ObjectiveThis study systematically analyzed the arginine metabolic dysregulation in the rat model of heart failure （HF）， providing a modern scientific basis for elucidating the pathogenesis of HF and offering new insights for the prevention and treatment of HF with traditional Chinese medicine （TCM）. MethodsA thoracotomy was performed to ligate the left anterior descending coronary artery of rats， which induced acute myocardial ischemia and thus led to the development of post-myocardial infarction heart failure. The rats were divided into a sham surgery group and a model group， with eight rats in each group. Serum targeted metabolomics analysis was performed using ultra-performance liquid chromatography-triple quadrupole mass spectrometry （UPLC-TQ-S）， and the spatial distribution of metabolites in cardiac tissue was observed using airflow-assisted desorption electrospray ionizationmass spectrometry imaging （AFADESI-MSI）. Targets associated with HF and arginine metabolism were screened from databases including GeneCards and the Gene Expression Omnibus （GEO）， a protein-protein interaction （PPI） network was constructed， and enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway and Gene Ontology （GO） was performed. Finally， molecular docking was conducted to verify the binding between core metabolic components and key targets， and potential TCMs were predicted based on the core pathways and targets. ResultsCompared with the sham surgery group， the levels of arginine and citrulline in the serum of model rats were significantly decreased （P<0.01）， while those of proline， ornithine， creatine， creatinine and glutamate were significantly increased （P<0.05， P<0.01）. Cardiac mass spectrometry imaging showed a decreased abundance of arginine in the local myocardial tissue. Bioinformatics analysis identified 24 core functional targets， such as the angiotensin-converting enzyme （ACE）， neuronal nitric oxide synthase （NOS1）， 5-hydroxytryptamine receptor 2A （HTR2A）， and epidermal growth factor receptor （EGFR）， and enrichment analysis indicated that these targets were significantly involved in the calcium signaling pathway， neuroactive ligand-receptor interactions， and phosphatidylinositol signaling pathway. Molecular docking confirmed strong binding activities between arginine， citrulline and HTR2A， as well as between creatine， creatinine and EGFR. Based on pathway-target prediction， potential TCM interventions， such as ginseng and magnolia， were identified. ConclusionThis study revealed characteristic arginine metabolic disorder in HF， and the core targets of HF were closely associated with the phosphatidylinositol signaling pathway. It provides a modern biological interpretation of the pathogenesis of HF in TCM from the perspectives of metabolites and signaling pathways， and offers valuable insights for targeted therapy of HF and the development of TCM.

ObjectiveThis study systematically analyzed the arginine metabolic dysregulation in the rat model of heart failure （HF）， providing a modern scientific basis for elucidating the pathogenesis of HF and offering new insights for the prevention and treatment of HF with traditional Chinese medicine （TCM）. MethodsA thoracotomy was performed to ligate the left anterior descending coronary artery of rats， which induced acute myocardial ischemia and thus led to the development of post-myocardial infarction heart failure. The rats were divided into a sham surgery group and a model group， with eight rats in each group. Serum targeted metabolomics analysis was performed using ultra-performance liquid chromatography-triple quadrupole mass spectrometry （UPLC-TQ-S）， and the spatial distribution of metabolites in cardiac tissue was observed using airflow-assisted desorption electrospray ionizationmass spectrometry imaging （AFADESI-MSI）. Targets associated with HF and arginine metabolism were screened from databases including GeneCards and the Gene Expression Omnibus （GEO）， a protein-protein interaction （PPI） network was constructed， and enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway and Gene Ontology （GO） was performed. Finally， molecular docking was conducted to verify the binding between core metabolic components and key targets， and potential TCMs were predicted based on the core pathways and targets. ResultsCompared with the sham surgery group， the levels of arginine and citrulline in the serum of model rats were significantly decreased （P<0.01）， while those of proline， ornithine， creatine， creatinine and glutamate were significantly increased （P<0.05， P<0.01）. Cardiac mass spectrometry imaging showed a decreased abundance of arginine in the local myocardial tissue. Bioinformatics analysis identified 24 core functional targets， such as the angiotensin-converting enzyme （ACE）， neuronal nitric oxide synthase （NOS1）， 5-hydroxytryptamine receptor 2A （HTR2A）， and epidermal growth factor receptor （EGFR）， and enrichment analysis indicated that these targets were significantly involved in the calcium signaling pathway， neuroactive ligand-receptor interactions， and phosphatidylinositol signaling pathway. Molecular docking confirmed strong binding activities between arginine， citrulline and HTR2A， as well as between creatine， creatinine and EGFR. Based on pathway-target prediction， potential TCM interventions， such as ginseng and magnolia， were identified. ConclusionThis study revealed characteristic arginine metabolic disorder in HF， and the core targets of HF were closely associated with the phosphatidylinositol signaling pathway. It provides a modern biological interpretation of the pathogenesis of HF in TCM from the perspectives of metabolites and signaling pathways， and offers valuable insights for targeted therapy of HF and the development of TCM.

