Objective To propose a lung artery segmentation method that integrates shape and position prior knowledge, aiming to solve the issues of inaccurate segmentation caused by the high similarity and small size differences between the lung arteries and surrounding tissues in CT images. Methods Based on the three-dimensional U-Net network architecture and relying on the PARSE 2022 database image data, shape and position prior knowledge was introduced to design feature extraction and fusion strategies to enhance the ability of lung artery segmentation. The data of the patients were divided into three groups: a training set, a validation set, and a test set. The performance metrics for evaluating the model included Dice Similarity Coefficient (DSC), sensitivity, accuracy, and Hausdorff distance (HD95). Results The study included lung artery imaging data from 203 patients, including 100 patients in the training set, 30 patients in the validation set, and 73 patients in the test set. Through the backbone network, a rough segmentation of the lung arteries was performed to obtain a complete vascular structure; the branch network integrating shape and position information was used to extract features of small pulmonary arteries, reducing interference from the pulmonary artery trunk and left and right pulmonary arteries. Experimental results showed that the segmentation model based on shape and position prior knowledge had a higher DSC (82.81%±3.20% vs. 80.47%±3.17% vs. 80.36%±3.43%), sensitivity (85.30%±8.04% vs. 80.95%±6.89% vs. 82.82%±7.29%), and accuracy (81.63%±7.53% vs. 81.19%±8.35% vs. 79.36%±8.98%) compared to traditional three-dimensional U-Net and V-Net methods. HD95 could reach (9.52±4.29) mm, which was 6.05 mm shorter than traditional methods, showing excellent performance in segmentation boundaries. Conclusion The lung artery segmentation method based on shape and position prior knowledge can achieve precise segmentation of lung artery vessels and has potential application value in tasks such as bronchoscopy or percutaneous puncture surgery navigation.

Umbilical cord mesenchymal stem cells (UC-MSCs) have been widely used in regenerative medicine, but there is limited research on the stability of UC-MSCs formulation during production. This study aims to assess the stability of the cell stock solution and intermediate product throughout the production process, as well as the final product following reconstitution, in order to offer guidance for the manufacturing process and serve as a reference for formulation reconstitution methods. Three batches of cell formulation were produced and stored under low temperature (2-8 ℃) and room temperature (20-26 ℃) during cell stock solution and intermediate product stages. The storage time intervals for cell stock solution were 0, 2, 4, and 6 h, while for intermediate products, the intervals were 0, 1, 2, and 3 h. The evaluation items included visual inspection, viable cell concentration, cell viability, cell surface markers, lymphocyte proliferation inhibition rate, and sterility. Additionally, dilution and culture stability studies were performed after reconstitution of the cell product. The reconstitution diluents included 0.9% sodium chloride injection, 0.9% sodium chloride injection + 1% human serum albumin, and 0.9% sodium chloride injection + 2% human serum albumin, with dilution ratios of 10-fold and 40-fold. The storage time intervals after dilution were 0, 1, 2, 3, and 4 h. The reconstitution culture media included DMEM medium, DMEM + 2% platelet lysate, 0.9% sodium chloride injection, and 0.9% sodium chloride injection + 1% human serum albumin, and the culture duration was 24 h. The evaluation items were viable cell concentration and cell viability. The results showed that the cell stock solution remained stable for up to 6 h under both low temperature (2-8 ℃) and room temperature (20-26 ℃) conditions, while the intermediate product remained stable for up to 3 h under the same conditions. After formulation reconstitution, using sodium chloride injection diluted with 1% or 2% human serum albumin maintained a viability of over 80% within 4 h. It was observed that different dilution factors had an impact on cell viability. After formulation reconstitution, cultivation in medium with 2% platelet lysate resulted in a cell viability of over 80% after 24 h. In conclusion, the stability of cell stock solution within 6 h and intermediate product within 3 h meets the requirements. The addition of 1% or 2% human serum albumin in the reconstitution diluent can better protect the post-reconstitution cell viability.

