The concept of holism is the core idea of traditional Chinese medicine （TCM）. Various organs and tissues coordinate with each other to maintain the body's life activities， with a close and mutual influence between the spleen， stomach， and the central nervous system （brain）. The gut-brain axis plays an important bridging role between the digestive system and the central nervous system， achieving bidirectional information exchange between the brain and the gastrointestinal tract through complex neuroendocrine and immune mechanisms. The theory of cross-organ interaction involves the mutual influence， coordination， and integration between different organs and systems； multimodality， on the other hand， utilizes multiple sensory modalities， such as vision， hearing， and touch， to convey information. By combining TCM theory with the gut-brain axis theory， a cross-organ multimodal characterization system is established to explore its mechanism and application value in refractory diseases such as functional gastrointestinal disorders， precancerous gastrointestinal diseases， Alzheimer's disease， Parkinson's syndrome， type 2 diabetes， and depression.

OBJECTIVE To investigate the effect and potential mechanism of astilbin （AST） on renal injury in chronic renal failure （CRF） rats based on the Jagged-1/Notch-1 signaling pathway. METHODS CRF model was constructed by 5/6 nephrotomy. The successfully modeled rats were randomly separated into Model group， AST low-dose group （AST-L group）， AST high-dose group （AST-H group）， high-dose of AST+Notch pathway activator （Jagged-1/FC chimerin， referred to as “JFC”） group （AST-H+ JFC group）， and control group （CK group） for open surgery without resection was set up， with 10 rats in each group. The rats in the AST-L group and AST-H group were given 40 and 80 mg/kg AST， respectively； the rats in the AST-H+JFC group were simultaneously given 80 mg/kg AST and 0.5 mg/kg JFC， and the rats in the CK group and Model group were given an equal volume of normal saline， once a day， for 4 weeks. After the last administration， the serum levels of blood urea nitrogen （BUN）， serum creatinine （SCr）， and the level of 24 h urinary protein （UP） in urine， as well as the serum levels of lactate dehydrogenase （LDH）， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and IL-10 in each group were detected. The morphology and fibrosis of renal tissue were observed. The content of adenosine triphosphate （ATP） and the activities of sodium-potassium ATPase and calcium-magnesium ATPase in mitochondria of renal tissue were detected. The protein expressions of transforming growth factor- β （TGF- β）， hypoxia-inducible factor-1α （HIF-1α）， α-smooth muscle actin （α-SMA）， cleaved-caspase-3， Jagged-1 and Notch-1 in renal tissue were also observed. RESULTS Compared with CK group， the renal tissue of rats in the Model group was obviously damaged， renal tissue fibrosis was severe； the serum BUN and SCr levels， urine UP level， serum 4 LDH， TNF-α and IL-6 levels， as well as the protein expressions of TGF-β， HIF-1α， α-SMA， cleaved-caspase-3， Jagged-1 and Notch-1 in renal tissue were significantly increased， while the serum IL-10 level， ATP content and activities of sodium-potassium ATPase and calcium-magnesium ATPase in mitochondria of renal tissue were significantly decreased （P＜0.05）. Compared with Model group， the renal tissue damage and fibrosis in the AST groups were reduced， the serum BUN and SCr levels， urine UP level， serum LDH， TNF-α and IL-6 levels， and the protein expressions of TGF-β， HIF-1α， α-SMA， cleaved-caspase-3， Jagged-1 and Notch-1 were significantly decreased， while the serum IL-10 level， ATP content and the activities of sodium-potassium ATPase and calcium-magnesium ATPase in mitochondria were significantly increased； the changes in the aforementioned indicators in AST- H group were more significant than those in the AST-L group（P＜0.05）. JFC could significantly reverse the improvement effect of high dose of AST on renal injury in CRF rats （P＜0.05）. CONCLUSIONS AST can reduce inflammation in CRF rats， alleviate renal tissue damage and fibrosis， and improve renal mitochondrial capacity metabolism， possibly by inhibiting the Jagged-1/Notch-1 signaling pathway.

