1.Dilemmas and challenges in the clinical diagnosis of Wilson disease
Journal of Clinical Hepatology 2026;42(3):509-514
Wilson disease (WD) is characterized by marked heterogeneity in clinical phenotype, and it often overlaps with liver diseases (such as cholestatic liver diseases and active hepatitis) and neuropsychiatric diseases, which may easily lead to misdiagnosis or missed diagnosis. This article focuses on the confusing scenarios in clinical practice, reviews the pathophysiological basis of ATPase copper transporting beta (ATP7B) gene dysfunction, and systematically elaborates on the key interpretation points and limitations of ceruloplasmin, total serum copper/non-ceruloplasmin-bound copper, 24-hour urinary copper excretion, D-penicillamine challenge test, hepatic copper quantification, and histopathological assessment across different clinical scenarios. This article also summarizes the potential application of emerging dynamic copper indicators, such as relative exchangeable copper, in diagnosis, family screening, and treatment monitoring. In addition, it discusses the role of ATP7B genetic testing in “gray-zone” cases, difficulties in interpreting variants of uncertain significance, and the features of mutation spectrum in Chinese population, as well as the potential decline in diagnostic performance of the Leipzig scoring system in the context of complex liver diseases. Overall, the diagnosis of WD should not rely on a single indicator, and it is recommended to adopt a multidimensional hierarchical decision-making pathway that integrates phenotype, biochemical tests, dynamic copper indices, tissue/genetic evidence, and scoring systems. Furthermore, key thresholds and workflows should be optimized using real-world data from China, so as to enhance the efficiency of early identification and familial management, thereby improving the long-term prognosis of patients.
2.Clinical features of muscle changes and related risk factors in patients with porto-sinusoidal vascular disorder
Ruijia LI ; Yuxiang GONG ; Yu ZHANG ; Shasha LI ; Yongfeng YANG
Journal of Clinical Hepatology 2026;42(3):639-646
ObjectiveTo investigate the prevalence of muscle changes (including sarcopenia and myosteatosis) and related influencing factors in patients with porto-sinusoidal vascular disorder (PSVD), and to provide a theoretical basis for the early identification, prevention, and intervention of muscle changes in PSVD patients. MethodsA total of 132 PSVD patients who were diagnosed in Nanjing Second Hospital from July 2017 to July 2024 were enrolled as case group, and the hospital staff who underwent physical examination in 2025 were enrolled as healthy control group. Propensity score matching was performed based on age and sex at a ratio of 1∶1. According to muscle status assessed by abdominal CT, the subjects were divided into non-muscle change group, mild muscle change group (myosteatosis alone), and severe muscle change group (sarcopenia alone or sarcopenia comorbid with myosteatosis), with the type and severity of muscle change as the exposure factors. General information, laboratory tests, L3-level CT images, and liver biopsy data were collected for the patients in the case group, and general information and CT images were collected for the individuals in the healthy control group. Sarcopenia was diagnosed by measuring skeletal muscle index at the L3 level (<44.77 cm2/m2 for men and <32.50 cm2/m2 for women), and myosteatosis was defined by mean muscle attenuation combined with BMI (BMI <24.9 kg/m2 with attenuation <41 HU or BMI ≥25 kg/m2 with attenuation <33 HU). Demographic, laboratory, and clinical parameters were compared between the case group and the healthy control group. The independent-samples t test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. The univariate and multivariate Logistic regression analyses were used to identify the factors associated with sarcopenia in PSVD. ResultsAmong the 132 patients with PSVD, there were 83 patients with portal hypertension (PH) and 49 patients without PH, and there were