Based on the theory of "sweet-flavored medicinals retaining and restoring body fluid"， this paper proposed that the core pathogenesis of hypercoagulable state in malignant tumors is qi deficiency and fluid consumption， blood stasis and vessels stagnation， which evolves dynamically according to the pattern "qi deficiency → fluid consumption → blood stasis". Accordingly， a staged treatment system is established with the general principle of "fortifying the middle jiao， restoring fluid and activating blood circulation". In the initial stage， invigorating the spleen and boosting qi to generate body fluid， targeting the onset of middle jiao deficiency and body fluid consumption； in the middle stage， nourishing yin and unblocking collaterals to facilitate body fluid circulation， addressing the disorder of body fluid transportation and collateral injury caused by internal dryness； in the late stage， consolidating yin and resolving blood stasis to retain body fluid， resolving yin impairment， fluid exhaustion， and binding of stasis and toxin. By regulating body fluid metabolism to improve the hypercoagulable state， this system is intended to provide insights for the prevention and treatment of hypercoagulable state in malignant tumors with traditional Chinese medicine.

Objective: To systematically evaluate the association between random urinary electrolyte levels and hypertension among children and adolescents in Guizhou Province, so as to provide evidence for region specific dietary guidance and interventions. Methods: In 2023, a total of 2 480 children and adolescents aged 6 to 17 years were recruited from a nine-year coherent style school in Guizhou Province in a children health cohort, with follow ups conducted in 2024 and 2025. Random urine samples were collected to measure urinary sodium, potassium, calcium, and chloride, and the urinary sodium to potassium ratio (Na/K) was calculated. The diagnosis of hypertension was based on the criteria established by the Chinese Guidelines for Hypertension Prevention and Treatment (2024 revised edition) and relevant research. Linear mixed models and multinomial Logistic regression were used to assess the associations of urinary electrolytes with systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and the risk of hypertension. Results: At baseline, SBP, DBP, and MAP were 102.33 (94.33, 110.33), 61.33 (56.33, 67.00) and 75.22 (69.67, 81.33)mmHg among children and adolescents, respectively. After adjusting for potential confounders and two follow-ups, higher urinary Na/K ratio was positively associated with higher of SBP ( β=0.054, 95%CI =0.028- 0.081 ) and MAP ( β=0.038, 95%CI =0.010-0.066), as well as higher risks of hypertension ( OR=1.248, 95%CI =1.006-1.548) (all P <0.05). Higher of urinary chloride levels were positively associated with higher of SBP ( β=0.088, 95%CI = 0.009- 0.167), whereas higher of urinary potassium (SBP: β=-0.062, 95%CI =-0.096 to -0.028; MAP: β=-0.041, 95%CI = -0.078 to -0.005) and calcium levels (SBP: β=-0.036, 95%CI =-0.065 to -0.007) were negatively associated with blood pressure (all P < 0.05 ). Conclusion The urinary Na/K, as a comprehensive electrolyte marker, more stably reflects sodium load and excretory pressure in children and adolescents, and may serve as an early predictor of hypertension risk.

Objective: To establish a rapid, accurate, and decentralized workflow for bacterial whole-genome sequencing (WGS) and risk profiling within the shelf-life of platelet concentrates, and to characterize the species, virulence, antimicrobial resistance (AMR), and immune evasion mechanisms of co-existing bacteria in qualified platelet products, thereby providing a scientific basis for transfusion safety assessment. Methods: Three units of platelet concentrates, which tested negative by routine bacterial screening, were collected from the Chengdu Blood Center between May and June 2025. Samples were enriched at 37℃under six aerobic and nine anaerobic conditions for 7 days. Using a culturomics strategy, aliquots were plated for isolation on days 1, 3, 5, and 7 to obtain cultivable isolates, with negative culture controls included to exclude contamination. High-molecular-weight genomic DNA was extracted via mechanical grinding, purified, and size-selected. Sequencing libraries were constructed and sequenced on the G-seq500 single-molecule nanopore sequencing platform. Genomes were assembled using Flye and polished with NextPolish, with quality evaluated by BUSCO and CheckM. Taxonomic identification was performed using GTDB-Tk. Functional annotation and database comparisons were conducted to analyze virulence factors, AMR genes, and genes related to immune evasion and environmental adaptation. Results: Viable bacteria were successfully isolated from all three qualified platelet units within their shelf life. The isolates were identified as Bacillus albus, Niallia taxi, and Staphylococcus warneri. Nanopore sequencing generated 92 227-109 813 reads (totaling 680-758 Mb) with an N50 of 7 625-8 584 bp and Q20/Q30 scores of 97%/93%, respectively. All three genomes were assembled into complete circular chromosomes with 1-3 plasmids, achieving >93% completeness. Functional analysis revealed that B. albus carried multiple hemolysins, metalloproteases, and multidrug resistance genes, indicating the highest potential pathogenicity and AMR risk. S. warneri exhibited a typical multidrug resistance profile and regulatory network characteristic of coagulase-negative staphylococci, suggesting intermediate virulence. N. taxi harbored few canonical virulence factors and lacked functional AMR determinants, presenting a "low-virulence, low-resistance" profile. Notably, all three strains were enriched in genes encoding antimicrobial peptide resistance systems (e.g., dltABCD, mprF, GraRS, BceAB) and antioxidant enzymes, suggesting a strong capacity to withstand immune stress in the blood environment. Conclusion: Viable bacteria can be recovered from qualified platelet concentrates that test negative by routine screening. Nanopore WGS enables rapid strain-level identification and comprehensive risk profiling of virulence, resistance, and immune adaptation traits. The functional repertoires of these "co-existing" isolates range from environmental adaptation to potential pathogenicity, representing an underappreciated risk for transfusion-transmitted infections in susceptible recipients.