Objective Studies on the expression and location of zinc finger protein A20 (A20) and connective tissue growth factor (CTGF) in liver tissues of patients with chronic hepatitis B were conducted, and the relationship between them and liver fibrosis was determined by FibroScan. Methods Studies on A20 and CTGF in liver tissues of 160 patients with chronic hepatitis B were conducted in accordance with the stage of pathological fibrosis and inflammation of the liver, and quantitative immunohistochemistry test was conducted, and statistical analysis was conducted by FibroScan. Results The expressions of A20 and CTGF in liver tissues increased with the aggravation of liver pathological fibrosis and inflammation, and there were significant differences between each stage and the control group (P<0.05), and there were significant differences between adjacent groups (P<0.05). Studies have shown that FibroScan increases along with pathological fibrosis and inflammation in the liver. There are significant differences between the stage and the control group (P<0.05), and no significant differences between the adjacent groups (P>0.05). There was positive correlation between liver A20 and CTGF, r=0.796 (P<0.05). Conclusions In patients with chronic hepatitis B, A20, CTGF and FibroScan are positively correlated with the degree of liver fibrosis, and A20 and CTGF are also positively correlated with the degree of liver inflammation, which can be used as indicators to evaluate the degree of liver inflammation and fibrosis, and further guide the anti-inflammatory and anti-fibrosis treatment of patients.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

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.

AIM To determine the contents of aspartic acid,glutamic acid,serine,glycine,threonine,citrulline,arginine,alanine,γ-amino-butyric acid,tyrosine,valine,phenlalanine,isoleucine,ornithine,leucine,lysine and proline in Gualoupi Injection and its intermediates,and to analyze their change laws.METHODS The OPA-FMOC online derivatization analysis was performed on a 45℃ thermostatic Waters XBridge C18 column(4.6 mm×100 mm,3.5 μm),with the mobile phase comprising of phosphate buffer solution-[methanol-acetonitrile-water(45 : 45 : 10)]flowing at 1 mL/min in a gradient elution manner,and the detection wavelengths were set at 262,338 nm.Principal component analysis and heatmap analysis were adopted in chemical pattern recognition for the corresponding intermediates in ten processes of six batches of samples.RESULTS Seventeen amino acids showed good linear relationships within their own ranges(R2>0.998 0),whose average recoveries were 83.4％-119.5％with the RSDs of 0.91％-7.94％.Different batches of samples in the same process were clustered,and the corresponding intermediates in different processed were clustered into three groups.Alcohol precipitation and cation exchange column demonstrated the biggest influences on amino acid composition.CONCLUSION This experiment can provide important references for the critical factors on quality control of Gualoupi Injection,thus ensure the stability and uniformity of final product.

Pneumococcal vaccine plays a key role in preventing diseases such as pneumonia and meningitis caused by Streptococcus pneumoniae(S.pneumoniae).Capsular polysaccharide,C-polysaccharide and phosphorus content are important indicators for quality control of polysaccharide antigens in vaccine development and production.In this study,a quantitative 1H NMR and 31P NMR method based on a single internal standard hexamethylphosphoramide(HMPA)was developed to achieve simultaneous determination of capsular polysaccharide,C-polysaccharide and phosphorus content in 6A,6B,18C,19A,19F and 23F S.pneumoniae polysaccharide antigens.Using the internal reference comparison method,the effect of solubility of polysaccharide on quantitative 1H NMR determination was investigated.It was found that the determination results of quantitative 1H NMR were affected by the viscosity and concentration of polysaccharide solution.It was found that high viscosity polysaccharides at 3-15 mg/mL and low viscosity polysaccharides at 5-25 mg/mL were the optimal detection solution concentration range.This"one internal standard three quantitative"NMR method has good precision,specificity and accuracy,and provides a valuable new strategy for the quality control of pneumococcal vaccine.

Diabetes mellitus(DM)is a disease syndrome characterized by chronic hyperglycaemia.A long-term high-glucose environment leads to reactive oxygen species(ROS)production and nuclear DNA damage.Human umbilical cord mesenchymal stem cell(HUcMSC)infusion induces significant antidiabetic effects in type 2 diabetes mellitus(T2DM)rats.Insulin-like growth factor 1(IGF1)receptor(IGF1R)is important in promoting glucose metabolism in diabetes;however,the mechanism by which HUcMSC can treat diabetes through IGF1R and DNA damage repair remains unclear.In this study,a DM rat model was induced with high-fat diet feeding and streptozotocin(STZ)administration and rats were infused four times with HUcMSC.Blood glucose,interleukin-6(IL-6),IL-10,glomerular basement membrane,and renal function were examined.Proteins that interacted with IGF1R were determined through coimmunoprecipitation assays.The expression of IGF1R,phosphorylated checkpoint kinase 2(p-CHK2),and phosphorylated protein 53(p-p53)was examined using immunohistochemistry(IHC)and western blot analysis.Enzyme-linked immunosorbent assay(ELISA)was used to determine the serum levels of 8-hydroxydeoxyguanosine(8-OHdG).Flow cytometry experiments were used to detect the surface markers of HUcMSC.The identification of the morphology and phenotype of HUcMSC was performed by way of oil red"O"staining and Alizarin red staining.DM rats exhibited abnormal blood glucose and IL-6/10 levels and renal function changes in the glomerular basement membrane,increased the expression of IGF1 and IGF1R.IGF1R interacted with CHK2,and the expression of p-CHK2 was significantly decreased in IGF1R-knockdown cells.When cisplatin was used to induce DNA damage,the expression of p-CHK2 was higher than that in the IGF1R-knockdown group without cisplatin treatment.HUcMSC infusion ameliorated abnormalities and preserved kidney structure and function in DM rats.The expression of IGF1,IGF1R,p-CHK2,and p-p53,and the level of 8-OHdG in the DM group increased significantly compared with those in the control group,and decreased after HUcMSC treatment.Our results suggested that IGF1R could interact with CHK2 and mediate DNA damage.HUcMSC infusion protected against kidney injury in DM rats.The underlying mechanisms may include HUcMSC-mediated enhancement of diabetes treatment via the IGF1R-CHK2-p53 signalling pathway.