significant differences between these two groups in age, albumin, albumin/globulin ratio, leukocyte count, neutrophil count, red blood cell count, platelet count, direct bilirubin, indirect bilirubin, hemoglobin, blood calcium, cholinesterase, total bile acid, triglyceride, total cholesterol, prothrombin time, international normalized ratio, activated partial thromboplastin time, decompensation, gastroesophageal or ectopic varices, bleeding and ascites (all P<0.05). The analyses after matching showed that compared with the healthy control group, the case group had significantly higher prevalence rates of abnormal muscle structure (43.18% vs 18.94%, P<0.001), mild muscle changes (22.73% vs 7.58%, P<0.001), and severe muscle changes (20.45% vs 11.36%, P<0.001). Further comparison showed that there was no significant difference in the proportion of patients with muscle changes between the PSVD patients with PH and those without PH (42.17% vs 44.90%, P=0.760). The binary Logistic regression analysis with the presence or absence of muscle changes as the dependent variable showed that age (odds ratio [OR]=1.05, 95% confidence interval [CI]: 1.02 — 1.09, P<0.05), subcutaneous fat index (OR=1.03, 95%CI: 1.01 — 1.06, P<0.05), hemoglobin (OR=0.97, 95%CI: 0.95 — 0.99, P<0.05), and thrombin time (OR=1.26, 95%CI: 1.06 — 1.49, P<0.05) were independent influencing factors for muscle changes in PSVD patients. The multivariate ordinal Logistic regression analysis with the severity of muscle changes as the dependent variable showed that age (OR=1.04, 95%CI: 1.01 — 1.07, P<0.05) and thrombin time (OR=1.17, 95%CI: 1.01 — 1.36, P<0.05) were independent risk factors for the grading of muscle changes. ConclusionMuscle changes are common in PSVD patients, and these changes may be caused by PSVD itself rather than PH. Age, fat distribution, thrombin time, and hemoglobin are important influencing factors for muscle changes.
3.Survey on the awareness and clinical application of guidelines for the prevention and treatment of chronic hepatitis B (2022 edition) among clinicians
Yuanyuan KONG ; Yujie GUO ; Yujuan GUAN ; Xuan LIANG ; Zhongjie HU ; Xiaobo LU ; Mingqin LU ; Yongfeng YANG ; Meifang HAN ; Hong YOU ; Zhiyun YANG ; Jidong JIA
Journal of Clinical Hepatology 2025;41(6):1068-1074
ObjectiveTo investigate the awareness and clinical practice of guidelines for the prevention and treatment of chronic hepatitis B (2022 edition) among clinicians. MethodsFrom July 19 to December 31, 2024, a self-designed electronic questionnaire was distributed via the WeChat mini program to collect related data from 1 588 clinicians nationwide, including their awareness and practice based on 18 questions regarding testing and referral, diagnosis and treatment, and follow-up. ResultsAmong all respondents, only 350 clinicians correctly understood all the updated key points of antiviral indications and treatment for special populations in the 2022 edition of guidelines for the prevention and treatment of chronic hepatitis B, with an overall awareness rate of 22.0%. Only 20% — 40% of the patients with positive HBV DNA and an age of >30 years receive antiviral therapy, while 80% — 100% of the patients with positive HBV DNA and a family history of hepatitis B cirrhosis or hepatocellular carcinoma receive antiviral therapy. The median follow-up rates at 1 year, 3 years, and 5 years were 67.5% 57.5% and 47.5%,respectively, showing a trend of gradual reduction, which might be associated with the influencing factors such as insufficient time for follow-up management by clinicians, insufficient awareness of the disease among patients, and poor adherence to follow-up. ConclusionThere is a gap between the awareness and practice of guidelines for the prevention and treatment of chronic hepatitis B (2022 edition) among clinicians. It is recommended to further strengthen training and focus on the whole process of “detection, diagnosis, treatment, and management” for patients with chronic hepatitis B in healthcare institutions, in order to promote the implementation of the guidelines.