Colorectal cancer is a common and malignant tumor in the digestive tract. Invasion and metastasis of cancer cells are key factors leading to the high mortality rate and postoperative recurrence of colorectal cancer. Chemotherapy is the main treatment method for preventing recurrence of this disease. However， there are many toxic side effects in clinical application， which seriously hinder the treatment process. Therefore， it is imperative to search for efficient and low-toxicity drugs. Traditional Chinese medicine （TCM） has a long history of treating colorectal cancer and offers advantages such as safety， effectiveness， multiple targets， multiple pathways and minimal toxic side effects， which have made it increasingly popular worldwide. According to TCM， the pathogenesis of colorectal cancer is rooted in both deficiency and excess. TCM formulas mainly focus on tonifying the body to address the invasion and metastasis of colorectal cancer， such as Jianpi compound， Jianpi Xiaoai decoction， and Bushen Jiedu Sanjie decoction. TCM monomers， such as emodin， berberine， and tanshinone， mainly focus on clearing heat and removing toxin， circulating blood and transforming stasis， and resolving swelling and dispersing nodules. Signaling pathways play a crucial role for analyzing invasion and metastasis， and research has shown that pathways such as Wnt/β-catenin， phosphatidylinositol-3 kinase/protein kinase （PI3K/Akt）， Janus kinase 2/signal transduction and transcription activating factor 3 （JAK2/STAT3）， nuclear factors-κB （NF-κB）， vascular endothelial growth factor （VEGF） play important roles in the invasion and metastasis of colorectal cancer. The invasion and metastasis of colorectal cancer can be inhibited via regulating the key proteins and related factors in these pathways. In this review， we searched various literature databases， such as PubMed， China National Knowledge Infrastructure （CNKI）， and VIP， using keywords such as "colorectal cancer"， "signaling pathway"， "invasion and metastasis"， and "traditional Chinese medicine"， to summarize and analyze the relevant pathways of TCM compounds and monomers against invasion and metastasis of colorectal cancer published in the past five years. The review aims to provide new insights and references for in-depth research on the therapy for invasion and metastasis of colorectal cancer and new drug development.

ObjectiveTo evaluate the clinical efficacy of Huayu Tongluo Formula （化瘀通络方， HTF） in patients with mid-stage diabetic kidney disease of blood stasis syndrome and explore its potential mechanisms. MethodsA multi-center， randomized， double-blind， placebo-controlled clinical trial was conducted. Ninety patients of mid-stage diabetic kidney disease of blood stasis syndrome were divided into a control group of 46 cases and a treatment group of 44 cases. Both groups received conventional western medicine treatment， the treatment group additionally taking HTF， while the control group taking a placebo of the formula. The treatment was administered once daily for 24 weeks. The primary outcomes included 24-hour urine total protein （24 h-UTP）， serum albumin （Alb）， glycated hemoglobin （HbA1c）， and serum creatinine （Scr）.The secondary outcomes included changes in levels of endothelin-1 （ET-1）， nitric oxide （NO）， vascular endothelial growth factor （VEGF）， and traditional Chinese medicine （TCM） syndrome scores before and after treatment. Clinical efficacy was evaluated based on TCM syndrome scores and overall disease outcomes. Adverse reactions and endpoint events were recorded. ResultsIn the treatment group after treatment， 24 h-UTP， ET-1， and VEGF levels significantly decreased （P＜0.05）， Alb and NO levels significantly increased （P＜0.05）； while the TCM syndrome scores for edema， lumbar pain， numbness of limbs， dark purple lips， dark purple tongue or purpura， and thin， rough pulse all significantly decreased （P＜0.05）. In the control group， no significant changes were observed in any of the indicators after treatment （P＞0.05）.Compared with the control group， the treatment group showed significant reductions in 24 h-UTP， ET-1， and VEGF levels， and increases in Alb and NO levels （P＜0.05）. The TCM syndrome scores for edema， lumbar pain， dark purple tongue or purpura， and thin， rough pulse were all lower in the treatment group than in the control group （P＜0.05）. The total effective rate of TCM syndrome in the treatment group was 59.09% （26/44）， and the overall clinical effective rate was 45.45% （20/44）. In the control group， these rates were 15.22% （7/46） and 8.7% （4/46）， respectively， with the treatment group showing significantly better outcomes （P＜0.05）. A total of 7 adverse events occurred across both groups， with no significant difference （P＞0.05）. No endpoint events occurred during the study. ConclusionOn the basis of conventional treatment of Western medicine， HTF can further reduce urinary protein levels and improve clinical symptoms in patients with mid-stage diabetic kidney disease of blood stasis syndrome. The mechanism may be related to its effects on endothelial function.