INTRODUCTION: Trastuzumab deruxtecan (T-DXd) has revolutionised treatment for metastatic breast cancer (MBC). While effective, its high cost and toxicities, such as fatigue and nausea, pose challenges. METHOD: Medical records from the Joint Breast Cancer Registry in Singapore were used to study MBC patients treated with T-DXd (February 2021-June 2024). This study was conducted to address whether reducing dose intensity and density may have an adverse effect on treatment outcomes. RESULTS: Eighty-seven MBC patients were treated with T-DXd, with a median age of 59 years. At the time of data cutoff, 32.1% of patients were still receiving T-DXd. Over half (54%) of the patients received treatment with an initial relative dose intensity (RDI) of <;85%. Overall median real-world progression-free survival (rwPFS) was 8.1 months. rwPFS was similar between RDI groups (<85%: 8.7 months, <85%: 8.1 months, P=0.62). However, human epidermal growth receptor 2 (HER2)-positive patients showed significantly better rwPFS outcomes compared to HER2-low patients (8.8 versus 2.5 months, P<0.001). Only 16% with central nervous system (CNS) involvement had CNS progressive disease on treatment. No significant progression-free survival (PFS) differences were found between patients with or without CNS disease, regardless of RDI groups. Five patients (5.7%) developed interstitial lung disease (ILD), with 3 (3.4%) having grade 3 events. Two required high-dose steroids and none were rechallenged after ILD. There were no fatalities. CONCLUSION Our study demonstrated that reduced dose intensity and density had no significant impact on rwPFS or treatment-related toxicities. Furthermore, only 5.7% of patients developed ILD. T-Dxd provided good control of CNS disease, with 82% of patients achieving CNS disease control.
Humans ; Female ; Breast Neoplasms/mortality* ; Middle Aged ; Trastuzumab/adverse effects* ; Aged ; Adult ; Singapore/epidemiology* ; Antineoplastic Agents, Immunological/adverse effects* ; Camptothecin/adverse effects* ; Immunoconjugates/adverse effects* ; Retrospective Studies ; Progression-Free Survival ; Receptor, ErbB-2/metabolism* ; Neoplasm Metastasis ; Dose-Response Relationship, Drug ; Treatment Outcome ; Registries

This study established the HPLC fingerprints, characteristic chromatograms, and a multi-component content determination method for Bidens bipinnata and B. biternata. The chemical pattern recognition analysis was then employed to clarify the characteristic indexes of quality differences between the two original plants of Bidentis Herba, providing a reference for establishing the quality standards of Bidentis Herba. HPLC was launched on an Agilent Poroshell 120 EC-C_(18) chromatographic column(4.6 mm×250 mm, 4 μm) by gradient elution with a mobile phase of 0.1% aqueous phosphoric acid-acetonitrile at a flow rate of 0.7 mL·min~(-1), detection wavelength of 270 nm, column temperature of 25 ℃, and an injection volume of 5 μL. The similarity between the fingerprints of 18 batches of Bidentis Herba samples and the common pattern(R) ranged from 0.572 to 0.933. A total of 23 chromatographic peaks were calibrated. Through comparison with the reference substances, six components(neochlorogenic acid, chlorogenic acid, isochlorogenic acid A, isochlorogenic acid B, rutin, and hyperoside) were identified and subjected to quantitative analysis. The characteristic fingerprints of B. bipinnata and B. biternata were calibrated with 20 and 17 characteristic peaks, respectively. Among them, peaks 8, 9, 22, and 23 were the characteristic peaks of B. bipinnata, and peak 7 was the characteristic peak of B. biternata, which can be used to distinguish the two original plants of Bidentis Herba. The relative standard deviation of the content of the above-mentioned six components ranged from 36% to 123%. The cluster analysis, principal component analysis, and orthogonal partial least squares-discriminant analysis(OPLS-DA) classified the 18 batches of Bidentis Herba samples into two categories. Additionally, through the analysis of variable importance in projection(VIP) under OPLS-DA, three characteristic indexes, rutin, isochlorogenic acid A, and isochlorogenic acid B, were identified. The analytical method established in this study can comprehensively evaluate the consistency of Bidentis Herba samples derived from different original plants, specifically identify the differential components between them, and effectively distinguish the two original plants of Bidentis Herba, providing a basis for the differentiation between different original plants and the quality control of Bidentis Herba.
Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Quality Control ; Bidens/chemistry*