4.Analysis of the learning curve of transurethral 450 nm blue light vaporization of the prostate in a district hospital
Tao LI ; Lida CHEN ; Zhongyi WANG ; Yongfeng TIAN ; Qirui CAO ; Yangbo NIE
Journal of Modern Urology 2025;30(3):232-235
Objective: To explore the learning curve of transurethral 450 nm blue light vaporization of the prostate (TUBVP) in a district hospital,in order to provide reference for clinicians who plan to perform TUBVP. Methods: The clinical data of 56 patients with benign prostatic hyperplasia (BPH) who received TUBVP performed by the same group of surgeons in Chang'an District Hospital during Jun. and Dec. 2023 were retrospectively analyzed. Cumulative sum (CUSUM) was used to fit the learning curve of ratio of volume to operating time (RVOT) of prostate volume /450 nm blue light. The learning curve was divided into different stages according to the inflection points,and the clinical data of patients operated at different stages were analyzed and compared. Results: The learning curve of TUBVP was 21 cases,including 1-21 cases in the learning stage,22-38 cases in the improvement stage and 39-56 cases in the maturity stage. With the increase of cases,the postoperative bladder irrigation time reduced \[40.00 (26.00,44.50) h vs. 23.00(20.50,34.00) h vs. 23.50(14.75,40.75) h\],with statistical difference (P<0.05). The surgical efficiency increased \[(0.51±0.14) vs. (0.55±0.17) vs. (0.63±0.23)\],while the reduction of hemoglobin \[(6.43±7.35) g/L vs. (5.65±10.91) g/L vs. (2.61±7.36) g/L\],catheter indwelling time \[70.0 (66.0,106.0) h vs. 71.0 (66.0,89.0) h vs. 66.0 (58.5,78.5) h\],and incidence of complications (9.5% vs. 5.9% vs. 0) in the three stages showed a gradually decreasing trend,but with no statistical significance (P>0.05). Conclusion: The learning curve of TUBVP is 21 cases. For clinicians in district hospitals,TUBVP is a worthy choice.
5.Prevalence of common diseases among primary and secondary school students in Xinzhou District, Wuhan City in 2019-2022
Yongfeng HU ; Li MEI ; Shufeng WANG ; Haiyan CHEN ; Jiyun PEI
Journal of Public Health and Preventive Medicine 2025;36(4):133-136
Objective To investigate the growth, development and health status of primary and secondary school students in Xinzhou District of Wuhan, and analyze the detection and change trend of common diseases in primary and secondary school students, and to provide a basis for relevant departments to formulate prevention and control measures of common diseases in students. Methods The monitoring data of common diseases and health influencing factors of primary and secondary school students in Xinzhou District from 2019 to 2022 were analyzed and compared according to different genders, different grades and ages. SPSS 20.0 software was used to analyze the data of detection rates of myopia, dental caries, obesity, malnutrition and abnormal spinal curvature. Results The overall detection rates of myopia, dental caries, malnutrition, obesity and abnormal spinal curvature were 57.00%, 58.45%, 4.60%, 14.91%, and 6.33%, respectively, in Xinzhou District from 2019 to 2022. The annual change rates were 7.22%, 15.10%, -2.72%, 13.29%, and 4.91%, respectively. The detection rates of myopia, dental caries, obesity and abnormal spinal curvature showed an increasing trend in each year (χ2 ≥17.22, P<0.001). The detection rates of myopia and malnutrition increased with the increase of age and school level (both χ2≥42.37, P<0.001), while the opposite was true for the detection rates of dental caries and obesity (both χ2≥14.26, P<0.001). The detection rates of myopia and dental caries were higher in girls than in boys (both χ2≥33.66, P<0.001), while the detection rates of obesity and abnormal spinal curvature were higher in boys than in girls (both χ2≥8.22, P<0.005). The detection rates of myopia, dental caries, obesity and abnormal spinal curvature in 2019 were lower than those in 2020-2022 (χ2≥4.11, P<0.05), while the detection rates of malnutrition had decreased. Conclusion The growth, development and health status of primary and secondary school students in Xinzhou District are serious. The detection rate of common diseases such as myopia, dental caries, obesity and abnormal curvature of the spine is on the rise, which should be the focus of the surveillance work of common diseases in primary and secondary school students in the future, and comprehensive intervention measures are urgently needed to prevent and control these common diseases.
