OBJECTIVE To compare the predictive accuracy and clinical applicability of four vancomycin individualized dosing tools （SmartDose， ClinCalc， Gulou， Pharmado） and provide a basis for rational clinical medication use. METHODS A retrospective cohort study was conducted， enrolling 479 adult patients who received vancomycin therapy and underwent steady-state trough concentration monitoring in Zhongshan Hospital， Fudan University （Xiamen Branch） from January 1， 2022， to June 30， 2024. The predictive accuracy of each tool was evaluated using indicators， such as mean error （ME）, mean absolute error （MAE）， mean percentage error （MPE）， mean absolute percentage error （MAPE）， the proportion of patients with an absolute percentage error （APE） of less than 30%， the 95% limits of agreement， and the overall relative percentage difference between predicted and measured values. Using indicators such as accessibility， patient management， and recommendation of multiple treatment options， the clinical panxso@163.com applicability of the tools for all patients was evaluated； using the discrepancy in accuracy between the predicted and actual measured blood drug concentrations as an indicator， the clinical applicability was assessed for patients in different renal function subgroups （hyperfunction， normal， mild impairment， moderate impairment， and severe impairment）. RESULTS In terms of accuracy， SmartDose demonstrated the best overall performance with an MAPE of 46.40% and a proportion of APE ＜30% （46.56%）. Bland-Altman analysis indicated that SmartDose had the smallest overall relative percentage difference （－7.25%）， although the 95% limits of agreement were broad for all tools， with differences between the upper and lower limits exceeding 200%. In terms of applicability， all four dosing tools were freely accessible and demonstrated good availability； SmartDose and Pharmado provided the most comprehensive solutions， offering features such as patient management， multiple regimen recommendations， and drug concentration-time curve plotting. Stratified analysis based on renal function revealed that Pharmado showed optimal prediction for hyperfiltration patients （mean difference： 0.11 mg/L）. SmartDose and ClinCalc showed relatively better performance in normal and mild renal impaiment （mean difference： 0.37， 0.51 mg/L and －1.13， －1.33 mg/L，respectively）. SmartDose performed best in moderate renal impairment （mean difference： －2.60 mg/L）. Pharmado and Gulou had smaller prediction biases in severe renal impairment （mean differences： 1.52 mg/L and －0.23 mg/L， respectively）. CONCLUSIONS The four individualized dosing tools demonstrated limited accuracy in the initial prediction of vancomycin concentrations. Among them， SmartDose demonstrates the highest overall prediction accuracy and possesses comprehensive clinical management features. It is recommended that Pharmado be preferred for patients with renal hyperfiltration； SmartDose or ClinCalc can be used for patients with normal or mildly impaired renal function； SmartDose is recommended for patients with moderately impaired renal function； Pharmado or Gulou may be considered for patients with severely impaired renal function.

Objective: To investigate the expression of programmed death ligand-1 (PD-L1, SP142) and PD-L1 (22C3) in triple-negative breast cancer (TNBC), and analyze their correlation with the clinicopathological factors and prognosis. Methods: The clinicopathologic data of 259 patients with TNBC treated in Cancer Hospital from August 2010 to December 2013 were collected. Whole section of surgical tissue samples were collected to conduct PD-L1 (SP142) and PD-L1 (22C3) immunohistochemical (IHC) staining. The PD-L1 expression in tumor cells and tumor infiltrating immune cells were visually assessed respectively, the relationship between PD-L1 expression and clinicopathologic characterizes were analyzed. Univariable and multivariable Cox proportional hazards regression models were used to test the correlations between PD-L1 expression and disease-free survival (DFS) and overall survival (OS). Results: The positive rates of SP142 (immune cell score, ICs≥1%) and 22C3 (combined positive score, CPS≥1) were 42.1%(109/259) and 41.3%(107/259) in TNBC tissues, respectively, with a total coincidence rate of 82.3%. The Kappa value of positive expression cases was 0.571 and the distribution difference of SP142 and 22C3 positive expression cases was statistically significant (P<0.001). The PD-L1 positive patients were less likely to have vascular invasion (P<0.05), but with higher histological grade and Ki-67 proliferation index (P<0.05). The recurrence/metastasis cases(8) of the patients with positive PD-L1 (SP142) was significantly lower than that of patients with negative PD-L1(SP142, 27, P=0.016). The positive expression of PD-L1 (SP142) patients were longer DFS (P=0.019). The OS of patients with positive PD-L1 (SP142) were longer than those with negative PD-L1 (SP142), but without significance (P=0.116). The positive expression of PD-L1 (22C3) was marginally associated with DFS and OS of patients (P>0.05). Conclusions: The expression of PD-L1 (22C3) is different from that of PD-L1 (SP142) in TNBC, and the two antibodies can't be interchangeable for each other in clinical tests. PD-L1 (SP142) status is an independent prognostic factor of DFS in TNBC. The DFS is significantly prolonged in patients with positive expression of PD-L1 (SP142).
B7-H1 Antigen/genetics* ; Humans ; Immunohistochemistry ; Prognosis ; Triple Negative Breast Neoplasms/pathology*