Stem cell treatment may enhance erectile dysfunction (ED) in individuals with cavernous nerve injury (CNI). Nevertheless, no investigations have directly ascertained the implications of varying amounts of human umbilical cord-derived mesenchymal stem cells (HUC-MSCs) on ED. We compare the efficacy of three various doses of HUC-MSCs as a therapeutic strategy for ED. Sprague-Dawley rats (total = 175) were randomly allocated into five groups. A total of 35 rats underwent sham surgery and 140 rats endured bilateral CNI and were treated with vehicles or doses of HUC-MSCs (1 × 10 6 cells, 5 × 10 6 cells, and 1 × 10 7 cells in 0.1 ml, respectively). Penile tissues were harvested for histological analysis on 1 day, 3 days, 7 days, 14 days, 28 days, 60 days, and 90 days postsurgery. It was found that varying dosages of HUC-MSCs enhanced the erectile function of rats with bilateral CNI and ED. Moreover, there was no significant disparity in the effectiveness of various dosages of HUC-MSCs. However, the expression of endothelial markers (rat endothelial cell antigen-1 [RECA-1] and endothelial nitric oxide synthase [eNOS]), smooth muscle markers (alpha smooth muscle actin [α-SMA] and desmin), and neural markers (neurofilament [RECA-1] and neurogenic nitric oxide synthase [nNOS]) increased significantly with prolonged treatment time. Masson's staining demonstrated an increased in the smooth muscle cell (SMC)/collagen ratio. Significant changes were detected in the microstructures of various types of cells. In vivo imaging system (IVIS) analysis showed that at the 1 st day, the HUC-MSCs implanted moved to the site of damage. Additionally, the oxidative stress levels were dramatically reduced in the penises of rats administered with HUC-MSCs.
Male ; Animals ; Erectile Dysfunction/metabolism* ; Rats, Sprague-Dawley ; Mesenchymal Stem Cell Transplantation/methods* ; Rats ; Penis/pathology* ; Humans ; Disease Models, Animal ; Umbilical Cord/cytology* ; Peripheral Nerve Injuries/complications* ; Mesenchymal Stem Cells ; Nitric Oxide Synthase Type III/metabolism* ; Actins/metabolism* ; Nitric Oxide Synthase Type I/metabolism*

Immunotherapy has emerged as a revolutionary approach to treat immune-related diseases. Dendritic cells (DCs) play a pivotal role in orchestrating immune responses, making them an attractive target for immunotherapeutic interventions. Modulation of gene expression in DCs using genome editing techniques, such as the CRISPR-Cas system, is important for regulating DC functions. However, the precise delivery of CRISPR-based therapies to DCs has posed a significant challenge. While lipid nanoparticles (LNPs) have been extensively studied for gene editing in tumor cells, their potential application in DCs has remained relatively unexplored. This study investigates the important role of cholesterol in regulating the efficiency of BAMEA-O16B lipid-assisted nanoparticles (BLANs) as carriers of CRISPR/Cas9 for gene editing in DCs. Remarkably, BLANs with low cholesterol density exhibit exceptional mRNA uptake, improved endosomal escape, and efficient single-guide RNA release capabilities. Administration of BLAN_mCas9/gPD-L1 results in substantial PD-L1 gene knockout in conventional dendritic cells (cDCs), accompanied by heightened cDC1 activation, T cell stimulation, and significant suppression of tumor growth. The study underscores the pivotal role of cholesterol density within LNPs, revealing potent influence on gene editing efficacy within DCs. This strategy holds immense promise for the field of cancer immunotherapy, offering a novel avenue for treating immune-related diseases.

