This paper proposes a two-stage method integrating visual foundation models （VFM） and diffusion models. The segment anything model （SAM） as VFM is combined with the SegRefiner diffusion model to construct the SAM-SegRefiner framework for automated segmentation of edema， inflammation， and thrombus regions in histopathological images of hemorrhoidal tissue， providing a reproducible technical tool for the objective quantification of pathological morphology and its application in traditional Chinese medicine （TCM） syndrome research. Trained and validated on multi-center retrospective data， the SAM-SegRefiner model achieved an average pixel accuracy of 95.32% and a mean intersection over union （mIoU） of 66.81% on an independent test set， significantly outperfor-ming comparative models such as U-Net， MixU-Net， and SAM-Med2D， and also demonstrating robust cross-center generalization capability. Furthermore， by correlating the quantitatively segmented results from the model with the patients' TCM syndrome types， the potential associations between pathomorphological features and TCM syndrome differentiation have been explored. The analysis revealed no statistically significant differences in the degree of inflammatory infiltration and thrombus formation among different syndrome types， suggesting a complex relationship between local pathological changes and systemic syndrome manifestations.

Xiaoji Yinzi is one of the classic prescriptions for treating urinary diseases， originated from the Yan's Prescriptions to Aid the Living （Yan Shi Ji Sheng Fang） written by YAN Yonghe in the Song dynasty. Xiaoji Yinzi is composed of Rehmanniae Radix， Cirsii Herba， Talcum， Akebiae Caulis， Typhae Pollen， Nelumbinis Rhizomatis Nodus， Lophatheri Herba， Angelicae Sinensis Radix， Gardeniae Fructus， and Glycyrrhizae Radix et Rhizoma and has the effects of cooling blood and stopping bleeding， draining water and relieving stranguria. The medical experts of later generations have inherited the original prescription recorded in the Yan's Prescriptions to Aid the Living， while dispute has emerged during the inheritance of this prescription. In this study， the method of bibliometrics was employed to review and analyze the ancient documents and modern clinical studies involving Xiaoji Yinzi. The results showed that Xiaoji Yinzi has two dosage forms： powder and decoction. According to the measurement system in the Song Dynasty， the modern doses of hers in Xiaoji Yinzi were transformed. In the prepration of Xiaoji Yinzi powder， 149.2 g of Rehmanniae Radix and 20.65 g each of Cirsii Herba， Talcum， Akebiae Caulis， stir-fried Typhae Pollen， Nelumbinis Rhizomatis Nodus， Lophatheri Herba， wine-processed Angelicae Sinensis Radix， stir-fried Gardeniae Fructus， and stir-fried Glycyrrhizae Radix et Rhizoma are grounded into fine powder with the particle size of 4-10 meshes and a decocted with 450 mL water to reach a volume of 240 mL. After removal of the residue， the decoction was taken warm before meals， 3 times a day （i.e.， 7.77 g Rehmanniae Radix and 0.97 g each of the other herbs each time）. In the preparation of Xiaoji Yinzi decoction， 20.65 g each of the above 10 herbs are used， with stir-fried Typhae Pollen， wine-processed Angelica Sinensis Radix， stir-fired Gardeniae Fructus， stir-fired Glycyrrhizae Radix et Rhizoma， and raw materials of other herbs. Xiaoji Yinzi is specialized in treating hematuresis and blood stranguria due to heat accumulation in lower energizer， which causes injury of the blood collaterals of gallbladder and dysfunction of Qi transformation. In modern clinical practice， Xiaoji Yinzi is specifically used for treating urinary diseases and can be expanded to treat diseases of the cardiovascular system and other systems according to pathogenesis. The comprehensive research on the key information could provide a scientific reference for the future development of Xiaoji Yinzi.

