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.Research advances in the disease burden of viral hepatitis in China
Jian LI ; Fuzhen WANG ; Zhongdan CHEN ; Jinlei QI ; Ailing WANG ; Fanghui ZHAO ; Yuanyuan KONG ; Jing SUN ; Jiaqi KANG ; Zundong YIN ; Zhongfu LIU ; Jidong JIA ; Yu WANG
Journal of Clinical Hepatology 2025;41(2):221-227
Over the past three decades, China has made significant progress in the prevention and control of viral hepatitis, and the incidence rates of new-onset pediatric hepatitis B virus infections and acute viral hepatitis in the population have reduced to a relatively low level; however, there is still a heavy disease burden of chronic viral hepatitis in China, which severely affects the health status of the population. This study systematically summarizes the achievements of viral hepatitis prevention and control in China, analyzes existing problems and challenges, and proposes comprehensive prevention and control strategies and measures to eliminate viral hepatitis as a public health threat based on the national conditions of China, in order to provide a reference for related departments in China on how to achieve the action targets for eliminating viral hepatitis as a public health threat by 2030.
3.Palpitations, Shortness of Breath, Weakness in Limbs, Edema, and Dyspnea: A Rare Inflammatory Myopathy with Positive Aniti-mitochondrial Antibodies and Cardiac Involvement
Chunsu LIANG ; Xuchang ZHANG ; Ning ZHANG ; Lin KANG ; Xiaohong LIU ; Jiaqi YU ; Yingxian LIU ; Lin QIAO ; Yanli YANG ; Xiaoyi ZHAO ; Ruijie ZHAO ; Na NIU ; Xuelian YAN
Medical Journal of Peking Union Medical College Hospital 2025;16(1):248-255
This article presents a case study of a patient who visited the Geriatric Department of Peking Union Medical College Hospital due to "palpitations, shortness of breath for more than 2 years, limb weakness for 6 months, edema, and nocturnal dyspnea for 2 months". The patient exhibited decreased muscle strength in the limbs and involvement of swallowing and respiratory muscles, alongside complications of heart failure and various arrhythmias which were predominantly atrial. Laboratory tests revealed the presence of multiple autoantibodies and notably anti-mitochondrial antibodies. Following a comprehensive multidisciplinary evaluation, the patient was diagnosed with anti-mitochondrial antibody-associated inflammatory myopathy. Treatment involved a combination of glucocorticoids and immunosuppressants, along with resistance exercises for muscle strength and rehabilitation training for lung function, resulting in significant improvement of clinical symptoms. The case underscores the importance of collaborative multidisciplinary approaches in diagnosing and treating rare diseases in elderly patients, where careful consideration of clinical manifestations and subtle abnormal clinical data can lead to effective interventions.
4.The Role of Gut Microbiota in Male Erectile Dysfunction of Rats
Zhunan XU ; Shangren WANG ; Chunxiang LIU ; Jiaqi KANG ; Yang PAN ; Zhexin ZHANG ; Hang ZHOU ; Mingming XU ; Xia LI ; Haoyu WANG ; Shuai NIU ; Li LIU ; Daqing SUN ; Xiaoqiang LIU
The World Journal of Men's Health 2025;43(1):213-227
Purpose:
Erectile dysfunction (ED) is a common male sexual dysfunction. Gut microbiota plays an important role in various diseases. To investigate the effects and mechanisms of intestinal flora dysregulation induced by high-fat diet (HFD) on erectile function.
Materials and Methods:
Male Sprague–Dawley rats aged 8 weeks were randomly divided into the normal diet (ND) and HFD groups. After 24 weeks, a measurement of erectile function was performed. We performed 16S rRNA sequencing of stool samples. Then, we established fecal microbiota transplantation (FMT) rat models by transplanting fecal microbiota from rats of ND group and HFD group to two new groups of rats respectively. After 24 weeks, erectile function of the rats was evaluated and 16S rRNA sequencing was performed, and serum samples were collected for the untargeted metabolomics detection.
