1.Targeting ER lipid raft-associated 1 reveals a coordinated cholesterol-dependent vulnerability in hepatocellular carcinoma
Yiming ZHANG ; Yushan HOU ; Xinxin WANG ; Kaikun XU ; Pei JIANG ; Siqi WANG ; Huimin KANG ; Hu ZHANG ; Jingzhuo JIN ; Xiaofen HUANG ; Zifeng LIU ; Songpeng YANG ; Jiaqi LIU ; Lingqiang ZHANG ; Fuchu HE ; Chunyan TIAN ; Aihua SUN
Clinical and Molecular Hepatology 2026;32(2):866-883
Background/Aims:
Dysregulated cholesterol metabolism is a hallmark of hepatocellular carcinoma (HCC) that drives tumor initiation and progression. However, clinical targeting of cholesterol metabolism has yielded limited benefits due to stringent feedback in tumor cells. Identifying a central mediator capable of restoring cholesterol homeostasis within the cell’s intrinsically fine-tuned regulatory framework is urgently needed.
Methods:
We integrated a proteomic dataset from patients with cholesterol-dysregulated HCC into a global cholesterol metabolic regulatory network to identify potential therapeutic targets for disrupted cholesterol homeostasis. The prognostic significance of the candidate targets was further validated in an independent cohort through immunohistochemistry. Functional and mechanistic studies were conducted in vitro using HCC cell lines and in vivo using mouse models. The pharmacological efficacy of the candidate agent was evaluated in both subcutaneous and orthotopic HCC mouse models.
Results:
ER lipid raft-associated 1 (ERLIN1), a pivotal regulator of cholesterol metabolism reprogramming, was identified as an independent favorable prognostic indicator in HCC. ERLIN1 constrains HCC progression both in vitro and in vivo by stabilizing the INSIG1–SCAP–SREBP2 axis and maintaining the metabolic balance of intracellular cholesterol. Under hypoxia, impaired factor-inhibiting hypoxia-1-dependent hydroxylation of ASB11 at asparagine residues 90 and 92 enhances ASB11-mediated ERLIN1 degradation. Pharmacological targeting of this axis using zoledronic acid (ZoA) attenuated HCC progression by weakening the ASB11–ERLIN1 interaction and restoring cholesterol homeostasis.
Conclusions
ERLIN1 represents a druggable metabolic vulnerability in cholesterol-dysregulated HCC. Targeting the ASB11–ERLIN1 axis with the clinically approved ZoA reestablishes cholesterol homeostasis and offers a promising therapeutic strategy to overcome the current limitations of cholesterol-targeted HCC therapies.
2.Prognostic value and immunomodulatory role of DNAJC5B in esophageal squamous cell carcinoma
Junxi HU ; Qingwen LIU ; Jiaqi HOU ; Jie YOU ; Shuyu TIAN ; Hao KONG ; Xiaolin WANG ; Yusheng SHU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(10):1634-1639
Objective To explore the role of DNAJC5B in immunotherapy for esophageal squamous cell carcinoma (ESCC). Methods Using the ESCC dataset from The Cancer Genome Atlas (TCGA) database, genes correlated with DNAJC5B expression were identified through Pearson correlation analysis. Subsequently, Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed. Additionally, single-cell RNA sequencing (scRNA-seq) data were utilized to analyze the expression of DNAJC5B in different T-cell subsets. The prognostic value of DNAJC5B was evaluated using Kaplan-Meier survival curves, receiver operating characteristic curves, and Cox proportional hazards models. Results DNAJC5B was highly expressed in patients with advanced-stage ESCC, particularly in males. GO and KEGG analyses revealed a significant correlation between DNAJC5B expression and immune-related processes, such as the adaptive immune response and cell surface receptor signaling pathways. Single-cell analysis results indicated that DNAJC5B expression was positively correlated with immune function, with DNAJC5B predominantly accumulating in CD8+ T cells. Kaplan-Meier survival curves showed that the median survival time for patients with high DNAJC5B expression was 681 days, significantly shorter than the 1 361 days for patients with low expression (P<0.05). Furthermore, univariate and multivariate independent prognostic analyses demonstrated that DNAJC5B was an independent risk factor, with hazard ratios (HRs) of 3.577 and 4.114, respectively (both P<0.05). Conclusion DNAJC5B may play a crucial immunomodulatory role in ESCC, particularly in regulating CD8+ T-cell function and tumor immune escape. These findings support the potential of DNAJC5B as a biomarker for the treatment and prognostic assessment of ESCC.