Sinisan is a classical prescription developed and applied by ancient medical experts and it is first recorded in the Treatise on Cold Damage written by ZHANG Zhongjing in the Eastern Han Dynasty. Later physicians have modified this prescription based on this original one. The bibliometrics methods were used to analyze the key information and research trend of Sinisan. According to the inclusion and exclusion criteria， 69 pieces of effective data were extracted， involving 67 ancient traditional Chinese medicine （TCM） books. The results showed that the name， composition， and decocting methods of Sinisan in later generations were inherited from the original record in the Treatise on Cold Damage. The original plants of medicinal materials used in Sinisan are basically clear. We recommend Bupleuri Radix as the dried root of Bupleurem scorzonerifolium， Paeoniae Radix Alba as the dried root of Paeonia lactiflora， Aurantii Fructus as the dried fruit of Citrus aurantium， Glycyrrhizae Radix et Rhizoma as the dry root and rhizome of Glycyrrhiza uralensis. Raw materials of Bupleuri Radix and Paeoniae Radix Alba， Aurantii Fructus stir-fried with bran， and stir-fried Glycyrrhizae Radix et Rhizoma should be used for preparation of Sinisan. According to measurement system in the Han Dynasty， a bag of Sinisan is composed of 1.25 g Bupleuri Radix， 1.25 g Paeoniae Radix Alba， 1.25 g Aurantii Fructus， and 1.25 g Glycyrrhizae Radix et Rhizoma. The materials should be grounded into coarse powder and taken with a proper amount of rice soup， 3 times a day. Sinisan has the effects of regulating qi movement and harmonizing the liver and spleen. It can be used for treating reversal cold in limbs and cold damage. In modern clinical practice， Sinisan can be used to treat chronic gastritis， irritable bowel syndrome， and dyspepsia. The above research results provide scientific reference for the future research and development of Sinisan.

Human epidermal growth factor receptor 2 (HER2) mutations play a role as a driver gene in non-small cell lung cancer (NSCLC). Patients with advanced NSCLC harboring HER2 mutations exhibit poor responses to conventional chemotherapy and immunotherapy, hence targeted therapies against HER2 are under extensive investigation. This review analyzes the biological characteristics of HER2, an overview of clinical trials for targeted therapy drugs, including monoclonal antibodies, tyrosine kinase inhibitors (TKIs), and antibody-drug conjugate, and research directions for drug resistance in NSCLC. Currently, Pyrotinib and Trastuzumab deruxtecan have been approved for the treatment of advanced NSCLC with HER2 mutations, suitable for patients who have failed standard therapy, which is far from meeting the clinical demands. Novel selective HER2 TKIs are gradually emerging. Future exploration trends are gradually shifting from single drugs to combination strategies, and are exploring more precise selection strategies as well as research on resistance mechanisms. These studies will provide a theoretical basis for clinical treatment strategies for advanced NSCLC with HER2 mutations, promoting the development of personalized therapy.
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Humans ; Carcinoma, Non-Small-Cell Lung/pathology* ; Lung Neoplasms/pathology* ; Receptor, ErbB-2/metabolism* ; Mutation ; Molecular Targeted Therapy ; Protein Kinase Inhibitors/therapeutic use* ; Antineoplastic Agents/therapeutic use*

To effectively exploit the tumor microenvironment (TME), TME-responsive nanocarriers based on cascade reactions have received much attention. In this study, we designed a novel nanoparticle PB@SiO₂@MnO₂@P-Arg (PMP) to construct a cascade reaction nanoplatform. While using biosafety Prussian blue (PB) for photothermal therapy (PTT), this nanoplatform uses silica (SiO₂) as an intermediate layer to assemble Prussian blue and manganese dioxide (MnO₂) into a core-shell structure, which effectively enhances the response of the nanoplatform to TME and promotes the effect of chemodynamic therapy (CDT) resulting from glutathione (GSH) depletion and Fenton-like reaction. The released Mn²⁺ can also be used for magnetic resonance imaging (MRI). Through the cascade reaction, poly-l-arginine (P-Arg) coated on the surface of the nanoparticles can react with hydroxyl radical (•OH) obtained from the Fenton-like reaction to release nitric oxide (NO), which further reacts with O₂•^- to produce the more toxic peroxynitrite anion (ONOO^-). The photothermal effect of PB further enhances the effect of the cascade reaction while reducing the amount of heat required for treatment. In vitro and in vivo studies confirmed the antitumor effects of cascade reaction-based nanoplatforms in combined photothermal/chemodynamic/gas cancer therapies, providing new strategies for the design and fabrication of multifunctional nanoplatforms that integrate diagnostic and therapeutic functions, as well as the application of cascade reactions in multimodal synergistic therapy.

