19 cinnamamide/ester-triazole compounds were designed, synthesized and evaluated for their anti-Alzheimer's disease (AD) activity. Among them, compound 4f displayed excellent anti-β-amyloid protein (Aβ)-mediated cytotoxicity (EC₅₀ = 2.03 ± 2.45 μmol·L^-1) in APPswe cells and acetylcholinesterase inhibiton (IC₅₀ = 4.88 ± 4.70 μmol·L^-1). Further study indicated that, at dosages of (1, 5 and 25 mg·kg^-1), compound 4f was effective in improving spatial learning and memory deficits in Aβ_1-42-impaired mice, which was achieved by promoting the nonamyloidogenic signaling and inhibiting the amyloidogenic pathway, along with the suppression of Aβ-induced Tau phosphorylation. All animal experiments in this study were approved by the Experimental Animal Care and Use Committee of the Institute of Medicinal Biotechnology (IMB-20220908D701). In conclusion, compound 4f holds promise as a lead candidate for AD treatment, and the present study lays the foundation for its subsequent development.

Ulcerative colitis （UC）， a chronic， non-specific inflammatory bowel disease with typical symptoms such as abdominal pain， diarrhea， and bloody stools， demonstrates a high relapse rate and difficulty in curing. Sishenwan， first recorded in Internal Medicine Abstract （Nei Ke Zhai Yao）， are a classic prescription for treating diarrhea caused by deficiency of the spleen and kidney Yang. The core therapeutic principle of Sishenwan is warming and tonifying the spleen and kidney， and astringing the intestine and stopping diarrhea. In recent years， Sishenwan have demonstrated distinct advantages in the clinical treatment of UC. The pathogenesis of UC involves multiple factors， including immune dysregulation and gut microbiota imbalance. Although Western medicine is effective in the short term， its side effects， high relapse rate， and resistance associated with long-term use pose substantial challenges. Sishenwan have shown excellent clinical outcomes in the treatment of UC due to deficiency of the spleen and kidney Yang. Modern clinical studies indicate that Sishenwan， used alone or in combination with Western medicine or other Chinese medicine compound prescriptions， significantly improve the clinical efficacy in treating UC due to deficiency of the spleen and kidney Yang. Sishenwan effectively alleviate core symptoms such as mucus， pus， and blood in stools， and persistent abdominal pain， reduce Mayo scores and the relapse rate， and improve patients' quality of life. Research on the material basis reveals that Sishenwan contain multiple active ingredients such as psoralen， isopsoralen， and evodiamine. Mechanism studies indicate that Sishenwan inhibit the inflammatory cascade reactions by regulating the signal network through multiple targets. Sishenwan regulate cellular immunity and restore intestinal immune homeostasis. At the microecological level， Sishenwan promote the intestinal barrier repair through the "microbiota-metabolism-immunity" axis. The current research still needs to be deepened in aspects such as the mining of specific biomarkers for syndromes and the exploration of the collaborative mechanism of traditional Chinese and Western medicine. In the future， a full-chain system covering syndrome differentiation， targeting， and monitoring needs to be constructed for promoting the paradigm transformation of Sishenwan into precision drugs. This review systematically explains the treatment mechanism of Sishenwan regarding the combination of disease and syndrome and its multi-target regulatory characteristics， providing a theoretical basis and transformation direction for the treatment of UC with integrated traditional Chinese and Western medicine.