6.Influence of COVID-19 infection on the early clinical efficacy of patients undergoing single valve replacement surgery: A retrospective cohort study
Liu XU ; Yongfeng HUO ; Lijun TIAN ; Yun ZHU ; Juan XIAO ; Ruiyan MA
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(05):634-638
Objective To investigate the impact of COVID-19 infection on the early clinical outcomes of patients undergoing valve replacement. Methods Perioperative data of patients who underwent single valve replacement at the Second Affiliated Hospital of Chinese People's Liberation Army Medical University from January to February 2023 were consecutively collected. Based on COVID-19 infection status, patients were divided into a COVID-19 group and a non-COVID-19 group. The perioperative data were compared between the two groups. Results A total of 136 patients were included, comprising 53 males and 83 females, with a mean age of (53.4±10.2) years. There were 32 patients receiving aortic valve replacements, 102 mitral valve replacements, and 2 tricuspid valve replacements. The COVID-19 group comprised 70 patients, and the non-COVID-19 group included 66 patients. No statistical difference was observed in the incidence of postoperative complications between the two groups [9.09% (6/66) vs. 11.43% (8/70), P=0.654]. However, the COVID-19 group had longer postoperative mechanical ventilation duration [1 201.00 (1 003.75, 1 347.75) min vs. 913.50 (465.50, 1 251.00) min, P=0.001] and ICU stay [3 (2, 3) days vs. 2 (2, 3) days, P<0.001] compared to the non-COVID-19 group. Additionally, troponin I [4.76 (2.55, 7.93) ng/mL vs. 2.66 (1.19, 5.65) ng/mL, P=0.001] and brain natriuretic peptide [608.50 (249.75, 1 150.00) pg/mL vs. 192.00 (100.93, 314.75) pg/mL, P<0.001] levels were significantly higher in the COVID-19 group. Conclusion For patients with single valve disease undergoing elective surgery, short-term outcomes after recovery from COVID-19 infection are favorable, with no significant increase in in-hospital mortality or postoperative complication rates.
7.Clinical practice guidelines for perioperative multimodality treatment of non-small cell lung cancer.
Wenjie JIAO ; Liang ZHAO ; Jiandong MEI ; Jia ZHONG ; Yongfeng YU ; Nan BI ; Lan ZHANG ; Lvhua WANG ; Xiaolong FU ; Jie WANG ; Shun LU ; Lunxu LIU ; Shugeng GAO
Chinese Medical Journal 2025;138(21):2702-2721
BACKGROUND:
Lung cancer is currently the most prevalent malignancy and the leading cause of cancer deaths worldwide. Although the early stage non-small cell lung cancer (NSCLC) presents a relatively good prognosis, a considerable number of lung cancer cases are still detected and diagnosed at locally advanced or late stages. Surgical treatment combined with perioperative multimodality treatment is the mainstay of treatment for locally advanced NSCLC and has been shown to improve patient survival. Following the standard methods of neoadjuvant therapy, perioperative management, postoperative adjuvant therapy, and other therapeutic strategies are important for improving patients' prognosis and quality of life. However, controversies remain over the perioperative management of NSCLC and presently consensus and standardized guidelines are lacking for addressing critical clinical issues in multimodality treatment.
METHODS:
The working group consisted of 125 multidisciplinary experts from thoracic surgery, medical oncology, radiotherapy, epidemiology, and psychology. This guideline was developed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. The clinical questions were collected and selected based on preliminary open-ended questionnaires and subsequent discussions during the Guideline Working Group meetings. PubMed, Web of Science, Cochrane Library, Scopus, and China National Knowledge Infrastructure (CNKI) were searched for available evidence. The GRADE system was used to evaluate the quality of evidence and grade the strengths of recommendations. Finally, the recommendations were developed through a structured consensus-building process.
RESULTS:
The Guideline Development Group initially collected a total of 62 important clinical questions. After a series of consensus-building conferences, 24 clinical questions were identified and corresponding recommendations were ultimately developed, focusing on neoadjuvant therapy, perioperative management, adjuvant therapy, postoperative psychological rehabilitation, prognosis assement, and follow-up protocols for NSCLC.
