ObjectiveTo improve the efficiency of drug delivery, a mannose vinyl stearate mannose ligand (Man ligand) with active liver-targeting properties was synthesized.MethodsNon-aqueous enzymatic synthesis was used to modify the structure of mannose. Glycyrrhetinic acid-tanshinone lipid nanoparticles (GT-LN) and liver-targeted glycyrrhetinic acid-tanshinone mannose-modified lipid nanoparticles (GT-MLN) were prepared. The physicochemical properties and release profiles of both formulations were evaluated, and their pharmacokinetic behavior and tissue distribution were investigated.ResultsThe average particle sizes of GT-LN and GT-MLN were 190.20 ± 1.35 and 204.83 ± 3.86 nm, respectively, with corresponding surface Zeta potentials of −28.0 ± 1.68 and −30.24 ± 2.10 mV. The drug release profile of GT-LN conformed to the Higuchi equation, whereas that of GT-MLN followed both the first-order kinetic and Ritger–Peppas equations. Both formulations significantly enhanced the gastrointestinal stability of the drug. In vivo studies in mice demonstrated that hepatic GA and TSN concentrations in both groups were significantly higher than those in the original drug suspension group (P = .01). Notably, the concentrations in the GT-MLN group were significantly higher compared to the GT-LN group (P = .01).ConclusionMan ligand was formed via the linkage of vinyl stearate with the hydroxyl group at C-6 in mannose. The Man ligand endowed these lipid nanoparticles with obvious active liver-targeting properties. Our results provide an efficient and stable route of drug delivery to the liver with improved drug availability.

Objective:To construct a machine-learning model for predicting the progression of pancreatic cystic lesions (PCLs) based on clinical and CT features, and to evaluate its predictive performance in internal/external testing cohorts.Methods:Baseline clinical and radiological data of 200 PCLs in 177 patients undergoing abdominal thin slice enhanced CT examination at Peking Union Medical College Hospital from July 2014 to December 2022 were retrospectively collected. PCLs were divided into progressive and non-progressive groups according to whether the signs indicated for surgery by the guidelines of the European study group on PCLs were present during three-year follow-up. 200 PCLs were randomly divided into training (150 PCLs) and internal testing cohorts (50 PCLs) at the ratio of 1∶3. 15 PCLs in 14 patients at Jinling Affiliated Hospital of Medical School of Nanjing University from October 2011 to May 2020 were enrolled as external testing cohort. The clinical and CT radiological features were recorded. Multiple feature selection methods and machine-learning models were implemented and combined to identify the optimal machine-learning model based on the 10-fold cross-validation method. Receiver operating characteristics (ROC) curve was drawn and area under curve (AUC) was calculated. The model with the highest AUC was determined as the optimal model. The optimal model's predictive performance was evaluated on testing cohort by calculating AUC, sensitivity, specificity and accuracy. Permutation importance was used to assess the importance of optimal model features. Calibration curves of the optimal model were established to evaluate the model's clinical applicability by Hosmer-Lemeshow test.Results:In training and internal testing cohorts, the progressive and non-progressive groups were significantly different on history of pancreatitis, lesions size, main pancreatic duct diameter and dilation, thick cyst wall, presence of septation and thick septation (all P value <0.05) In internal testing cohort, the two groups were significantly different on gender, lesion calcification and pancreatic atrophy (all P value <0.05). In external testing cohort, the two groups were significantly different on lesions size and pancreatic duct dilation (both P<0.05). The support vector machine (SVM) model based on five features selected by F test (lesion size, thick cyst wall, history of pancreatitis, main pancreatic duct diameter and dilation) achieved the highest AUC of 0.899 during cross-validation. SVM model for predicting the progression of PCLs demonstrated an AUC of 0.909, sensitivity of 82.4%, specificity of 72.7%, and accuracy of 76.0% in the internal testing cohort, and 0.944, 100%, 77.8%, and 86.7% in the external testing cohort. Calibration curved showed that the predicted probability by the model was comparable to the real progression of PCLs. Hosmer-Lemeshow goodness-of-fit test affirmed the model's consistency with actual PCLs progression in testing cohorts. Conclusions:The SVM model based on clinical and CT features can help doctors predict the PCLs progression within three-year follow-up, thus achieving efficient patient management and rational allocation of medical resource.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0％ were gram-positive and 71.0％ were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species (excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi) (MRSA,MRSE and MRCNS) was 29.6％,81.9％ and 78.5％,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9％ of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4％ of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 93.1％ in the isolates from children and and 95.9％ in the isolates from adults.The resistance rate to carbapenems was lower than 15.0％ for most Enterobacterales species except for Klebsiella,22.5％ and 23.6％ of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6％ to 10.0％.The resistance rate to imipenem and meropenem was 21.9％ and 17.4％ for Pseudomonas aeruginosa,respectively,and 67.5％ and 68.1％ for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.

