Antibody-drug conjugates （ADCs） are a novel class of anti-tumor agents composed of a targeted monoclonal antibody， a cytotoxic drug， and a linker connecting the two. They combine the high specificity of antibodies with the potent cytotoxicity of chemotherapeutic agents. Triple-negative breast cancer （TNBC） is characterized by high aggressiveness， elevated risks of recurrence and metastasis， and poor prognosis， largely due to the lack of effective therapeutic targets. This review summarizes the research progress of ADCs in the treatment of TNBC. It has been found that ADCs targeting human epidermal growth factor receptor 2 （such as trastuzumab deruxtecan）， trophoblast cell surface antigen 2 （such as sacituzumab govitecan and datopotamab deruxtecan）， zinc transporter LIV-1 （such as ladiratuzumab vedotin）， HER-3 （such as patritumab deruxtecan）， epidermal growth factor receptor （such as AVID100）， and glycoprotein non-metastatic melanoma protein B （such as glembatumumab vedotin） have all demonstrated promising therapeutic effects against TNBC. Despite challenges including acquired resistance and treatment-related toxicities， ADCs are undoubtedly reshaping the therapeutic landscape for TNBC and are expected to occupy a more central position in TNBC treatment in the future.

ObjectiveTo evaluate the clinical efficacy and safety of Baoshen prescription in the treatment of stage Ⅳ diabetic nephropathy （DN） in the patients with syndromes of Qi-Yin deficiency and kidney collateral stasis and obstruction， and to explore the mechanism of this prescription delaying the disease progression. MethodsA randomized， controlled， double-blind， multicenter clinical trial was conducted， in which 94 stage Ⅳ DN patients with syndromes of Qi-Yin deficiency and kidney collateral stasis and obstruction were randomly assigned into Baoshen prescription and control groups （47 cases）. The treatment lasted for 12 weeks. The primary efficacy indicators were mainly renal function indexes， including urine albumin-to-creatinine ratio （UACR）， 24-hour urine total protein （24 h-UTP）， serum creatinine （SCr）， and estimated glomerular filtration rate （eGFR）. The secondary efficacy indicators were metabolic memory of hyperglycemia， podocyte epithelial-to-mesenchymal transdifferentiation-related indexes， and TCM syndrome score. ResultsAfter 12 weeks of treatment， the Baoshen prescription group showed lowered levels of advanced glycation end products （lgAGEs）， connective tissue growth factor （CTGF）， type Ⅳ collagen （Col-Ⅳ）， receptor of AGEs （RAGE）， urinary fibroblast-specific protein-1 （FSP-1）， UACR， 24 h-UTP， and glycated hemoglobin （HbAlc） （P<0.05）， and an upward trend of miR-21 mRNA. The control group showed elevated levels of SCr and UREA and lowered levels of urinary FSP-1， eGFR， and HbAlc （P<0.05）. After treatment， the Baoshen prescription group had lower levels of lgAGEs， CTGF， urinary FSP-1， SCr， UACR， and 24 h-UTP and higher levels of Col-Ⅳ and eGFR than the control group （P<0.05）. In addition， the Baoshen prescription group showed statistically significant differences in SCr， eGFR， UACR， and 24 h-UTP before and after treatment （P<0.05）. ConclusionBaoshen prescription can effectively improve the renal function， reduce the urinary protein level， and alleviate clinical symptoms in stage Ⅳ DN patients with syndromes of Qi-Yin deficiency and kidney collateral stasis and obstruction. The mechanism may be related to the metabolic memory of hyperglycemia and epithelial-to-mesenchymal transdifferentiation of podocytes.

Objective: To explore the correlation and lag effects of environmental factors on pediatric respiratory disease visits at hospital, so as to provide scientific basis for disease prediction and optimizing clinical diagnosis and treatment. Methods: Data from 503 889 pediatric respiratory disease outpatient and emergency visits a central hospital in Minhang District of Shanghai between 2017 and 2019, along with concurrent meteorological data were collected. A distributed lag non-linear models (DLNM) was constructed to explore the specific relationship between pediatric respiratory disease consultations and various environmental factors and to quantify the cumulative lag effects of environmental factors on respiratory disease consultations. Results: Among the environmental factors, temperature, fine particulate matter (PM 2.5 ), inhalable particulate matter (PM 10 ), nitrogen dioxide (NO 2), and sulfur dioxide (SO 2) were associated with pediatric respiratory disease visits. After adjusting for temperature, PM 2.5 and PM 10 concentrations did not show significant immediate or lag effects. The relative risk (RR) of pediatric respiratory disease visits increased with rising NO 2 concentrations. When NO 2 concentration ≥55 μg/m 3, significant immediate and lagged effects (lag 3, 5, and 7 days) were observed. The RR values were 1.05, 1.13, 1.17, and 1.21( P <0.05). The RR values showed an inverted “U” shaped relationship with SO 2 concentrations. When SO 2 concentration ≥5 μg/m 3, significant lagged effects (lag 3, 5, and 7 days) were observed. The RR values were 1.03 , 1.03, and 1.04 ( P <0.05). Conclusion High concentrations of NO 2 and SO 2 increase the risk of pediatric respiratory disease visits, with observable lag effects.

