Linxian County in Henan Province, Northern China is known as the region with the highest incidence and mortality rate of esophageal cancer worldwide. Since 1959, the Henan medical team has conducted field work on esophageal cancer prevention and treatment in Linxian. Through three generations of effort exerted by oncologists over 65 years of research on esophageal cancer prevention and treatment in Linxian, the incidence rate of esophageal squamous cell carcinoma in this area has dropped by nearly 50%, and the 5-year survival rate has increased to 40%, reaching the international leading level. This article aims to summarize the history, present opportunities and new challenges, and explore the experience of esophageal cancer prevention and treatment in Linxian (referred to as the “Linxian experience”), providing reference and guidance to cancer prevention and treatment research in China.

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.

Immobilized enzyme-based enzyme electrode biosensors, characterized by high sensitivity and efficiency, strong specificity, and compact size, demonstrate broad application prospects in life science research, disease diagnosis and monitoring, etc. Immobilization of enzyme is a critical step in determining the performance (stability, sensitivity, and reproducibility) of the biosensors. Random immobilization (physical adsorption, covalent cross-linking, etc.) can easily bring about problems, such as decreased enzyme activity and relatively unstable immobilization. Whereas, directional immobilization utilizing amino acid residue mutation, affinity peptide fusion, or nucleotide-specific binding to restrict the orientation of the enzymes provides new possibilities to solve the problems caused by random immobilization. In this paper, the principles, advantages and disadvantages and the application progress of enzyme electrode biosensors of different directional immobilization strategies for enzyme molecular sensing elements by specific amino acids (lysine, histidine, cysteine, unnatural amino acid) with functional groups introduced based on site-specific mutation, affinity peptides (gold binding peptides, carbon binding peptides, carbohydrate binding domains) fused through genetic engineering, and specific binding between nucleotides and target enzymes (proteins) were reviewed, and the application fields, advantages and limitations of various immobilized enzyme interface characterization techniques were discussed, hoping to provide theoretical and technical guidance for the creation of high-performance enzyme sensing elements and the manufacture of enzyme electrode sensors.

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 relationship between relative grip strength and hyperuricemia (HUA) levels in university freshmen, and to explore the potential value of muscle function indicators in HUA prevention among young populations, so as to provide new scientific evidences for HUA control in the demographic. Methods: Utilizing health examination data from 1 744 freshmen enrolled in a Shaanxi Province university in September 2024, absolute grip strength was measured using CAMRY electronic dynamometers, with relative grip strength subsequently calculated. Spearman correlation analysis was employed to examine relationships between student characteristics and relative grip strength, and binary Logistic regression models assessed the association strength between relative grip strength and HUA. Results: The overall HUA detection rate among freshmen was 29.8%, with significant gender differences (male:43.1%; female:24.0%; χ 2=64.62, P <0.01). Correlation analysis revealed significant associations between relative grip strength, body weight, height, body mass index (BMI) and HUA in both genders (boys: r =-0.27, 0.54, 0.11 , 0.53; girls: r =-0.18, 0.33, 0.08, 0.33, all P <0.05). Binary Logistic regression demonstrated that each standard deviation increase in relative grip strength reduced HUA risk by 77% in males ( OR=0.23, 95%CI =0.14-0.37) and 80% in females ( OR=0.20, 95%CI =0.11-0.36) (both P <0.01). Conclusions Relative grip strength represents a significant factor associated with HUA in university students. Incorporating muscle strength training into HUA prevention programs and establishing muscle function based HUA risk warning systems should be considered.