3.The effects of resveratrol on the level of autophagy in the spleen of mice with OSAHS
Liru ZHAO ; Guanzhou HOU ; Bowen DAI ; Xiaolei GE ; Xiuge GU ; Yang LIU ; Linna WANG ; Xinyu XIE ; Jiaqi MAO
Journal of Practical Stomatology 2025;41(2):200-205
Objective:To study the effects of hypoxia on the autophagy level in the spleen of mice with OSAHS.Methods:Mouse OSAHS hypoxia model was established in 24 C57BL/6 mice and the mice were divided into 3 groups:normoxic group,hypoxic group and resveratrol group(n=8).Real time PCR,Western blot and immunohistochemical staining(IHC)were used to detect the mRNA and protein expression of autophagy related proteins microtube associated protein 1 light chain 3 B(LC3B),myosin-like BCL2 inteacting protein(Beclin1)and autophagy related gene 5(ATG5)in mouse spleen respectively.Results:The mRNA expres-sion of LC3B,Beclin1,and ATG5 in the hypoxic group was lower than that in the normoxic group(P<0.01,P<0.01,P<0.001),resveratrol upregulated the expression levels of LC3B and ATG5 mRNA in the hypoxic group(P<0.05,P<0.001),but did not up-regulate the expression of Beclin1(P>0.05).The protein expression levels of LC3B,Beclin1 and ATG5 in the hypoxic group were lower than that in the normoxic group(P<0.05,P<0.05,P<0.01).Resveratrol upregulated the expression levels of LC3B and ATG5 in the hypoxic group(P<0.05,P<0.01),but did not upregulated the expression of Beclin1(P>0.05).IHC test showed that the expression level of LC3B,Beclin1 and ATG5 in the hypoxic group was lower than that in the normoxic group(P<0.01,P<0.01,P<0.001).Resveratrol increased the expression level of LC3B and ATG5 in the hypoxic group(P<0.05,P<0.01),but did not upregulate the expression of Beclin1(P>0.05).Conclusion:Hypoxia may inhibite the autophagy level of spleen in mice.Resvera-trol derivatives increases the autophagy level of mice under hypoxia condition,but has no significant effect on Beclin1 expression.
4.Efficacy and safety of double crossover bandaging technique in composite rhytidectomy
Lehao WU ; Mingyu ZHAO ; Yihao XU ; Yuanshun NAN ; Huimin LUO ; Zhiliang HE ; Yao WANG ; Bin HOU ; Tailing WANG ; Jiaqi WANG
Chinese Journal of Medical Aesthetics and Cosmetology 2025;31(3):258-263
Objective:To investigate the effect and safety of the double-cross dressing technique for composite rhytidectomy.Methods:A retrospective analysis was performed on a total of 121 patients with face and neck ageing, who were admitted to the Facial and Neck Plastic Surgery Center, the Plastic Surgery Hospital of the Chinese Academy of Medical Sciences from June 2020 to May 2023, all female with the age ranged 34-72 years old. All the patients underwent a full facial and neck composite rhytidectomy. Immediately after surgery, a double-cross bandaging was applied. The cotton pad was nested on the outer auricle, so that the front of the ear and the back of the ear were the first cross. This cross aimed to accurately pressurized the temporal, buccal region and postauricle flap. The second cross occurred at the radix. It secured composite tissue flap at the zygomatic arch and the buccal fat pad zone. Patient′s external auricle was not compressed after bandaging. The healing and the occurrence of complications were observed.Results:All the patients were satisfied with the comfort of the bandaging, the satisfied rate was 100% (121/121). All the patients had different degrees of periocular and perioral swelling 72 hours after surgery. Conjunctival edema and xanthochromia occurred in 30 patients, and oral mucosal congestion occurred in 25 patients, all of which were spontaneously resolved 2-4 weeks after surgery. Postoperative nursing was easily managed. There were no events such as dressing loosening, blocked draining tubes, and difficulty in replacing tubes. All the patients were followed up for 3-12 months after surgery, the flap in the postauricular area of all patients healed well, and there were no adverse complications such as wound infection, necrosis of the flap in the operative area, and delayed healing of the incision.Conclusion:The double-cross bandaging technique achieves the comfort bandaging and good protection of the face, which is safe and effective.
