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.

Objective: To investigate the distribution of IgM anti-A/B titers among group O whole blood donors in Jiangsu, establish a low-titer threshold, and analyze the demographic characteristics of low-titer donors, so as to provide data for recruiting low-titer group O whole blood (LTOWB) donors. Methods: Plasma samples from 1 009 group O whole blood donors were tested for IgM anti-A and anti-B titers using the microplate technique. The distribution of antibody titers was analyzed to establish a low-titer threshold. The distribution trends of titers across different demographic groups were also analyzed. Results: The peak titer for anti-A, anti-B were 64 (31.5%), 4 (23.8%), respectively, The proportion of donors with both anti-A and anti-B titers below 64 was 97.3% (982/1 009). The mean anti-A titer was higher than anti-B titer. Anti-A titers were higher in female donors than in male donors (P<0.05). The anti-A titers differed significantly among different age groups (P<0.05). However, no significant difference in titers was observed based on the number of donations (P>0.05). Conclusion: A titer of 64 can be used as the reference threshold of LTOWB in Jiangsu. Male donors of appropriate age are more suitable than female donors for establishing an emergency panel of LTOWB mobile donors.

Objective To investigate the role of pulmonary neuroendocrine cells(PNEC)and γ-aminobutyric acid(GABA)in patients with pulmonary neuroendocrine tumors(PNET).Methods The pathological specimens of 29 cases of PNET treated in the eighth Medical Center of Chinese PLA General Hospital from October 2018 to January 2022 were collected.The morphological characteristics were observed by HE staining,and the expression levels of synaptophysin(Syn),chromogranin A(CgA),CD56,Ki-67,CD86 and CD163 were observed by immunohistochemical staining.Calcitonin gene-related peptide(CGRP)and glutamic acid decarboxylase(GAD)65/67 in different types of PNETs were detected by double antibody immunofluorescence co-staining,and the correlation between GAD65/67 positive PNEC and macrophage polarization was analyzed.Results The results of HE staining showed that all four types of PNET tissues had neuroendocrine(NE)characteristics:rosette structure and organ nesting or palisade pattern,but they were different,and the proportion of mitotic cells from low to high was typical carcinoid(TC),atypical carcinoid(AC),large cell neuroendocrine carcinoma(LCNEC)and small cell lung cancer(SCLC).The results of immunohistochemical staining showed that the positive expression rate of Syn and CgA and the positive degree of Syn,CgA and CD56 in carcinoid(TC and AC)were significantly higher than those in LCNEC and SCLC(P＜0.05).The Ki-67 indices of the four types of PNET are:TC＜5%,AC 5%-20%,LCNEC and SCLC＞75%respectively.The number of PNEC in carcinoid was significantly higher than that in LCNEC,SCLC and paratumoral tissues(P＜0.05),but there was no significant difference in the number of PNEC between LCNEC and SCLC and para-tumor tissues(P＞0.05).The results of immunofluorescence staining showed that the number of GAD65/67 positive cells co-expressing GAD65/67 in 95%PNEC was significantly higher than that in LCNEC,SCLC and para-tumor tissues(P＜0.05),but there was no significant difference between LCNEC and SCLC GAD65/67 positive cells and para-tumor tissues(P＞0.05).The results of immunohistochemical staining also showed that the number of CD86 positive M1 macrophages was significantly higher than that of CD163 positive M2 macrophages in para-tumor tissues(P＜0.05),while M2 macrophages were significantly more than M1 macrophages in AC,LCNEC and SCLC(P＜0.01).Correlation analysis showed that the number of GAD65/67 positive PNEC cells in PNET was negatively correlated with the number of CD163 positive M2 macrophages in tumor stroma(r=-0.6336,P=0.0174).Conclusions PNEC is the main source of GABA in lung tissue and plays an immunomodulatory role in the lung,which may be involved in the progression of PNET.