Objective To introduce a partially nested design based on the characteristics of TCM in treating the same disease with different treatments and syndrome differentiation and treatment.Methods Partially nested design was used for standardized treatment of complex interventions.The TCM group was divided into multiple subsets according to"syndrome type-treatment method-prescription"(with nested structure),while the control group was treated with standardized Western medicine(without nested structure);taking a case study of"different treatments for the same disease"data for ulcerative colitis,this design type was applied and analyzed using a multi-level model.Results The partially nested design was consistent with the feature of TCM of"different treatments for the same disease"and met the methodological requirements for evidence-based evaluation.Multilevel models allowed analyses with this type of data.Conclusion The use of partially nested design enables the evaluation of the comprehensive effectiveness of"different treatments for the same disease",which can provide a methodological reference for the assessment of clinical effectiveness of TCM.

Objective:To determine incidence of seasonal influenza virus infection in the community and to analyze the factors influencing seasonal influenza virus infection.Methods:This study recruited residents aged 6-59 years to build a cohort in 15 villages/streets in Macheng city in November 2019. Meanwhile, a cross-sectional baseline survey was conducted immediately to collect sera, information on demographics and child protection knowledge, behaviors, as well as attitudes using a questionnaire from the participants enrolled in the cohort (i.e., before the influenza epidemic season). In July 2020, a cross-sectional follow-up survey was conducted to collect sera once again (i.e., after the influenza season). Paired sera from the two cross-sectional surveys were tested for influenza virus-specific antibodies by hemagglutination inhibition (HI) test or micro-neutralization (MN) test using a circulating representative strain of each subtype/lineage of influenza virus as the test antigen. The infections with influenza virus subtype/lineage was confirmed if there was a four-fold or more increase in titers of antibodies against circulating representative strain of the subtype/lineage of influenza virus. Factors influencing infection with influenza A (H3N2) and B/Victoria viruses were analyzed using univariable and multivariable logistic regression.Results:In November 2019, 800 study participants were enrolled in the cohort, including 340 children aged 6-17 years and 460 adults aged 18-59 years; 605 study participants (including 224 children and 381 adults) were followed up in July 2020 and their paired sera were obtained before and after the influenza season. 25.3% (153/605) of the participants were confirmed to be infected with at least one subtype/lineage of seasonal influenza virus by HI and MN tests. The overall incidence of influenza viruses of all subtypes/lineages in children was 44.2% (95% CI: 37.6%-50.8%) which was significantly higher than the incidence of 14.1% in adults (95% CI: 10.7%-17.7%). Children had the highest incidence of influenza A (H3N2) virus infection, followed by B/Victoria. MN or HI antibody titers in A (H3N2)[ OR=0.88 (95% CI: 0.84-0.93)] and B/Victoria[ OR=0.97 (95% CI: 0.95-0.99)] before the influenza season were significantly associated with whether children were infected with that subtype/lineage of influenza virus. Conclusions:The residents aged 6-59 years in Macheng city had a substantial incidence of seasonal influenza virus infection during the influenza season from winter 2019 to spring 2020. Notably, almost half of children aged 6-17 years have been infected with seasonal influenza virus. Higher titers of HI/MN antibodies against seasonal influenza virus before the influenza season would be likely to reduce the risk of infection with influenza A (H3N2) and B/Victoria.