OBJECTIVE To investigate the effects of evolocumab combined with atorvastatin on post-percutaneous coronary intervention （PCI） efficacy and coronary microcirculation in patients with acute ST-segment elevation myocardial infarction （STEMI）. METHODS This retrospective cohort study included 194 hospitalized patients with acute STEMI who underwent PCI in the First Affiliated Hospital of Nanyang Medical College from Jan. 2022 to Dec. 2024. The patients were divided into control group （100 cases） and combination therapy group （94 cases） according to the different therapy plans. The control group was given Atorvastatin calcium tablets orally， at a dose of 20 mg， once a day. On the basis of the control group， the combination therapy group received an initial injection of Evolocumab injection 140 mg within 24 hours after PCI， followed by subsequent injections every 2 weeks. Both groups received continuous treatment for at least 30 days. Blood lipid indicators [total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C） and high-density lipoprotein cholesterol]， inflammation indicators [C-reactive protein （CRP） and interleukin-6 （IL-6）]， vascular Δ 基金项目河南省医学科技攻关计划项目（No.LHGJ20230971） endothelial function and microcirculation indicators [fibrinogen， ankle-brachial index （ABI） and nitric oxide （NO）]， cardiac function indicators [left ventricular ejection （LVEF）， left ventricular end-diastolic diameter and left ventricular end-systolic diameter] before treatment and after 30 days of treatment， as well as the occurrence of adverse reactions during the treatment， were compared between the two groups. RESULTS Before treatment， there were no statistically significant differences in the levels of the indicators of blood lipid， inflammation， vascular endothelial function and microcirculation， and cardiac function between the two groups （P＞0.05）. After 30 days of treatment， the levels of TC， TG， LDL-C， CRP， IL-6 and fibrinogen in both groups were significantly reduced compared to those before treatment within the same group. The levels of NO and LVEF in both groups， as well as ABI in the combination therapy group， were significantly elevated compared to those before treatment within the same group. Moreover， the improvements in the levels of TC， LDL-C， CRP， IL-6， fibrinogen and NO in the combination therapy group were more pronounced than those in the control group during the same period （P＜0.05）. There were no statistically significant differences in the incidence of liver function impairment， gastrointestinal adverse reactions， or the overall incidence of adverse reactions between the two groups （P＞0.05）. CONCLUSIONS Compared with atorvastatin alone， evolocumab combined with atorvastatin more effectively reduces the blood lipid levels， improves the inflammatory status， vascular endothelial function and coronary microcirculation in patients with acute STEMI after PCI， while the safety is comparable to that of atorvastatin alone.

Objective:To investigate the accurate diagnosis and differential diagnosis of non-primary solid malignant tumors in breast needle core biopsy.Methods:Twenty-three cases of breast, axilla or neck lymph nodes pathologically diagnosed as non-primary solid malignant tumors were collected at the First Affiliated Hospital of Nanjing Medical University, Nanjing, China from January 2013 to March 2023. The differential diagnoses and diagnostic features were analyzed, based on combining clinical data, histology, and expression characteristics of biomarkers.Results:All patients were female, with age ranging from 29 to 75 years (average 56 years). The average time from the diagnosis of primary tumor to the current diagnosis was 21 months (0 to 204 months).The primary sites included the ovary (9 cases), the lung (5 cases), the gastrointestinal tract (4 cases), the pancreas, intrahepatic bile duct, thyroid gland, nasal cavity and forearm skin (1 case each). No carcinoma in situ was found in any of the cases. The morphological differences were significant among the tumors, but similar to the primary tumors. The tumors of neuroendocrine and female reproductive tract had great morphological and immunophenotypic overlaps with breast cancer. Metastatic lung cancer cells showed obvious atypia and tumor giant cells. The morphology and immunophenotype of metastatic serous carcinoma of female reproductive system might resemble invasive micropapillary carcinoma of the breast. Metastatic adenocarcinoma of the gastrointestinal tract often had features of mucous secretion. Metastatic neuroendocrine tumors were bland in appearance and morphologically similar to solid papillary carcinoma of breast, but negative for ER. TRPS1 was mostly negative (18/23) and variably positive in ovarian (4/9) and intrahepatic bile duct (1/1) tumors.Conclusions:The diagnosis of breast needle core biopsy specimen should be combined with clinical history, imaging study, and careful examination of histological features, such as presence of in situ component, morphological similarity between the primary and metastatic tumors, and using appropriate markers to differentiate the primary from metastatic tumors.

Objective:To systematically evaluate qualitative studies on the perceptions and feelings of nursing staffs implementing neonatal palliative care, aiming to provide insights for advancing clinical practice in China.Methods:The databases including China National Knowledge Infrastructure, Wanfang, VIP, Chinese Biomedical Literature Database, PubMed, CINAHL, Embase, Cochrane Library, Web of Science, and PsycINFO were included to retrieve the literature on the perceptions and feelings of nursing staffs from inception until March 28, 2024. The literature quality was assessed utilizing the Joanna Briggs Institute Australian Centre for Evidence-Based Health Care Quality Assessment Criteria for Qualitative Research (2016), and the findings were synthesized through Meta-integration techniques.Results:A total of 12 studies were included, yielding 46 themes were extracted; 8 categories were summarized and 3 synthesis results were obtained: nursing staffs experience both negative and positive aspects, the real-life challenges faced by nursing staffs in implementing neonatal palliative care, and the practical experiences and needs of nursing staffs regarding neonatal palliative care.Conclusions:It is crucial to continually address nursing staffs′ negative emotions and tackle challenges related to staffing, training, communication, and ethical dilemmas to ensure appropriate end-of-life symptom management in neonatal palliative care.