Ulcerative colitis （UC）， a chronic， non-specific inflammatory bowel disease with typical symptoms such as abdominal pain， diarrhea， and bloody stools， demonstrates a high relapse rate and difficulty in curing. Sishenwan， first recorded in Internal Medicine Abstract （Nei Ke Zhai Yao）， are a classic prescription for treating diarrhea caused by deficiency of the spleen and kidney Yang. The core therapeutic principle of Sishenwan is warming and tonifying the spleen and kidney， and astringing the intestine and stopping diarrhea. In recent years， Sishenwan have demonstrated distinct advantages in the clinical treatment of UC. The pathogenesis of UC involves multiple factors， including immune dysregulation and gut microbiota imbalance. Although Western medicine is effective in the short term， its side effects， high relapse rate， and resistance associated with long-term use pose substantial challenges. Sishenwan have shown excellent clinical outcomes in the treatment of UC due to deficiency of the spleen and kidney Yang. Modern clinical studies indicate that Sishenwan， used alone or in combination with Western medicine or other Chinese medicine compound prescriptions， significantly improve the clinical efficacy in treating UC due to deficiency of the spleen and kidney Yang. Sishenwan effectively alleviate core symptoms such as mucus， pus， and blood in stools， and persistent abdominal pain， reduce Mayo scores and the relapse rate， and improve patients' quality of life. Research on the material basis reveals that Sishenwan contain multiple active ingredients such as psoralen， isopsoralen， and evodiamine. Mechanism studies indicate that Sishenwan inhibit the inflammatory cascade reactions by regulating the signal network through multiple targets. Sishenwan regulate cellular immunity and restore intestinal immune homeostasis. At the microecological level， Sishenwan promote the intestinal barrier repair through the "microbiota-metabolism-immunity" axis. The current research still needs to be deepened in aspects such as the mining of specific biomarkers for syndromes and the exploration of the collaborative mechanism of traditional Chinese and Western medicine. In the future， a full-chain system covering syndrome differentiation， targeting， and monitoring needs to be constructed for promoting the paradigm transformation of Sishenwan into precision drugs. This review systematically explains the treatment mechanism of Sishenwan regarding the combination of disease and syndrome and its multi-target regulatory characteristics， providing a theoretical basis and transformation direction for the treatment of UC with integrated traditional Chinese and Western medicine.

Background::Dual-energy computed tomography (DECT) is purported to accurately distinguish uric acid stones from non-uric acid stones. However, whether DECT can accurately discriminate ammonium urate stones from uric acid stones remains unknown. Therefore, we aimed to explore whether they can be accurately identified by DECT and to develop a radiomics model to assist in distinguishing them.Methods::This research included two steps. For the first purpose to evaluate the accuracy of DECT in the diagnosis of uric acid stones, 178 urolithiasis patients who underwent preoperative DECT between September 2016 and December 2019 were enrolled. For model construction, 93, 40, and 109 eligible urolithiasis patients treated between February 2013 and October 2022 were assigned to the training, internal validation, and external validation sets, respectively. Radiomics features were extracted from non-contrast CT images, and the least absolute shrinkage and selection operator (LASSO) algorithm was used to develop a radiomics signature. Then, a radiomics model incorporating the radiomics signature and clinical predictors was constructed. The performance of the model (discrimination, calibration, and clinical usefulness) was evaluated.Results::When patients with ammonium urate stones were included in the analysis, the accuracy of DECT in the diagnosis of uric acid stones was significantly decreased. Sixty-two percent of ammonium urate stones were mistakenly diagnosed as uric acid stones by DECT. A radiomics model incorporating the radiomics signature, urine pH value, and urine white blood cell count was constructed. The model achieved good calibration and discrimination {area under the receiver operating characteristic curve (AUC; 95% confidence interval [CI]), 0.944 (0.899–0.989)}, which was internally and externally validated with AUCs of 0.895 (95% CI, 0.796–0.995) and 0.870 (95% CI, 0.769–0.972), respectively. Decision curve analysis revealed the clinical usefulness of the model.Conclusions::DECT cannot accurately differentiate ammonium urate stones from uric acid stones. Our proposed radiomics model can serve as a complementary diagnostic tool for distinguishing them in vivo.

Objective:To explore the mediating effect of distress disclosure between perceived social support and psychological distress in colorectal cancer patients.Methods:The convenient sampling method was used to select 220 postoperative colorectal cancer patients who were reviewed in China-Japan Union Hospital of Jilin University from February to August 2023 as the research objetcs. The Distress Disclosure Index (DDI), Perceived Social Support Scale (PSSS), and Chinese version of Screening Tool for Psychological Distress in Cancer Patients were used to conduct the survey.Results:A total of 220 questionnaires were distributed in this study, and 213 valid questionnaires were recovered, with a valid recovery rate of 96.82%. The total score of the Chinese version of Screening Tool for Psychological Distress in Cancer Patients for colorectal cancer patients was (4.31±2.46), the total score of the DDI was (37.26±9.97), and the total score of the PSSS was (57.82±14.60). Pearson correlation analysis showed that psychological distress was negatively correlated with distress disclosure in colorectal patients ( P<0.01), distress disclosure was positively correlated with perceived social support ( P<0.01), and psychological distress was negatively correlated with perceived social support ( P<0.01). The mediating effect results showed that the direct effect of perceived social support on psychological distress was -0.359 ( P<0.01), and the mediating effect between perceived social support and psychological distress was -0.227 ( P<0.01), which acted as a partial mediating effect with the mediating effect accounting for 38.74% of the total effect. Conclusions:Perceived social support can not only directly affect the psychological distress of colorectal cancer patients, but also indirectly affect psychological distress through distress disclosure. Clinical staffs should take certain interventions to improve the level of patients' perceived social support and distress disclosure, so as to improve the psychological distress of patients.