Purpose To investigate the correlation and prognostic value of tumor-stroma ratio(TSR)combined with fi-brotic focus(FF)and stromal tumor-infiltrating lymphocytes(sTILs)with pathological complete response(pCR)after neoad-juvant therapy in triple-negative breast cancer(TNBC).Meth-ods The clinical data of 170 cases of TNBC were collected.Af-ter double-blind reading of the sections by two senior patholo-gists,the pathological examination results of all cases were re-viewed,and the results of TSR,FF,sTILs and the expression of CD4 and CD8 were evaluated.Then the relationship between the above information and PCR and prognosis was analyzed.Results 170 cases of TNBC after neoadjuvant therapy,57 patients a-chieved pCR,while 113 patients did not achieve pCR.Statistical analysis revealed the following findings:TSR,FF,sTILs,CD4,CD8,Ki67,vascular invasion,and lymph node metastasis exhib-ited significant differences between the pCR and non-pCR groups.There were also significant differences in TSR,FF and sTILs between different Miller-Payne(MP)grades.TSR,sTILs,TSR combined with FF,sTILs and Ki67 were positively correlated with PCR.Meanwhile,TSR,sTILs,TSR combined with FF and sTILs were also positively correlated with MP grade,while FF,intravascular tumor thrombus and lymph node metasta-sis were negatively correlated with PCR.At the same time,TSR and sTILs were also positively correlated with MP grade,and FF was also negatively correlated with MP grade.The prognosis of patients was optimal with TSR＞1,G0 FF and sTILs＞50％.When TSR combined with FF and sTILs,the prognosis of PCR group was better than that of non-PCR group.Conclusion TSR,FF,and sTILs are anticipated to serve as predictive bio-markers for assessing the efficacy and prognosis of neoadjuvant therapy in TNBC patients.These findings offer novel insights into the treatment and research strategies for TNBC.

Objective To develop the assessment scale of proactive health behavior ability for the disabled elderly in nursing homes and to test its reliability and validity.Methods The first draft of the scale was formed by literature review,qualitative interviews and Delphi method.From December 2023 to March 2024,525 disabled elderly people from 9 nursing homes in Sichuan Province and Chongqing City were selected as the survey subjects,and item analysis and reliability and validity test were carried out on the scale.30 disabled elderly people were re-investigated after 2 weeks to calculate the retest reliability of the scale.Results The scale consisted of 4 dimensions and 27 items.Exploratory factor analysis extracted 4 common factors,with the cumulative vanance contribution rate of 65.992％,and confirmatory factor analysis showed that the modified model fitting index was within acceptable range.The content validity index at item level was 0.917-1.000,and that at scale level was 0.997.The Cronbach's α coefficient,test-retest reliability and split-half reliability of the total scale were 0.944,0.997 and 0.882,respectively.Conclusion The scale has good reliability and validity,and it can be used to evaluate the proactive health behavior ability of the disabled elderly in nursing homes.

Objective:To explore the clinical features and prognosis of macrophage activation syndrome（MAS）in children with histiocytic necrotizing lymphadenitis（HNL）.Methods:The clinical data of eight children with HNL combined with MAS admitted to the Department of Pediatrics,Qilu Hospital,Shandong University,from January 2021 to February 2023 were retrospectively analyzed for clinical symptoms,laboratory tests,pathological findings,treatments,and prognosis,and a literature review was performed.Results:Among the eigh patients，five were male and three were female,with an average age of onset of（10.91±4.07）years.All children presented with fever and lymph node enlargement，which were occasionally accompanied by symptoms such as rash and arthralgia.Laboratory tests mainly showed decreased blood cells，elevated ferritin，lactate dehydrogenase and liver enzymes，normal natural killer cell function，and increased inflammatory cytokines,particalarly interleukin-6,interleukin-10,interferon-γ,and tumor necrosis factor-α.All cases were pathologically diagnosed with HNL through lymph node biopsy.All children were treated with glucocorticoids combined with immunoglobulin and/or cyclosporine.Treatment outcomes indicated that one case relapsed，one progressed to Still's disease，while the remaining six patients survived.The literature review showed that a total of 32 cases of HNL complicated by MAS were reported over the past ten years，including 25 males and seven females，with an average age of（9.66±3.77）years old.All children initially presented with fever and lymph node enlargement，and laboratory tests showed that leukopenia and/or neutrophilia，along with increased lactate dehydrogenase，ferritin and liver enzymes.Hemophagocytosis in bone marrow was observed in 70.6% of the patients.Among the 30 children with documented medication records，19 patients showed imprevement following treatment with corticosteroids and intravenous inmunoglobulin，nine patients improved with corticosteroids combined with immunosuppressive therapy，one patient improved with symptomatic treatment alone，and one patient died.Conclusion:HNL in children can be combined with MAS.Most patients have a favorable prognosis.Elevated ferritin，lactate dehydrogenase and liver enzymes may be useful diagnostic markers for MAS in HNL.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0％ were gram-positive and 71.0％ were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species (excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi) (MRSA,MRSE and MRCNS) was 29.6％,81.9％ and 78.5％,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9％ of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4％ of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 93.1％ in the isolates from children and and 95.9％ in the isolates from adults.The resistance rate to carbapenems was lower than 15.0％ for most Enterobacterales species except for Klebsiella,22.5％ and 23.6％ of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6％ to 10.0％.The resistance rate to imipenem and meropenem was 21.9％ and 17.4％ for Pseudomonas aeruginosa,respectively,and 67.5％ and 68.1％ for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.