RNA editing, an essential post-transcriptional reaction occurring in double-stranded RNA (dsRNA), generates informational diversity in the transcriptome and proteome. In mammals, the main type of RNA editing is the conversion of adenosine to inosine (A-to-I), processed by adenosine deaminases acting on the RNAs (ADARs) family, and interpreted as guanosine during nucleotide base-pairing. It has been reported that millions of nucleotide sites in human transcriptome undergo A-to-I editing events, catalyzed by the primarily responsible enzyme, ADAR1. In hematological malignancies including myeloid/lymphocytic leukemia and multiple myeloma, dysregulation of ADAR1 directly impacts the A-to-I editing states occurring in coding regions, non-coding regions, and immature miRNA precursors. Subsequently, aberrant A-to-I editing states result in altered molecular events, such as protein-coding sequence changes, intron retention, alternative splicing, and miRNA biogenesis inhibition. As a vital factor of the generation and stemness maintenance in leukemia stem cells (LSCs), disordered RNA editing drives the chaos of molecular regulatory network and ultimately promotes the cell proliferation, apoptosis inhibition and drug resistance. At present, novel drugs designed to target RNA editing(e.g., rebecsinib) are under development and have achieved outstanding results in animal experiments. Compared with traditional antitumor drugs, epigenetic antitumor drugs are expected to overcome the shackle of drug resistance and recurrence in hematological malignancies, and provide new treatment options for patients. This review summarized the recent advances in the regulation mechanism of ADAR1-mediated RNA editing events in hematologic malignancies, and further discussed the medical potential and clinical application of ADAR1.

Coronary artery calcification commonly results in reduced vascular compliance,facilitating incomplete stent expansion and in-stent restenosis after stent implantation,thereby leading to the failure of interventional treatment.Conventional approaches to managing calcified lesions are constrained by the intricate nature and properties of calcified plaques,which frequently pose challenges in their manipulation,consequently giving rise to numerous approaches complications and an elevated likelihood of adverse cardiovascular events following the procedure.Percutaneous coronary intraluminal shock wave balloon catheter angioplasty,also known as coronary intravascular lithotripsy,utilizing a balloon catheter system,demonstrates the capacity to safely and efficiently modify superficial and deep-seated calcifications,regardless of their concentric or eccentric nature.This intervention significantly enhances vascular compliance,thereby facilitating subsequent interventional therapies.Presently,coronary intravascular lithotripsy has emerged as a crucial approach in the management of coronary artery calcification.This article primarily offers a comprehensive examination of the mechanism of intravascular lithotripsy and the research pertaining to the treatment of coronary artery calcification.

Objective To explore the medication rules of Professor HUANG Li for the treatment of recurrent angina pectoris after percutaneous coronary intervention(PCI)for coronary heart disease by data mining method.Methods The prescriptions for effective cases of recurrent angina pectoris after PCI for coronary heart disease treated by Professor HUANG Li in the outpatient department of China-Japan Friendship Hospital were collected.SPSS Statistics 26.0 software and SPSS Modeler 18.0 software were used for frequency statistics,analysis of the therapeutic actions,properties,flavors and meridian tropism of the prescribed herbs as well as association rule analysis,cluster analysis and factor analysis of the herbs.Results A total of 344 Chinese medicine prescriptions were obtained,involving 209 herbs,with a cumulative frequency of 5 874 times.The top 30 Chinese medicinals were named as the high-frequency Chinese medicines,and the herbs with the frequency over 100 times in descending order were Astragali Radix,Chuanxiong Rhizoma,Puerariae Lobatae Radix,Rhodiolae Crenulatae Radix et Rhizoma,Notoginseng Radix et Rhizoma,Poria,Dalbergiae Odoriferae Lignum,Atractylodis Macrocephalae Rhizoma,Curcumae Rhizoma,Sparganii Rhizoma,Dioscoreae Rhizoma,Citri Reticulatae Pericarpium,Pinelliae Rhizoma Praeparatum,Codonopsis Radix,and Glycyrrhizae Radix et Rhizoma.The high-frequency Chinese medicinals were mostly classified as blood-activating and stasis-resolving drugs and qi-replenishing drugs.The medicinal properties of the drugs were characterized by being warm,mild,or cold,the flavors were predominated by being sweet,pungent or bitter,and the medicinals usually had the meridian tropism of the spleen,lung and liver meridians.A total of 30 association rules were mined out,cluster analysis yielded 5 herbal groups,and factor analysis yielded 11 groups of common factors.Conclusion For the treatment of cardiovascular diseases,Professor HUANG Li follows the theory of qi,blood and water,and especially pays more attention to the ascending and descending of qi movement.For qi deficiency and blood stasis contribute to the basic pathogenesis of recurrent angina pectoris after PCI,the therapy of benefiting qi,activating blood and removing stasis is recommended.Moreover,the simultaneous regulation of five zang-organs and simultaneous use of the cold and warm herbs are performed,and the herbs of benefiting qi and invigorating spleen,resolving phlegm and inducing diuresis,tranquilizing mind,promoting qi and dissipating masses,and activating blood to eliminate stasis are used for adjuvant therapy.

