Antibody-drug conjugates(ADCs)represent a breakthrough in precision therapy for breast cancer,offering a unique targeted drug delivery mechanism that enhances tumor selectivity while reducing the nonspecific toxicity associated with conventional chemotherapy.In recent years,the clinical applications of ADCs in breast cancer have expanded significantly,particularly in human epidermal growth factor receptor 2(HER2)-positive and HER2-low breast cancer,reshaping the therapeutic landscape.Trastuzumab emtanserin(T-DM1)was the first ADC drug to replace lapatinib plus capecitabine as a second-line treatment for HER2-positive breast cancer,while trastuzumab deruxtecan(T-DXd)demonstrated remarkable efficacy in HER2-low breast cancer in the DESTINY-Breast04 trial,becoming the first approved ADC for this patient subgroup.Furthermore,trophoblast cell surface antigen 2(Trop-2)-targeting ADCs,such as sacituzumab govitecan(SG),have shown promising clinical benefits in patients with triple-negative breast cancer(TNBC)and hormone receptor-positive/HER2-negative breast cancer.Advances in next-generation ADC technologies,including improvements in linker stability,drug-to-antibody ratio(DAR)optimization,and enhanced bystander effects,have further improved the therapeutic efficacy and safety profile of these agents,reinforcing their role in the precision treatment of breast cancer.Although ADCs have demonstrated substantial clinical benefits,they are associated with target-and payload-related toxicities.However,with ongoing advancements in management strategies,their safety profile has been significantly improved.HER2-targeting ADCs present specific adverse events,including interstitial lung disease(ILD)associated with T-DXd,thrombocytopenia,and liver function abnormalities observed with T-DM1,while Trop-2-targeting ADCs such as SG are linked to hematologic toxicity and gastrointestinal side effects.Notably,structural optimizations in next-generation ADCs have led to significant improvements in their safety profile.Early monitoring,individualized dose modifications,and supportive care measures have been shown to effectively reduce the incidence of severe adverse events.Clinical studies indicate that toxicity management strategies for ADCs have matured,with most adverse effects being effectively controlled through optimized treatment regimens and adjunctive supportive care.Thus,in clinical practice,it is essential to consider patient-specific factors,prior treatment history,and comorbidities to devise an optimal ADC treatment strategy that maximizes both efficacy and safety.As ADC technology continues to evolve,breast cancer treatment is expected to become increasingly precise.The development of novel HER2-Trop-2 bispecific ADCs offers new therapeutic options for patients with HER2-low and HER2-negative breast cancer.Additionally,studies investigating the combination of T-DXd with immune checkpoint inhibitors(ICIs),CDK4/6 inhibitors,and poly(ADP-ribose)polymerase(PARP)inhibitors have demonstrated synergistic antitumor effects,further expanding the prospects for precision medicine in breast cancer.This review systematically summarized the latest advancements in ADCs for breast cancer,with a focus on the clinical applications,safety management strategies,and future development of HER2-and Trop-2-targeting ADCs,aiming to provide valuable insights for the future of precision breast cancer treatment.

