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.

Objective To investigate the factors affecting the distribution of Pomacea and project the trends in the spread of suitable distribution areas of Pomacea in 2050 and 2070 in Dali Bai Autonomous Prefecture, so as to provide insights into Pomacea control in the prefecture. Methods The longitudes and latitudes of Pomacea sampling sites were captured based on Pomacea field survey data in 12 cities (counties) of Dali Bai Autonomous Prefecture from 2023 to 2024. A total of 19 climatic factors (annual mean temperature, mean diurnal range, isothermality, temperature seasonality, maximum temperature of the warmest month, minimum temperature of the coldest month, temperature annual range, mean temperature of the wettest quarter, mean temperature of the driest quarter, mean temperature of the warmest month, mean temperature of the coldest month, annual precipitation, precipitation of the wettest month, precipitation of the driest month, precipitation seasonality, precipitation of the wettest quarter, precipitation of the driest quarter, mean temperature of the warmest quarter, and mean temperature of the coldest quarter) and representative concentration pathways (RCPs) were retrieved from the world climate database (www.worldclim.org). All climatic variables were employed to create a maximum entropy (MaxEnt) model. The predictive accuracy of the model was assessed with the area under the receiver operating characteristic (ROC) curve (AUC), and the contributions of these 19 climatic factors to the distribution of Pomacea were analyzed in Dali Bai Autonomous Prefecture using Jackknife test. In addition, the suitable distribution areas of Pomacea were predicted with the MaxEnt model in Dali Bai Autonomous Prefecture in 2024 and in 2050 and 2070 under RCP4.5. Results Data pertaining to 91 Pomacea sampling sites were captured. ROC analysis revealed the MaxEnt model had an AUC value of 0.885 ± 0.088 for predicting the suitable distribution areas of Pomacea in Dali Bai Autonomous Prefecture. Of the 19 climatic factors, the maximum temperature of the warmest month had the highest contribution to the distribution of Pomacea in Dali Bai Autonomous Prefecture, followed by mean temperature of the driest quarter, mean temperature of the wettest quarter and minimum temperature of the coldest month. The suitable distribution area of Pomacea was predicted to be 14 555.69 km² in Dali Bai Autonomous Prefecture in 2024, and would expand gradually to the southeastern part of the prefecture in the future due to climatic factors. The suitable distribution areas of Pomacea were projected to expand to 21 475.61 km² in 2050 and 25 782.52 km² in 2070 in Dali Bai Autonomous Prefecture, respectively. Conclusions Temperature is an important contributor to the distribution of Pomacea in Dali Bai Autonomous Prefecture, and the suitable distribution area of Pomacea will gradually expand to the southeastern part of the prefecture in 2050 and 2070.