Liver cancer is one of the most common malignant tumors worldwide. Currently, the available treatment methods cannot fully control its recurrence and mortality rate. Establishing appropriate animal models for liver cancer is crucial for developing new treatment technologies and strategies. The patient-derived xenograft (PDX) model preserves the tumor's microenvironment and heterogeneity, which makes it advantageous for biological research, drug evaluation, personalized medicine, and other purposes. This article reviews the development, preparation techniques, application fields, and challenges of PDX models in liver cancer, providing insights for the research and exploration of PDX models in diagnostic and therapeutic strategies of liver cancer.
Liver Neoplasms/drug therapy* ; Animals ; Humans ; Xenograft Model Antitumor Assays/methods* ; Mice ; Disease Models, Animal

OBJECTIVES: To investigate the mechanism of Qihuang Jianpi Zishen Granules (QJZ) for ameliorating renal damage in MRL/lpr mice. METHODS: With 6 female C57BL/6 mice as the normal control group, 30 female MRL/lpr mice were randomized into model group, QJZ treatment groups at low, moderate and high doses, and prednisone treatment group (n=6). After 8 weeks of treatment, the mice were examined for 24-h urine protein, creatinine and albumin levels, serum levels of IgG, complement 3 (C3), C4, anti-dsDNA, interferon γ (IFN‑γ) and interleukin 17 (IL-17). Kidney tissues were sampled for histopathological examination with HE staining and observation of glomerular ultrastructure changes using transmission electron microscopy (TEM). The expressions of MyD88/NF-κB pathway-related molecules in the kidney tissue were detected using RT-qPCR, Western blotting and immunohistochemistry. RESULTS: Compared with those in the model group, the mice treated with QJZ at the 3 doses and prednisone showed significant reductions in the renal injury biomarkers and serum IgG, anti-dsDNA, IFN‑γ and IL-17 levels and elevation of serum C3 and C4 levels. HE staining revealed lessened glomerular endothelial cell proliferation and mesangial thickening in all the treatment groups. TEM observation further demonstrated reduced electron-dense deposits and diminished inflammatory cell infiltration in the glomeruli in the intervention groups. QJZ at the 3 doses and prednisone treatment all significantly lowered renal expression levels of MyD88, NF-κB, p65 and p52 in the mouse models. CONCLUSIONS QJZ can improve renal damage in MRL/lpr mice possibly by inhibiting overactivation of the MyD88/NF-κB pathway.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Female ; Mice, Inbred C57BL ; Mice, Inbred MRL lpr ; Myeloid Differentiation Factor 88/metabolism* ; Mice ; NF-kappa B/metabolism* ; Signal Transduction/drug effects* ; Kidney/metabolism* ; Interleukin-17