Objective To explore the effectiveness of the diffusion of innovation theory in com-bination with multidisciplinary nursing collaboration in intervention for patients with severe pneumonia complicated by heart failure.Methods A total of 120 patients with severe pneumonia complicated by heart failure admitted between April 2021 and April 2024 were enrolled and randomly divided into observation group(n=60)and control group(n=60)using a random black-and-white ball method.The control group received conventional nursing intervention,while the observation group received an intervention model combining the diffusion of innovations theory with multidisciplinary collaboration on top of the conventional nursing.Rehabilitation outcomes(time to control of pulmonary inflammation,time to resolution of cough and expectoration,length of hospital stay)and post-intervention cardiac function[left ventricular ejection fraction(LVEF),left ventricular end-systolic volume(LVESV)]were compared between the two groups.The Minnesota Living with Heart Failure Questionnaire(MLHFQ)was used to assess quality of life,and the Self-Care Heart Failure Index(SCHFI)was used to evaluate self-care behaviors.Complications were compared between the two groups,and cost-effectiveness was analyzed(patient medical expenses and re-hospitalization rates).Results The observation group had shorter time to resolution of cough and expectoration,control of pulmonary inflammation,and length of hospital stay compared with the control group,with statistically significant differences(P＜0.05).After intervention,LVEF increased in both groups compared with pre-intervention lev-els,and was higher in the observation group than in the control group,with a statistically significant difference(P＜0.05);ESV decreased in both groups compared with pre-intervention levels,and was lower in the observation group than in the control group,with a statistically significant difference(P＜0.05).After intervention,physiological,emotional,and social functioning scores in the MLHFQ decreased in both groups compared with pre-intervention levels,and were lower in the ob-servation group than in the control group,with statistically significant differences(P＜0.05).After intervention,scores for self-care maintenance,self-care management,and self-care confidence in the SCHFI increased in both groups,and were higher in the observation group than in the control group,with statistically significant differences(P＜0.05).There was no statistically significant difference in the incidence of complications between the two groups(P＞0.05).Conclusion The combination of the diffusion of innovations theory and multidisciplinary collaboration nursing model can accelerate the rehabilitation process in patients with severe pneumonia complicated by heart fail-ure,improve their quality of life,and effectively enhance their self-care abilities.

Zhigancao Tang （also known as Fumaitang） is a classic formula for treating "intermittent pulse and palpitations" and is widely used in clinical practice. Sanjia Fumaitang， included in the Catalogue of Ancient Classical Formulas （First Batch） published by the National Administration of Traditional Chinese Medicine of China in 2018， is derived from this formula. This paper employed bibliometric methods to comprehensively investigate and summarize the historical evolution， drug composition， herb origins and preparation， prescription meanings， and ancient and modern applications of Zhigancao Tang， analyzed the composition and usage of Zhigancao Tang， and discussed the reasons and applications of the "Fumaitang" variants created by Wu Jutong. A total of 47 valid pieces of data from 38 ancient texts were included. Results showe that Zhigancao Tang originates from the Treatise on Cold Damage （Shang Han Lun）， and the name "Fumaitang" is also recorded in the formula's description. Converted to modern measurements from the Han dynasty system， the recommended preparation for Zhigancao Tang includes 55.2 g of fried Glycyrrhizae Radix et Rhizoma， 41.4 g of Cinnamomi Ramulus， 27.6 g of Ginseng Radix et Rhizoma， 220 g of fresh Rehmannia glutinosa， 27.6 g of Asini Corii Colla， 53 g of Ophiopogonis Radix， 45 g of Cannabis Fructus， and 90 g of Jujubae Fructus. All herbs should be decocted with 1 400 mL of yellow rice wine and 1 600 mL of water until 600 mL. Once the Asini Corii Colla is fully dissolved， the decoction should be taken warm at a dosage of 200 mL， three times a day. Zhigancao Tang is effective for replenishing Qi， warming Yang， nourishing Yin， and nourishing blood and is primarily used to treat “intermittent pulse and palpitations” caused by deficiencies in heart Yin and Yang， as well as malnutrition of the heart meridian and conditions like lung atrophy. Modern applications mainly focus on cardiovascular and cerebrovascular diseases， including arrhythmias， coronary heart disease， and premature ventricular contractions. The findings from this research provide a reference for the further development of Zhigancao Tang.