ObjectiveA multiplex amplification system was constructed based on the capillary electrophoresis platform for simultaneous detection of saliva, semen, and vaginal secretions using tissue-specific RNA markers. The aim of this study is to identify the tissue origin of suspicious body fluid stains found at crime scenes and determine whether the body fluid stains at the crime scene are one or several types among saliva, semen, and vaginal secretions. MethodsThirty saliva samples, forty semen samples, and forty vaginal secretion samples (half from 2015 and half from 2024) were collected from healthy adult volunteers. Through primer designing, system formulation, and PCR condition optimization, a multiplex fluorescent amplification system was constructed. The specificity, sensitivity, and detection ability for mixed samples of this system were investigated, and it was tested using real crime scene materials. In the primer design stage, to reduce the requirements for RNA template quality, the amplification products were set within 80-300 bp. In the system formulation stage, dominant and subordinate primers were mainly considered. By reducing the concentration of dominant primers and increasing that of subordinate primers, a capillary electrophoresis spectrum with an appropriate peak height ratio was finally obtained. Additionally, gradient experiments were designed to adjust the concentrations of PCR reagents and PCR amplification conditions, and multiple versions of DNA amplification enzymes were optimized to achieve the best experimental results. ResultsThrough statistical analysis, there was no significant difference in the capillary electrophoresis of the 3 types of body fluid samples from the two years (2015 and 2024), demonstrating that the sample preservation method in this study can preserve samples for a relatively long time. The composite amplification system constructed in this study exhibited high specificity for all 3 types of body fluid, with no cross-reactions between the markers of each type of body fluid. The minimum detection thresholds for the 3 types of body fluid reached 0.002 9, 0.001 5, and 0.42 mg/L, respectively. This system also had a high degree of discrimination for mixed samples, especially for semen-saliva mixtures, where each body fluid marker could still be successfully detected when the concentration ratio of semen to saliva was 100:1. Meanwhile, in the two actual cases presented in this article, the application of this composite amplification system performed outstandingly. ConclusionThe composite amplification detection system constructed in this study can achieve the correct screening of saliva, semen, and vaginal secretions, overcoming the problems such as low specificity and sensitivity of marker tests and unbalanced RFU values of each marker in previous studies. The specificity and sensitivity meet the practical work requirements, and the operation is simple. It provides an analytical and identification method for body fluid stains in actual case and is applicable to the identification of the tissue origin of biological evidence at crime scenes involving sexual assault, indecent assault, and other criminal acts. In the future, more types of body fluid markers will be screened to expand the types of body fluids detected by the system, and body fluid-specific cSNP and cInDel genetic markers will be introduced to infer the sources (individuals and types) of mixed and complex stains more accurately.

Based on the high-fat diet-induced hyperlipidemia rat model, this study aimed to evaluate the lipid-lowering effect of Arisaema Cum Bile and explore its mechanisms, providing experimental evidence for its clinical application. Biochemical analysis was used to detect serum levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), triglycerides(TG), and total cholesterol(TC) to assess the lipid-lowering activity of Arisaema Cum Bile. Additionally, 16S rDNA sequencing and metabolomics techniques were employed to jointly elucidate the lipid-lowering mechanisms of Arisaema Cum Bile. The experimental results showed that high-dose Arisaema Cum Bile(PBA-H) significantly reduced serum ALT, AST, LDL-C, TG, and TC levels(P<0.01), and significantly increased HDL-C levels(P<0.01). The effect was similar to that of fenofibrate, with no significant difference. Furthermore, Arisaema Cum Bile significantly alleviated hepatocyte ballooning and mitigated fatty degeneration in liver tissues. As indicated by 16S rDNA sequencing results, PBA-H significantly enhanced both alpha and beta diversity of the gut microbiota in the model rats, notably increasing the relative abundance of Akkermansia and Subdoligranulum species(P<0.01). Liver metabolomics analysis revealed that PBA-H primarily regulated pathways involved in arachidonic acid metabolism, vitamin B_6 metabolism, and steroid biosynthesis. In summary, Arisaema Cum Bile significantly improved abnormal blood lipid levels and liver pathology induced by a high-fat diet, regulated hepatic metabolic disorders, and improved the abundance and structural composition of gut microbiota, thereby exerting its lipid-lowering effect. The findings of this study provide experimental evidence for the clinical application of Arisaema Cum Bile and the treatment of hyperlipidemia.
Animals ; Gastrointestinal Microbiome/drug effects* ; Rats ; Male ; Metabolomics ; Hyperlipidemias/microbiology* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Hypolipidemic Agents/pharmacology* ; Liver/metabolism* ; Humans ; Alanine Transaminase/metabolism* ; Triglycerides/metabolism* ; Aspartate Aminotransferases/metabolism*