Objective To explore the effect of diet therapy on alcohol-induced chronic liver injury in rats and its relationship with TLR4 pathway.Methods According to Pueraria:Poria:Amomum villosum:Pericarpium Citri Reticulatae:Codonopsis:Zingiberis Rhizoma=15∶15∶10∶10∶10∶6,the water extract of the therapeutic prescription was prepared.A total of 78 female SD rats were randomly divided into 6 groups:normal group(n=12),model group(n=18),Hugan tablet group(0.35 g·kg-1,n=12),low-,medium-and high-dose Shiliaofang groups(2,6,18 g·kg-1,n=12).Except for the normal group,the rats in each group were induced alcoholic liver disease(ALD)by gradient alcohol gavage.After 10 weeks of intervention,the changes of body weight and water intake of rats were observed.The whole blood routine,serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),triglyceride(TG),total cholesterol(TC)and liver malondialdehyde(MDA)were measured.The levels of serum alcohol dehydrogenase(ADH),aldehyde dehydrogenase(ALDH),lipopolysaccharide(LPS),D-lactic acid(D-LA),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and interleukin-10(IL-10)were detected by enzyme-linked immunosorbent assay.HE staining was used to observe the pathological changes of liver and ileum.Oil red staining was used to observe liver fat deposition.Immunohistochemistry was used to detect the expression of ileal tight junction component occludin.Western blot was used to detect the expression of TLR4,MyD88 and NF-κB p65 protein in liver.Results Compared with the model group,the levels of WBC,LYC,TC,ALT,AST,LPS,D-LA,TNF-α and IL-6 in each diet group decreased,IL-10 increased,liver inflammatory cell infiltration and red lipid droplets decreased,intestinal villi were intact and densely arranged,the expression of occludin protein in ileum increased,and the expression of TLR4,MyD88 and NF-κB p65 protein in liver decreased.Conclusion The self-made dietotherapy prescription has a significant protective effect on chronic liver injury induced by alcohol in rats,which may be related to its down-regulation of TLR4-MyD88-NF-κB p65 protein expression and up-regulation of ileal occludin protein expression,improvement of intestinal mucosal barrier function,reduction of endotoxin entry into the liver,activation of TLR4/MyD88/NF-κB pathway,thereby reducing the second hit to the liver.This diet can be developed as a potential anti-alcoholic liver injury drug.

Antibody-drug conjugates(ADCs)represent a breakthrough in precision therapy for breast cancer,offering a unique targeted drug delivery mechanism that enhances tumor selectivity while reducing the nonspecific toxicity associated with conventional chemotherapy.In recent years,the clinical applications of ADCs in breast cancer have expanded significantly,particularly in human epidermal growth factor receptor 2(HER2)-positive and HER2-low breast cancer,reshaping the therapeutic landscape.Trastuzumab emtanserin(T-DM1)was the first ADC drug to replace lapatinib plus capecitabine as a second-line treatment for HER2-positive breast cancer,while trastuzumab deruxtecan(T-DXd)demonstrated remarkable efficacy in HER2-low breast cancer in the DESTINY-Breast04 trial,becoming the first approved ADC for this patient subgroup.Furthermore,trophoblast cell surface antigen 2(Trop-2)-targeting ADCs,such as sacituzumab govitecan(SG),have shown promising clinical benefits in patients with triple-negative breast cancer(TNBC)and hormone receptor-positive/HER2-negative breast cancer.Advances in next-generation ADC technologies,including improvements in linker stability,drug-to-antibody ratio(DAR)optimization,and enhanced bystander effects,have further improved the therapeutic efficacy and safety profile of these agents,reinforcing their role in the precision treatment of breast cancer.Although ADCs have demonstrated substantial clinical benefits,they are associated with target-and payload-related toxicities.However,with ongoing advancements in management strategies,their safety profile has been significantly improved.HER2-targeting ADCs present specific adverse events,including interstitial lung disease(ILD)associated with T-DXd,thrombocytopenia,and liver function abnormalities observed with T-DM1,while Trop-2-targeting ADCs such as SG are linked to hematologic toxicity and gastrointestinal side effects.Notably,structural optimizations in next-generation ADCs have led to significant improvements in their safety profile.Early monitoring,individualized dose modifications,and supportive care measures have been shown to effectively reduce the incidence of severe adverse events.Clinical studies indicate that toxicity management strategies for ADCs have matured,with most adverse effects being effectively controlled through optimized treatment regimens and adjunctive supportive care.Thus,in clinical practice,it is essential to consider patient-specific factors,prior treatment history,and comorbidities to devise an optimal ADC treatment strategy that maximizes both efficacy and safety.As ADC technology continues to evolve,breast cancer treatment is expected to become increasingly precise.The development of novel HER2-Trop-2 bispecific ADCs offers new therapeutic options for patients with HER2-low and HER2-negative breast cancer.Additionally,studies investigating the combination of T-DXd with immune checkpoint inhibitors(ICIs),CDK4/6 inhibitors,and poly(ADP-ribose)polymerase(PARP)inhibitors have demonstrated synergistic antitumor effects,further expanding the prospects for precision medicine in breast cancer.This review systematically summarized the latest advancements in ADCs for breast cancer,with a focus on the clinical applications,safety management strategies,and future development of HER2-and Trop-2-targeting ADCs,aiming to provide valuable insights for the future of precision breast cancer treatment.