OBJECTIVES: To investigate the efficacy of Qihuang Jianpi Zishen Granules (QJZ) for inhibiting renal B cell differentiation in MRL/lpr mice and explore its underlying mechanism. METHODS: Thirty 8-week-old female MRL/lpr mice were randomly divided into model group, QJZ group, prednisone (Pred) group, QJZ+Pred group, and AIM2 inhibitor group (n=6), with 6 8-week-old female C57BL/6 mice as the normal control group. After treatments with normal saline, QJZ, Pred, or AIM2 inhibitor for 8 weeks, the mice were examined for urinary total protein-to-creatinine ratio (TPCR) and albumin-to-creatinine ratio (ACR), serum creatinine (Cr) and blood urea nitrogen (BUN) levels, and renal histopathology (with HE, Masson, and PAS staining) and ultrastructural changes (with electron microscopy). ELISA, immunohistochemistry, immunofluorescence staining and flow cytometry were used to detect blood levels of anti-dsDNA antibodies, cytokines and chemokines, renal deposition of complement components C3 and C4, renal expressions of AIM2, CD19, CD27 and CD138, and changes in splenic B lymphocyte subsets. The effect of QJZ on the AIM2/Blimp-1/Bcl-6 signaling axis was examined using Western blotting. RESULTS: QJZ treatment significantly improved Cr, BUN, TPCR and ACR in MRL/lpr mice, ameliorated renal pathologies, reduced the expressions of ds-DNA, BAFF, IL-21, CXCL12, CXCL13, C3 and C4, and increased IL-10 levels. QJZ significantly downregulated renal expressions of the key B-cell transcription factors Blimp-1 and XBP-1, upregulated Bcl-6 and PAX5 expressions, inhibited B-cell differentiation, and lowered the expressions of AIM2, CD27, CD138 and CD69. Inhibition of AIM2 similarly reduced renal Blimp-1 and XBP-1 expressions, increased Bcl-6 and PAX5 levels, suppressed B-cell differentiation, decreased IgG production, reduced C3 and C4 deposition, and alleviated renal pathology in MRL/lpr mice. CONCLUSIONS QJZ inhibits B cell differentiation and alleviates renal damage in systemic lupus erythematosus possibly by suppressing the AIM2/Blimp-1/Bcl-6 signaling pathway.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Mice, Inbred MRL lpr ; Female ; Mice ; Mice, Inbred C57BL ; Cell Differentiation/drug effects* ; B-Lymphocytes/drug effects* ; Proto-Oncogene Proteins c-bcl-6/metabolism* ; Kidney/drug effects* ; DNA-Binding Proteins/metabolism* ; Signal Transduction ; Lupus Nephritis

ObjectiveTo investigate the clinical efficacy of Qihuang Jianpi Zishen Granules in the treatment of systemic lupus erythematosus （SLE） and its effect on the signal transducer and activator of tranSCription 3/mammalian target of rapamycin （STAT3/mTOR） signaling pathway， and to decipher the possible mechanism. MethodSixty female SLE patients who met the criteria in the First Affiliated Hospital of Anhui University of Chinese Medicine from May 2022 to May 2023 were selected and randomized into a control group and an observation group （30 cases in each group）. The control group was treated with prednisone acetate + hydroxychloroquine sulfate orally， and the observation group was additionally treated with Qihuang Jianpi Zishen granules. The treatment lasted for 8 weeks. The SLE disease activity （SLEDAI）， TCM syndrome score， erythrocyte sedimentation rate （ESR）， hypersensitive C-reactive protein （hs-CRP）， immune indexes ［immunoglobulin G （IgG）， C3， C4， CD4⁺， and CD8⁺］， interleukin （IL）-17， IL-23， interferon （IFN）-γ， 24 h urinary protein （24 h PRO）， serum creatinine （SCr）， and expression of proteins ［STAT3， phosphorylated （p）-STAT3， mTOR protein and STAT3，mTOR mRNA］ in the STAT3/mTOR signaling pathway were determined before and after treatment. In addition， the adverse reactions were recorded. ResultAfter 8 weeks of treatment， the total response rate in the observation group was 93.33% （28/30）， which was higher than that （70.00%， 21/30） in the control group （χ²=4.007， P<0.05）. After treatment， both groups showed declined SLEDAI， TCM syndrome score， ESR， hs-CRP， IgG， CD8⁺， IL-17， IL-23， IFN-γ， 24 h PRO， SCr， and expression of proteins in the STAT3/mTOR pathway （P<0.01） and elevated levels of C3， C4， and CD4⁺ （P<0.01）. Moreover， the observation group had lower SLEDAI， TCM syndrome score， ESR， hs-CRP， IgG， CD8⁺， IL-17， IL-23， IFN-γ， 24 h PRO， SCr， and expression of proteins in the STAT3/mTOR pathway （P<0.05， P<0.01） and higher levels of C3， C4， and CD4⁺ （P<0.05， P<0.01） than the control group after treatment. Neither group showed serious adverse reactions during the treatment period. ConclusionQihuang Jianpi Zishen Granules can ameliorate the inflammatory response， reduce the disease activity， and mitigate the kidney injury in SLE by inhibiting the STAT3/mTOR signaling pathway to regulate the immune function.