5.Two cases of female monozygotic twins with schizophrenia carrying a balanced translocation between 22q11.2 and 4p15.3
Xuyuan YIN ; Chuanwei LI ; Qing YANG ; Yuan CAI ; Wenlong HOU ; Lijuan MAN ; Nannan ZHUANG ; Jiaqi CAO ; Qi QI ; Zhenhua ZHU ; Li HUI
Chinese Journal of Psychiatry 2025;58(1):47-50
Schizophrenia is a common, severe, and complex psychiatric disorder worldwide. Genetic factors account for around 80% of the etiology of schizophrenia, yet objective diagnostic biomarkers remain lacking. This article reports two cases of female monozygotic twins diagnosed with schizophrenia, exhibiting a balanced translocation between 22q11.2 and 4p15.3. Reviewing the literature, we analyze and discuss the correlation between chromosomal balanced translocation regions and the pathogenesis of mental disorders. This aims to encourage psychiatrists to consider new perspectives on the diagnosis of schizophrenia.
6.The effects of resveratrol on the level of autophagy in the spleen of mice with OSAHS
Liru ZHAO ; Guanzhou HOU ; Bowen DAI ; Xiaolei GE ; Xiuge GU ; Yang LIU ; Linna WANG ; Xinyu XIE ; Jiaqi MAO
Journal of Practical Stomatology 2025;41(2):200-205
Objective:To study the effects of hypoxia on the autophagy level in the spleen of mice with OSAHS.Methods:Mouse OSAHS hypoxia model was established in 24 C57BL/6 mice and the mice were divided into 3 groups:normoxic group,hypoxic group and resveratrol group(n=8).Real time PCR,Western blot and immunohistochemical staining(IHC)were used to detect the mRNA and protein expression of autophagy related proteins microtube associated protein 1 light chain 3 B(LC3B),myosin-like BCL2 inteacting protein(Beclin1)and autophagy related gene 5(ATG5)in mouse spleen respectively.Results:The mRNA expres-sion of LC3B,Beclin1,and ATG5 in the hypoxic group was lower than that in the normoxic group(P<0.01,P<0.01,P<0.001),resveratrol upregulated the expression levels of LC3B and ATG5 mRNA in the hypoxic group(P<0.05,P<0.001),but did not up-regulate the expression of Beclin1(P>0.05).The protein expression levels of LC3B,Beclin1 and ATG5 in the hypoxic group were lower than that in the normoxic group(P<0.05,P<0.05,P<0.01).Resveratrol upregulated the expression levels of LC3B and ATG5 in the hypoxic group(P<0.05,P<0.01),but did not upregulated the expression of Beclin1(P>0.05).IHC test showed that the expression level of LC3B,Beclin1 and ATG5 in the hypoxic group was lower than that in the normoxic group(P<0.01,P<0.01,P<0.001).Resveratrol increased the expression level of LC3B and ATG5 in the hypoxic group(P<0.05,P<0.01),but did not upregulate the expression of Beclin1(P>0.05).Conclusion:Hypoxia may inhibite the autophagy level of spleen in mice.Resvera-trol derivatives increases the autophagy level of mice under hypoxia condition,but has no significant effect on Beclin1 expression.