As a new type of production factor that can empower the development of new quality productivity, the data element is an important engine to promote the high quality development of the industry. Traditional Chinese medicine(TCM) dispensing is the most basic work of TCM clinical pharmacy, and its quality directly affects the clinical efficacy of TCM. The integration of data elements and TCM dispensing can stimulate the innovation and vitality of the TCM dispensing industry and promote the high-quality and sustainable development of the industry. A large-scale, detailed, and systematic study on TCM dispensing was conducted. The innovative practice path of data fusion construction in the whole process of TCM dispensing was investigated by integrating the digital resources "nine full activities" of TCM dispensing, creating the digital dictionary of "TCM clinical information data elements", and exploring innovative applications of TCM dispensing driven by data and technology, so as to promote the standardized, digital, and intelligent development of TCM dispensing in medical health services. The research content of this project was successfully selected as the second batch of "Data element×" typical cases of National Data Administration in 2024, which is the only selected case in the field of TCM.
Medicine, Chinese Traditional/methods* ; Drugs, Chinese Herbal ; Humans

Intestinal aging is central to systemic aging, characterized by a progressive decline in intestinal structure and function. The core mechanisms involve dysregulation of epithelial cell renewal and gut microbiota dysbiosis. In addition to previous results in model organisms like Drosophila melanogaster, recent studies have shown that in mammalian models, aging causes increased intestinal permeability and intestinal-derived systemic inflammation, thereby affecting longevity. Therefore, anti-intestinal aging can be an important strategy for reducing frailty and promoting longevity. There are three key gaps remaining in the study of intestinal aging: (1) overemphasis on aging-related diseases rather than the primary aging mechanisms; (2) lack of specific drugs or treatments to prevent or treat intestinal aging; (3) limited aging-specific dysbiosis research. In this review, the basic structures and renewal mechanisms of intestinal epithelium, and mechanisms and potential therapies for intestinal aging are discussed to advance understanding of the causes, consequences, and treatments of age-related intestinal dysfunction.

An ideal dermal filler should integrate filling, repair, and anti-aging effects, with immediate tissue augmentation, slow degradation, and progressive stimulation of collagen regeneration. However, commonly used hyaluronic acid (HA) hydrogels, while effective for rapid filling, suffer from limited duration of support, weak cell adhesion, and an inability to promote collagen regeneration. Silk fibroin (SF), a natural protein from silkworm cocoons, is known for its excellent cell adhesion and collagen-stimulating abilities. However, its limited gelation capability restricts its potential application as a standalone injectable hydrogel. Based on a complementary strategy, this study combines the rapid gelling properties of HA with the collagen regenerative properties of SF to create a co-crosslinked HA-SF hydrogel. The composite hydrogel merges HA's rapid filling effect with SF's strong tissue adhesion and collagen-stimulating abilities. The formulation, physicochemical properties, degradation, biocompatibility, and filling effects of the HA-SF hydrogel were systematically investigated. HA-SF hydrogel exhibits excellent mechanical properties and ensures long-term support while maintaining injectability. Interestingly, after intradermal injection in the UVB-induced photoaging model, HA-SF hydrogel not only enhances hydrogel-cell interaction but also continues to stimulate collagen regeneration, especially type III collagen. This dual action achieves the biological effects of repair and anti-aging while maintaining the filling effect. Proteomic analysis confirms that repair and anti-aging effects are enhanced by the regulation of skin fibroblasts and modulation of amino acid and lipid metabolism. This composite hydrogel holds strong promise for clinical applications, offering a safer, long-lasting, and more natural injectable filler that combines filling, repair, and anti-aging into one system.

Lysosomes represent a promising target for cancer therapy and reducing drug resistance. However, the short treatment time and low efficiency of lysosomal targeting have limited the application in lysosome-targeting anticancer drugs. In this study, we proposed an adhesive-bandage approach and synthesized a new lysosomal targeting drug, namely long-term lysosome-targeting anticancer drug (LLAD). It contains a SLC38A9-targeting covalently bound moiety and an alkaline component both to prolong the inhibition of SLC38A9 in lysosomes and alkalinize lysosomes. Upon short term and low-dose treatment of HeLa cells, at passage 0, with LLAD, it rapidly alkalinized lysosomes and also can be detected in lysosomes even at passage 15. LLAD induced apoptosis in HeLa cells through long-term lysosomal damage, and showed better long-term anticancer effect than cisplatin in vivo. Overall, our study paves the way for developing long-term lysosomal targeting drugs to treat cancer and overcome the drug resistance of cancer cells, and also provides a candidate drug, LLAD, for treating cancer.

