1.Inhibition of Epithelial-mesenchymal Transition Mechanism in Chronic Atrophic Gastritis Rats by Banxia Xiexintang via Regulating IL-17/ERK/C/EBPβ Signaling Pathway
Wenyu WU ; Xinyu ZENG ; Hao LI ; Weiqi SUN ; Jiahui REN ; Yang YU ; Tingting ZHOU ; Aili XU ; Wei WEI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(4):1-10
ObjectiveThis study aimed to investigate the action mechanism by which Banxia Xiexintang (BXT) inhibits epithelial-mesenchymal transition (EMT) in chronic atrophic gastritis (CAG) rats by regulating the interleukin-17(IL-17)/extracellular regulated protein kinases(ERK)/CCAAT enhancer binding protein β(C/EBPβ)signaling pathway, thereby providing new theoretical evidence for the treatment of CAG with classic traditional Chinese medicine formulas. MethodsA CAG rat model was established by using the combined factor method. After successful modeling, the rats were randomly divided into the model group, low-, medium-, and high-dose groups (0.549, 1.098, 2.196 g·kg-1, respectively) of BXT, and the positive drug group (vitacoenzyme, 0.3 g·kg-1). A normal control group was also set up. After 8 weeks of intervention, the pathological changes of gastric tissue were evaluated. The enzyme-linked immunosorbent assay (ELISA) was used to detect the contents of IL-17, tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), and C/EBPβ in serum, as well as the contents of EMT markers in gastric mucosal tissue including E-cadherin, N-cadherin, and vimentin. The immunohistochemistry method was employed to determine the localization and protein expression levels of IL-17, p-ERK, and C/EBPβ in gastric mucosal tissue. Western blot was used to detect the protein expressions of C/EBPβ, ERK, and its phosphorylated form (p)-ERK in gastric mucosa. Real-time polymerase chain reaction (Real-time PCR) was applied to measure the mRNA expression levels of ERK, COX-2, and C/EBPβ in gastric mucosa. ResultsCompared with those in the normal control group, the rats in the model group showed gastric mucosal glandular atrophy and inflammatory cell infiltration. The protein and their related mRNA expressions of C/EBPβ, ERK, and p-ERK in gastric mucosa were significantly increased (P<0.05,P<0.01). The levels of IL-17, TNF-α, COX-2, and C/EBPβ in serum were significantly increased (P<0.01). The contents of N-cadherin and vimentin in gastric mucosal tissue were significantly increased, while the content of E-cadherin was significantly decreased (P<0.01). Compared with the model group, after intervention with different doses of BXT, the pathological damage of the gastric mucosa was improved to varying degrees. The protein and mRNA expressions of C/EBPβ, ERK, and p-ERK in gastric mucosa were significantly reduced (P<0.05,P<0.01). The levels of IL-17, TNF-α, COX-2, and C/EBP β in serum were significantly decreased (P<0.01). The contents of N-cadherin and vimentin in gastric mucosa tissue were decreased, while the content of E-cadherin was increased (P<0.05,P<0.01). ConclusionBXT can effectively improve the pathological damage of gastric mucosal tissue in CAG rats. Its action mechanism may be related to reducing the levels of IL-17 and TNF-α in serum, regulating the IL-17/ERK/C/EBPβ signaling pathway and inhibiting the EMT process.
