Qualitative analysis of the ingredients absorbed into blood and their metabolites of Xihuang pill (XHP) were conducted using high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS/MS) technology. Network pharmacology was used to explore the potential anticancer mechanisms of the ingredients against glioma, and their specific mechanisms were validated through molecular docking and experimental verification. SD rats were intragastrically administered with XHP, and rat serum samples were collected. Ingredients absorbed into blood and their metabolites were identified based on the retention time of chromatographic peaks, accurate molecular mass, characteristic fragment ions, and comparisons with reference substances and literature data. PharmMapper and SwissTarget Prediction databases were used to obtain the targets of the XHP-medicated serum, while GeneCards, OMIM, PharmGKB, TTD, and DrugBank databases were used to obtain glioma disease targets. The "component-target" network relationship diagram was constructed using Cytoscape 3.9.1 software. The protein-protein interaction (PPI) network diagram was constructed using the STRING database, and the targets were analyzed using GO and KEGG analyses. Molecular docking was used to verify the binding ability of core targets with their corresponding compounds in XHP-medicated serum. The potential mechanism of the anti-glioma effect of 11-keto-β-boswellic acid (KBA), a representative component of XHP-medicated serum, was verified using CCK-8 and Western blot assays. A total of 40 compounds were identified in the XHP-medicated serum, including 28 prototype components and 12 metabolites. The network pharmacology results showed that elemonic acid, 3-acetyl-β-boswellic acid, KBA, α-boswellic acid, and other 5 compounds might be the active ingredients of XHP-medicated serum in the treatment of glioma. Glutathione reductase (GSR), glucose-6-phosphate dehydrogenase (G6PD), ATP-citrate lyase (ACLY), aldo-keto reductase family 1 member B1 (AKR1B1) and glutaredoxin (GLRX) were identified as key targets, involving pathways such as glutathione metabolism and the pentose phosphate pathway. Further cell experiments showed that KBA significantly inhibited the proliferation of T98G cells with an IC₅₀ of 30.96 μmol·L^-1, and KBA (30 μmol·L^-1) significantly downregulated the protein expression levels of GSR in T98G cells. In summary, XHP-medicated serum may exert its anti-glioma effect by regulating GSR and G6PD-targeted pathways involved in glutathione metabolism. These results provide valuable evidence for further investigating the mechanism of XHP in treating glioma. The animal welfare and experimental procedures were approved by the Ethical Committee of Laboratory Animals at Nanjing University of Chinese Medicine (approval No. ACU221001).

Objective To make an epidemiological investigation on traditional Chinese medicine(TCM)dampness syndrome manifestations in the population at risk of cerebrovascular diseases in Guangdong area.Methods A cross-sectional study was conducted to analyze the clinical data related to the risk of cerebrovascular diseases in 330 Guangdong permanent residents.The diagnosis of dampness syndrome,quantitative scoring of dampness syndrome and rating of the risk of stroke were performed for the investigation of the distribution pattern of dampness syndrome and its influencing factors.Results(1)A total of 306(92.73%)study subjects were diagnosed as dampness syndrome.The percentage of dampness syndrome in the risk group was 93.82%(258/275),which was slightly higher than that of the healthy group(48/55,87.27%),but the difference was not statistically significant(χ2 = 2.91,P = 0.112).The quantitative score of dampness syndrome in the risk group was higher than that of the healthy group,and the difference was statistically significance(Z =-2.24,P = 0.025).(2)Among the study subjects at risk of cerebrovascular disease,evaluation time(χ2 = 26.11,P = 0.001),stroke risk grading(χ2= 8.85,P = 0.031),and history of stroke or transient ischemic attack(TIA)(χ2 = 9.28,P = 0.015)were the factors influencing the grading of dampness syndrome in the population at risk of cerebrovascular disease.Conclusion Dampness syndrome is the common TCM syndrome in the population of Guangdong area.The manifestations of dampness syndrome are more obvious in the population with risk factors of cerebrovascular disease,especially in the population at high risk of stroke,and in the population with a history of stroke or TIA.The assessment and intervention of dampness syndrome should be taken into account for future project of stroke prevention in Guangdong.

Objective To study the microscopic structure and morphological characteristics of Zebrafish eyeball and retina at different developmental stages, and to lay a foundation for visual research model. Methods Select eight groups of zebrafish at different ages, with six fish in each group, 48 fish in total. Optical microscopy and transmission electron microscopy were used to observe the eyeball structure of Zebrafish at different developmental stages, and the thickness of retinal each layer was measured to analyze the temporal and spatial development pattern. The morphological characteristics of various cells in the retina and the way of nerve connection were observed from the microscopic and ultrastructural aspects, especially the structural differences between rod cells and cone cells. Results The retina of Zebrafish can be divided into ten layers including retinal pigment epithelial layer, rod cells and cone cells layer, outer limiting membrane, outer nuclear layer, outer plexiform layer, inner nuclear layer, inner plexiform layer, ganglion cell layer, nerve fiber layer, inner limiting membrane. Rod cells had a smaller nucleus and a higher electron density than cone cells. Photoreceptor terminals were neatly arranged in the outer plexiform layer, forming neural connections with horizontal cells and bipolar cells, and several synaptic ribbons are clearly visible within them. In Zebrafish retina, ganglion cell layer and inner plexiform layer are the earliest developed. With the growth and development of Zebrafish, the thickness of rod cells and cone cells layer and retinal pigment epithelial layer gradually increases, and the retinal structure was basically developed in about 10 weeks. Conclusion The retinal structure of Zebrafish is typical, with obvious stratification and highly differentiated nerve cells. There are abundant neural connections in the outer plexiform layer. The ocular development characteristics of Zebrafish are similar to those of most mammals.

