Objective:To establish a paired organoid culture system for primary pancreatic cancer lesions and liver metastatic lesions in mice, and to investigate their morphological and biological behaviors.Methods:C57BL/6 mice aged 6 to 8 weeks were selected. Pancreatic cancer PANC02 cells carrying luciferase were injected into the pancreatic tail. After monitoring the formation of liver metastases using an in vivo imaging system, mice were sacrificed, and paired primary pancreatic cancer lesions and liver metastatic lesions were extracted and cultured in an in vitro organoid culture system. The formation process of organoids was observed under an inverted phase-contrast microscope. Hematoxylin and eosin staining was used to examine the morphological structure of the organoids. The expression of epithelial cell marker CK19 and proliferation marker Ki67 in the organoids was detected by immunohistochemistry and immunofluorescence staining. The expression of invasion markers N-cadherin, E-cadherin, vimentin, snail, and MMP9 was assessed by Western blotting and immunohistochemistry. The drug sensitivity of organoids to gemcitabine was evaluated using the CellTiter-Glo ? 3D Cell Viability Assay, and the half-maximal inhibitory concentration (IC 50) of the organoids was calculated. Results:A spontaneous liver metastasis model of pancreatic cancer in mice was successfully established, along with a paired organoid culture system for primary pancreatic cancer lesions and liver metastatic lesions. The organoids grew in a spherical shape and could be passaged up to 10 generations in vitro. Both liver metastatic lesion organoids and primary pancreatic cancer lesion organoids exhibited lumen-like structures, expressed the epithelial cell marker CK19, and the proliferation marker Ki67, with a significantly higher positive ratio of Ki67 in the liver metastatic lesions compared to the primary pancreatic cancer lesions. The expression levels of invasion markers N-cadherin, vimentin, snail, and MMP9 were significantly higher in liver metastatic organoids than in primary pancreatic cancer organoids, whereas the expression level of E-cadherin was significantly lower in liver metastatic organoids. The IC 50 value of gemcitabine for liver metastatic organoids was 165.0 nM, higher than the 108.5 nM for primary pancreatic cancer organoids. Conclusions:A stable, passagable organoids of primary pancreatic cancer lesions and liver metastatic lesions in mice were successfully established.

Objective The aim of this study was to investigate the prognostic value of body composition indicators in evaluating the development risk of gestational diabetes mellitus(GDM).Methods A total of 1431 pregnant women who were registered and underwent prenatal examinations in the Clinical Nutrition Department of Guizhou Hospital of Beijing Jishuitan Hospital were selected in this study from January 2018 to September 2021.Among them,263 participants were diagnosed with GDM(GDM group),and 1168 healthy individuals underwent physical examinations were enrolled as Con group.Results The GDM detection rate was 18.38%(263/1431).Logistic regression analysis showed that age and percent body fat were risk factors for the development of GDM.The area under the ROC curve of percent body fat for GDM prediction was 0.732,with sensitivity,specificity of 67.7%,68.3%.Conclusions High percentage of body fat during pregnancy is a risk factor for the development of GDM in late pregnancy,and the risk of developing diabetes during pregnancy can be predicted by the percentage of body fat index.