7.Efficacy and safety of double crossover bandaging technique in composite rhytidectomy
Lehao WU ; Mingyu ZHAO ; Yihao XU ; Yuanshun NAN ; Huimin LUO ; Zhiliang HE ; Yao WANG ; Bin HOU ; Tailing WANG ; Jiaqi WANG
Chinese Journal of Medical Aesthetics and Cosmetology 2025;31(3):258-263
Objective:To investigate the effect and safety of the double-cross dressing technique for composite rhytidectomy.Methods:A retrospective analysis was performed on a total of 121 patients with face and neck ageing, who were admitted to the Facial and Neck Plastic Surgery Center, the Plastic Surgery Hospital of the Chinese Academy of Medical Sciences from June 2020 to May 2023, all female with the age ranged 34-72 years old. All the patients underwent a full facial and neck composite rhytidectomy. Immediately after surgery, a double-cross bandaging was applied. The cotton pad was nested on the outer auricle, so that the front of the ear and the back of the ear were the first cross. This cross aimed to accurately pressurized the temporal, buccal region and postauricle flap. The second cross occurred at the radix. It secured composite tissue flap at the zygomatic arch and the buccal fat pad zone. Patient′s external auricle was not compressed after bandaging. The healing and the occurrence of complications were observed.Results:All the patients were satisfied with the comfort of the bandaging, the satisfied rate was 100% (121/121). All the patients had different degrees of periocular and perioral swelling 72 hours after surgery. Conjunctival edema and xanthochromia occurred in 30 patients, and oral mucosal congestion occurred in 25 patients, all of which were spontaneously resolved 2-4 weeks after surgery. Postoperative nursing was easily managed. There were no events such as dressing loosening, blocked draining tubes, and difficulty in replacing tubes. All the patients were followed up for 3-12 months after surgery, the flap in the postauricular area of all patients healed well, and there were no adverse complications such as wound infection, necrosis of the flap in the operative area, and delayed healing of the incision.Conclusion:The double-cross bandaging technique achieves the comfort bandaging and good protection of the face, which is safe and effective.
8.Two cases of female monozygotic twins with schizophrenia carrying a balanced translocation between 22q11.2 and 4p15.3
Xuyuan YIN ; Chuanwei LI ; Qing YANG ; Yuan CAI ; Wenlong HOU ; Lijuan MAN ; Nannan ZHUANG ; Jiaqi CAO ; Qi QI ; Zhenhua ZHU ; Li HUI
Chinese Journal of Psychiatry 2025;58(1):47-50
Schizophrenia is a common, severe, and complex psychiatric disorder worldwide. Genetic factors account for around 80% of the etiology of schizophrenia, yet objective diagnostic biomarkers remain lacking. This article reports two cases of female monozygotic twins diagnosed with schizophrenia, exhibiting a balanced translocation between 22q11.2 and 4p15.3. Reviewing the literature, we analyze and discuss the correlation between chromosomal balanced translocation regions and the pathogenesis of mental disorders. This aims to encourage psychiatrists to consider new perspectives on the diagnosis of schizophrenia.
