating evidence has demonstrated that aberrant expression of deubiquitinating enzymes is associated with regulating microglia function. Here, we use RNA sequencing to identify a deubiquitinase YOD1 as a regulator of microglial function and AD pathology. Further study showed that YOD1 knockout significantly improved the migration, phagocytosis, and inflammatory response of microglia, thereby improving the cognitive impairment of AD model mice. Through LC-MS/MS analysis combined with Co-IP, we found that Myosin heavy chain 9 (MYH9), a key regulator maintaining microglia homeostasis, is an interacting protein of YOD1. Mechanistically, YOD1 binds to MYH9 and maintains its stability by removing the K48 ubiquitin chain from MYH9, thereby mediating the microglia polarization signaling pathway to mediate microglia homeostasis. Taken together, our study reveals a specific role of microglial YOD1 in mediating microglia homeostasis and AD pathology, which provides a potential strategy for targeting microglia to treat AD.
7.Deubiquitinase JOSD2 alleviates colitis by inhibiting inflammation via deubiquitination of IMPDH2 in macrophages.
Xin LIU ; Yi FANG ; Mincong HUANG ; Shiliang TU ; Boan ZHENG ; Hang YUAN ; Peng YU ; Mengyao LAN ; Wu LUO ; Yongqiang ZHOU ; Guorong CHEN ; Zhe SHEN ; Yi WANG ; Guang LIANG
Acta Pharmaceutica Sinica B 2025;15(2):1039-1055
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, which increases the incidence of colorectal cancer (CRC). In the pathophysiology of IBD, ubiquitination/deubiquitination plays a critical regulatory function. Josephin domain containing 2 (JOSD2), a deubiquitinating enzyme, controls cell proliferation and carcinogenesis. However, its role in IBD remains unknown. Colitis mice model developed by dextran sodium sulfate (DSS) or colon tissues from individuals with ulcerative colitis and Crohn's disease showed a significant upregulation of JOSD2 expression in the macrophages. JOSD2 deficiency exacerbated the phenotypes of DSS-induced colitis by enhancing colon inflammation. DSS-challenged mice with myeloid-specific JOSD2 deletion developed severe colitis after bone marrow transplantation. Mechanistically, JOSD2 binds to the C-terminal of inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) and preferentially cleaves K63-linked polyubiquitin chains at the K134 site, suppressing IMPDH2 activity and preventing activation of nuclear factor kappa B (NF-κB) and inflammation in macrophages. It was also shown that JOSD2 knockout significantly exacerbated increased azoxymethane (AOM)/DSS-induced CRC, and AAV6-mediated JOSD2 overexpression in macrophages prevented the development of colitis in mice. These outcomes reveal a novel role for JOSD2 in colitis through deubiquitinating IMPDH2, suggesting that targeting JOSD2 is a potential strategy for treating IBD.
8.Remodeling tumor immunosuppressive microenvironment through dual activation of immunogenic panoptosis and ferroptosis by H2S-amplified nanoformulation to enhance cancer immunotherapy.
Yingli LUO ; Maoyuan LINGHU ; Xianyu LUO ; Dongdong LI ; Jilong WANG ; Shaojun PENG ; Yinchu MA
Acta Pharmaceutica Sinica B 2025;15(3):1242-1254
The deficiency in immunogenicity and the presence of immunosuppression within the tumor microenvironment significantly hindered the efficacy of immunotherapy. Consequently, a nanoformulation containing metal sulfide of FeS and GSDMD plasmid (NPFeS/GD) had been developed to effectively augment antitumor immune responses through dual activation of immunogenic PANoptosis and ferroptosis, as well as reprogramming immunosuppressive effects via H2S amplification. The bioactive NPFeS/GD exhibited controlled release of GSDMD plasmid, H2S, and Fe2+ in response to the tumor microenvironment. Fe2+, H2S, and the expression of GSDMD protein could effectively elicit highly immunogenic PANoptosis and ferroptosis. Furthermore, releasing H2S could mitigate the overexpression of indoleamine 2,3-dioxygenase1 (IDO1) induced by immunogenic PANoptotic and ferroptotic cell death and disrupt the activity of IDO1. Consequently, NPFeS/GD effectively triggered the antitumor innate and adaptive immune responses through induction of PANoptotic and ferroptotic cell death and reshaped the tumor immunosuppressive microenvironment to enhance antitumor immunotherapy for metastasis inhibition. This study unveiled the significant potential of immunogenic PANoptosis and ferroptosis in H2S gas therapy for enhancing tumor immunotherapy, offering novel insights and ideas for the rational design of nanomedicine to enhance tumor immunogenicity while reprogramming the tumor immunosuppressive microenvironment.
9.USP25 ameliorates vascular remodeling by deubiquitinating FOXO3 and promoting autophagic degradation of FOXO3.
Yanghao CHEN ; Bozhi YE ; Diyun XU ; Wante LIN ; Zimin FANG ; Xuefeng QU ; Xue HAN ; Wu LUO ; Chen CHEN ; Weijian HUANG ; Hao ZHOU ; Gaojun WU ; Yi WANG ; Guang LIANG
Acta Pharmaceutica Sinica B 2025;15(3):1643-1658
Long-term hypertension causes excessive vascular remodeling and leads to adverse cardiovascular events. Balance of ubiquitination and deubiquitination has been linked to several chronic conditions, including pathological vascular remodeling. In this study, we discovered that the expression of ubiquitin-specific protease 25 (USP25) is significantly up-regulated in angiotensin II (Ang II)-challenged mouse aorta. Knockout of Usp25 augments Ang II-induced vascular injury such as fibrosis and endothelial to mesenchymal transition (EndMT). Mechanistically, we found that USP25 interacts directly with Forkhead box O3 (FOXO3) and removes the K63-linked ubiquitin chain on the K258 site of FOXO3. We also showed that this USP25-mediated deubiquitination of FOXO3 increases its binding to light chain 3 beta isoform and autophagosomic-lysosomal degradation of FOXO3. In addition, we further validated the biological function of USP25 by overexpressing USP25 in the mouse aorta with AAV9 vectors. Our studies identified FOXO3 as a new substrate of USP25 and showed that USP25 may be a potential therapeutic target for excessive vascular remodeling-associated diseases.
10.Guidelines for the diagnosis and treatment of prurigo nodularis.
Li ZHANG ; Qingchun DIAO ; Xia DOU ; Hong FANG ; Songmei GENG ; Hao GUO ; Yaolong CHEN ; Chao JI ; Chengxin LI ; Linfeng LI ; Jie LI ; Jingyi LI ; Wei LI ; Zhiming LI ; Yunsheng LIANG ; Jianjun QIAO ; Zhiqiang SONG ; Qing SUN ; Juan TAO ; Fang WANG ; Zhiqiang XIE ; Jinhua XU ; Suling XU ; Hongwei YAN ; Xu YAO ; Jianzhong ZHANG ; Litao ZHANG ; Gang ZHU ; Fei HAO ; Xinghua GAO
Chinese Medical Journal 2025;138(22):2859-2861


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