Biliary atresia （BA） is characterized by progressive inflammation and fibrous obstruction of bile ducts， ultimately leading to cholestatic liver cirrhosis. Kasai surgery is the standard procedure for the treatment of BA， and early diagnosis is a key influencing factor for the prognosis of BA. Indocyanine green （ICG） is a near-infrared photosensitive dye that is efficiently and selectively absorbed by hepatocytes after intravenous injection， and it enters the intestine via bile and is excreted with the feces in the free form， with a favorable safety profile. In addition， ICG can emit fluorescence under near-infrared light， which can be captured by camera instruments and converted into visual images， and ICG fluorescence imaging technology can reflect the intraoperative situation in real time and significantly improve the success rate of the surgical procedure. This article reviews the advances in the application of ICG in early preoperative diagnosis， intraoperative imaging， and postoperative liver function assessment in recent years.

This case report presents a 16-year-old male patient with deficiency of adenosine deaminase 2(DADA2). The patient had a history of Raynaud′s phenomenon with digital ulcers since childhood. As the disease progressed, the patient developed retinal vasculitis, intracranial hemorrhage, skin necrosis, severe malnutrition, refractory hypertension, and gastrointestinal bleeding. Genetic testing revealed compound heterozygous mutations in the ADA2 gene (paternal c.1072G > A pathogenic mutation + maternal c.1065C > A variant of unknown clinical significance). ADA2 enzyme activity was significantly reduced (0.1 U/L). A multidisciplinary treatment team developed an individualized plan to address key issues, including nutritional support, blood pressure control, rehabilitation, pain management, and balancing anticoagulation/bleeding risks. After systematic intervention, the patient′s condition showed partial improvement. This case reveals clinical challenges such as anticoagulation decisions and nutritional support of DADA2. It also emphasizes the importance of early molecular diagnosis, tumor necrosis factor-α inhibitor targeted therapy, and multidisciplinary collaboration in management, underlining the core value of precision medicine in rare disease management.

OBJECTIVE To investigate the inhibitory effects of Ginkgo biloba extract （GBE） on renal inflammation in diabetic nephropathy （DN） model mice， and its potential mechanism. METHODS KK/Ay mice were fed with high fat and high sugar to induce DN model. They were divided into model group， positive control group [metformin 200 mg/（kg·d）]， GBE low-dose and high-dose groups [100， 200 mg/（kg·d）]， with 6 mice in each group. Six C57BL/6J mice were fed with a regular diet as the control group. Administration groups were given relevant liquid intragastrically， control group and model group were given constant volume of normal saline intragastrically， once a day， for 8 consecutive weeks. The body weight， fasting blood glucose， 24-hour food intake， 24-hour urine output， monocyte chemoattractant protein-1 （MCP-1）， interleukin-12 （IL-12）， IL-10， advanced glycation end products （AGEs）， blood urea nitrogen （BUN） and serum creatinine （Scr） of mice were measured， and the ratio of bilateral kidneys to body weight was also calculated. The pathological injury and fibrotic changes of the renal cortex were observed， and the expressions of macrophage polarization marker proteins [type M1： inducible nitric oxide synthase （iNOS）； type M2： arginase-1 （Arg-1）] and AGEs-the receptor of advanced glycation end products （RAGE）/Ras homolog gene pharm_chenjing@163.com family member A （RhoA）/Rho-associated coiled-coil forming protein kinase （ROCK） signaling pathway-related proteins were determined in renal cortex. RESULTS Compared with the model group， the symptoms such as renal cortical hyperplasia， vacuoles， infiltration of inflammatory cells， and renal cortical fibrosis had been improved in GBE low-dose and high-dose groups； body weight， serum level of IL-10， the expression of Arg-1 in the renal cortex were significantly higher than model group （P＜ 0.01）； fasting blood glucose， 24-hour food intake， 24-hour urine output， serum levels of MCP-1， IL-12， BUN， Scr and AGEs， the ratio of bilateral kidneys to body weight， renal injury score， the proportion of renal interstitial fibrosis， the protein expressions of iNOS， RAGE， RhoA and ROCK1 （except for GBE low-dose group） in renal cortex were significantly lower than model group （P＜0.01）. CONCLUSIONS GBE could improve kidney damage and alleviate inflammatory response in DN model mice， the mechanism of which may be related to inhibiting the AGEs-RAGE/RhoA/ROCK signaling pathway and regulating macrophage polarization.

