Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

The chemical constituents were systematically separated from the roots of Berberis polyantha by various chromatographic methods, including silica gel column chromatography, HP20 column chromatography, polyamide column chromatography, reversed-phase C_(18) column chromatography, and preparative high-performance liquid chromatography. The structures of the compounds were identified by physicochemical properties and spectroscopic techniques(1D NMR, 2D NMR, UV, MS, and CD). Four phenylpropanoids were isolated from the methanol extract of the roots of B. polyantha, and they were identified as(2R)-1-(4-hydroxy-3,5-dimethoxyphenyl)-1-propanone-O-β-D-glucopyranoside(1), methyl 4-hydroxy-3,5-dimethoxybenzoate(2),(+)-syringaresinol(3), and syringaresinol-4-O-β-D-glucopyranoside(4). Compound 1 was a new compound, and other compounds were isolated from this plant for the first time. The anti-inflammatory activity of these compounds was evaluated based on the release of nitric oxide(NO) in the culture of lipopolysaccharide(LPS)-induced RAW264.7 macrophages. At a concentration of 10 μmol·L~(-1), all the four compounds inhibited the LPS-induced release of NO in RAW264.7 cells, demonstrating potential anti-inflammatory properties.
Plant Roots/chemistry* ; Animals ; Mice ; Berberis/chemistry* ; RAW 264.7 Cells ; Macrophages/immunology* ; Drugs, Chinese Herbal/isolation & purification* ; Nitric Oxide/metabolism* ; Molecular Structure ; Anti-Inflammatory Agents/isolation & purification*

OBJECTIVE: To evaluate the clinical efficacy and safety of Yangxue Qingnao Pills (YXQNP) combined with amlodipine in treating patients with grade 1 hypertension. METHODS: This is a multicenter, randomized, double-blind, and placebo-controlled study. Adult patients with grade 1 hypertension of blood deficiency and Gan (Liver)-yang hyperactivity syndrome were randomly divided into the treatment or the control groups at a 1:1 ratio. The treatment group received YXQNP and amlodipine besylate, while the control group received YXQNP's placebo and amlodipine besylate. The treatment duration lasted for 180 days. Outcomes assessed included changes in blood pressure, Chinese medicine (CM) syndrome scores, symptoms and target organ functions before and after treatment in both groups. Additionally, adverse events, such as nausea, vomiting, rash, itching, and diarrhea, were recorded in both groups. RESULTS: A total of 662 subjects were enrolled, of whom 608 (91.8%) completed the trial (306 in the treatment and 302 in the control groups). After 180 days of treatment, the standard deviations and coefficients of variation of systolic and diastolic blood pressure levels were lower in the treatment group compared with the control group. The improvement rates of dizziness, headache, insomnia, and waist soreness were significantly higher in the treatment group compared with the control group (P<0.05). After 30 days of treatment, the overall therapeutic effects on CM clinical syndromes were significantly increased in the treatment group as compared with the control group (P<0.05). After 180 days of treatment, brachial-ankle pulse wave velocity, ankle brachial index and albumin-to-creatinine ratio were improved in both groups, with no statistically significant differences (P>0.05). No serious treatment-related adverse events occurred during the study period. CONCLUSIONS Combination therapy of YXQNP with amlodipine significantly improved symptoms such as dizziness and headache, reduced blood pressure variability, and showed a trend toward lowering urinary microalbumin in hypertensive patients. These findings suggest that this regimen has good clinical efficacy and safety. (Registration No. ChiCTR1900022470).
Humans ; Amlodipine/adverse effects* ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Hypertension/complications* ; Middle Aged ; Treatment Outcome ; Drug Therapy, Combination ; Adult ; Blood Pressure/drug effects* ; Double-Blind Method ; Aged ; Antihypertensive Agents/adverse effects*