Objective To establish an oxidative stress mouse model of atopic dermatitis (AD) by applying 2,4-dinitrofluorobenzene (DNFB) to the back and post-auricular skin of KM mice, and to evaluate the regulatory role of the RAGE-NLRP3 axis (receptor for advanced glycation end products-NOD-like receptor family, pyrin domain containing 3 axis) in AD-related oxidative stress, thereby providing a potential therapeutic target for AD treatment. Methods Twenty SPF-grade female KM mice were randomly divided into a control group (Control group) and an experimental group (DNFB group), with 10 mice in each group. Mice in the Control group were treated with an acetone-olive oil vehicle (acetone: olive oil = 3:1) on their back and post-auricular skin. Mice in the DNFB group were treated with 0.5% DNFB (prepared by adding 0.5 g DNFB per 100 mL of acetone-olive oil vehicle) on the same areas, once daily for 14 consecutive days. The severity of skin lesions was scored on days 2, 4, 6, 9, 12, and 14 of treatment. On day 14, scratching behavior and ear thickness were evaluated. Ear swelling was evaluated on the final day by measuring bilateral ear thickness three times with a vernier caliper; the three measurements were averaged. HE staining was used to observe morphological and structural changes of cells in the back skin tissues. The mRNA and protein expression levels of RAGE (receptor for advanced glycation end products) in skin tissues were detected by quantitative real-time PCR, Western blot, and immunohistochemical staining. The mRNA expression levels of oxidative stress-related molecules, including NLRP3 (NOD-like receptor family, pyrin domain containing 3), caspase-1 (cysteine-dependent aspartate-specific protease 1), and IL-1β (Interleukin-1β), were detected by quantitative real-time PCR. Results On day 14, the back skin lesion scores of the Control group and DNFB group were (0.20±0.42) and (9.93±1.30) (P<0.000 1), respectively. Scratching behavior scores were (5.00±2.05) and (49.26±8.49) episodes, respectively (P<0.000 1), and ear thicknesses were (213.00±11.87) μm and (765.93±140.47) μm (P<0.000 1), respectively. The DNFB group exhibited marked skin dryness, desquamation, and thickening. HE staining results showed that skin inflammation was obvious in the DNFB group, consistent with the pathological features of AD. Quantitative real-time PCR and Western blot results showed that compared with the Control group, the mRNA expression level of RAGE in skin tissues of the DNFB group was significantly increased (P<0.05), and the protein expression level of RAGE was also significantly increased (P<0.01). Immunohistochemical staining results showed that compared with the Control group, skin tissue sections of the DNFB group exhibited thickened stratum corneum and fibrotic proliferation of fibroblasts in the interstitium under microscopic observation, with a significant increase in RAGE protein expression in the skin tissues (P<0.01). Quantitative real-time PCR results showed that the mRNA expression levels of NLRP3, caspase-1, and IL-1β in skin tissues of the DNFB group were all significantly increased (P<0.01). Conclusion The AD mouse oxidative stress model has been successfully established by topical DNFB application. RAGE may promote the development of AD by regulating the NLRP3 inflammasome and IL-1β release, forming an oxidative-inflammatory cascade, suggesting that it could be a potential therapeutic target for AD.