Objective To prepare Zishen pills as gel plaster according to the prescription,and investigate its transdermal absorption characteristics in vitro.Methods Based on preliminary experiments,the matrix prescription of the gel plaster was optimized by single-factor tests and the Box-Behnken design.Evaluation indicators included initial viscosity,viscosity retention and sensory scores.The modified Franz diffusion cell was used to investigate the effect of penetration enhancers on the transdermal characteristics of gel plaster in vitro,with the permeability of neomangiferin,phellodendrine hydrochloride,mangiferin and berberine hydrochloride as evaluation indicators.Results The prescription dosage of the preferred matrix for the Zishen gel plaster was sodium polyacrylate NP700 2.55 g,glycerin 11.04 g,polyvinylpyrrolidone K90 1.13 g,tartaric acid 0.1 g,glycyrrhizin 0.1 g,kaolin 0.3 g,and distilled water 15 g.Among different types and concentrations of permeation enhancers,5%aminoketone showed the best permeation performance.The permeation rates for neomangiferin,phellodendrine hydrochloride,mangiferin,and berberine hydrochloride were 1.5338,1.7809,2.3247 and 20.0899 μg·(cm2)-1·h-1,and the penetration rates were 2.4319,1.9408,1.9604 and 1.4701,respectively.The percutaneous absorption curve of the drug conformed to the zero-order kinetic equation.Conclusion The preparation process of the obtained gel plaste is stable and feasible,with good adhesive properties,sustained drug release,and favorable in vitro percutaneous permeability,indicating potential clinical application value.

In the past 20 years,near infrared spectrum technology has been widely used in human body monitoring due to its non-invasive and real-time characteristics.Oxygen,as the main metabolic substance of the human body,is consumed the most in brain tissue.In order to prevent complications caused by a decrease in brain tissue oxygen during treatment,the patient's brain tissue blood oxygen saturation needs to be monitored in real time.Currently,most of the clinically used non-invasive cerebral blood oxygen detection equipments use dual wavelengths.Other substances on the detection path will cause errors in the measurement results.Therefore,this article proposes a three-wavelength method based on the basic principle of non-invasive monitoring of cerebral blood oxygen using near-infrared spectrum.The brain tissue oxygen saturation monitoring method of detecting light sources was initially verified through the built system,laying the foundation for subsequent system engineering.

ECG signals and sleep monitoring parameters complement each other and can be used for qualitative diagnosis of sleep apnea syndrome and cardio-related diseases.However,due to the limitations of the instrument volume and the detection environment,it is often challenging to integrate these two functions in practical applications.In this paper,a 12-lead dynamic electrocardiograph integrated with sleep monitoring is designed.The system's volume is reduced by combining the integrated ECG simulation front end with a miniature sensor.The system achieves the extraction,conditioning,and calculation of 12-lead ECG signals and sleep-related parameters and writes the data to a memory card in real time,which offers convenience for users and doctors in the diagnostic process.

Cardiopulmonary exercise testing(CPET)refers to a method of measuring various indicators of the human body under gradually increasing exercise loads to objectively evaluate cardiopulmonary reserve function and exercise endurance.Currently,CPET detection systems primarily measure subjects'ECG,respiratory flow,oxygen(O2),and carbon dioxide(CO2)parameters.This paper introduces a non-invasive multi-parameter exercise cardiopulmonary function evaluation system that incorporates impedance cardiography monitoring.The system integrates impedance cardiography monitoring with conventional CPET detection parameters and detects changes in the hemodynamic parameters of the body during exercise,aiding in the evaluation of exercise capacity.Additionally,the system features a portable design with Wi-Fi wireless transmission,which enhances its applicability.

A cerebral oximeter based on 3-wavelength spatially resolved spectroscopy and the modified Lambert-Beer law is proposed.A platform for monitoring the regional cerebral oxygen saturation(rSO2)is established,and the system reliability is verified through spectral stability and background noise test.Eighteen volunteers are recruited to participate in the controlled hypoxia test for exploring the trend of rSO2 with the sequence of stepped hypoxia platform and discussing the relationship between rSO2 and arterial blood oxygen saturation.The results show that the established system can effectively monitor rSO2 and meet the measurement requirements.During the controlled hypoxia sequence,as the fraction of inspired oxygen decreases,rSO2 shows a downward trend,and the individual rSO2 has a high correlation with arterial blood oxygen saturation.