2.Exploration of the Intervention Mechanism of Qingshi Anti-itch Ointment (青石止痒软膏) on Psoriasis Model Mice Based on Caspase-1/GSDMD Protein Pathway
Yatong LI ; Yuanwen LI ; Yutong DENG ; Xuewen REN ; Xuewan WANG ; Xinhui YU ; Tangyunni LIU
Journal of Traditional Chinese Medicine 2025;66(2):170-177
ObjectiveTo explore the possible action mechanism of Qingshi Anti-itch Ointment (青石止痒软膏, QAO) in the treatment of psoriasis. MethodsForty mice were randomly divided into four groups, blank group, model group, calcipotriol group and QAO group, with 10 mice in each group. Except for the blank group, psoriasis was induced by applying imiquimod cream to the dorsal skin. After modeling for 6 hours daily, the calcipotriol group and QAO group were treated with 0.5 g of calcipotriol ointment or 0.5 g of QAO, respectively, applied to the treated dorsal skin. The blank group and the model group received no treatment. The skin lesions were observed, and the psoriasis area and severity index (PASI) score was assessed every other day. After 7 days, Hematoxylin and Eosin (HE) staining was performed on dorsal skin tissue to observe pathological changes. The levels of interleukin 1β (IL-1β) and interleukin 18 (IL-18) were determined by enzym-linked immunosorbent assay (ELISA). The protein levels of Caspase-1,Pro-Caspase-1, gasdermin D (GSDMD) and gasdermin-D-N (GSDMD-N) were detected by Western Blot (WB). The protein levels of GSDMD were observed by immunohistochemistry. ResultsCompared with the blank group, the model group mice showed redness, erythema, and white scales on their skin, with histological observations indicating epidermal thickening, elongated spines, and infiltration of inflammatory cells. The PASI scores of the skin tissue on days 1, 3, 5, and 7 were elevated; the IOD and AOD values of GSDMD protein increased; the protein levels of Caspase-1, Pro-Caspase-1,GSDMD, GSDMD-N, and IL-1β and IL-18 were significantly elevated (P<0.05 or P<0.01). Compared with the model group, the QAO group and calcipotriol group showed lighter skin lesions; the PASI scores on day 5 and day 7 in the QAO group, and on day 3, 5, and 7 in the calcipotriol group, were reduced; the IOD and AOD values of GSDMD protein, and the protein level of Caspase-1, GSDMD, and GSDMD-N, as well as level of IL-18 and IL-1β decreased in both groups; in the calcipotriol group, Pro-Caspase-1 protein level also decreased (P<0.05 or P<0.01). Compared with the calcipotriol group, the QAO group showed slightly redder skin, more obvious thickening of the stratum corneum, and less capillary dilation; the PASI scores on day 3 and day 7 increased, while the score on day 5 was reduced; the protein level of Pro-Caspase-1, GSDMD, GSDMD-N, and the level of IL-18 and IL-1β were increased in the QAO group (P<0.05). ConclusionQAO can effectively relieve psoriasis dermatitis in mice. Its potential mechanism may be related to the regulation of the Caspase-1/GSDMD protein pathway, down-regulation of IL-18 and IL-1β levels, and alleviation of pyroptosis.
3.Acute Inflammatory Pain Induces Sex-different Brain Alpha Activity in Anesthetized Rats Through Optically Pumped Magnetometer Magnetoencephalography
Meng-Meng MIAO ; Yu-Xuan REN ; Wen-Wei WU ; Yu ZHANG ; Chen PAN ; Xiang-Hong LIN ; Hui-Dan LIN ; Xiao-Wei CHEN
Progress in Biochemistry and Biophysics 2025;52(1):244-257
ObjectiveMagnetoencephalography (MEG), a non-invasive neuroimaging technique, meticulously captures the magnetic fields emanating from brain electrical activity. Compared with MEG based on superconducting quantum interference devices (SQUID), MEG based on optically pump magnetometer (OPM) has the advantages of higher sensitivity, better spatial resolution and lower cost. However, most of the current studies are clinical studies, and there is a lack of animal studies on MEG based on OPM technology. Pain, a multifaceted sensory and emotional phenomenon, induces intricate alterations in brain activity, exhibiting notable sex differences. Despite clinical revelations of pain-related neuronal activity through MEG, specific properties remain elusive, and comprehensive laboratory studies on pain-associated brain activity alterations are lacking. The aim of this study was to investigate the effects of inflammatory pain (induced by Complete Freund’s Adjuvant (CFA)) on brain activity in a rat model using the MEG technique, to analysis changes in brain activity during pain perception, and to explore sex differences in pain-related MEG signaling. MethodsThis study utilized adult male and female Sprague-Dawley rats. Inflammatory pain was induced via intraplantar injection of CFA (100 μl, 50% in saline) in the left hind paw, with control