Objective To investigate the correlation of triacylglycerol glucose(TyG)index,monocyte to high-density lipoprotein cholesterol ratio(MHR)with coronary artery disease and myocardial ischemia degree in coronary heart disease(CHD),and to analyze the two Predictive value of coronary artery disease and myocardial ischemia degree.Methods CHD patients from the 920th Hospital of the Chinese People's Liberation Army Joint Logistics Support Force from January 2019 to January 2022 were selected as the study group(n = 150),and healthy physical examination subjects from the same period were selected as the control group(n = 75).The TyG index and MHR of the two groups were compared and analyzed.The extent of coronary artery disease was evaluated based on the Gensini score,and the TyG index and MHR of patients with different coronary lesions and myocardial ischemia were compared,and their correlation with Gensini score and myocardial ischemia was analyzed.The predictive value of TyG index,MHR,and the combined detection of both for coronary lesions and myocardial ischemia was evaluated using receiver operating characteristic(ROC)curves and area under the curve(AUC).Results The TyG index and MHR of the study group were(4.12±0.35)and(0.26±0.08)×109,respectively,which were higher than those of the control group(4.94±0.55)and(0.43±0.12)×109,and the TyG index and MHR of severe coronary artery disease>moderate coronary artery disease>mild coronary artery disease,acute myocardial infarction TyG index,MHR>unstable angina pectoris>stable angina pectoris(P<0.05);TyG index and MHR were positively correlated with Gensini score(r = 0.621,0.635,P<0.05),and positively correlated with the severity of myocardial ischemia(r = 0.617,0.642,P<0.05).The AUC of TyG index and MHR for the joint identification of mild coronary artery disease and moderate coronary artery disease was 0.917,which was greater than the AUCs of 0.749 and 0.832 for the two conditions individually.The AUC of TyG index and MHR for the joint identification of mild to moderate coronary artery disease and severe coronary artery disease was 0.935,which was greater than the AUCs of 0.770 and 0.767 for the two conditions individually(P<0.05).The AUC of TyG index and MHR for the joint identification of stable angina pectoris and unstable angina pectoris was 0.922,which was greater than the AUCs of 0.812 and 0.824 for the two conditions individually.The AUC of TyG index and MHR for the joint identification of stable angina pectoris,unstable angina pectoris,and acute myocardial infarction was 0.913,which was greater than the AUCs of 0.708 and 0.714 for the two conditions individually(P<0.05).Conclusions TyG index and MHR are positively correlated with Gensini score and myocardial ischemia degree.The combined detection of the two has a higher application value in the evaluation of coronary artery disease and myocardial ischemia degree.

Objective Based on the limited time theory,taking tonsillectomy day operation as an example,the whole process nursing list of day operation was constructed,and its application effect was evaluated.Methods The nursing service list of tonsillectomy was constructed based on literature research,field observation and expert correspondence.A total of 197 patients who underwent tonsillectomy in the day ward of a tertiary A general hospital in Hangzhou,Zhejiang Province were selected.Among them,98 patients from April to June 2023 were taken as an experimental group and treated with the whole-process nursing list of daytime tonsillectomy constructed in this study,and 99 patients from January to March 2023 were taken as a control group and routine nursing was adopted.The anxiety degree,postoperative pain score,postoperative complication rate and patients'satisfaction with nursing service were compared between the 2 groups.Results Anxiety scores before operation and at discharge,pain scores at 6 h,12 h and 24 h after operation,and incidence of complications such as infection and gastrointestinal reaction within 14 days after operation in the experimental group were lower than those in the control group,with statistical significance(P＜0.05).The satisfaction of nursing service in the experimental group(99.40±0.69)score was significantly higher than that in the control group(90.36±1.04)score,and the difference was statistically significant(P＜0.001).Conclusion The use of tonsillectomy day whole-process nursing list can improve perioperative anxiety,relieve postoperative pain and reduce the incidence of postoperative complications,and improve patient satisfaction.

An animal biosafety level-3 laboratory(ABSL-3)is a high-level biosafety installation that can conduct experiments on animals infected with highly pathogenic microorganisms.In recent years,with the continuous characterization of emerging and re-emerging infectious diseases,high-level biosafety laboratories have played increasingly important roles in pathogenic mechanism and drug and vaccine research and development.The demand for ABSL-3 is increasing year by year.At the same time,there is also a growing demand for personnel who are competent in working in ABSL-3.The systematization,normalization,and standardization of pre-service training have become important to guarantee a reduction in the risks to personnel working in ABSL-3.Training of ABSL-3 staff needs to be carried out in specific simulated laboratories.Therefore,it is necessary to construct simulated ABSL-3 and establish scientific and effective operating standards and mechanisms.This paper comprehensively introduces the design,construction,operation,and functions of a simulated ABSL-3 installation.