ObjectiveTo address the limitations of the current quality standard for Polygalae Radix（PR）， which relies on a single component for quality assessment and struggles to holistically control its intrinsic quality， by constructing a comprehensive quality evaluation system integrating "macro-characterization of chemical profile， synchronous quantification of multiple index components， and quantitative analysis of multi-components by single marker（QAMS） for key component groups". This study aims to facilitate the scientific revision of the quality standard for PR. MethodsHigh performance liquid chromatography（HPLC） characteristic chromatograms were established for 11 batches of PR medicinal materials（YZ）， 10 batches of PR decoction pieces（YP）， and 10 batches of licorice-processed PR decoction pieces（ZYZ）， followed by similarity evaluation and identification of common peaks. HPLC-QAMS was developed for xanthones（sibiricaxanthone B， polygalaxanthone Ⅺ， polygalaxanthone Ⅲ） in the characteristic chromatograms. Simultaneously， the external standard method（ESM） was used to determine the contents of the corresponding xanthones and 3，6'-disinapoyl sucrose in YZ， YP， and ZYZ， followed by multivariate statistical analysis and Spearman correlation analysis. ResultsThe similarity between the characteristic chromatograms of 31 batches of PR samples and the reference chromatogram was>0.9. A total of 13 common peaks were identified， and 10 of these peaks were characterized through reference standard comparison. The successfully constructed QAMS method showed that the relative correction factors（RCFs） of sibiricaxanthone B and polygalaxanthone Ⅺ to polygalaxanthone Ⅲ were 0.76 and 0.88， and their relative retention times（RRTs） were 0.85 and 0.97， respectively. The results calculated by the QAMS method showed no significant difference from those obtained by the ESM. According to the limit standard for polygalaxanthone Ⅲ in the 2020 edition of the Pharmacopoeia of the People's Republic of China（hereinafter referred to as the Chinese Pharmacopoeia）， the pass rate of 31 batches of samples was only 19.35%. Multivariate statistical analysis indicated certain compositional differences between different batches of YZ and YP， as well as between YP and ZYZ， with 3，6'-disinapoyl sucrose identified as the main differentiating component. Furthermore， correlation analysis revealed that the content of polygalaxanthone Ⅲ was positively correlated with the contents of sibiricaxanthone B and polygalaxanthone Ⅺ， but showed no association with the content of 3，6'-disinapoyl sucrose. ConclusionIt is recommended that the content limit for polygalaxanthone Ⅲ in YZ，YP and ZYZ be revised to not less than 0.07%， or the total content of polygalaxanthone Ⅲ， sibiricaxanthone B and polygalaxanthone Ⅺ be not less than 0.18%. The newly established triple quality control model of "holistic control via characteristic chromatograms， precise quantification of oligosaccharide esters， and efficient detection of xanthones by QAMS" provides a systematic and precise solution for quality evaluation of PR and similar Chinese herbal medicines.