groups receiving saline. Pain behavior was assessed using von Frey filaments at baseline and 1 h post-injection. For MEG recording, anesthetized rats had an OPM positioned on their head within a magnetic shield, undergoing two 15-minute sessions: a 5-minute baseline followed by a 10-minute mechanical stimulation phase. Data analysis included artifact removal and time-frequency analysis of spontaneous brain activity using accumulated spectrograms, generating spectrograms focused on the 4-30 Hz frequency range. ResultsMEG recordings in anesthetized rats during resting states and hind paw mechanical stimulation were compared, before and after saline/CFA injections. Mechanical stimulation elevated alpha activity in both male and female rats pre- and post-saline/CFA injections. Saline/CFA injections augmented average power in both sexes compared to pre-injection states. Remarkably, female rats exhibited higher average spectral power 1 h after CFA injection than after saline injection during resting states. Furthermore, despite comparable pain thresholds measured by classical pain behavioral tests post-CFA treatment, female rats displayed higher average power than males in the resting state after CFA injection. ConclusionThese results imply an enhanced perception of inflammatory pain in female rats compared to their male counterparts. Our study exhibits sex differences in alpha activities following CFA injection, highlighting heightened brain alpha activity in female rats during acute inflammatory pain in the resting state. Our study provides a method for OPM-based MEG recordings to be used to study brain activity in anaesthetized animals. In addition, the findings of this study contribute to a deeper understanding of pain-related neural activity and pain sex differences.
4.The distribution pattern of traditional Chinese medicine syndromes and influencing factors for primary liver cancer: An analysis of 415 cases
Zhiyao SHI ; Xiaofei FAN ; Yu GAO ; Shaojian REN ; Shiyu WU ; Xixing WANG
Journal of Clinical Hepatology 2025;41(1):84-91
ObjectiveTo investigate the influencing factors for traditional Chinese medicine (TCM) syndromes of primary liver cancer, and to provide a theoretical basis for the TCM syndrome differentiation and standardized treatment of liver cancer. MethodsTCM syndrome differentiation was performed for 415 patients who were admitted to Shanxi Institute of Traditional Chinese Medicine and were diagnosed with primary liver cancer based on pathological or clinical examinations from January 2019 to December 2023. The chi-square test was used for comparison of categorical data between groups, and the unordered polytomous logistic regression model was used to investigate the influencing factors for TCM syndromes of liver cancer. ResultsThe common initial symptoms of the 415 patients with primary liver cancer included pain in the liver area (31.81%), abdominal distension (25.30%), abdominal pain (15.18%), and weakness (13.98%), and the main clinical symptoms included poor appetite (70.84%), fatigue (69.16%), pain in the liver area (67.47%), poor sleep (59.04%), abdominal distension (53.01%), and constipation (52.53%). There were significant differences in TCM syndromes between patients with different sexes, courses of the disease, clinical stages, Child-Pugh classes, presence or absence of intrahepatic and extrahepatic metastasis, and presence or absence of transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (all P<0.05). The logistic regression analysis showed that male sex was a risk factor for damp-heat accumulation (odds ratio [OR]=2.036, P=0.048) and the syndrome of spleen-kidney Yang deficiency (OR=5.240, P<0.001); a course of disease of<1 year was a risk factor for damp-heat accumulation (OR=2.837, P=0.004) and syndrome of Qi stagnation and blood stasis (OR=2.317, P=0.021), but it was a protective factor against syndrome of spleen-kidney Yang deficiency (OR=0.385, P=0.005); Child-Pugh class A/B was a protective factor against liver-kidney Yin deficiency (OR=0.079, P<0.001); intrahepatic metastasis was a risk factor for liver-kidney Yin deficiency (OR=5.117, P=0.003) and syndrome of spleen-kidney Yang deficiency (OR=3.303, P=0.010); TACE was a protective factor against liver-kidney Yin deficiency (OR=0.171, P<0.001) and syndrome of spleen-kidney Yang deficiency (OR=0.138, P<0.001); radiofrequency ablation was a risk factor for damp-heat accumulation (OR=4.408, P<0.001) and liver-kidney Yin deficiency (OR=32.036, P<0.001). ConclusionSex, course of disease, Child-Pugh class, intrahepatic metastasis, TACE, and radiofrequency ablation are the main influencing factors for TCM syndromes of liver cancer.