Objective To explore the effect of diet therapy on alcohol-induced chronic liver injury in rats and its relationship with TLR4 pathway.Methods According to Pueraria:Poria:Amomum villosum:Pericarpium Citri Reticulatae:Codonopsis:Zingiberis Rhizoma=15∶15∶10∶10∶10∶6,the water extract of the therapeutic prescription was prepared.A total of 78 female SD rats were randomly divided into 6 groups:normal group(n=12),model group(n=18),Hugan tablet group(0.35 g·kg-1,n=12),low-,medium-and high-dose Shiliaofang groups(2,6,18 g·kg-1,n=12).Except for the normal group,the rats in each group were induced alcoholic liver disease(ALD)by gradient alcohol gavage.After 10 weeks of intervention,the changes of body weight and water intake of rats were observed.The whole blood routine,serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),triglyceride(TG),total cholesterol(TC)and liver malondialdehyde(MDA)were measured.The levels of serum alcohol dehydrogenase(ADH),aldehyde dehydrogenase(ALDH),lipopolysaccharide(LPS),D-lactic acid(D-LA),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and interleukin-10(IL-10)were detected by enzyme-linked immunosorbent assay.HE staining was used to observe the pathological changes of liver and ileum.Oil red staining was used to observe liver fat deposition.Immunohistochemistry was used to detect the expression of ileal tight junction component occludin.Western blot was used to detect the expression of TLR4,MyD88 and NF-κB p65 protein in liver.Results Compared with the model group,the levels of WBC,LYC,TC,ALT,AST,LPS,D-LA,TNF-α and IL-6 in each diet group decreased,IL-10 increased,liver inflammatory cell infiltration and red lipid droplets decreased,intestinal villi were intact and densely arranged,the expression of occludin protein in ileum increased,and the expression of TLR4,MyD88 and NF-κB p65 protein in liver decreased.Conclusion The self-made dietotherapy prescription has a significant protective effect on chronic liver injury induced by alcohol in rats,which may be related to its down-regulation of TLR4-MyD88-NF-κB p65 protein expression and up-regulation of ileal occludin protein expression,improvement of intestinal mucosal barrier function,reduction of endotoxin entry into the liver,activation of TLR4/MyD88/NF-κB pathway,thereby reducing the second hit to the liver.This diet can be developed as a potential anti-alcoholic liver injury drug.

Gallstone is a common and frequent disease and frequent incidence, secondary infection and cancer seriously affect the health of patients. Academic organizations in different regions have issued multiple guidelines and consensus to promote the normative diagnosis and treatment of gallstones. However, in clinical practice, most symptomatic gallstones are treated, while the formation and prevention process of gallstones are ignored, making the concept of treating without a disease has not been strengthened.This article reviews the risk factors and mechanisms of gallstone formation, and points out the importance of effective prevention during stone formation. In the stage of gallstone formation, the high risk factors of stone formation can be analyzed through two aspects of injury factors and protective factors, and the high risk groups of stone formation can be screened out. According to the pathophysiological progression of gallstones, personalized prevention and follow-up strategies can be developed for the stone formation stage of gallstones.

Objective:To discuss the composition and connotation of practical training objectives for nurses specialized in intravenous therapy, and provide guidance and reference for standardizing the practical training of nurses specialized in intravenous therapy.Methods:In this phenomenological analysis in qualitative research, 13 intravenous treatment and nursing experts from Shandong, Zhejiang, Sichuan, and Shaanxi provinces were selected from May to July 2021 for semi-structured interviews. Colaizzi's 7-step method and Nvivo 12.0 were used to organize data and analyze and refine themes.Results:Three themes and 12 subthemes were extracted for the practical training of intravenous therapy nurses, including knowledge objectives, ability objectives, and well-rounded objectives.Conclusions:Attention should be paid to the setting of clinical professional knowledge, skills and comprehensive quality goals for nurses specialized in intravenous therapy, so as to improve the pertinence and timeliness of training, promote the quality of training and the professional development of specialized training for intravenous therapy.

