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.

BACKGROUND:At present,bone marrow mesenchymal stem cells are the main seed cells used in cell therapy for the treatment of intervertebral disc degeneration.However,the use of bone marrow mesenchymal stem cells as seed cells for the regeneration of fibrous rings is at risk of heterotopic ossification and teratoma at the repair site.Therefore,it is of great economic and social significance to find a new kind of seed cells for tissue engineering of annulus fibrosus for the treatment of intervertebral disc degeneration. OBJECTIVE:To isolate and purify rat annulus fibrosus-derived stem cells by adherent method combined with fibronectin differential adhesion screening method,and to observe its purification effect and biological characteristics. METHODS:Annulus fibrosus tissue was obtained from a SD rat intervertebral disc.Primary annulus fibrosus-derived stem cells were obtained by the mechanical-enzymatic digestion method.Annulus fibronectin differential adhesion method was used to purify annulus fibrosus-derived stem cells.Morphological changes and proliferation of cells were observed through a microscope.The expression levels of stem cell markers were detected by immunofluorescence technique and qPCR.The screened cells were subjected to multi-lineage cell differentiation and characteristic gene detection. RESULTS AND CONCLUSION:(1)The purified cells grew well,and most of them were angular and star-shaped multi-process cells,which had good proliferation ability.(2)Cells were positive for cell membrane surface antigens CD73,CD90 and CD105,while negative for CD45 and CD34.(3)After specific induction,cells could successfully differentiate into osteoblasts,chondroblasts and lipoblasts.(4)Collagen-I,Runx-2 after osteogenic induction,Collagen Ⅱ,Sox-9 after chondrogenic induction,and PPAR-γ and LPL after lipogenic induction were highly expressed in cells,and the difference was significant compared with that before induction(P<0.05).(5)These findings confirm that the adherent method combined with fibronectin differential adhesion method is effective enough to screen,isolate and purify rat annulus fibrosus-derived stem cells,and has good cell biological properties,good proliferation ability and multiple differentiation potential.

Objective:To investigate the analgesic effect of ultrasound-guided posterior quadratus lumborum block (QLB) combined with cocktail therapy after arthroscopic anterior cruciate ligament reconstruction (ACLR) surgery.Methods:A randomized controlled study was conducted on 87 patients who underwent arthroscopic ACLR surgery at the Yan'an Branch of Peking University Third Hospital (Yan'an Hospital of Traditional Chinese Medicine) from February 2021 to April 2023. The patients were randomly divided into three groups using the random number table method: Group A ( n = 29), Group B ( n = 29), and Group C ( n = 29). Group A received ultrasound-guided posterior QLB, Group B received cocktail therapy, and Group C received a combination of ultrasound-guided posterior QLB and cocktail therapy. Visual Analogue Scale (VAS) scores, knee function, intraoperative and postoperative general conditions, stress responses, inflammatory pain mediators, and adverse reactions were compared among the three groups. Results:At 2, 12, and 24 hours after surgery, VAS scores in Group C were (3.25 ± 0.41) points, (2.03 ± 0.28) points, and (0.65 ± 0.09) points, respectively, which were significantly lower than those in Group A [(4.68 ± 0.65) points, (3.28 ± 0.39) points, (1.68 ± 0.22) points, t = 10.02, 14.02, 23.34, all P < 0.001] and Group B [(4.79 ± 0.72) points, (3.20 ± 0.36) points, (1.72 ± 0.24) points, t = 9.49, 13.82, 22.48, all P < 0.001]. At 1 month after surgery, the Knee Society Score and Hospital for Special Surgery knee score in Group C were (92.02 ± 3.33) points and (90.05 ± 3.46) points, respectively, both of which were significantly higher than those in Group A [(81.85 ± 2.27) points, (82.57 ± 2.34) points, t = 13.59, 9.64, both P < 0.001] and Group B [(81.46 ± 2.38) points, (83.22 ± 2.40) points, t = 13.89, 8.73, both P < 0.001]. There were no statistically significant differences in maximum active range of motion and quadriceps strength among the three groups at 72 hours after surgery (both P > 0.05). The time to first ambulation, time to first straight leg raise, rate of rescue analgesia, and the number of effective activations of the analgesic pump in Group C were (22.08 ± 4.36) hours, (2.26 ± 0.30) hours, 3.45%, and (0.75 ± 0.16) times, respectively, all of which were significantly lower than those in Group A ( t = 3.24, 8.20, χ2 = 7.73, t = 19.29, all P < 0.001) and Group B ( t = 3.01, 7.51, χ2 = 6.44, t = 17.34, all P < 0.001). At 24 hours after surgery, serum levels of angiotensin II, adrenocorticotropin, β-endorphin, and prostaglandin E 2 in Group C were significantly lower than those in Groups A and B (all P < 0.05). There was no statistically significant difference in the incidence of adverse reactions among the three groups ( P > 0.05). Conclusion:The combination of cocktail therapy and ultrasound-guided posterior QLB can improve knee function in patients after arthroscopic ACLR surgery and provides effective and safe analgesia.