Objective This study aimed to explore the diagnostic concordance of fractional flow reserve(FFR)and quantitative flow ratio(QFR)and the characteristics affecting this concordance.Methods Patients with non-acute myocardial infarction admitted to the Department of Cardiology,Peking University Third Hospital between January 2019 and December 2021 were enrolled.The patients were divided into four groups:FFR+/QFR+and FFR-/QFR-,FFR+/QFR-and FFR-/QFR+with FFR or QFR≤0.80 as positive and＞0.80 as negative.Using FFR as the gold standard,the diagnostic value of QFR was analyzed,and differences in clinical features and pathological characteristics among the groups were compared.Results A total of 236 patients were included.The mean age was(64.48±9.63)years,and 67.8％were male.All patients had 30％-70％coronary stenosis.The consistency rate of QFR and FFR was 78.0％(n=184),and the Person correlation coefficient was 0.557(P＜0.001).Among FFR+patients,the minimum lumen diameter was larger[(1.56±0.34)mm vs.(1.39±0.31)mm,P=0.019],lesion length was shorter[(21.37±11.73)mm vs.(36.86±18.09)mm,P＜0.001],and coronary angiography-based index of microcirculartory resistance(AMR)was higher[(277.50±28.87)mmHg·s/m vs.(178.02±49.13)mmHg·s/m,P＜0.001]in the disconcordance group.Multivariate regression analysis suggested that AMR[OR 0.93,95％CI 0.88-0.99,P=0.030]and lesion length[OR 1.27,95％CI 1.01-1.60,P=0.045]were independent predictors of disconcordance.In the FFR-group,the lesion length was longer[(33.08±16.05)mm vs.(21.40±13.36)mm,P=0.020],and AMR[(169.66±24.01)mmHg·s/m vs.(265.95±44.78)mmHg·s/m,P＜0.001]and low-density lipoprotein-C[1.57(1.10,1.97)mmol/L vs.2.15(1.79,2.74)mmol/L,P=0.031]were lower in the disconcordance group.No statistically significant variables were identified by multivariate regression.Conclusions QFR had high diagnostic value compared with FFR.In the FFR+group,AMR and lesion length may have affected the diagnostic consistency of QFR and FFR.The study provided more evidence for the clinical application of QFR.

Objective To compare the effects of visual rigid laryngoscope and visual laryngoscope in nasotracheal intubation(NTI)for patients with cervical spine immobilization simulated difficult airway.Methods Ninety patients scheduled for selective surgery under general anesthesia requiring NTI,52 males and 38 females,aged 18-64 years,BMI 18.5-25.0 kg/m2,ASA physical status Ⅰ or Ⅱ,were scheduled for selective surgery under general anesthesia requiring NTI.Before anesthesia induction,the spinal surgeon selected an appropriate cervical collar and adjusted it to fix patient's neck to establishing difficult airway sim-ulation model.All patients were randomly assigned into two groups:visual rigid laryngoscope(group R)and common visual laryngoscope(group C),45 patients in each group.NTI was performed using either visual rigid laryngoscope or visual laryngoscope in groups R and C,respectively.The nasal passage time,glottic exposure time,intubation time,number of successful first intubation attempts,and intubation attempts were recorded.Glottic exposure was assessed using the Cormack-Lehane(C-L)grading system,and the intuba-tion condition was quantitatively evaluated using the modified nasal intubation difficulty scale(NIDS).The blood pressure and heart rate were measured at baseline(T1),immediately after intubation(T2),and at 1 minute(T3)and 3 minutes(T4)after intubation.The occurrence of intubation-related complications(nasal bleeding,sore throat,hoarseness)was recorded.Results Compared with group C,the nasal passage time and proportion of successful intubations without difficulty were significantly increased in group R,and the glottic exposure time and intubation time were significantly decreased in group R(P<0.05).Compared with group C,the HR and MAP at T2 and T3 were significantly decreased in group R(P<0.05).Com-pared with group C,group R had significantly lower incidence rates of nasal bleeding,sore throat,and hoarseness(P<0.05).There were no statistically significant differences in the first intubation success rate,number of intubation attempts,or C-L grade between the two groups.Conclusion Patients with cer-vical spine immobilization simulated difficult airway,both visual rigid laryngoscope and visual laryngoscope can be performed safely and effectively in NTI.Compared with visual laryngoscope,visual rigid laryngoscope can provide faster glottic exposure,shorter intubation time,lower intubation difficulty,less hemodynamic impact,and lower incidence of complications.