Objective To explore the application effect of advanced lung rehabilitation programs in patients un-dergoing high flow nasal cannula oxygen therapy(HFNC).Methods Convenience sampling method was used to se-lect 40 HFNC patients admitted to the respiratory department,ICU,coronary heart disease monitoring unit,and other departments of a tertiary A comprehensive hospital in Tianjin from January to June 2023 as the experimental group,and 40 HFNC patients admitted from June to December 2022 as the control group.Both groups of patients received HFNC treatment during hospitalization and continued at home,while the experimental group adopts the information-motivation-behavioral skills(IMB)model as the theoretical basis,implements advanced pulmonary rehabili-tation during the stable condition period,discharge preparation period,and home rehabilitation period,and imple-ments compliance management of home pulmonary rehabilitation through cloud follow-up,and the control group re-ceived routine lung rehabilitation and home follow-up.The degree of respiratory distress,6-minute walking distance,exercise self-efficacy,quality of life were compared between the 2 groups before intervention,2 months and 6 months after intervention,and compliance with home pulmonary rehabilitation was compared between the 2 groups 6 months after intervention.Results The repeated measures analysis of variance showed that there was an interaction effect between time and the 2 groups in terms of difficulty in breathing,6-minute walking distance,exercise self-ef-ficacy,and quality of life(P＜0.05).Simple effect analysis showed that after 2 and 6 months of intervention,the ex-perimental group performed better than the control group in the respiratory distress,6-minute walking distance,exer-cise self-efficacy,and quality of life(P＜0.05).Within 6 months of intervention,the compliance of home pulmonary rehabilitation in the experimental group was better than that in the control group,and the difference was statistically significant(P＜0.05).Conclusion The application of advanced pulmonary rehabilitation programme based on IMB can improve respiratory symptoms and improve exercise self-efficacy and adherence to pulmonary rehabilitation,en-hance activity endurance and improve quality of life.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-positive bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-positive 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:A total of 3 163 strains of Gram-positive pathogens were collected from 51 member units，and the top five bacteria were Staphylococcus aureus（ n=1 147，36.3%），coagulase-negative Staphylococci（ n=928，29.3%）， Enterococcus faecalis（ n=369，11.7%）， Enterococcus faecium（ n=296，9.4%）and alpha-hemolyticus Streptococci（ n=192，6.1%）. The detection rates of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）were 26.4%（303/1 147）and 66.7%（619/928），respectively. No glycopeptide and daptomycin-resistant Staphylococci were detected. The sensitivity rates of Staphylococcus aureus to cefpirome，rifampin，compound sulfamethoxazole，linezolid，minocycline and tigecycline were all >95.0%. Enterococcus faecium was more prevalent than Enterococcus faecalis. The resistance rates of Enterococcus faecium to vancomycin and teicoplanin were both 0.5%（2/369），and no vancomycin-resistant Enterococcus faecium was detected. The detection rate of MRSA in southern China was significantly lower than that in other regions（ χ2=14.578， P=0.002），while the detection rate of MRCNS in northern China was significantly higher than that in other regions（ χ2=15.195， P=0.002）. The detection rates of MRSA and MRCNS in provincial hospitals were higher than those in municipal hospitals（ χ2=13.519 and 12.136， P<0.001）. The detection rates of MRSA and MRCNS in economically more advanced regions（per capita GDP≥92 059 Yuan in 2022）were higher than those in economically less advanced regions（per capita GDP<92 059 Yuan）（ χ2=9.969 and 7.606， P=0.002和0.006）. Conclusions:Among the Gram-positive pathogens causing bloodstream infections in China， Staphylococci is the most common while the MRSA incidence decreases continuously with time；the detection rate of Enterococcus faecium exceeds that of Enterococcus faecalis. The overall prevalence of vancomycin-resistant Enterococci is still at a low level. The composition ratio of Gram-positive pathogens and resistant profiles varies slightly across regions of China，with the prevalence of MRSA and MRCNS being more pronounced in provincial hospitals and areas with a per capita GDP≥92 059 yuan.

Objective:To explore the effectiveness and safety of endoscopic ultrasound-guided pancreatic duct drainage (EUS-PD).Methods:A retrospective analysis was conducted on data of 16 patients who underwent EUS-PD because of endoscopic retrograde pancreatography (ERP) failure, poor effectiveness or anatomical changes and couldn't undergo the routine ERP in Nanjing Drum Tower Hospital from June 2018 to July 2022. The technical success of EUS-PD, clinical efficacy and post-procedure adverse events were analyzed.Results:In the 16 patients, there were 14 males and 2 females, with age of 50.69±12.95 years. A total of 19 times of EUS-PD operations were included, 3 of them were rendezvous-assisted endoscopic retrograde pancreatography (RV-ERP), 15 transgastric or transenteric EUS-guided stent placement and 1 was EUS-guided nasopancreatic duct placement. Technical success was achieved in 84.21% (16/19) patients, and among whom 93.75% (15/16) achieved clinical success. The overall incidence of postoperative adverse events was 52.63% (10/19) including 47.37% (9/19) abdominal pain, 15.79% (3/19) fever and 15.79% (3/19) postoperative pancreatitis. All adverse effects were relieved after general conservative treatment and no primary disease or surgery-related death occurred. The mean follow-up was 17.6 (8.2,22.3) months and 93.75% (15/16) of the patients were followed up. By the time of follow-up, 76.92% (10/13) of the patients who had successfully received EUS-PD had no recurrence of abdominal pain or distension.Conclusion:EUS-PD is a safe and effective alternative therapy for those with pancreatic diseases with ERP failure, poor efficacy or anatomical changes.