CONCLUSIONS
This guideline puts forward reasonable recommendations focusing on neoadjuvant therapy, perioperative management, adjuvant therapy, postoperative psychological rehabilitation, prognosis assessment, and follow-up protocol of NSCLC. It standardizes perioperative multimodality treatment and provides guidance for clinical practice among thoracic surgeons, medical oncologists, and radiotherapists, aiming to reduce postoperative recurrence, improve patient survival, accelerate recovery, and minimize postoperative complications such as atelectasis.
Humans
;
Carcinoma, Non-Small-Cell Lung/therapy*
;
Lung Neoplasms/therapy*
;
Combined Modality Therapy
;
Perioperative Care
8.Digital three-dimensional assisted unilateral biportal endoscopy in treatment of highly isolated lumbar disc herniation with translaminar approach.
Weiliang SU ; Suni LU ; Dong LIU ; Jianqiang XING ; Peng HU ; Yongfeng DOU ; Xiaopeng GENG ; Dawei WANG
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(3):346-353
OBJECTIVE:
To investigate the effectiveness of digital three-dimensional (3D) assisted unilateral biportal endoscopy (UBE) in the treatment of highly isolated lumbar disc herniation (LDH) with translaminar approach.
METHODS:
The clinical data of 59 patients who met the selection criteria and underwent UBE treatment due to highly isolated LDH between January 2022 and December 2023 were retrospectively analyzed. Among them, 25 cases were treated with digital 3D assisted translaminar approach (observation group) and 34 cases were treated with interlaminar approach (control group). There was no significant difference in gender, age, disease duration, surgical segment, and preoperative visual analogue scale (VAS) score and Oswestry disability index (ODI) between the two groups ( P>0.05). The operation time, intraoperative blood loss, and lateral articular surface preservation rate were recorded and compared between the two groups. VAS score and ODI were used to evaluate the improvements of pain and function before operation and at 3 and 6 months after operation. The modified MacNab criteria was used to evaluate the effectiveness at last follow-up.
RESULTS:
One patient in the control group had dural tear, and the other patients had no nerve injury, infection, dural tear, or other related complications. There was no significant difference in operation time and intraoperative blood loss between the two groups ( P>0.05). Patients in both groups were followed up 6-13 months, with an average of 8.3 months. The lateral articular surface preservation rate in the observation group was significantly higher than that in the control group ( P<0.05). Three patients in the observation group and 2 patients in the control group had calf muscle venous thrombosis, which was cured after anticoagulant treatment with rivaroxaban and delayed exercise time. There was no recurrence or second operation during the follow-up period. The VAS score and ODI of the two groups at 3 and 6 months after operation significantly improved when compared with those before operation ( P<0.05). There was no significant difference between the two groups at each time point after operation ( P>0.05). At last follow-up, the effectiveness was evaluated according to the modified MacNab criteria, and there was no significant difference in the evaluation grade and excellent and good rate between the two groups ( P>0.05).
CONCLUTION
UBE via translaminar approach is safe and effective for the treatment of highly isolated LDH, which is beneficial to protect the facet joint, maintain spinal stability, and reduce soft tissue injury. With the assistance of digital 3D technique, preoperative planning can be performed accurately.
Humans
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Intervertebral Disc Displacement/diagnostic imaging*
;
Lumbar Vertebrae/diagnostic imaging*
;
Male
;
Retrospective Studies
;
Female
;
Endoscopy/methods*
;
Treatment Outcome
;
Middle Aged
;
Adult
;
Imaging, Three-Dimensional
;
Operative Time
;
Pain Measurement
9.Early effectiveness of posterior 180-degree decompression via unilateral biportal endoscopy in treatment of lumbar spinal stenosis combined with MSU-1 lumbar disc herniation.
Feiyu ZHAO ; Xiaoting QIU ; Jie YUAN ; Ruxing LIU ; Xinyuan WEI ; Wei ZHAO ; Yongfeng WANG
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(6):735-740
OBJECTIVE:
To evaluate early effectiveness of posterior 180-degree decompression via unilateral biportal endoscopy (UBE) in the treatment of lumbar spinal stenosis (LSS) combined with Michigan State University (MSU)-1 lumbar disc herniation (LDH).
