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 effects of simvastatin mediated adenylate activated protein kinase/peroxisome proliferator-activated receptor-γ-coactivator 1 α(AMPK/PGC-1α)pathway on neural function in rats with Parkinson's disease.Methods Parkinson's disease model was established in SD rats.After successful modeling,they were divided into model group,positive group(1.67 mg·kg-1 metoba),experimental-L group(10 mg·kg-1 simvastatin),experimental-H group(20 mg·kg-1 simvastatin),BML-275 group(20 mg·kg-1 simvastatin+0.25 mg·kg-1 AMPK inhibitor BML-275)and 10 normal rats were selected as control group.Enzyme-linked immunosorbent assay(ELISA)was used to detect dopamine(DA),3,4 dihydroxyphenylacetic acid(DOPAC),homovanillic acid(HVA),5-hydroxyindoleacetic acid(5-HIAA),5-hydroxytryptamine(5-HT);Western blot was used to detect the expression of tyrosine hydroxylase(TH)and AMPK/PGC-1α pathway-related proteins;TH expression was detected by immunohistochemistry,malondialdehyde(MDA),superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)were detected by kit.Results The DA of control group,model group,experimental-H group and BML-275 group were(495.63±34.30),(207.53±24.10),(429.39±44.89)and(285.55±20.79)pg·mL-1,respectively;DOPAC were(33.38±2.48),(17.70±1.31),(29.12±1.72)and(20.67±1.45)ng·mL-1,respectively;HVA were(58.75±6.25),(25.27±2.00),(46.16±2.83)and(30.58±1.91)ng·mL-1,respectively;5-HT were(5.62±0.45),(2.37±0.13),(4.42±0.26)and(3.23±0.29)ng·mL-1,respectively;5-HIAA were(11.11±1.08),(3.88±0.30),(7.99±0.63)and(6.04±0.51)ng·mL-1,respectively;p-AMPK protein expression were 0.98±0.06,0.35±0.04,0.80±0.05 and 0.21±0.02,respectively;PGC-1α protein expression were 1.12±0.11,0.40±0.04,0.90±0.08 and 0.58±0.05,respectively.There were statistically significant differences in the above indexes between control group and model group,and between model group and experimental-H group and inhibitor group(all P＜0.05).Conclusion Simvastatin can improve the neural function of Parkinson's disease rats by regulating AMPK/PGC-1α pathway.

To promote the development of extracellular vesicles of herbal medicine especially the establishment of standardization, led by the National Expert Committee on Research and Application of Chinese Herbal Vesicles, research experts in the field of herbal medicine and extracellular vesicles were invited nationwide with the support of the Expert Committee on Research and Application of Chinese Herbal Vesicles, Professional Committee on Extracellular Vesicle Research and Application, Chinese Society of Research Hospitals and the Guangdong Engineering Research Center of Chinese Herbal Vesicles. Based on the collation of relevant literature, we have adopted the Delphi method, the consensus meeting method combined with the nominal group method to form a discussion draft of "Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023)". The first draft was discussed in online and offline meetings on October 12, 14, November 2, 2022 and April and May 2023 on the current status of research, nomenclature, isolation methods, quality standards and research applications of extracellular vesicles of Chinese herbal medicines, and 13 consensus opinions were finally formed. At the Third Academic Conference on Research and Application of Chinese Herbal Vesicles, held on May 26, 2023, Kewei Zhao, convenor of the consensus, presented and read the consensus to the experts of the Expert Committee on Research and Application of Chinese Herbal Vesicles. The consensus highlights the characteristics and advantages of Chinese medicine, inherits the essence, and keeps the righteousness and innovation, aiming to provide a reference for colleagues engaged in research and application of Chinese herbal vesicles at home and abroad, decode the mystery behind Chinese herbal vesicles together, establish a safe, effective and controllable accurate Chinese herbal vesicle prevention and treatment system, and build a bridge for Chinese medicine to the world.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.

ObjectiveTo establish the Shanghai twin birth cohort （STBC） and analyze the effects of genetic factors， shared environment， and non-shared environment interactions on birth health and growth and development of newborns. MethodsBased on the population-wide birth cohort in Shanghai， a comprehensive survey was conducted on the families with double and multiple babies born after January 1， 2015 to collect information on birth health， growth and development， and the family environment of the babies. ResultsBy December 31， 2021， a total of 7 195 pairs （14 405 cases） of twins were successfully included in the STBC survey. The average birth length of twins was 47.2 cm and average birth weight was 2 465.3 g. Heterozygous twins accounted for 69.05% and preterm babies accounted for 57.07%. The average age of the mothers of twins was 31.82 years， and the average age of the fathers was 33.87 years， with more than 80% of the parents having a college degree or above. 44.50% of the mothers used assisted reproductive technologies， 7.40% had illnesses during pregnancy， and 15.90% were exposed to passive smoking during pregnancy. During the survey period， the average monthly increase in the length of the twin infants was 2.09 cm， and the average monthly weight gain was 0.53 kg. ConclusionThe incidence of adverse outcomes such as maternal cesarean section rate， preterm birth， and low birth weight is higher in the twin birth population. Information on birth health as well as growth and development in childhood and adolescence in the twin birth population is collected based on STBC， which can provide a solid data foundation for studying children’s chronic non-communicable diseases， psychological and behavioral disorders and other complex health problems caused by the combined effects of genetics and the environment.