Aim To investigate the effect of Toddalia asiatica(TA)on bone destruction in rheumatoid ar-thritis(RA)and its possible mechanism by network pharmacology and in vitro experiments.Methods The active components and targets of TA against RA bone damage were analyzed by network pharmacology.Mo-lecular docking was performed by using AutoDock and PyMOL software pairs.MC3T3-e1 cells were cultured in vitro,and the effect of Toddalia asiatica alcohol ex-tract(TAAE)on cell viability was detected by CCK-8,and appropriate drug concentration and intervention time were screened.The osteoblast model was induced by osteogenic induction medium,and the osteogenic differentiation was detected by ALP staining,activity detection and alizarin red staining.The expression of pathway-related proteins Wnt3a and β-catenin was de-tected by Western blot,and the pathway inhibitor DKK-1 was used to further verify whether TAAE regulated osteoblast differentiation through the Wnt/β-catenin signaling pathway.Results A total of 158 anti-RA bone destruction targets and 56 core targets were se-lected.The enrichment of KEGG signaling pathway mainly included cancer pathway,phosphatidylinositol 3-kinase/protein kinase B signaling pathway and cAMP signaling pathway.The results of CCK-8 showed that 1 g·L-1 TAAE could significantly improve cell survival rate.The results of ALP staining and ALP activity de-tection showed that TAAE could significantly increase the staining positive rate and ALP activity of cells in-duced by osteogenic induction medium.Western blot showed that TAAE could increase the expression of Wnt3a and β-catenin.The expression of these proteins decreased after DKK-1 inhibitors were used.Conclu-sion TAAE can regulate osteoblast differentiation through Wnt/β-catenin signaling pathway to treat os-teodestruction in rheumatoid arthritis.

Objective:To understand the whole genome and genetic evolution characteristics of the first epidemic influenza A (H3N2) viruses in Wuxi from 2022-2023.Methods:Real time fluorescence quantitative RT-PCR method was used to perform typing on respiratory samples of influenza cases. Virus isolation was performed on samples with positive nucleic acid of subtype A H3N2 influenza virus detected. After cell culture, nucleic acid was extracted from strains with red blood cell agglutination test (HA) ≥ 1∶8, whole genome sequence was amplified, library was constructed, and computer sequencing was performed using MiSeq sequencer. Using NC_007366.1 as reference strain, the data were analyzed using CLC Genomics Workbench (Version 23) software. The phylogenetic tree was constructed using MEGA 7.0 software, and the N-glycosylation sites were predicted by NetNGlyc 1.0 Server software.Results:The nucleotide homology and amino acid homology among 35 strains of influenza A H3N2 virus from 2022 to 2023 were 96.4%-100% and 95.2%-100%, respectively. The 16 epidemic strains in 2022 belong to the 3C.2a1b.2a.1a evolutionary branch, while the 19 epidemic strains in 2023 belong to the 3C.2a1b.2a.2a.3a.1 evolutionary branch. There are 7 differences in the nucleotide sequence of the HA gene between the 2022 epidemic strain and the corresponding vaccine strain, sharing 15 mutation sites; There are 28 differences in the nucleotide sequence of the HA gene between the 2023 epidemic strain and the corresponding vaccine strain, sharing 17 mutation sites. The HA genes of 35 epidemic strains all lack N-glycosylation site 61: NSS, while in 2023, the HA genes of 19 epidemic strains added N-glycosylation site 110: NSS.Conclusions:The HA and NA genes of influenza A H3N2 virus in 2022 and 2023 belong to two evolutionary branches, respectively, and both show specific amino acid site changes compared to the corresponding vaccine strains. The antigen matching between the 2022 epidemic strain and the vaccine strain is relatively good, while there is a risk of low antigen matching between the 2023 epidemic strain and the vaccine strain.

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 explore the standardized process and method of atrial septum puncture(ASP)in swine guided by X-ray fluoroscopy and make ASP more safe and effective.Methods ASP was performed in 48 Pudong swines guided by X-ray fluoroscopy.Three protocols for precise location of atrial septal puncture points were recommended.(1)Site of atrial septal puncture point in cranial-caudal direction was determined under posterior-anterior projection,which was confined to the cranial side of the coronary sinus(CS)orifice at a distance of 1 cone body height along the midline of spine.(2)With 10° intervals,the fluoroscopy of the CS catheter was completed according to the right anterior oblique 10°～60° and the left anterior oblique 10°～60°,and the connection line of the CS 5-6 and 7-8 electrodes was perpendicular to the oval fossa,so as to confirm the perspective angle of the CS 5-6 and 7-8 electrodes in the same straight line.(3)The arch feature of puncture needle and distal part of sheath turned into a straight line under the perspective angle,of which the CS 5-6 and 7-8 electrodes were in the same straight line.Results ASP was successfully performed in 48 Pudong swines without any complications.Echocardiography showed left to right shunt through atrial septum after ASP.The average time of ASP was(25.7±11.5)minutes,the average X-ray exposure time is(14.0±3.4)min and the average radiation dose was(47.6±20.2)Gmy.Conclusions Using the coronal sinus electrode as a reference,atrial septal puncture in swine guided by X-ray fluoroscopy was safe and reliable.