Objective: To investigate the response characteristics of patients with locally advanced/metastatic non-squamous non-small cell lung cancer (nsq-NSCLC) treated with tislelizumab in combination with chemotherapy in the first line. Methods: Patients with nsq-NSCLC who achieved complete or partial remission after treatment with tislelizumab in combination with chemotherapy or chemotherapy alone in the RATIONALE 304 study, as assessed by an independent review board, were selected to analyze the response characteristics and safety profile of the responders. Time to response (TTR) was defined as the time from randomization to the achievement of first objective response. Depth of response (DpR) was defined as the maximum percentage of tumor shrinkage compared with the sum of the baseline target lesion length diameters. Results: As of January 23, 2020, 128 patients treated with tislelizumab in combination with chemotherapy achieved objective tumor response (responders), representing 57.4%(128/223) of the intention-to-treat population, with a TTR of 5.1 to 33.3 weeks and a median TTR of 7.9 weeks. Of the responders (128), 50.8%(65) achieved first remission at the first efficacy assessment (week 6), 31.3%(40) at the second efficacy assessment (week 12), and 18.0%(23) at the third and subsequent tumor assessments. The percentages of responders who achieved a depth of tumor response of 30% to <50%, 50% to <70% and 70% to 100% were 45.3%(58/128), 28.1%(36/128) and 26.6%(34/128), respectively, with median progression-free survival (PFS) of 9.0 months (95% CI: 7.7 to 9.9 months), 11.5 months (95% CI: 7.7 months to not reached) and not reached (95% CI: 11.8 months to not estimable), respectively. Tislelizumab plus chemotherapy were generally well tolerated in responders with similar safety profile to the overall safety population. Conclusion: Among responders to tislelizumab in combination with chemotherapy for nsq-NSCLC, 82.0%(105/128) achieves response within the first two tumor assessments (12 weeks) and 18.0%(23/128) achieves response at later (18 to 33 weeks) assessments, and there is a trend toward prolonged PFS in responders with deeper tumor response.
Humans ; Antibodies, Monoclonal, Humanized/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Carcinoma, Non-Small-Cell Lung/pathology* ; Lung Neoplasms/pathology* ; Treatment Outcome

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

Most information used to evaluate diabetic statuses is collected at a special time-point, such as taking fasting plasma glucose test and providing a limited view of individual's health and disease risk. As a new parameter for continuously evaluating personal clinical statuses, the newly developed technique "continuous glucose monitoring" (CGM) can characterize glucose dynamics. By calculating the complexity of glucose time series index (CGI) with refined composite multi-scale entropy analysis of the CGM data, the study showed for the first time that the complexity of glucose time series in subjects decreased gradually from normal glucose tolerance to impaired glucose regulation and then to type 2 diabetes (P for trend < 0.01). Furthermore, CGI was significantly associated with various parameters such as insulin sensitivity/secretion (all P < 0.01), and multiple linear stepwise regression showed that the disposition index, which reflects β-cell function after adjusting for insulin sensitivity, was the only independent factor correlated with CGI (P < 0.01). Our findings indicate that the CGI derived from the CGM data may serve as a novel marker to evaluate glucose homeostasis.
Humans ; Glucose ; Blood Glucose ; Insulin Resistance/physiology* ; Diabetes Mellitus, Type 2/diagnosis* ; Blood Glucose Self-Monitoring ; Time Factors ; Insulin

Objective:To explore the relationship between the polymorphisms of AHNAK2 gene rs12882641,rs28583515 and rs2582497 loci and coronary heart disease(CHD)in the population of Xinjiang.Materials:This study used a case-control method,a total of 602 patients who were hospitalized and underwent coronary angiogra-phy(CAG)at ourheart center from Jan 2019 to Dec 2021 were selected.According toCAG results,the patients were divided into CHD group(n=301)and non-CHD group(n=301).The AHNAK2 gene rs12882641,rs28583515 and rs2582497 loci were genotyped using the improved multiple ligase detection reaction(iMLDR)technique,and the relationship between AHNAK2 gene polymorphisms and CHD was analyzed.Results:Compared with non-CHD group,there was significant rise in the distribution frequencies of AC+CC genotypes(52.8%vs.61.1%,P= 0.040)at rs2582497 locus of the AHNAK2 gene under the dominant model;there was significant reduction in distri-bution frequency of the CC genotype(65.8%vs.53.8%)at the rs28583515 locus of the AHNAK2 gene,and signif-icant rise in distribution frequencies of CT+TT(34.2%vs.46.2%)under the dominant model,TT under the re-cessive model(0.7%vs.3.0%)and CT under the additive model(33.6%vs.43.2%)in CHD group,P＜0.05 or＜0.01.After adjusting for confounding factors,logistic regression analysis indicated that the dominant model of the rs28583515 locus remained an independent risk factor for CHD(OR=1.509,P=0.036).Conclusion:The AH-NAK2 gene rs28583515 locus is closely related to the occurrence and development of CHD in the Xinjiang popula-tion.The dominant model of the AHNAK2 gene rs28583515 locus is an independent risk factor for CHD.

The RET(REarranged during transfection) gene as a novel has broken the therapeutic deadlock in the last two years, whith is attributed to the rapid approval of targeted therapies and inclusion in treatment guidelines, bringing more hope for the survival of patients with non-small cell lung cancer(NSCLC). Usually, the main activation of the RET proto-oncogene contributes to the development of lung cancer via somatic rearrangements. Thus, this study reviews the biological characteristics of RET gene, the classification of RET fusion in lung cancer and the detection of RET fusion. Meanwhile the pathological and clinical features, targeted therapies, drug resistance, prognosis of lung cancer patients with RET fusion were further discussed.