The human oral microbiota includes over 700 microorganisms such as fungi, bacteria, archaebacteria, and viruses. The interaction between fungi and bacteria, as well as their impact on the host immune system, is currently a popular topic in the field of oral disease research. Porphyromonas gingivalis (P.g) is the key pathogenic bacterium of chronic periodontitis, while Candida albicans (C.a) is a common opportunistic pathogen. P.g and C.a are associated with various oral diseases. A review of the literature suggests that P.g and C.a synergistically increase the amount of biofilm. They adhere to each other, promoting the formation of mixed biofilms. At the same time, C.a can utilize its dense hyphae and metabolic activities to consume oxygen, providing a low-oxygen microenvironment for P.g, thereby enhancing its vitality and virulence. C.a and P.g can also enhance their virulence through heme competition mechanisms and maintain the normal morphology of P.g by extracellular polysaccharides. In addition, P.g and C.a can synergistically invade the host and escape from the host’s immune system, ultimately leading to a state of chronic infection in the host. Based on the interactions of P.g and C.a, numerous studies on prevention and treatment strategies have been conducted, including those of various composite materials and natural plants. However, such drugs are mostly limited to phenotypes and suffer from poor selectivity, thus resulting in a lack of specific drugs and research on their mechanisms. This review aims to explore the latest advances in the bacterial-fungal interactions, highlighting the roles of P.g and C.a in oral diseases, emphasizing the importance of developing treatment strategies for co-infection of P.g and C.a, and providing new ideas for the prevention and treatment of related diseases.

Objective To assess the clinical value of multimodal ultrasound score for assessment of endometrial receptivity among patients with polycystic ovary syndrome (PCOS), and to provide guidance for improving pregnancy outcomes among PCOS patients. Methods A total of 48 PCOS patients admitted to Jiangning Hospital Affiliated to Nanjing Medical University between January and December 2023 were enrolled as the case group, while 50 healthy women of childbearing age received ovulation monitoring at the same hospital during the same period served as the control group. Subjects received two-dimensional grayscale ultrasound during the implantation window (19 to 23 days of the menstrual cycle) for measurement of endometrial thickness, Gonen classification, and endometrial peristalsis. Two-dimensional color Doppler ultrasound was used for assessment of endometrial blood flow and three-dimensional ultrasound was used for assessment of endometrial volume and vascularization flow index (VFI). The endometrium multimodal ultrasound scores were estimated, and various parameters were compared between the two groups. The diagnostic performance of these parameters for PCOS was evaluated with receiver operating characteristic (ROC) curves. Results The age of subjects in the case group ranged from 20 to 38 years, with a mean age of (28.20 ± 2.82) years, and their body mass index (BMI) ranged from 21.23 to 29.11 kg/m², with a mean BMI of (26.25 ± 1.60) kg/m². The age of subjects in the control group ranged from 22 to 38 years, with a mean age of (28.10 ± 1.99) years, and their BMI ranged from 21.33 to 29.03 kg/m², with a mean BMI of (26.10 ± 1.78) kg/m². There were no significant differences between the case and control groups in terms of mean age, BMI, estradiol, and testosterone (t = 0.218, 0.422, 0.010, and 0.221; all P > 0.05). The endometrial thickness, endometrial volume, and VFI were significantly higher in the control group than in the case group (t = 4.838, 4.978, and 7.115; all P < 0.05). There were significant differences between the two groups in terms of endometrial classification, endometrial peristalsis pattern, and endometrial and sub-endometrial blood flow (Z = −4.136, −4.048, and −3.884; all P < 0.05). The scores of endometrial classification, endometrial peristalsis, endometrial and sub-endometrial blood flow, endometrial volume, VFI, and multimodal ultrasound were significantly lower in the case group than in the control group (t = 4.539, 4.449, 4.205, 3.209, 5.206, and 4.495; all P < 0.05). No significant difference was detected in the endometrial thickness score between the two groups (t = -0.149, P = 0.882). The areas under the ROC curves for endometrial thickness, endometrial volume, VFI, and multimodal ultrasound scores in diagnosis of PCOS were 0.753, 0.747, 0.809, and 0.858, respectively. Conclusion Multimodal ultrasound score provides a comprehensive assessment of the endometrium, and is effective in the assessment of endometrial receptivity, which may provide a reference for guiding pregnancy planning in PCOS patients.