Objective This paper aims to investigate the application of intraoral scanning and cone beam computed tomography(CBCT)registration implant robot in dental implant surgery.Methods The data of 40 cases with dental de-fect of robot-assisted implantation from November 2023 to May 2024 were retrospectively analyzed.Before the opera-tion,the intraoral scan data and CBCT data of the posi-tioning markers were automatically fused with the initial CBCT images,and the registration error was calculated.The average registration error of positioning markers was determined during the operation,and the implantation ac-curacy was analyzed after the operation.Results The intraoral scan data and CBCT data of 40 patients with dental defect wearing positioning markers were successfully registered with the initial CBCT image,and the registration errors were(0.157±0.026)mm and(0.154±0.033)mm,respectively.Statistical analysis showed no statistical significance between them.The registration errors of the marker was(0.037 3±0.003 6)mm.A total of 55 implants were performed,and the total deviations of the implant point and the apical point were(0.78±0.41)and(0.89±0.28)mm,respectively.The transverse deviations of the implant point and the apical point were(0.44±0.36)and(0.58±0.25)mm,respectively.The depth deviations of the implant point and the apical point were(0.51±0.32)and(0.54±0.36)mm,respectively.The devia-tion of the implant angle was 1.24°±0.67°.Conclusion The fusion technology based on intraoral scanning and CBCT registration can meet the accuracy requirements of preoperative registration of oral implant robots.The technology in-creases the choice of registration methods before robot-assisted dental implant surgery and reduces the multiple radiation exposuresof the patient.

Objective To study the bioequivalence of test and reference olmesartan tablet in Chinese healthy subjects after single dose under fasting and fed conditions.Methods A single-center,random,open,single-dose,two-preparations,double-period,crossover study was adopted.A total of 48 healthy adult male and female subjects(24 cases of fasting test and 24 cases of fed test)were included in the random crossover administration.Single oral dose 20 mg of test and reference were taken under fasting and postprandial conditions,respectively.Plasma concentration of olmesartan in plasma were determined by liquid chromatography tandem mass spectrometry.The main pharmacokinetic parameters were calculated by Phoenix WinNonlin 8.0 software.Results The main pharmacokinetic parameters of the test and reference preparations of olmesartan tablets in the fasting group were as follows:Cmax were(653.06±133.53)and(617.37±151.16)ng·mL-1,AUC0-t were(4 201.18±1 035.21)and(4 087.38±889.99)ng·mL-1·h,AUC0-∞ were(4 254.30±1 058.90)and(4 135.69±905.29)ng·mL-1·h.The main pharmacokinetic parameters of the test and reference preparations of olmesartan tablets in the postprandial group were as follows:Cmax were(574.78±177.05)and(579.98±107.74)ng·mL-1,AUC0-t were(3 288.37±866.06)and(3 181.51±801.06)ng·mL-1·h,AUC0-∞ were(3 326.11±874.26)and(3 242.01±823.09)ng·mL-1·h.Under fasting and postprandial conditions,the 90％confidence intervals of the main pharmacokinetic parameters of the test and reference preparations are both 80.00％-125.00％.Conclusion Under fasting and postprandial conditions,a single oral dose of test and reference preparations olmesartan tablets in Chinese healthy adult volunteers showed bioequivalence.

Cervical spondylotic radiculopathy(CSR)is a condition caused by the degeneration of cervical intervertebral discs and facet joints,primarily manifesting as the pain,sensory abnormalities,and motor dysfunction in the cervical nerve innervation area of neck,shoulder,and upper limb.For the treatment of CSR,tendon-bone syndrome differentiation in traditional Chinese medicine often faces the issues of conceptual confusion and non-standard syndrome differentiation.Based on the traditional tendon-bone syndrome differentiation and by integrating modern anatomical insights,Professor LIN Ding-Kun,an esteemed scholar of Traditional Chinese Medicine,proposed a classification system for the cervical spine that includes the categories of tendons,joints,bones and marrow.This paper explored the thoughts of Professor LIN for the tendon-bone syndrome differentiation of CSR,summarized the targets of manual therapy,and proposed the four kinds of pathological changes such as tendon overstrain,joint dislocation,bone lesion,and marrow injury,as well as the four techniques of traditional Chinese medicine manipulations,i.e.relaxation of tendons,reduction of joints,protection of marrow,and treatment of bones.The aim is to improve the syndrome-differentiation and treatment for CSR with orthopedic and traumatologic manipulations,and to provide reference for clinical practice.