Epigenetic therapies that cause genome-wide epigenetic alterations, could trigger local interplay between different histone marks, leading to a switch of transcriptional outcome and therapeutic responses of epigenetic treatment. However, in human cancers with diverse oncogenic activation, how oncogenic pathways cooperate with epigenetic modifiers to regulate the histone mark interplay is poorly understood. We herein discover that the hedgehog (Hh) pathway reprograms the histone methylation landscape in breast cancer, especially in triple-negative breast cancer (TNBC). This facilitates the histone acetylation caused by histone deacetylase (HDAC) inhibitors and gives rise to new therapeutic vulnerability of combination therapies. Specifically, overexpression of zinc finger protein of the cerebellum 1 (ZIC1) in breast cancer promotes Hh activation, facilitating the switch of H3K27 methylation (H3K27me) to acetylation (H3K27ac). The mutually exclusive relationship of H3K27me and H3K27ac allows their functional interplay at oncogenic gene locus and switches therapeutic outcomes. Using multiple in vivo breast cancer models including patient-derived TNBC xenograft, we show that Hh signaling-orchestrated H3K27me and H3K27ac interplay tailors combination epigenetic drugs in treating breast cancer. Together, this study reveals the new role of Hh signaling-regulated histone modifications interplay in responding to HDAC inhibitors and suggests new epigenetically-targeted therapeutic solutions for treating TNBC.

Genkwa Fols, Kansui Radix, and Euphorbiae Pekinensis Radix in Shizao Decoction(SZD) are toxic to intestinal tract. Jujubae Fructus in this prescription can alleviate the toxicity, but the mechanism is still unclear. Therefore, this study aims to explore the mechanism. To be specific, 40 normal Sprague-Dawley(SD) rats were classified into the normal group, high-dose and low-dose SZD groups, and high-dose and low-dose SZD without Jujubae Fructus(SZD-JF) groups. The SZD groups were given(ig) SZD, while SZD-JF groups received the decoction without Jujubae Fructus. The variation of body weight and spleen index were recorded. The patho-logical changes of intestinal tissue were observed based on hematoxylin and eosin(HE) staining. The content of malondialdehyde(MDA) and glutathione(GSH) and activity of superoxide dismutase(SOD) in intestinal tissue were measured to evaluate the intestinal injury. Fresh feces of rats were collected to detect intestinal flora structure by 16S ribosomal RNA gene(16S rDNA) sequencing technology. The content of fecal short chain fatty acids and fecal metabolites was determined by gas chromatography-mass spectrometer(GC-MS) and liquid chromatography-mass spectrometer ultra-fast liquid chromatography-quadrupole-time-of-flight mass spectrometer(UFLC-Q-TOF-MS), separately. Spearman's correlation analysis was employed to analyze the differential bacteria genera and differential metabolites. RESULTS:: showed that high-dose and low-dose SZD-JF groups had high content of MDA in intestinal tissue, low GSH content and SOD activity, short intestinal villi(P<0.05), low diversity and abundance of intestinal flora, variation in the intestinal flora structure, and low content of short chain fatty acids(P<0.05) compared with the normal group. Compared with high-dose and low-dose SZD-JF groups, high-dose and low-dose SZD groups displayed low content of MDA in intestinal tissue, high GSH content and SOD activity, recovery of the length of intestinal villi, increased abundance and diversity of intestinal flora, alleviation of dysbacteria, and recovery of the content of short chain fatty acids(P<0.05). According to the variation of intestinal flora and fecal metabolites after the addition of Jujubae Fructus, 6 differential bacterial genera(Lactobacillus, Butyricimonas, Clostridia＿UCG-014, Prevotella, Escherichia-Shigella, Alistipes),4 differential short chain fatty acids(such as acetic acid, propionic acid, butyric acid, valeric acid) and 18 differential metabolites(such as urolithin A, lithocholic acid, and creatinine) were screened out. Beneficial bacteria such as Lactobacillus were in positive correlation with butyric acid and urolithin A(P<0.05). The pathogenic bacteria such as Escherichia-Shigella were in negative correlation with propionic acid and urolithin A(P<0.05). In summary, SZD-JF caused obvious intestinal injury to normal rats, which could lead to intestinal flora disorder. The addition of Jujubae Fructus can alleviate the disorder and relieve the injury by regulating intestinal flora and the metabolites. This study discusses the effect of Jujubae Fructus in relieving the intestinal injury caused by SZD and the mechanism from the perspective of intestinal flora-host metabolism, which is expected to serve as a reference for clinical application of this prescription.
Rats ; Animals ; Rats, Sprague-Dawley ; Propionates/pharmacology* ; Gastrointestinal Microbiome ; Fatty Acids, Volatile/pharmacology* ; Butyrates/pharmacology*