5.Association of the adipokine Chemerin with the development and progression of liver fibrosis
Xinyuan ZHANG ; Nuoqi ZHANG ; Guohui YU ; Wenshuai REN ; Yaling WANG
Journal of Clinical Hepatology 2025;41(1):164-169
Liver fibrosis is the common pathological process in the progression of various chronic liver diseases to liver cirrhosis, and it greatly affects the prognosis of patients with chronic liver diseases. As a novel adipokine, Chemerin participates in the metabolism of glucose and lipids and inflammation, and various studies have shown that the expression level of Chemerin is correlated with the degree of liver fibrosis, suggesting that Chemerin may be involved in the process of liver fibrosis by regulating metabolism and inflammation. Chemerin has shown certain potential in the auxiliary diagnosis of liver fibrosis and the intervention against the progression of liver fibrosis. This article reviews the potential role and mechanism of action of Chemerin in the process of liver fibrosis, in order to provide new ideas for the diagnosis and treatment of liver fibrosis.
6.Clinical and Radiological Outcomes of Transarterial Embolization for Adhesive Capsulitis
Keng-Wei LIANG ; Hsuan Yin LIN ; Kai-Lan HSU ; Fa-Chuan KUAN ; Chia-Yu GEAN ; Chien-Kuo WANG ; Wei-Ren SU ; Bow WANG
Korean Journal of Radiology 2025;26(3):230-238
Objective:
To assess the effect of transarterial embolization (TAE) for adhesive capsulitis (AC) by evaluating clinical outcomes and changes in inflammation using magnetic resonance imaging (MRI).
Materials and Methods:
Patients who had undergone TAE between August 2020 and August 2023 for AC refractory to conservative treatments without any invasive procedures for more than 3 months, and had undergone baseline and 3-month post-AC follow-up contrast-enhanced MRI evaluations, were included. A suspension mixture of 500 mg imipenem/cilastatin in 10 mL of iodinated contrast agent was used for TAE. MRI results were analyzed to assess periarticular capsule/ligament inflammation. Clinical assessments included pain scores using the numeric rating scale (NRS) and functional scores using the quick disabilities of the arm, shoulder, and hand (Quick DASH) questionnaire.
Results:
Twenty-five patients (female:male, 14:11; age, 54.9 ± 7.1 years) were included. Significant reductions in average NRS pain scores as well as improvements in Quick DASH scores and range of motion, including anterior flexion and abduction, were observed at 1, 3, and 6 months after TAE (all P < 0.001). MRI analyses revealed that TAE significantly decreased the grades of axillary recess capsule enhancement, rotator interval (RI) capsule T2 signal intensity, and RI capsule enhancement (all P ≤ 0.004).
Conclusion
TAE may be an effective and safe therapeutic approach for AC refractory to conservative treatments, alleviating pain and supporting functional recovery. The observed MRI findings suggest that the effectiveness of TAE for AC may be attributed to the reduction of inflammation and the elimination of angiogenesis.
7.Effect of mild hypercapnia during the recovery period on the emergence time from total intravenous anesthesia: a randomized controlled trial
Lan LIU ; Xiangde CHEN ; Qingjuan CHEN ; Xiuyi LU ; Lili FANG ; Jinxuan REN ; Yue MING ; Dawei SUN ; Pei CHEN ; Weidong WU ; Lina YU
Korean Journal of Anesthesiology 2025;78(3):215-223
Background:
Intraoperative hypercapnia reduces the time to emergence from volatile anesthetics, but few clinical studies have explored the effect of hypercapnia on the emergence time from intravenous (IV) anesthesia. We investigated the effect of inducing mild hypercapnia during the recovery period on the emergence time after total IV anesthesia (TIVA).
Methods:
Adult patients undergoing transurethral lithotripsy under TIVA were randomly allocated to normocapnia group (end-tidal carbon dioxide [ETCO2] 35–40 mmHg) or mild hypercapnia group (ETCO2 50-55 mmHg) during the recovery period. The primary outcome was the extubation time. The spontaneous breathing-onset time, voluntary eye-opening time, and hemodynamic data were collected. Changes in the cerebral blood flow velocity in the middle cerebral artery were assessed using transcranial Doppler ultrasound.