Tendinopathies are chronic diseases of an unknown etiology and associated with inflammation. Mesenchymal stem cells (MSCs) have emerged as a viable therapeutic option to combat the pathological progression of tendinopathies, not only because of their potential for multidirectional differentiation and self-renewal, but also their excellent immunomodulatory properties. The immunomodulatory effects of MSCs are increasingly being recognized as playing a crucial role in the treatment of tendinopathies, with MSCs being pivotal in regulating the inflammatory microenvironment by modulating the immune response, ultimately contributing to improved tissue repair. This review will discuss the current knowledge regarding the application of MSCs in tendinopathy treatments through the modulation of the immune response.

2-(4-Methylthiazol-5-yl) ethyl nitrate hydrochloride (W1302) is a nitro containing derivative of clomethiazole, which is a novel neuroprotective agent with both carbon monoxide (NO) donor and weak γ-aminobutyric acid type A (GABA_A) receptor allosteric regulatory excitatory effect. The current study used a rat model of transient middle cerebral arteryocclusion (tMCAO) brain injury to evaluate the therapeutic effect of W1302 on ischemic stroke and explore its potential mechanisms of action. This experiment has been reviewed and approved by the Laboratory Animal Management and Use Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences (ethical review forms No. 620, 632, 5013). The results showed that gavage administration of 1, 3, and 10 mg·kg^-1 of W1302 can significantly reduce the volume of cerebral infarction in rats with ischemia for 2 h and reperfusion for 24 h, and the therapeutic effect was better than that of 200 mg·kg^-1 of DL-3n-butylphthalide. W1302 significantly increased NO levels in blood and brain tissue. It increased cerebral blood flow and brain adenosine triphosphate (ATP) content after reperfusion, as well as, inhibited the expressions of inflammatory factors tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in brain tissue. The time window of W1302 was between 120-180 min after ischemia. These research results demonstrated that W1302 could increase NO release, dilate blood vessels, and increase cerebral blood flow, improve energy supply to brain tissue and increase ATP levels, and inhibit neuro-inflammation, which playing the protective roles in tMCAO stroke model rats. This provides theoretical support for the clinical application of W1302 in the treatment of ischemic stroke.

Background: Genetic defects in the human thyroid-stimulating hormone (TSH) receptor (TSHR) gene can cause congenital hypothyroidism (CH). However, the biological functions and comprehensive genotype–phenotype relationships for most TSHR variants associated with CH remain unexplored. We aimed to identify TSHR variants in Chinese patients with CH, analyze the functions of the variants, and explore the relationships between TSHR genotypes and clinical phenotypes. Methods: In total, 367 patients with CH were recruited for TSHR variant screening using whole-exome sequencing. The effects of the variants were evaluated by in-silico programs such as SIFT and polyphen2. Furthermore, these variants were transfected into 293T cells to detect their Gs/cyclic AMP and Gq/11 signaling activity. Results: Among the 367 patients with CH, 17 TSHR variants, including three novel variants, were identified in 45 patients, and 18 patients carried biallelic TSHR variants. In vitro experiments showed that 10 variants were associated with Gs/cyclic AMP and Gq/11 signaling pathway impairment to varying degrees. Patients with TSHR biallelic variants had lower serum TSH levels and higher free triiodothyronine and thyroxine levels at diagnosis than those with DUOX2 biallelic variants. Conclusions We found a high frequency of TSHR variants in Chinese patients with CH (12.3%), and 4.9% of cases were caused by TSHR biallelic variants. Ten variants were identified as loss-of-function variants. The data suggest that the clinical phenotype of CH patients caused by TSHR biallelic variants is relatively mild. Our study expands the TSHR variant spectrum and provides further evidence for the elucidation of the genetic etiology of CH.

Nutritional therapy is a core component of critically ill patient management,and the enteral route has become the preferred method due to its dual roles of nutrition and non-nutrition. The use of vasoactive medications makes enteral nutrition decisions more challenging for these patients. This review systematically examines the pathophysiological effects of vasoactive medications on gastrointestinal tract of critically ill patients,the current value and safety of enteral nutrition in this patient's population,summarizes the optimal strategies for implementing enteral nutrition in these patients for clinical reference.