Objective:To analyze the clinical characteristics and all-cause mortality influencing factors of patients with Keshan disease.Methods:Clinical data of patients with Keshan disease from Keshan disease areas in Sichuan Province and Yunnan Province were collected and retrospectively analyzed for clinical characteristics and survival status during regular follow-up. According to the survival status of patients, the survey subjects were divided into a survival group and a death group. All-cause mortality (referring to the death caused by various reasons throughout the follow-up period) was used as the study endpoint. Kaplan-Meier (K-M) survival curve analysis and log-rank χ 2 test were performed, univariate and multivariate Cox regression analysis were used for all-cause mortality factor analysis. Results:A total of 176 patients with Keshan disease were collected, including 92 cases in Sichuan Province and 84 cases in Yunnan Province. Among all the patients, there were 105 males, accounting for 59.66%, and 71 females, accounting for 40.34%. The age was (53.89 ± 13.19) years old. Thirty-five cases died from all causes, with a mortality rate of 19.89%. There were significant differences in age ( t = 2.09, P = 0.038), New York Heart Association (NYHA) cardiac function grading (χ 2 = 14.62, P < 0.001) and ventricular premature contraction (χ 2 = 6.82, P = 0.009) between the survival group and the death group. K-M survival curve analysis showed that patients with Keshan disease complicated by premature ventricular contraction and high NYHA cardiac function grading (Ⅲ and Ⅳ) had higher all-cause mortality (log-rank χ 2 = 8.72, 22.49, P < 0.05). Univariate Cox regression analysis showed that NYHA cardiac function grading and ventricular premature contraction ( HR = 3.09, 2.71, P < 0.05) were predictive influencing factors for all-cause mortality in patients with Keshan disease. Multivariate Cox regression analysis showed that NYHA cardiac function grading ( HR = 6.57, P = 0.002) and ventricular premature contraction ( HR = 2.98, P = 0.050) were independent factors for all-cause mortality in patients with Keshan disease. Conclusions:Among 176 patients with Keshan disease, the number of patients with poor cardiac function (NYHA cardiac function grading Ⅲ and Ⅳ) and arrhythmia is high. NYHA cardiac function grading and ventricular premature contractions are independent influencing factors for all-cause mortality in patients with Keshan disease.

Objective:To analyze the clinical characteristics, prognosis and gene mutation in patients with dilated cardiomyopathy (DCM) in Keshan disease area of Sichuan Province, and to explore the risk factors for all-cause death in DCM patients.Methods:In June 2016, 55 DCM patients diagnosed at the local disease prevention and control center through clinical manifestations, electrocardiogram examination, and echocardiography were selected as the survey subjects in Mianning County, Liangshan Yi Autonomous Prefecture, and Renhe District, Panzhihua City, Keshan disease areas of Sichuan Province. Baseline clinical data were analyzed and long-term follow-up was conducted. The follow-up period ended June 15, 2021, with the endpoint of all-cause death. Univariate Cox regression was used to analyze the influencing factors of all-cause death in patients, and Kaplan-Meier (K-M) survival curve was used to analyze the survival time of patients. At the same time, peripheral venous blood was collected from 27 DCM patients. After separating white blood cells, DNA was extracted, and whole exome sequencing was performed to screen potential pathogenic genes.Results:Among the 55 DCM patients, 40 were males and 15 were females. The age was (54.09 ± 12.38) years old. The heart function classification of New York Heart Association (NYHA) was mainly grade Ⅱ and Ⅲ, accounting for 94.55% (52/55). The follow-up time for 55 DCM patients was (7.02 ± 2.96) years, and 17 patients experienced all-cause death, accounting for 30.91% (17/55), including 15 males and 2 females. Compared with the survival group, the death group had a lower incidence of syncope (χ 2 = 6.57, P = 0.010), but higher rates of bilateral lower limb edema (χ 2 = 6.43, P = 0.017), pulmonary congestion (χ 2 = 7.61, P = 0.006), intraventricular conduction block (χ 2 = 6.41, P = 0.011), and angiotensin-converting enzyme inhibitor (ACEI) use (χ 2 = 6.57, P = 0.010), as well as increased left ventricular diameter ( t = 2.36, P = 0.022). Univariate Cox regression analysis showed that bilateral lower limb edema [hazard ratio ( HR) = 4.61, P = 0.042] and intraventricular conduction block ( HR = 3.20, P = 0.019) were risk factors for all-cause death of DCM patients. The results of K-M survival curve analysis showed that patients with bilateral lower limb edema and intraventricular conduction block had higher all-cause death rates (log-rank χ 2 = 5.02, 6.24, P = 0.025, 0.012). Whole exome sequencing results showed that 4 patients were detected to carry pathogenic or suspected pathogenic gene mutations, with a positive rate of 14.81% (4/27), involving three genes: β-myosin heavy chain 7 (MYH7), calreticulin 3 (CALR3), and gelsolin (GSN). Conclusions:The all-cause death rate of DCM patients in the Keshan disease area of Sichuan Province is relatively high. Dead patients are prone to bilateral lower limb edema, pulmonary congestion, and intraventricular conduction block, as well as increased left ventricular diameter. Bilateral lower limb edema and intraventricular conduction block are independent predictive risk factors for all-cause death in DCM patients. MYH7, CALR3 and GSN are involved in the pathogenesis of DCM.