With the global pandemic of COVID-19, cytokine storms in critical patients with pneumonia is really a problem and need to be solved immediately.Low dose radiation therapy (LDRT) has been temporarily used to treat pneumonia.In the past decades, researchers were dedicated to clarify the biological mechanism of LDRT.LDRT plays a unique role in the suppression of inflammation, preliminary outcomes have been acquired in critical patients with COVID-19 pneumonia, and radiotherapy community is paying attention to this treatment strategy.This review summarizes the application of LDRT in pneumonia, its biological mechanism, the result of LDRT in COVID-19 pneumonia, the existing problems and prospective in clinic.

Objective:To understand the influence and lag effect of meteorological factors on the incidence of hand, foot and mouth disease (HFMD) in Shijiazhuang.Methods:The daily incidence data of HFMD in Shijiazhuang during 2017-2019 were collected from Chinese Information System for Disease Control and Prevention. The hourly meteorological data were collected form meteorological stations of Shijiazhuang of Chinese meteorological data network. The distributed lag nonlinear model was built for statistical analysis by software R 3.6.2.Results:When the daily average temperature was 15-26 ℃, the risk of incidence of HFMD increased at lag 3-6 days. However, the risk was highest when the temperature was 25 ℃ at lag 3 days ( RR=1.03,95% CI:1.00-1.06). When the daily average relative humidity was more than 80%, the risk of incidence of HFMD increased at lag 5-18 days. However, the risk was highest at lag 9 days ( RR=1.04, 95% CI: 1.02-1.06).When the daily average air pressure ranged from 999 hPa to 1 007 hPa, the risk of incidence of HFMD increased at lag 5-8 days. However, the risk was highest at lag 6 days ( RR=1.01, 95% CI: 1.00-1.02).When the daily average precipitation ranged from 15 to 32 mm, the risk of incidence of HFMD increased at lag 3-18 days. However, the risk was highest at lag 6 days ( RR=1.11, 95% CI: 1.02-1.19). Conclusions:Meteorological factors increased the risk of incidence of HFMD such as higher daily average temperature (15-26 ℃), higher daily average humidity (>80%), lower daily average air pressure (999-1 007 hPa) and higher daily average precipitation (15-32 mm) in Shijiazhuang during 2017-2019. They were all correlated with the incidence of HFMD with certain lag days. It is suggested to use these meteorological indicators for the early warning of HFMD.

OBJECTIVE： To establish a method for simultaneous determination of 6 components in Chaihuang tablets， such as baicalin， wogonoside， baicalein， wogonin， saikosaponin a and saikosaponin d in Chaihuang tablets. METHODS： HPLC-DAD method was used to detect 3 batches of Chaihuang tablets from same manufacturers. The determination was performed on Agilent Eclipse XDB-C18 column with mobile phase consisted of acetonitrile-triethylamine phosphate aqueous solution （pH adjusted to 7.0， gradient elution） at flow rate of 1.0 mL/min. The detection wavelengths were set at 210 nm （saikosaponin a， saikosaponin d） and 277 nm （baicalin， wogonoside， baicalein， wogonin）. The column temperature was 30 ℃， and sample size was 5 μL. RESULTS： The linear ranges of baicalin， wogonoside， baicalein， wogonin， saikosaponin a and saikosaponin d were 0.379 5-7.590 4 μg，   0.082 96-1.659 2 μg， 0.039 39-0.787 8 μg， 0.040 72-0.814 4 μg， 0.040 45-0.809 0 μg， 0.038 63-0.772 6 μg （all r≥0.999 3）， respectively. The limits of detection were 0.008， 0.007， 0.005， 0.005， 0.020 and 0.018 μg/mL. The limits of quantitation were 0.025， 0.022， 0.015， 0.015， 0.060， 0.054 μg/mL. RSDs of precision， reproducibility and stability tests （48 h） were all lower than 1.5％ （n＝6）. Average recoveries were 98.46％， 97.06％， 100.90％， 96.13％， 96.91％， 96.57％ （RSD＜2.0％， n＝6）. CONCLUSIONS： Established method is simple， accurate and reproducible for 6 components in Chaihuang tablets， and can be used for quality control of the tablet.