An analytical method based on ultra high performance liquid chromatography-high resolution tandem mass spectrometry(UHPLC-HRMS/MS)and high performance liquid chromatography-triple quadrupole mass spectrometry(HPLC-TQ MS)was established to reveal the characteristics of various sulfur mustard analogs with different active thiol molecules in CWC Schedule 1.A.04.Firstly,the toxic agents were prepared by micro-directed synthesis,and then the differences of the reactivity and abundance of formed adducts between different sulfur mustards and glutathione(GSH),cysteine(Cys)and N-acetylcysteine(NAC)in incubation solution,plasma and cell were investigated,respectively.The results indicated that all target sulfur mustards could react with three kinds of thiol molecules.The content of Cys and sulfur mustard adducts in plasma was higher than that of GSH and sulfur mustard adducts,while NAC and sulfur mustard adducts might have fewer types of adducts due to low content or poor mass spectrometry response.Additionally,the content of GSH and sulfur mustard adducts in exposed cells was higher than that of Cys,which should be due to the significant difference in the content of thiol molecules in plasma and cells.

Objective To analyze the changes of B lymphocyte(B cells)subsets in peripheral blood of patients with chronic hepatitis B(CHB)and to explore its clinical significance.Methods Peripheral blood samples were collected from 37 treatment-na?ve CHB patients who were admitted to the Fifth Medical Center of PLA General Hospital from July 2022 to October 2022,and peripheral blood samples collected from 18 healthy individuals who have received the hepatitis B vaccine as healthy controls(HC).The study subjects'clinical indexes such as age,HBV DNA viral load,HBsAg quantification,HBeAg semi quantification,ALT,AST,and AST/ALT ratio were collected.The change characteristics of the frequency,phenotypic and functional markers of peripheral blood B lymphocytes and their subsets were compared between CHB and HC.Using multi-color flow cytometry,and the correlation between them and clinical indexes was analyzed.Results Frequency analysis of each subset of B cells showed that compared with HC,the frequency of total B cells,transitional B cells and naive B cells was decreased(P<0.05),while the frequency of mature B cells,memory B cells,atypical memory B cells and activated memory B cells was increased in CHB patients(P<0.01).And there was no significant difference in the frequency of resting memory B cells between the two groups(P>0.05).The results of functional analysis showed that compared with HC,the expression levels of CD79b on total B cells,mature B cells,memory B cells,naive B cells,activated memory B cells,atypical memory B cells and resting memory B cells in CHB patients were increased(P<0.05).The expression level of programmed cell death protein-1(PD-1)on atypical memory B cells in CHB patients was also higher than that in HC group(P<0.05).The results of correlation analysis showed that the frequency of total B cells in CHB patients was slightly negatively correlated with age(r=-0.39,P<0.05),while the expression of programmed death-1(PD-1)on total B cells,mature B cells,transitional B cells,memory B cells and naive B cells were slightly positively correlated with age(r>0.36,P<0.05).Conclusions Chronic HBV infection leads to depletion of the frequency and function of a portion of B cells in the peripheral blood of CHB patients,and age is a potential risk factor for the decline in humoral immune function in CHB patients.

Objective To focus on the imaging features of liposclerosing myxofibrous tumor(LSMFT)and diagnostic chal-lenges to enhance clinical recognition and differential diagnosis accuracy.Methods Retrospective analysis was conducted on the imaging and pathological data from 21 cases diagnosed with LSMFT between January 2014 and November 2022,including 14 males and 7 females(aged from 21 to 73 years;the course of disease ranged from 4 to 48 months).Patient demographics,clinical presentations,and imaging modalities including X-ray,CT,and MRI were reviewed.Pathological findings were corre-lated with imaging features to delineate diagnostic criteria and identify causes of misdiagnosis.Results All 21 patients repre-sented primary lesions,located in 14 bilateral femurs[9 on the right and 5 on the left;12 proximal femurs(intertrochanteric and peripheral)and 2 distal femurs],2 proximal tibia,2 proximal humerus,1 proximal radius,and 1 ilium and 1 calcaneus.On X-ray and CT,all lesions showed cartographical or quasi-circular osteolytic destruction with distinct and sclerotic margins,continuous bone cortex,absence of periosteal reaction and surrounding soft tissue mass.Calcification,bone ridge and varying degrees of fat components were observed in 16 lesions,displaying mixed density;5 lesions showed ground-glass density with minimal bone ridge.On MRI,the signal intensity of the lesion was heterogeneous.T1-weighted imaging showed iso-to slightly high signal intensity,while T2-weighted imaging demonstrated unevenly high signal intensity.Fat-suppressed sequences de-picted significantly elevated signal intensity within lesions,with post-contrast enhancement showing uneven patterns.5 Cases were initially misdiagnosed as fibrous dysplasia.Conclusion LSMFT is an uncommon benign bone tumor,typically localized in the proximal femur but occasionally found in other skeletal sites.Understanding its distinct imaging characteristics is crucial for accurate diagnosis.Typical cases exhibit identifiable imaging patterns,whereas atypical presentations may lead to misdiagnosis as fibrous dysplasia.