Results:
The erectile function of rats and the species diversity of intestinal microbiota in the HFD group was significantly lower, and the characteristics of the intestinal microbiota community structure were also significantly different between the two groups. The erectile function of rats in the HFD-FMT group was significantly lower than that of rats in the ND-FMT group. The characteristics of the intestinal microbiota community structure were significantly different. In the HFD-FMT group, 27 metabolites were significantly different and they were mainly involved in the several inflammation-related pathways.
Conclusions
Intestinal microbiota disorders induced by HFD can damage the intestinal barrier of rats, change the serum metabolic profile, induce low-grade inflammation and apoptosis in the corpus cavernosum of the penis, and lead to ED.
5.The Role of Gut Microbiota in Male Erectile Dysfunction of Rats
Zhunan XU ; Shangren WANG ; Chunxiang LIU ; Jiaqi KANG ; Yang PAN ; Zhexin ZHANG ; Hang ZHOU ; Mingming XU ; Xia LI ; Haoyu WANG ; Shuai NIU ; Li LIU ; Daqing SUN ; Xiaoqiang LIU
The World Journal of Men's Health 2025;43(1):213-227
Purpose:
Erectile dysfunction (ED) is a common male sexual dysfunction. Gut microbiota plays an important role in various diseases. To investigate the effects and mechanisms of intestinal flora dysregulation induced by high-fat diet (HFD) on erectile function.
Materials and Methods:
Male Sprague–Dawley rats aged 8 weeks were randomly divided into the normal diet (ND) and HFD groups. After 24 weeks, a measurement of erectile function was performed. We performed 16S rRNA sequencing of stool samples. Then, we established fecal microbiota transplantation (FMT) rat models by transplanting fecal microbiota from rats of ND group and HFD group to two new groups of rats respectively. After 24 weeks, erectile function of the rats was evaluated and 16S rRNA sequencing was performed, and serum samples were collected for the untargeted metabolomics detection.
Results:
The erectile function of rats and the species diversity of intestinal microbiota in the HFD group was significantly lower, and the characteristics of the intestinal microbiota community structure were also significantly different between the two groups. The erectile function of rats in the HFD-FMT group was significantly lower than that of rats in the ND-FMT group. The characteristics of the intestinal microbiota community structure were significantly different. In the HFD-FMT group, 27 metabolites were significantly different and they were mainly involved in the several inflammation-related pathways.
Conclusions
Intestinal microbiota disorders induced by HFD can damage the intestinal barrier of rats, change the serum metabolic profile, induce low-grade inflammation and apoptosis in the corpus cavernosum of the penis, and lead to ED.
6.The Role of Gut Microbiota in Male Erectile Dysfunction of Rats
Zhunan XU ; Shangren WANG ; Chunxiang LIU ; Jiaqi KANG ; Yang PAN ; Zhexin ZHANG ; Hang ZHOU ; Mingming XU ; Xia LI ; Haoyu WANG ; Shuai NIU ; Li LIU ; Daqing SUN ; Xiaoqiang LIU
The World Journal of Men's Health 2025;43(1):213-227
Purpose:
Erectile dysfunction (ED) is a common male sexual dysfunction. Gut microbiota plays an important role in various diseases. To investigate the effects and mechanisms of intestinal flora dysregulation induced by high-fat diet (HFD) on erectile function.
Materials and Methods:
Male Sprague–Dawley rats aged 8 weeks were randomly divided into the normal diet (ND) and HFD groups. After 24 weeks, a measurement of erectile function was performed. We performed 16S rRNA sequencing of stool samples. Then, we established fecal microbiota transplantation (FMT) rat models by transplanting fecal microbiota from rats of ND group and HFD group to two new groups of rats respectively. After 24 weeks, erectile function of the rats was evaluated and 16S rRNA sequencing was performed, and serum samples were collected for the untargeted metabolomics detection.
Results:
The erectile function of rats and the species diversity of intestinal microbiota in the HFD group was significantly lower, and the characteristics of the intestinal microbiota community structure were also significantly different between the two groups. The erectile function of rats in the HFD-FMT group was significantly lower than that of rats in the ND-FMT group. The characteristics of the intestinal microbiota community structure were significantly different. In the HFD-FMT group, 27 metabolites were significantly different and they were mainly involved in the several inflammation-related pathways.