9.Characteristics of cerebral cortex activation in different swallowing periods based on near-infrared spectroscopy
Jiaqi LIU ; Shanshan HOU ; Xinyu WANG ; Chongtian ZHU ; Xiaowen WANG
Chinese Journal of Rehabilitation Theory and Practice 2024;30(6):709-718
Objective To explore the cerebral cortex activation in different swallowing periods using functional near-infrared spec-troscopy(fNIRS). Methods From October to December 2023,a total of 18 healthy adults were recruited to perform four tasks of visual stimulation,chewing,tongue tip sliding and repeated swallowing during fNIRS acquisition,to calculate the corti-cal activation β values covering a total of 41 channels in frontal,parietal and occipital lobes. Results During the preoral period,the bilateral pre-motor and supplementary motor cortex(PSMC),bilateral inferior pre-frontal gyrus,right visual association cortex(AVC),and left primary motor cortex(PMC)were significantly acti-vated(P<0.05).During oral preparation,the right pars triangularis(PTG),right frontal polar area(FPA),right dorsolateral prefrontal cortex(DPC),left primary somatosensory cortex(PSC),left PSMC and left PMC were sig-nificantly activated(P<0.05).During the transition between oral and pharyngeal phases,bilateral PSMC and bi-lateral PMC were significantly activated(P<0.05).Bilateral PSC,bilateral PTG,bilateral FPA,bilateral orbito-frontal area,bilateral PSMC,bilateral DPC and bilateral PMC were significantly activated during two consecu-tive periods of oral and pharyngeal phases(P<0.05). Conclusion The swallowing movement requires the coordination of the frontal,parietal and occipital cortex.The main activated brain areas are different in different swallowing stages,and the PSMC and PMC are involved in most swallowing stages.
10.Immunoregulatory Effect of Jiedu Tongluo Shengjin Prescription on Sjögren's Syndrome Mice Based on Stability of Treg Cells
Dandan CHENG ; Yongming LI ; Jiaqi HOU ; Luan XUE
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(9):119-128
ObjectiveTo investigate the effect of different doses of Jiedu Tongluo Shengjin prescription (JTSP) on serum interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and forkhead box P3 (FoxP3) in submandibular gland of NOD/Ltj mice with Sjögren's syndrome, and to explore the mechanism of JTSP on immune regulation in NOD/Ltj mice. MethodThirty NOD/Ltj mice (eight weeks old) were randomly divided into model group, JTSP low-dose group, JTSP medium-dose group, JTSP high-dose group and hydroxychloroquine group, and were administrated with normal saline, JTSP 9, 18, and 36 g·kg-1, and hydroxychloroquine 60 mg·kg-1 daily, respectively from the age of 12 weeks. Six ICR mice were given an equal amount of normal saline by gavage as the control group. During the experiment, daily water consumption and saliva secretion of mice at the age of 9, 12, 16 weeks were recorded. After 4 weeks of administration, submandibular gland and spleen tissues were dissected to calculate corresponding indexes. The pathological morphology of submandibular gland was observed by hematoxylin-eosin (HE) staining. Meso Scale Discovery (MSD) and immunohistochemistry were employed to detect the serum levels of IL-6, TNF-α and IL-10, and the expression and distribution of FoxP3 in submandibular gland, respectively. The protein expression of FoxP3 in mouse submandibular gland was determined by Western blot, and the mRNA expressions of FoxP3 and TNF-α were determined by real-time polymerase chain reaction (Real-time PCR). ResultCompared with the control group, the model group presented increased daily water consumption, decreased saliva secretion, lowered submandibular gland index, elevated pathological score of submandibular gland, up-regulated serum IL-6 and TNF-α and mRNA expression of TNF-α while down-regulated serum IL-10 and protein and mRNA expressions of FoxP3 in submandibular gland (P<0.05). Compared with the conditions in model group, daily water consumption in JTSP groups was reduced while saliva secretion was increased, especially in medium-dose and high-dose groups (P<0.05), and there was an increase in the submandibular gland index of JTSP medium-dose group (P<0.05) while a decrease in the spleen index of JTSP high-dose group (P<0.05). Additionally, JTSP groups had lower pathological score of submandibular gland than the model group (P<0.05), especially high-dose group, as well as lower serum IL-6 and TNF-α and mRNA expression of TNF-α while higher serum IL-10 (P<0.05). JTSP at medium and high doses up-regulated the protein and mRNA expressions of FoxP3 in submandibular gland (P<0.05). ConclusionJTSP may inhibit the secretion of inflammatory cytokines by regulating the stability of FoxP3+ regulatory T (Treg) cells, thus alleviating the systemic immune inflammation in Sjögren's syndrome.

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