Objective: To analyze the potential categories and influencing factors of the compliance trajectory of orthokeratology lenses (OK lens) in myopic children and adolescents, so as to provide a basis for dynamic and accurate intervention of OK lens compliance in myopic children and adolescents. Methods: From January to June 2024, 310 myopic children and adolescents wearing OK lens were selected as research subjects from the Ophthalmology Medical Center of Cangzhou Central Hospital using a convenient sampling method. Data were collected at four time points: when the glasses were first fitted (T0), 2 weeks after fitting (T1), 1 month later (T2), 3 months later (T3), and 6 months later (T4). The data collection methods included general information questionnaires, compliance surveys for OK lens wearers, the Behavior Rating Inventory of Executive Function-Self-report Version (BRIEF-SR), family support scales, and a self-made questionnaire on myopia control attitudes. A growth mixed model was used to identify the trajectory categories of compliance with OK lens wearing among myopic children and adolescents, and multiple Logistic regression analysis was employed to examine the influencing factors. Results: The compliance with OK lens among myopic children and adolescents were roughly divided into four developmental trajectories: C1 exemplary adherent (58 cases, 18.71%), C2 gradual progressor (130 cases, 41.94%), C3 fluctuating (85 cases, 27.42%), and C4 stubborn low follower (37 cases, 11.94%). Multivariate Logistic regression analysis showed that, with C1 group as the reference, age (C3, OR = 0.74 ), parental education level (C4, OR =0.67), executive function (C2, OR =0.69; C4, OR =0.44), family support (C3, OR =0.75) and myopia control attitude (C2, OR =0.39) were all influencing factors for the compliance trajectory of OK lens; with C2 group as the reference, age (C3, OR = 0.55 ), parental education level (C3, OR =0.34; C4, OR =0.64), executive function (C3, OR =0.77), and family support (C4, OR =0.58) were all influencing factors for the compliance trajectory of OK lens; with C3 group as the reference, age (C4, OR = 0.68 ), and myopia control attitude (C4, OR =0.44) were both influencing factors for the compliance trajectory of OK lens ( P <0.05). Conclusions The compliance of wearing OK lens in children and adolescents with myopia can be roughly divided into four trajectories, and there is group heterogeneity. Dynamic and precise compliance intervention strategies should be given based on different trajectories and influencing factors.

OBJECTIVE To optimize the forming process of Yindan huoxue tongyu granules， and evaluate the quality of the granules. METHODS Taking forming rate， angle of repose， moisture， moisture absorption rate and dissolution rate as indexes， single factor experiment combined with Plackett-Burman design was adopted to screen key process parameters； analytic hierarchy process combined with entropy weight method and Box-Behnken response surface method were used to optimize the molding process of Yindan huoxue tongyu granules， and the forming process was verified. The relative homogeneity index， bulk density， vibration density， Hausner ratio， angle of repose， moisture and hygroscopicity were used as secondary physical indexes to establish the physical fingerprints of 10 batches of Yindan huoxue tongyu granules to evaluate particle quality consistency. RESULTS The optimal molding process of Yindan huoxue tongyu granules was as follows： mannitol as the fixed excipient， the drug-assisted ratio was 1∶1（m/m） and the drying time was 1 h； 90% ethanol was used as wetting agent and the amount of it was 32%， the drying temperature was 70 ℃. The results of validation tests showed that the average comprehensive score was 97.45， which was close to the predicted value of 97.18. The similarities between the physical fingerprints of 10 batches of Yindan huoxue tongyu granules prepared by the optimal molding process and the reference physical fingerprint were all higher than 0.99. CONCLUSIONS The molding process is stable and feasible， and the quality of Yindan huoxue tongyu granules produced is stable and controllable.