METHODS:
A retrospective analysis was conducted on clinical data from 33 patients with LSS combined with MSU-1 LDH, who met selection criteria and were treated between March 2022 and January 2024. All patients underwent UBE-assisted 180-degree spinal canal decompression. The cohort comprised 17 males and 16 females, aged 37-82 years (mean, 67.1 years). Preoperative presentations included bilateral lower limbs intermittent claudication and radiating pain, with disease duration ranging from 5 to 13 months (mean, 8.5 months). Affected segments included L 3, 4 in 4 cases, L 4, 5 in 28 cases, and L 5, S 1 in 1 case. LSS was rated as Schizas grade A in 4 cases, grade B in 5 cases, grade C in 13 cases, and grade D in 11 cases. LDH was categorized as MSU-1A in 24 cases, MSU-1B in 2 cases, and MSU-1AB in 7 cases. Intraoperative parameters (operation time, blood loss) and postoperative hospitalization length were recorded. The visual analogue scale (VAS) score and Oswestry Disability Index (ODI) were used to assess the lower limb pain and functional outcomes after operation. Clinical efficacy was evaluated at last follow-up via modified MacNab criteria. Quantitative radiological assessments included dural sac cross-sectional area (DSCA) measurements and spinal stenosis grading on lumbar MRI. Morphological classification of lumbar canal stenosis was determined according to the Schizas grading, categorized into four grades.
RESULTS:
The operation time was 60.4-90.8 minutes (mean, 80.3 minutes) and intraoperative blood loss was 13-47 mL (mean, 29.9 mL). The postoperative hospitalization length was 3-5 days (mean, 3.8 days). All patients were followed up 12-16 months (mean, 13.8 months). The VAS score and ODI improved at immediate and 3, 6, and 12 months after operation compared to before operation, and the differences between different time points were significant ( P<0.05). At last follow-up, the clinical efficacy assessed by the modified MacNab criteria were graded as excellent in 23 cases, good in 9 cases, and poor in 1 case, with an excellent and good rate of 96.97%. Postoperative lumbar MRI revealed the significant decompression of the dural sac in 32 cases, with 1 case showing inadequate dural expansion. DSCA measurements confirmed progressive enlargement and stenosis reduction over time. The differences were significant ( P<0.05) before operation, immediately after operation, and at 6 months after operation. At 6 months after operation, Schizas grading of spinal stenosis improved to grade A in 27 cases and grade B in 6 cases.
CONCLUSION
Posterior 180-degree decompression via UBE is a safe and feasible strategy for treating LSS combined with MSU-1 LDH, achieving effective neural decompression while preserving intervertebral disc integrity.
Humans
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Spinal Stenosis/diagnostic imaging*
;
Male
;
Female
;
Aged
;
Lumbar Vertebrae/surgery*
;
Middle Aged
;
Intervertebral Disc Displacement/complications*
;
Decompression, Surgical/methods*
;
Retrospective Studies
;
Endoscopy/methods*
;
Adult
;
Aged, 80 and over
;
Treatment Outcome
10.Research on the mechanism of gentiopicroside preventing macrophage-mediated liver fibrosis by regulating the MIF-SPP1 signaling pathway in hepatic stellate cells.