Objective:To explore the role of NK cells in allogeneic hematopoietic stem cell micro-transplantation(MST)in the treatment of patients with acute myeloid leukemia(AML).Methods:Data from 93 AML patients treated with MST at our center from 2013-2018 were retrospectively analyzed.The induction regimen was anthracycline and cytarabine combined with peripheral blood stem cells transplantation mobilization by granulocyte colony stimulating factor(GPBSC),followed by 2-4 courses of intensive treatment with medium to high doses of cytarabine combined with GPBSC after achieving complete remission(CR).The therapeutic effects of one and two courses of MST induction therapy on 42 patients who did not reach CR before transplantation were evaluated.Cox proportional hazards regression analysis was used to analyze the impact of donor NK cell dose and KIR genotype,including KIR ligand mismatch,2DS1,haplotype,and HLA-Cw ligands on survival prognosis of patients.Results:Forty-two patients received MST induction therapy,and the CR rate was 57.1％after 1 course and 73.7％after 2 courses.Multivariate analysis showed that,medium and high doses of NK cells was significantly associated with improved disease-free survival(DFS)of patients(HR=0.27,P=0.005;HR=0.21,P=0.001),and high doses of NK cells was significantly associated with improved overall survival(OS)of patients(HR=0.15,P=0.000).Donor 2DS1 positive significantly increases OS of patients(HR=0.25,P=0.011).For high-risk patients under 60 years old,patients of the donor-recipient KIR ligand mismatch group had longer DFS compared to the nonmismatch group(P=0.036);donor 2DS1 positive significantly prolonged OS of patients(P=0.009).Conclusion:NK cell dose,KIR ligand mismatch and 2DS1 influence the therapeutic effect of MST,improve the survival of AML patients.

Objective:To investigate the impact of small extracellular vesicles(sEVs) derived from perirenal adipose cells on the biological behavior of renal tubular epithelial cells under diabetic conditions and the underlying molecular mechanisms.Methods:Primary perirenal adipose cells were extracted from db/m and db/db mice for in vitro culture. The culture supernatant was collected and sEVs(NDM-sEVs PRAT-Adipo, DM-sEVs PRAT-Adipo) were extracted by ultracentrifugation. The sEVs were incubated with human renal tubular epithelial cell line(HK-2) to observe changes in their proliferation, apoptosis, autophagy, and epithelial-mesenchymal transition(EMT) levels. The protein composition of sEVs was analyzed using mass spectrometry to explore the molecular mechanisms. Results:CCK8 results showed that the proliferation level of HK-2 cells after DM-sEVs PRAT-Adipo intervention did not change significantly compared with the two control groups(Ctrl group and NDM-sEVs PRAT-Adipo intervention group). Western Blot(WB) results indicated that there were no significant changes in apoptosis levels(Bcl-2, Cleaved-caspase 3, Caspase 3) and autophagy levels(p62, LC3BⅠ, LC3BⅡ) in the DM-sEVs PRAT-Adipo intervention group compared with the two control groups. WB and immunofluorescence results demonstrated that DM-sEVs PRAT-Adipo intervention upregulated the expression levels of mesenchymal cell marker proteins(Vimentin, α-SMA, Snail2) and downregulated the expression level of epithelial cell marker protein ZO-1 in HK-2 cells compared with the two control groups. Mass spectrometry analysis of sEVs revealed that the differential proteins between DM-sEVs PRAT-Adipo and NDM-sEVs PRAT-Adipo were enriched in EMT-related pathways. Among them, the enrichment of thrombospondin(THBS1) in DM-sEVs PRAT-Adipo might be involved in the regulation of EMT in HK-2 cells. Conclusion:Under diabetic conditions, sEVs secreted by PRAT-derived adipocytes promote the upregulation of EMT in renal tubular epithelial cells, a process that may be mediated by the enrichment of THBS1 in sEVs.