OBJECTIVE: To observe the clinical effect and safety of Lu'e Biyan Formula (LBF) combined with loratadine in the treatment of moderate to severe allergic rhinitis (AR) patients with Fei (Lung)-qi deficiency-coldness (FQDC) syndrome. METHODS: From September 2023 to December 2024, moderate to severe AR patients with FQDC syndrome were recruited from the Outpatient Department of Integrated Traditional Chinese and Western Medicine for Pulmonary Diseases Part 1, China-Japan Friendship Hospital. Participants were randomly assigned to a test group and a control group by using a random number table at a ratio of 1:1. Both groups received oral loratadine tablets (10 mg, once daily) for 2 weeks. In addition, the test group received oral LBF (30 mL, twice daily), and the control group received a placebo of LBF. Changes in the Total Nasal Symptom Score (TNSS), Total Non-nasal Symptom Score (TNNSS), Visual Analog Scale (VAS), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), and Chinese medicine (CM) syndrome scores before and after treatment were compared between groups. Moreover, the total effective rates and disease recurrence rates were compared. Adverse events (AEs) during the study period were also recorded. RESULTS: Totally 109 participants were recruited, and the full analysis set included 105 cases, 54 in the test group and 51 in the control group. Compared with the pre-treatment values, the scores of sneezing, runny nose, nasal obstruction, nasal itching, TNSS, TNNSS, VAS, RQLQ, and CM syndrome were significantly reduced in both groups at 1 and 2 weeks post-treatment and 12 weeks post-drug withdrawal (P<0.01). After treatment, the aforementioned scores in the test group were all markedly lower than those in the control group (P<0.01). Moreover, the total effective rate in the test group was higher than that in the control group (98.15% vs. 70.59%, P<0.01). After 12 weeks of drug withdrawal, there was no significant difference in the recurrence rate between groups (13.21% vs. 22.22%, P>0.05). No obvious AEs were observed in either group following treatment. CONCLUSIONS The combination of LBF with loratadine can effectively alleviate the symptoms of moderate to severe AR patients with FQDC syndrome, thereby improving their quality of life. This therapy demonstrated both precise effect and high safety. (Trial registration No. ITMCTR2025000589).
Humans ; Drugs, Chinese Herbal/therapeutic use* ; Male ; Rhinitis, Allergic/drug therapy* ; Female ; Adult ; Double-Blind Method ; Quality of Life ; Qi ; Middle Aged ; Loratadine/therapeutic use* ; Medicine, Chinese Traditional ; Syndrome ; Lung/drug effects* ; Young Adult ; Treatment Outcome

Objective This study aimed to comprehensively analyze and compare the clinicopathological features and prognosis of Chinese patients with human epidermal growth factor receptor 2(HER2)-low early breast cancer(BC)and HER2-IHC0 BC. Methods Patients diagnosed with HER2-negative BC(N=999)at our institution between January 2011 and December 2015 formed our study population.Clinicopathological characteristics,association between estrogen receptor(ER)expression and HER2-low,and evolution of HER2 immunohistochemical(IHC)score were assessed.Kaplan-Meier method and log-rank test were used to compare the long-term survival outcomes(5-year follow-up)between the HER2-IHC0 and HER2-low groups. Results HER2-low BC group tended to demonstrate high expression of ER and more progesterone receptor(PgR)positivity than HER2-IHC0 BC group(P<0.001).The rate of HER2-low status increased with increasing ER expression levels(Mantel-Haenszel χ2 test,P<0.001,Pearson's R=0.159,P<0.001).Survival analysis revealed a significantly longer overall survival(OS)in HER2-low BC group than in HER2-IHC0 group(P=0.007)in the whole cohort and the hormone receptor(HR)-negative group.There were no significant differences between the two groups in terms of disease-free survival(DFS).The discordance rate of HER2 IHC scores between primary and metastatic sites was 36.84%. Conclusion HER2-low BC may not be regarded as a unique BC group in this population-based study due to similar clinicopathological features and prognostic roles.