Conclusions
Intestinal microbiota disorders induced by HFD can damage the intestinal barrier of rats, change the serum metabolic profile, induce low-grade inflammation and apoptosis in the corpus cavernosum of the penis, and lead to ED.
7.The Role of Gut Microbiota in Male Erectile Dysfunction of Rats
Zhunan XU ; Shangren WANG ; Chunxiang LIU ; Jiaqi KANG ; Yang PAN ; Zhexin ZHANG ; Hang ZHOU ; Mingming XU ; Xia LI ; Haoyu WANG ; Shuai NIU ; Li LIU ; Daqing SUN ; Xiaoqiang LIU
The World Journal of Men's Health 2025;43(1):213-227
Purpose:
Erectile dysfunction (ED) is a common male sexual dysfunction. Gut microbiota plays an important role in various diseases. To investigate the effects and mechanisms of intestinal flora dysregulation induced by high-fat diet (HFD) on erectile function.
Materials and Methods:
Male Sprague–Dawley rats aged 8 weeks were randomly divided into the normal diet (ND) and HFD groups. After 24 weeks, a measurement of erectile function was performed. We performed 16S rRNA sequencing of stool samples. Then, we established fecal microbiota transplantation (FMT) rat models by transplanting fecal microbiota from rats of ND group and HFD group to two new groups of rats respectively. After 24 weeks, erectile function of the rats was evaluated and 16S rRNA sequencing was performed, and serum samples were collected for the untargeted metabolomics detection.
Results:
The erectile function of rats and the species diversity of intestinal microbiota in the HFD group was significantly lower, and the characteristics of the intestinal microbiota community structure were also significantly different between the two groups. The erectile function of rats in the HFD-FMT group was significantly lower than that of rats in the ND-FMT group. The characteristics of the intestinal microbiota community structure were significantly different. In the HFD-FMT group, 27 metabolites were significantly different and they were mainly involved in the several inflammation-related pathways.
Conclusions
Intestinal microbiota disorders induced by HFD can damage the intestinal barrier of rats, change the serum metabolic profile, induce low-grade inflammation and apoptosis in the corpus cavernosum of the penis, and lead to ED.
8.Research progress on the mechanism of traditional Chinese medicine monomers acting on myelosuppression after chemotherapy based on the four properties theory
Sihan ZHANG ; Tingting WANG ; Zhifen ZHAO ; Hanyu KANG ; Jiaqi JI ; Ziqiang GUO ; Tong LIU ; Shiqing JIANG
China Pharmacy 2025;36(18):2341-2347
Chemotherapy is an important treatment for tumors, but most patients experience varying degrees of chemotherapy- induced myelosuppression. Four properties theory of traditional Chinese medicine (TCM) has unique advantages in improving chemotherapy-induced myelosuppression. The monomers from TCM with different properties and flavors, such as cold-natured (e.g. Scutellaria baicalensis, Rhus chinensis), cool-natured (e.g. Ligustrum lucidum, Ophiopogon japonicus), warm-natured (e.g. Panax ginseng, Epimedium brevicornu, Curcuma longa, Angelica sinensis), hot-natured (e.g. Cinnamomum cassia, Aconitum carmichaeli), and neutral-natured (e. g. donkey-hide gelatin, Lycium barbarum, Rhodiola rosea, fungi), can exert anti- myelosuppressive effects by reducing damage to hematopoietic stem/progenitor cells, improving the bone marrow hematopoietic microenvironment, inhibiting the oxidative stress response, regulating signaling pathways, so as to ultimately repaire inflammatory damage and improve hematopoietic function, thereby playing an anti-myelosuppressive role.