Oral diseases concern almost every individual and are a serious health risk to the popula-tion.The restorative treatment of tooth and jaw defects is an important means to achieve oral function and support the appearance of the contour.Based on the principle of"learning from the nature",Deng Xu-liang's group of Peking University School and Hospital of Stomatology has proposed a new concept of"microstructural biomimetic design and tissue adaptation of tooth/jaw materials"to address the worldwide problems of difficulty in treating dentine hypersensitivity,poor prognosis of restoration of tooth defects,and vertical bone augmentation of alveolar bone after tooth loss.The group has broken through the bottle-neck of multi-stage biomimetic technology from the design of microscopic features to the enhancement of macroscopic effects,and invented key technologies such as crystalline/amorphous multi-level assembly,ion-transportation blocking,and multi-physical properties of the micro-environment reconstruction,etc.The group also pioneered the cationic-hydrogel desensitizer,digital stump and core integrated restora-tions,and developed new crown and bridge restorative materials,gradient functionalisation guided tissue regeneration membrane,and electrically responsive alveolar bone augmentation restorative membranes,etc.These products have established new clinical strategies for tooth/jaw defect repair and achieved inno-vative results.In conclusion,the research results of our group have strongly supported the theoretical im-provement of stomatology,developed the technical system of oral hard tissue restoration,innovated the clinical treatment strategy,and led the progress of the stomatology industry.

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.

OBJECTIVE To explore the potential mechanism of anti-HeLa cell of triterpenoids from Inonotus obliquus by network pharmacology, molecular docking and in vivo verification experiments. METHODS Based on literature research and database, the main active components of triterpenoids from Inonotus obliquus were screened, and the active components and HeLa cell intersection targets were found. PPI network was constructed, GO and KEGG enrichment analysis were carried out, and molecular docking was verified. HeLa cell nude mice model was established, and Inonotus obliquus triterpenoids were administered by gavage. The indexes were detected and detected by Western blotting after euthanizing nude mice. RESULTS After screening, 274 associated targets of 15 qualified active components were obtained. Intersecting with 2 046 HeLa cell-related targets, 104 potential anti-HeLa cell targets of Inonotus obliquus triterpenoids were obtained. Through the "drug-component-target-disease" network analysis, PIK3CA, MAPK3, MDM2, AR and CCND1 might be potential targets for anti-HeLa cell of triterpenoids purified from Inonotus obliquus. The results of KEGG enrichment analysis showed that multiple signal pathways such as PI3K/Akt signal pathway, Ras signal pathway and MAPK signal pathway might be the potential anti-HeLa cell pathway of triterpenoids in Inonotus obliquus. The results of molecular docking showed that the core components and key targets had strong potential binding ability. The in vivo test results showed that Inonotus obliquus triterpenoids could inhibit tumor growth, regulate immune function, promote tumor apoptosis and inhibit PI3K and AKT phosphorylation in model mice. CONCLUSION Based on the methods of network pharmacology, molecular docking and in vivo verification, it is proved that the triterpenoids of Inonotus obliquus play the role of anti-HeLa cell through multi-components and multi-targets, which lays a foundation for further research and development of Inonotus obliquus and the discussion of its anti-tumor mechanism.