OBJECTIVE: To obtain the subtypes of the clinical hypertension population based on symptoms and to explore the relationship between hypertension and comorbidities. METHODS: The data set was collected from the Chinese medicine (CM) electronic medical records of 33,458 hypertension inpatients in the Affiliated Hospital of Shandong University of Traditional Chinese Medicine between July 2014 and May 2017. Then, a hypertension disease comorbidity network (HDCN) was built to investigate the complicated associations between hypertension and their comorbidities. Moreover, a hypertension patient similarity network (HPSN) was constructed with patients' shared symptoms, and 7 main hypertension patient subgroups were identified from HPSN with a community detection method to exhibit the characteristics of clinical phenotypes and molecular mechanisms. In addition, the significant symptoms, diseases, CM syndromes and pathways of each main patient subgroup were obtained by enrichment analysis. RESULTS: The significant symptoms and diseases of these patient subgroups were associated with different damaged target organs of hypertension. Additionally, the specific phenotypic features (symptoms, diseases, and CM syndromes) were consistent with specific molecular features (pathways) in the same patient subgroup. CONCLUSION The utility and comprehensiveness of disease classification based on community detection of patient networks using shared CM symptom phenotypes showed the importance of hypertension patient subgroups.

Aim To investigate the effect of resveratrol on the polarization of macrophages and its correlation with mitochondrion. Methods Fifty-five mice infected with Schistosoma japonicum for three weeks were randomly divided into three groups; infection group (A), resveratrol group (B) and praziquantel group (C). Fifteen normal mice were taken as normal control group (D). On 9th week of infection, M1 and M2 were measured by flow cytometry (FCM), the mRNA level of Ml and M2 related cytokines, PGC-la and mtDNA level were detected by RT-PCR, and the ATP production was detected by ATP kit. RAW264. 7 cells were stimulated by PBS and SEA respectively. Resveratrol and praziquantel were added after stimulation. The percents of Ml and M2 were detected by FCM. PGC-1 a and mtDNA level were detected by RT-PCR. The level of Ml and M2 related cytokines were measured by ELISA. ATP was detected by ATP assay kit. Results Compared to group A, the proportion of Ml in group B increased (P < 0. 05), and the proportion of M2 decreased (P <0. 01). The levels of M2 related cytokines, PGC-1 a, mtDNA, ATP, basal OCR (oxygen comsumpition rate) in liver macrophages in group B were lower than those in group A (P < 0. 05). The levels of Ml related cytokines in group B were evidently higher than those in group A (P < 0.05). RAW264.7 cells were polarized into Ml (P < 0. 05), but not M2 (P < 0. 05) under resveratrol treatment. Moreover, RAW264. 7 cells with resveratrol treatment produced less M2 related cytokines (P < 0. 05), mtDNA, PGC-1 a, ATP and basal OCR (P <0. 05), and more related cytokines (P < 0. 05). Conclusion Resveratrol shifts macrophage polarization from M2 towards Ml by inhibiting the synthesis and ATP production of mitochondria.

Objective:To find the natural environmental boundary of the origin of the authentic Ligusticum chuanxiong by analyzing the distribution characteristics of soil elements in the traditional geo-authentic area and the southern continuous expanding areas along the same longitude. Method:The contents of 24 elements both in soil and plant L. chuanxiong samples were determined by using X-ray fluorescence spectrometry （XRF） and ICP-MS，etc. Spearman correlation test was used to evaluate the correlations of rhizosphere soil and each portion of L. chuanxiong，to screen out “characteristic elements”. Bray-Curtis similarity indexes based on all elements and "characteristic elements" were used for hierarchical cluster analysis of soil samples, to identify the sample range with similar soil element charateristics to the traditional geo-authentic area of L. chuanxiong. Result:K，Mg，Mn and Rb elements were significantly correlated in rhizosphere soil and plant L. chuanxiong. Geographical differentiation of all elements and four characteristic elements showed that there was a highest similarity between geo-authentic area and its neighbor plots S1-S6 (except plot S4) in soil elements distribution, followed by plots S14-S16. The middle section plots S7-S13 in the expansion areas were quite different from the traditional geo-authentic production areas. Conclusion:The soil element characteristics in the study areas were not completely controlled by geographical distance，but demonstrated the "fault" variation in the areas along longitude. This study provides a theoretical basis for the detrrmination of suitable cultivation area for Ligusticum Chuanxiong, and the natural boundary of its geo-authentic area may be extended an additional 60 km southward along longitude beyond the traditional origin. Additionally， K，Mg，Mn and Rb characteristic elements may be the potential markers to evaluate the suitable soil environment for cultivating L. chuanxiong.