Objective:To explore the clinical features and prognosis of macrophage activation syndrome（MAS）in children with histiocytic necrotizing lymphadenitis（HNL）.Methods:The clinical data of eight children with HNL combined with MAS admitted to the Department of Pediatrics,Qilu Hospital,Shandong University,from January 2021 to February 2023 were retrospectively analyzed for clinical symptoms,laboratory tests,pathological findings,treatments,and prognosis,and a literature review was performed.Results:Among the eigh patients，five were male and three were female,with an average age of onset of（10.91±4.07）years.All children presented with fever and lymph node enlargement，which were occasionally accompanied by symptoms such as rash and arthralgia.Laboratory tests mainly showed decreased blood cells，elevated ferritin，lactate dehydrogenase and liver enzymes，normal natural killer cell function，and increased inflammatory cytokines,particalarly interleukin-6,interleukin-10,interferon-γ,and tumor necrosis factor-α.All cases were pathologically diagnosed with HNL through lymph node biopsy.All children were treated with glucocorticoids combined with immunoglobulin and/or cyclosporine.Treatment outcomes indicated that one case relapsed，one progressed to Still's disease，while the remaining six patients survived.The literature review showed that a total of 32 cases of HNL complicated by MAS were reported over the past ten years，including 25 males and seven females，with an average age of（9.66±3.77）years old.All children initially presented with fever and lymph node enlargement，and laboratory tests showed that leukopenia and/or neutrophilia，along with increased lactate dehydrogenase，ferritin and liver enzymes.Hemophagocytosis in bone marrow was observed in 70.6% of the patients.Among the 30 children with documented medication records，19 patients showed imprevement following treatment with corticosteroids and intravenous inmunoglobulin，nine patients improved with corticosteroids combined with immunosuppressive therapy，one patient improved with symptomatic treatment alone，and one patient died.Conclusion:HNL in children can be combined with MAS.Most patients have a favorable prognosis.Elevated ferritin，lactate dehydrogenase and liver enzymes may be useful diagnostic markers for MAS in HNL.

Purpose To investigate the correlation and prognostic value of tumor-stroma ratio(TSR)combined with fi-brotic focus(FF)and stromal tumor-infiltrating lymphocytes(sTILs)with pathological complete response(pCR)after neoad-juvant therapy in triple-negative breast cancer(TNBC).Meth-ods The clinical data of 170 cases of TNBC were collected.Af-ter double-blind reading of the sections by two senior patholo-gists,the pathological examination results of all cases were re-viewed,and the results of TSR,FF,sTILs and the expression of CD4 and CD8 were evaluated.Then the relationship between the above information and PCR and prognosis was analyzed.Results 170 cases of TNBC after neoadjuvant therapy,57 patients a-chieved pCR,while 113 patients did not achieve pCR.Statistical analysis revealed the following findings:TSR,FF,sTILs,CD4,CD8,Ki67,vascular invasion,and lymph node metastasis exhib-ited significant differences between the pCR and non-pCR groups.There were also significant differences in TSR,FF and sTILs between different Miller-Payne(MP)grades.TSR,sTILs,TSR combined with FF,sTILs and Ki67 were positively correlated with PCR.Meanwhile,TSR,sTILs,TSR combined with FF and sTILs were also positively correlated with MP grade,while FF,intravascular tumor thrombus and lymph node metasta-sis were negatively correlated with PCR.At the same time,TSR and sTILs were also positively correlated with MP grade,and FF was also negatively correlated with MP grade.The prognosis of patients was optimal with TSR＞1,G0 FF and sTILs＞50％.When TSR combined with FF and sTILs,the prognosis of PCR group was better than that of non-PCR group.Conclusion TSR,FF,and sTILs are anticipated to serve as predictive bio-markers for assessing the efficacy and prognosis of neoadjuvant therapy in TNBC patients.These findings offer novel insights into the treatment and research strategies for TNBC.

In recent years, the State has intensified efforts to develop folk Traditional Chinese Medicine (TCM). Shaanxi Province is a large province with rich TCM resources. However, the certificate holding rate of folk TCM in Shaanxi is low, the inheritance of medical skills is not optimistic; the core skills of folk TCM are lack of protection; the traditional folk diagnosis and treatment technology is lack of corresponding standards, and the clinical promotion is difficult, which makes the advantages of folk TCM not fully play. It was suggested that strengthen the assessment of Shaanxi Province’s real expertise, take measures to promote the inheritance, enhance the intellectual property protection of folk TCM in the province, intensify the research and formulation of local folk TCM screening and evaluation standards, and vigorously promote the clinical application of folk TCM in the province, so as to promote the inheritance, protection and development of folk TCM in Shaanxi Province.