9.Epidemiological study on traditional Chinese medicine treatment for inflammatory bowel disease in Jiangsu Province from 2019 to 2023
Chujun NI ; Zexing LIN ; Haiyang JIANG ; Jie WU ; Peizhao LIU ; Jiaqi KANG ; Chengliang QIAN ; Haiqing LIU ; Liting DENG ; Huan YANG ; Chenling WU ; Yun ZHAO
Chinese Journal of Inflammatory Bowel Diseases 2025;09(4):318-325
Objective:To explore patterns of traditional Chinese medicine (TCM) use among patients with inflammatory bowel disease (IBD) in Jiangsu Province, China from 2019 to 2023.Methods:Using data from the IBD health data platform of the National Healthcare Big Data (Eastern) Center, a retrospective cohort study was conducted. We performed descriptive analyses on hospitalised patients diagnosed with IBD between 2019 and 2023, who received TCM treatment.Results:The study included 11 095 case records from 4 760 patients, with TCM diagnoses primarily indicating diarrhoea and abdominal pain. Ulcerative colitis (UC) accounted for 4 782 hospitalizations (3 103 patients), while Crohn's disease (CD) accounted for 6 313 hospitalizations (1 657 patients). Patient demographics showed a trend towards younger age and a higher proportion of males. Treatment utilisation was highest in southern Jiangsu compared with the central and northern regions. In terms of disease burden, all treatment costs showed a downward trend. In terms of external TCM therapies, UC patients tend to prefer plasters and enemas, while CD patients are more inclined to use acupuncture. Regarding herbal medicine, licorice, white atractylodes, and white peony root are commonly used single herbs for IBD patients.Conclusions:The number of IBD patients treated with TCM in Jiangsu Province has steadily increased from 2019 to 2023. It is important to identify effective TCM treatment methods to reduce the burden of patients.
10.Role of DHA in long-term cognitive impairment after multiple sevoflurane anesthesia in newborn mice
Sufang JIANG ; Jiaqi LI ; Tianyu CAO ; Jiaqi YUE ; Lichao DI ; Shizhao WANG ; Fuzhen ZHANG ; Rongtian KANG ; Huan CHEN ; Huixian CUI ; Sha LI ; Lining HUANG
Chinese Journal of Anesthesiology 2025;45(5):559-563
Objective:To evaluate the role of docosahexaenoic acid (DHA) in long-term cognitive impairment after multiple sevoflurane anesthesia in newborn mice.Methods:Clean-grade healthy male C57BL/6 mice, aged 6 days, were used in this study. Ten mice were divided into 2 groups ( n=5 each) by the random number table method: control group (group C) and sevoflurane group (group S). The animals inhaled 3% sevoflurane for 2 h at 6, 7 and 8 days after birth. The DHA content was detected by ultra-high performance liquid chromatography-mass spectrometry at 9 days of age. Fifty-two mice were selected and divided into 4 groups ( n=13 each) by a random number table method: control+ normal saline group (group C+ S), sevoflurane anesthesia + normal saline group (group S+ S), control+ DHA group (group C+ D), and sevoflurane anesthesia+ DHA group (group S+ D). The sevoflurane anesthesia method was the same as the one mentioned above. DHA 50 mg/kg was administered by intragastric gavage from postnatal days 6-19 (at 6, 7 and 8 days after birth, 2 h before anesthesia) in C+ D and S+ D groups. The equal volume of normal saline was given instead in C+ S group and S+ S group. The novel object recognition test was conducted at 37 days of age, and the Morris water maze test was performed at 42 days of age. The corpus callosum and hippocampal tissues were isolated at 47 days of age for examination of the ultrastructure of myelin (with a transmission electron microscope) and for determination of the expression of myelin basic protein (MBP) in hippocampal tissues (by Western blot). The G-ratio was calculated. Results:Compared with group C, the content of DHA in hippocampal tissues was significantly decreased in group S ( P<0.05). Compared with group C+ S, the discrimination index was significantly decreased, the percentage of duration of staying at the target platform quadrant and the number of crossing the original platform were decreased, the expression of MBP was down-regulated, and the G-ratio in the original platform and hippocampus was increased in S+ S group ( P<0.05). Compared with group S+ S, the discrimination index was significantly increased, the percentage of duration of staying at the target platform quadrant and the number of crossing the original platform were increased, the expression of MBP was up-regulated, and the G-ratio in the original platform and hippocampus was decreased in S+ D group ( P<0.05). Conclusions:The mechanism of long-term cognitive impairment following multiple sevoflurane anesthesia may be related to a decrease in the content of DHA, which subsequently leads to myelin structural damage in neonatal mice.

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