Objective To investigate the effects of whole breast combined with regional nodal hypofractionated radiotherapy compared with conventional fractionated radiotherapy on peripheral lymphocyte count (PLC) and neutrophil-to-lymphocyte ratio (NLR) in patients with breast cancer after breast-conserving surgery. Methods This retrospective study enrolled 94 patients with breast cancer who underwent breast-conserving surgery in Tangshan People’s Hospital between April 2022 and April 2024. All patients received whole breast combined with regional nodal radiotherapy. These patients were divided into hypofractionated radiotherapy group (n = 42) and conventional fractionated radiotherapy group (n = 52) according to radiotherapy regimen. Differences in PLC and NLR before and after radiotherapy between the two groups were compared using the t-test. Results Before radiotherapy, the baseline PLC and NLR were comparable between the two groups (P > 0.05). After radiotherapy, PLC decreased and NLR increased in both groups (P < 0.05). The PLC in the hypofractionated radiotherapy group was significantly higher than that in the conventional fractionated radiotherapy group (0.95 ± 0.30 vs. 0.77 ± 0.26, P = 0.002), and the NLR was significantly lower in the hypofractionated radiotherapy group than in the conventional fractionated radiotherapy group (2.86 ± 1.27 vs. 3.67 ± 1.59, P = 0.010). Conclusion Compared with conventional fractionated radiotherapy, whole breast combined with regional nodal hypofractionated radiotherapy has less impact on PLC and NLR in patients with breast cancer after breast-conserving surgery.

The disturbance of the human microbiota influences the occurrence and progression of many diseases. Live therapeutic bacteria, with their genetic manipulability, anaerobic tendencies, and immunomodulatory properties, are emerging as promising therapeutic agents. However, their clinical applications face challenges in maintaining activity and achieving precise spatiotemporal release, particularly in the harsh gastrointestinal environment. This review highlights the innovative bacterial functionalized encapsulation strategies developed through advances in physicochemical and biological techniques. We comprehensively review how bacterial encapsulation strategies can be used to provide physical barriers and enhanced adhesion properties to live microorganisms, while introducing superior material properties to live bacteria. In addition, this review outlines how bacterial surface coating can facilitate targeted delivery and precise spatiotemporal release of live bacteria. Furthermore, it elucidates their potential applications for treating different diseases, along with critical perspectives on challenges in clinical translation. This review comprehensively analyzes the connection between functionalized bacterial encapsulation and innovative biomedical applications, providing a theoretical reference for the development of next-generation bacterial therapies.

Therapeutic resistance in cancer is responsible for numerous cancer deaths in clinical practice. While target mutations are well recognized as the basis of genetic resistance to targeted therapy, nontarget mutation resistance (or nongenetic resistance) remains poorly characterized. Despite its complex and unintegrated mechanisms in the literature, nongenetic resistance is considered from our perspective to be a collective response of innate or acquired resistant subpopulations in heterogeneous tumors to therapy. These subpopulations, e.g., cancer stem-like cells, cancer cells with epithelial-to-mesenchymal transition, and drug-tolerant persisters, are protected by their resistance traits at cellular and molecular levels. This review summarizes recent advances in the research on resistant populations and their resistance traits. NOTCH signaling, as a central regulator of nongenetic resistance, is discussed with a special focus on its canonical maintenance of resistant cancer cells and noncanonical regulation of their resistance traits. This novel view of canonical and noncanonical NOTCH signaling pathways is translated into our proposal of reshaping therapeutic strategies targeting NOTCH signaling in resistant cancer cells. We hope that this review will lead researchers to study the canonical and noncanonical arms of NOTCH signaling as an integrated resistant mechanism, thus promoting the development of innovative therapeutic strategies.
Neoplasms/metabolism* ; Receptors, Notch/metabolism* ; Disease Resistance/physiology* ; Signal Transduction/physiology* ; Humans ; Drug Resistance, Neoplasm/physiology* ; Molecular Targeted Therapy/methods*