Objective:To explore the efficacy of stage I modified posterior vertebral column resection (mPVCR) in the treatment of postoperative infection after percutaneous vertebroplasty (PVP) for osteoporotic vertebral compression fracture (OVCF).Methods:A retrospective case series study was conducted to analyze the clinical data of 11 OVCF patients with post-PVP infection who were admitted to Zhengzhou Orthopedics Hospital from January 2016 to June 2022, including 4 males and 7 females, aged 61-81 years [(70.2±6.4)years]. Injured segments included T 9 in 1 patient, T 11 in 2, T 12 in 3, L 1 in 1, L 2 in 2, T 11-T 12 in 1, and T 12-L 1 in 1. American Spinal Injury Association (ASIA) grading was grade D in 5 patients and grade E in 6. All the patients were treated with stage I mPVCR. The operation time and intraoperative bleeding volume were recorded. The values of Visual Analogue Scale (VAS), Oswestry Dysfunction Index (ODI), and Cobb angle of the lesion segments before, at 2 weeks, 3 months after surgery, and at the last follow-up were compared. The loss of Cobb angle of the lesion segments at 2 weeks after surgery and at the last follow-up were compared, and the ASIA grading at the last follow-up was recorded. The infection control, bone healing, and the incidence of complications were observed at the last follow-up. Results:All the patients were followed up for 12-44 months [(26.0±9.4)months]. The operation time and intraoperative bleeding volume were 230-330 minutes [(279.2±28.6)minutes] and 500-1 100 ml [(840.9±184.1)ml] respectively. At 2 weeks, 3 months after surgery and at the last follow-up, the VAS scores were (4.0±0.8)points, (2.7±0.9)points, and (2.4±0.7)points respectively, which were all lower than that before surgery [(8.1±1.2)points] ( P<0.01); the ODI was (45.5±5.1)%, (30.0±6.5)%, and (18.5±3.6)% respectively, which were all lower than that before surgery [(78.7±6.2)%] ( P<0.01); the Cobb angle of the lesion segments were (7.9±1.4)°, (8.5±1.4)°, and (9.2±1.5)° respectively, which were lower than that before surgery [(25.5±9.2)°] ( P<0.01). The VAS and ODI were both improved at 3 months after surgery compared with those at 2 weeks after surgery ( P<0.05), while there was no significant difference in Cobb angle of the lesion segments ( P>0.05). The ODI was further improved at the last follow-up compared with that at 3 months after surgery ( P<0.05), while there were no significant differences in VAS or Cobb angle of the lesion segments ( P>0.05). The loss of Cobb angle correction of the lesion segment at the last follow-up was 0.96 (0.69, 1.45)° compared with that at 2 weeks after surgery and the rate of loss of Cobb angle correction of the lesion segment was 4.4(2.2, 7.4)%. At the last follow-up, the ASIA grading was grade E for all the patients, who were able to walk normally independently. The infection was all cured and good bony fusion was observed in the operated area at the last follow-up. Two patients had pleural effusion and pulmonary atelectasis, 1 incision fat liquefaction, and 1 pneumonia after the surgery. None of the patients had internal fixation failure and serious complications such as worsening neurological symptoms or death. Conclusion:Stage I mPVCR for the treatment of post-PVP infection in patients with OVCF is proved to attain significant pain relief and functional improvement, good correction results, effective reconstruction of spinal stability, complete removal of infected lesions, and few serious complications.

Objective:To investigate the efficacy of one-stage posterior-anterior combined operation for the treatment of abnormal fusion after facet joint dislocation in the subaxial cervical spine.Methods:A retrospective study of case series was conducted to analyze the clinical data of 10 patients with abnormal fusion after facet joint dislocation in the subaxial cervical spine who had been admitted to Department of Spine Surgery, Zhengzhou Orthopedic Hospital from January 2015 to May 2023. There were 7 males and 3 females with an age of (41.2±3.1) years. Preoperative American Spinal Injury Association (ASIA) grading: 5 cases of grade A, 4 cases of grade B, and 1 cases of grade C. All the patients were treated with one-stage posterior-anterior combined operation. The surgical time and intraoperative bleeding volume were recorded. The ASIA grading was used to evaluate the improvements in nerve function of the spinal cord 3 months after surgery. The VAS scores, cervical intervertebral heights, and Cobb angles were compared between pre-surgery, 3 months after surgery, and the last follow-up. The fusion of intervertebral bone graft was evaluated 3 months after surgery using the Bridgell intervertebral fusion criteria. Complications were observed.Results:All patients were followed up for 15.5 (13.8, 20.5) months. The surgical time was (119.5±3.6) minutes, and the intraoperative bleeding volume (141.6±25.6) mL. Significant improvements in VAS score, cervical intervertebral height, and Cobb angle were observed at 3 months after surgery and the last follow-up compared with the pre-surgery values ( P<0.05), but there was no statistically significant difference between 3 months after surgery and the last follow-up ( P>0.05). ASIA grading 3 months after surgery: 4 cases of grade A, 4 cases of grade B, and 2 cases of grade C. By the Bridgell intervertebral fusion criteria at 3 months after surgery: 9 cases of grade Ⅰ and 1 cases of grade Ⅱ, showing good intervertebral fusion. Surgery went on well for all patients, showing no postoperative complications such as aggravation of nerve lesion or vascular injury. Conclusion:In the treatment of abnormal fusion after facet joint dislocation in the subaxial cervical spine, the efficacy of one-stage posterior-anterior combined operation is definite because it can effectively reduce pain, restore the height and physiological curvature of the cervical intervertebral space, and achieve good intervertebral fusion.