AIM To optimize the extraction process for uracil,hypoxanthine,xanthine,uridine,thymine,inosine,guanosine and 2'-deoxyguanosine from Pheretima guillelmi(Michaelsen),and to determine their contents.METHODS With solid-liquid ratio,ultrasonic time and ultrasonic temperature as influencing factors,contents of hypoxanthine and total nucleosides as evaluation indices,the extraction process was optimized by orthogonal test.HPLC was adopted in the content determination of varioud nucleosides,the analysis was performed on a 30℃thermostatic Agilent C18 column(4.6 mm×250 mm,5 μm),with the mobile phase comprising of methanol-water flowing at 1 mL/min in a gradient elution manner,and the detection wavelength was set at 260 nm.RESULTS The optimal conditions were determined to be 1∶250 for solid-liquid ratio,60 min for ultrasonic time,and 60℃for ultrasonic temperature.Eight nucleosides showed good linear relationships within their own ranges(R2＞0.999 0),whose average recoveries were 99.11%-103.27%with the RSDs of 0.85%-2.89%.CONCLUSION This stable and reliable method can be used for the extraction and content determination of nucleosides from P.guillelmi.

Objective:To explore the diagnostic value of laboratory examination in bronchoalveolar lavage fluid(BALF) for interstitial lung disease (ILD) and its application value in assessing the degree of fibrosis in the disease.Methods:Retrospective analysis. The clinical data of ILD patients treated in Shanghai First People′s Hospital from January 1, 2021 to December 31, 2023[104 cases, male︰female=48︰56, (62.79±1.24) years] were collected. According to the imaging scores, they were divided into a mild fibrosis ILD group [53 cases, male︰female=26︰27, (61.32±1.71) years] and a moderate to severe ILD fibrosis group [51 cases, male︰female=22︰29, (64.31±1.88) years]. Patients with community-acquired pneumonia without fibrotic lesions by HRCTduring the same period were selected as the control group [49 cases, male︰female=25︰24, (65.37±1.65)years]. The clinical information of all study subjects, as well as BALF lymphocyte subset analysis, cytokine and cytology count detection results were collected. Furthermore, the Kruskal-Wallis H test was used to screen the differential indexes, and the receiver operating characteristic (ROC) curve was used to evaluate the differential indexes to assess the degree of ILD pulmonary fibrosis.Results:Compared with the non-fibrotic pneumonia group, IL-6, IL-8, CD4+CD45RO+cells and macrophages (M%) were significantly upregulated in the mild fibrosis ILD group (P<0.05), and significantly higher in the moderate to severe fibrosis ILD group ( P<0.05). Compared with the non-fibrotic pneumonia group, IL-1β and white blood cell (WBC) count were significantly upregulated only in the moderate to severe fibrotic ILD group ( P<0.05). The correction model was constructed by stepwise logistic regression analysis, and the differential indexes were combined, and the proportion of IL-1β+IL-6+IL-8+CD4+CD45RO+cells+macrophages was finally screened as the optimal combined diagnostic mode, with an area under the curve of 0.925, sensitivity of 92.3%, and specificity of 80.0%. Conclusion:Compared with the non-fibrotic pneumonia group, BALF-derived IL-1β, IL-6, IL-8, CD4+CD45RO+cells, WBC count and M% can be used as potential biomarkers to assess the degree of fibrosis, and the combination of IL-1β+IL-6+IL-8+CD4+CD45RO+cells+macrophages has a better diagnostic efficacy for moderate to severe fibrotic ILD.

Objective To investigate the current status of infection management quality control centers in county-level hospitals in Guangdong Province,providing reference for the development of quality control management programs for county-level infection control centers by provincial infection control centers,and exploring corresponding management strategies.Methods A survey was conducted using the QuestionStar questionnaire platform to investigate county-level quality control centers established in Guangdong Province before December 31,2023.The survey covered the establishment time,personnel structure,level of in-formatization,management,quality control,and training of hospital infection management professional quality control centers.Results There are 68 county-level infection control centers in Guangdong Province,with a coverage rate of 50.37%,and 95.59%of them have been established within the past five years.Experts mainly come from clinical and nursing backgrounds(accounting for23.75%and62.97%respectively),and the majority have a bachelor's degree(71.06%).Only 13%have operational funding.Among them,39 have established hospital infection informatization monitoring,23 have not been equipped,and 6 are under construction.Twenty centers have conducted quality control supervision and issued quality control reports,ac-counting for 29.41%,while 41 have organized training,accounting for 60.29%.Conclusion The coverage rate of county-level infection management quality control centers in Guangdong Province is steadily increasing,but not all counties and districts are covered.There is a lack of policy and funding support,insufficient personnel allocation,and inadequate professional coverage.The health administrative departments and county-level infection control centers need to unify monitoring standards,quality con-trol specifications,and evaluation programs,improve infection control capabilities,and enhance the"four-level"management and training system to effectively promote the quality and safety management level of primary healthcare institutions.