Jixu WANG ; Yingbin ZHU ; Maoli CHEN ; Yongfeng HAN
Chinese Journal of Cellular and Molecular Immunology 2025;41(7):593-602
Objective To explore the mechanism by which gentiopicroside (GPS) prevents macrophage-mediated hepatic fibrosis by regulating the macrophage migration inhibitory factor (MIF)-secreted phosphoprotein 1 (SPP1) signaling pathway in hepatic stellate cells. Methods LX-2 cells were divided into control group, transforming growth factor β(TGF-β) group, and TGF-β combined with GPS (25, 50, 100, 150 μmol/mL) groups. Cell proliferation was detected by EDU assay, cell invasion was assessed by TranswellTM assay, and the protein expressions of α-smooth muscle actin (α-SMA) and type I collagen (COL1A1) were measured by Western blot. M1-type macrophage-conditioned medium (M1-CM) was used to treat LX-2 cells in the TGF-β group and TGF-β combined with GPS group. The concentrations of inducible nitric oxide synthase (iNOS) and arginase 1 (Arg1) in the cell supernatant, as well as cell proliferation, invasion ability, and the expressions of α-SMA and COL1A1 were detected. Bioinformatics analysis was performed to identify the target intersections of GPS, hepatic fibrosis, and macrophage-related genes. Drug affinity responsive target stability (DARTS) experiments and Western blot were used to verify the regulatory effect of GPS on MIF. Furthermore, LX-2 cells were divided into control group, TGF-β group, TGF-β combined with M2-CM group, TGF-β and oe-NC combined with M2-CM group, and TGF-β and oe-MIF combined with M2-CM group to analyze the concentrations of iNOS and Arg1 in the cell supernatant, as well as changes in cell proliferation, invasion, and the expressions of α-SMA and COL1A1. LX-2 cells were also divided into control group, TGF-β group, TGF-β combined with oe-NC group, TGF-β combined with oe-MIF group, and TGF-β and oe-MIF combined with GPS group to determine the protein expressions of MIF and SPP1 by Western blot. A rat model of hepatic fibrosis was constructed to explore the potential therapeutic effects of GPS on hepatic fibrosis in vivo. Results Compared with the control group, the proliferation and invasion abilities of LX-2 cells in the TGF-β group were increased, and the protein expressions of α-SMA and COL1A1 were enhanced. GPS intervention inhibited the proliferation and invasion of LX-2 cells under TGF-β conditions and reduced the expressions of α-SMA and COL1A1. Compared with the control group, the concentration of iNOS in the cell supernatant of the TGF-β group was upregulated, while the concentration of Arg1 was decreased. M1-CM treatment further increased the concentration of iNOS, decreased the concentration of Arg1, and promoted cell proliferation and invasion, as well as upregulated the expressions of α-SMA and COL1A1 on the basis of TGF-β intervention. However, GPS could reverse the effects of M1-CM intervention. Bioinformatics analysis revealed that MIF was one of the target intersections of GPS, hepatic fibrosis, and macrophage-related genes, and GPS could target and inhibit its expression. Compared with the TGF-β group, after M2-CM intervention, the concentration of iNOS in the cell supernatant decreased, the concentration of Arg1 increased, the proliferation and invasion abilities of LX-2 cells were reduced, and the expressions of α-SMA and COL1A1 were weakened. However, overexpression of MIF reversed the effects of M2-CM intervention. Western blot results showed that compared with the control group, the protein expressions of MIF and SPP1 were enhanced in the TGF-β group. Overexpression of MIF further enhanced the expressions of MIF and SPP1, while GPS intervention inhibited the expressions of MIF and SPP1. In the animal experiment, GPS intervention treatment alleviated liver injury in rats with hepatic fibrosis and inhibited the expressions of MIF and SPP1, as well as α-SMA and COL1A1 in liver tissue. Conclusion GPS may prevent macrophage-mediated hepatic fibrosis by inhibiting the MIF-SPP1 signaling pathway in hepatic stellate cells.
Hepatic Stellate Cells/metabolism*
;
Signal Transduction/drug effects*
;
Macrophage Migration-Inhibitory Factors/genetics*
;
Liver Cirrhosis/prevention & control*
;
Macrophages/drug effects*
;
Iridoid Glucosides/pharmacology*
;
Humans
;
Cell Proliferation/drug effects*
;
Animals
;
Cell Line
;
Collagen Type I/metabolism*
;
Collagen Type I, alpha 1 Chain
;
Intramolecular Oxidoreductases/genetics*
;
Rats
;
Transforming Growth Factor beta/pharmacology*
;
Actins/metabolism*


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