OBJECTIVE To establish the quality standard of the leaves of Litchi chinensis Sonn.. METHODS The identification of medicinal properties, microscopic characteristics, TLC and content determination method of the leaves of Litchi chinensis Sonn. was conducted. The moisture, total ash, acid insoluble ash and extract of the leaves of Litchi chinensis Sonn. were determined according to Chinese Pharmacopoeia(Volume IV), 2020. RESULTS The leaves of Litchi chinensis Sonn. under forest exhibited specific properties in characteristics, microscopic features and TLC results. The moisture content of the medicinal materials was 2.66%-6.42%, the total ash content was 2.96%-4.52%, the acid insoluble ash content was 0.17%-0.94%, the water soluble extract was 15.38%-19.87%, and the alcohol soluble extract was 24.94%-30.33%. The eight components of gallic acid, protocatechin, catechin, epicatechin, rutin, astragalin, quercetin and kaempferol had a good linear relationship in 0.003 3-0.052 0 mg·mL-1, 0.006 9-0.109 6 mg·mL-1, 0.013 0-0.208 0 mg·mL-1, 0.057 5-0.920 0 mg·mL-1, 0.013 4-0.213 6 mg·mL-1, 0.013 2-0.211 2 mg·mL-1, 0.002 9-0.045 6 mg·mL-1, 0.003 6-0.056 8 mg·mL-1(r>0.999). The average sample recovery rate was 97.43%-102.97% and the RSD was 1.70%-2.90%. CONCLUSION The established quality standard of the leaves of Litchi chinensis Sonn. medicinal material has good specificity, accuracy and reproducibility, which can be used for quality control research of the leaves of Litchi chinensis Sonn..

BACKGROUND: The literature recommends that reduced dosage of CPT-11 should be applied in patients with UGT1A1 homozygous mutations, but the impact of UGT1A1 heterozygous mutations on the adverse reactions of CPT-11 is still not fully clear. METHODS: A total of 107 patients with UGT1A1 heterozygous mutation or wild-type, who were treated with CPT-11 from January 2018 to September 2021 in Peking University Third Hospital, were retrospectively enrolled. The adverse reaction spectra of patients with UGT1A1*6 and UGT1A1*28 mutations were analyzed. Adverse reactions were evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) 5.0. The efficacy was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The genotypes of UGT1A1*6 and UGT1A1*28 were detected by digital fluorescence molecular hybridization. RESULTS: There were 43 patients with UGT1A1*6 heterozygous mutation, 26 patients with UGT1A1*28 heterozygous mutation, 8 patients with UGT1A1*6 and UGT1A1*28 double heterozygous mutations, 61 patients with heterozygous mutation at any gene locus of UGT1A1*6 and UGT1A1*28. Logistic regression analysis showed that the presence or absence of vomiting (P=0.013) and mucositis (P=0.005) was significantly correlated with heterozygous mutation of UGT1A1*28, and the severity of vomiting (P<0.001) and neutropenia (P=0.021) were significantly correlated with heterozygous mutation of UGT1A1*6. In colorectal cancer, UGT1A1*6 was significantly correlated to diarrhea (P=0.005), and the other adverse reactions spectrum was similar to that of the whole patient cohort, and efficacy and prognosis were similar between patients with different genotypes and patients treated with reduced CPT-11 dosage or not. CONCLUSIONS In clinical use, heterozygous mutations of UGT1A1*6 and UGT1A1*28 are related to the risk and severity of vomiting, diarrhea, neutropenia and mucositis in patients with Pan-tumor and colorectal cancer post CPT-11 therpy. In colorectal cancer, UGT1A1*6 is significantly related to diarrhea post CPT-11 use, efficacy and prognosis is not affected by various genotypes or CPT-11 dosage reduction.
Camptothecin/therapeutic use* ; Glucuronosyltransferase/genetics* ; Humans ; Lung Neoplasms/drug therapy* ; Mutation ; Polymorphism, Genetic ; Retrospective Studies

Stimulator of interferon genes (STING) is a cytosolic DNA sensor which is regarded as a potential target for antitumor immunotherapy. However, clinical trials of STING agonists display limited anti-tumor effects and dose-dependent side-effects like inflammatory damage and cell toxicity. Here, we showed that tetrahedral DNA nanostructures (TDNs) actively enter macrophages to promote STING activation and M1 polarization in a size-dependent manner, and synergized with Mn²⁺ to enhance the expressions of IFN-β and iNOS, as well as the co-stimulatory molecules for antigen presentation. Moreover, to reduce the cytotoxicity of Mn²⁺, we constructed a TDN-MnO₂ complex and found that it displayed a much higher efficacy than TDN plus Mn²⁺ to initiate macrophage activation and anti-tumor response both in vitro and in vivo. Together, our studies explored a novel immune activation effect of TDN in cancer therapy and its synergistic therapeutic outcomes with MnO₂. These findings provide new therapeutic opportunities for cancer therapy.