Results:
In total, 164 patients completed the study. The extubation time was significantly shorter in the mild hypercapnia (13.9 ± 5.9 min, P = 0.024) than in the normocapnia group (16.3 ± 7.6 min). A similar reduction was observed in spontaneous breathing-onset time (P = 0.021) and voluntary eye-opening time (P = 0.008). Multiple linear regression analysis revealed that the adjusted ETCO2 level was a negative predictor of extubation time. Middle cerebral artery blood flow velocity was significantly increased after ETCO2 adjustment for mild hypercapnia, which rapidly returned to baseline, without any adverse reactions, within 20 min after extubation.
Conclusions
Mild hypercapnia during the recovery period significantly reduces the extubation time after TIVA. Increased ETCO2 levels can potentially enhance rapid recovery from IV anesthesia.
8.Exon Sequencing of HNF1β in Chinese Patients with Early-Onset Diabetes
Siqian GONG ; Hong LIAN ; Yating LI ; Xiaoling CAI ; Wei LIU ; Yingying LUO ; Meng LI ; Si-min ZHANG ; Rui ZHANG ; Lingli ZHOU ; Yu ZHU ; Qian REN ; Xiuying ZHANG ; Jing CHEN ; Jing WU ; Xianghai ZHOU ; Xirui WANG ; Xueyao HAN ; Linong JI
Diabetes & Metabolism Journal 2025;49(2):321-330
Background:
Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients.
Methods:
Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines.
Results:
Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher.
Conclusion
MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.
9.Impact of Donor Age on Liver Transplant Outcomes in Patients with Acute-on-Chronic Liver Failure: A Cohort Study
Jie ZHOU ; Danni YE ; Shenli REN ; Jiawei DING ; Tao ZHANG ; Siyao ZHANG ; Zheng CHEN ; Fangshen XU ; Yu ZHANG ; Huilin ZHENG ; Zhenhua HU
Gut and Liver 2025;19(3):398-409
Background/Aims:
Liver transplantation is the most effective treatment for the sickest patients with acute-on-chronic liver failure (ACLF). However, the influence of donor age on liver transplantation, especially in ACLF patients, is still unclear.
Methods:
In this study, we used the data of the Scientific Registry of Transplant Recipients. We included patients with ACLF who received liver transplantation from January 1, 2007, to December 31, 2017, and the total number was 13,857. We allocated the ACLF recipients by age intogroup I (donor age ≤17 years, n=647); group II (donor age 18–59 years, n=11,423); and group III (donor age ≥60 years, n=1,787). Overall survival (OS), graft survival, and mortality were com-pared among the three age groups and the four ACLF grades. Cox regression was also analyzed.
Results:
The 1-, 3-, and 5-year OS rates were 89.6%, 85.5%, and 82.0% in group I; 89.4%, 83.4%, and 78.2% in group II; and 86.8%, 78.4%, and 71.4% in group III, respectively (p<0.001).When we analyzed the different effects of donor age on OS with different ACLF grades, in groupsII and III, we observed statistical differences. Finally, the cubic spline curve told us that the relative death rate changed linearly with increasing donor age.
Conclusions
Donor age is related to OS and graft survival of ACLF patients after transplanta-tion, and poorer results were associated with elderly donors. In addition, different donor ages have different effects on recipients with different ACLF grades.
10.Exon Sequencing of HNF1β in Chinese Patients with Early-Onset Diabetes
Siqian GONG ; Hong LIAN ; Yating LI ; Xiaoling CAI ; Wei LIU ; Yingying LUO ; Meng LI ; Si-min ZHANG ; Rui ZHANG ; Lingli ZHOU ; Yu ZHU ; Qian REN ; Xiuying ZHANG ; Jing CHEN ; Jing WU ; Xianghai ZHOU ; Xirui WANG ; Xueyao HAN ; Linong JI
Diabetes & Metabolism Journal 2025;49(2):321-330
Background:
Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients.
Methods:
Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines.
Results:
Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher.
Conclusion
MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

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