ObjectiveTo explore the characteristics of the tongue coating microbiota in patients of coronary heart disease （CHD） with qi deficiency and blood stasis syndrome. MethodsA total of 27 CHD patients with qi deficiency and blood stasis syndrome， 29 patients with non-qi deficiency and blood stasis syndrome， and 20 healthy individuals were included in this study. The tongue coating microbiota of the participants was analyzed using 16S rDNA high-throughput sequencing technology， followed by Alpha and Beta diversity analyses and comparisons of microbial abundance. ResultsA total of 479 operational taxonomic units （OTUs） were detected， among which 245 OTUs were shared across all three groups. There were 33 OTUs unique to the qi deficiency and blood stasis syndrome group， 21 OTUs unique to the non-qi deficiency and blood stasis syndrome group， and 121 OTUs unique to the healthy group. The observed species count （Sob）， total species richness （Chao1）， abundance-based coverage estimator （ACE）， and Shannon diversity index were significantly lower in the qi deficiency and blood stasis syndrome and non-qi deficiency and blood stasis syndrome groups compared to the healthy group （P＜0.05）. Principal coordinate analysis （PCoA） of the tongue coating microbiota showed significant differences in distance matrices among the three groups （P＜0.05）. Compared with the healthy group， the qi deficiency and blood stasis syndrome group exhibited an increased abundance of Actinobacteria， Patescibacteria， Spirochaetes， Verrucomicrobia， Rothia， TM7X， Gemella， and Corynebacterium， while Fusobacteria， Cyanobacteria， Leptotrichia， and Lactobacillus decreased （P＜0.05）. In the non-qi deficiency and blood stasis syndrome group， Actinobacteria， Verrucomicrobia， Rothia， and Corynebacterium increased， whereas Cyanobacteria and Lactobacillus reduced （P＜0.05）. When comparing with the non-qi deficiency and blood stasis syndrome group， the qi deficiency and blood stasis syndrome group had a significantly higher abundance of Patescibacteria， Peptostreptococcus， Solobacterium， Filifactor， Moraxella， Porphyromonas endodontalis， and Capnocytophaga， while Cyanobacteria reduced （P＜0.05）. Conclusuion Patients with CHD of qi deficiency and blood stasis syndrome exhibit a decrease in beneficial bacteria and an increase in pathogenic bacteria. Patescibacteria， Peptostreptococcus， Solobacterium， Filifactor， Moraxella， Porphyromonas endodontalis， and Capnocytophaga were identified as the key differential microbiota distinguishing qi deficiency and blood stasis syndrome from non-qi deficiency and blood stasis syndrome patients.

ObjectiveBased on the theory of "gut-prostate" axis， this study explored the effects and mechanisms of Zishen Tongguan formula and Cinnamomi Cortex in the formula in treating rats with chronic non-bacterial prostatitis（CNP） by detecting the levels of inflammatory factors， and the composition and structure of intestinal flora in CNP rats. MethodsEight out of 42 SD rats were randomly selected as the normal group， and the remaining rats were injected with carrageenan to prepare the CNP model. After successful modeling， 32 rats were randomly divided into the model group， Ningmitai capsule group（0.50 g·kg^-1）， Zishen Tongguan formula group（2.00 g·kg^-1）， and the Phellodendri Chinensis Cortex-Anemarrhenae Rhizoma pair group（PCC-AR group， 2.00 g·kg^-1）， with 8 rats in each group. The administered groups were given the corresponding medicinal solution by gavage， and the normal and model groups were intragastrically administered with an equal volume of normal saline， once a day for 14 consecutive days. The prostate tissues of rats were collected and subjected to hematoxylin-eosin（HE） staining and Masson staining to observe the pathological changes of the tissues in each group. Enzyme-linked immunosorbent assay（ELISA） was used to detect the levels of related inflammatory factors in rat serum， and 16S rDNA sequencing was used to analyze the abundance and diversity changes of gut microbiota before and after administration， and species difference analysis was performed. ResultsAll the administered groups could alleviate the inflammatory symptoms of CNP rats， increase the expression levels of anti-inflammatory factors and decrease the expression levels of pro-inflammatory factors， with the most sIgnificant effect observed in the Zishen Tongguan formula group. Compared with the normal group， the expression levels of interleukin（IL）-8， hypersensitive C-reactive protein（hs-CRP）， immunoglobulin（Ig）M， secretory IgA （sIgA）， and inducible nitric oxide synthase（iNOS） were sIgnificantly increased in the model group（P<0.01）. Compared with the model group， the expression levels of the above inflammatory factors in all administered groups were significantly reduced（P<0.01）. When compared with the PCC-AR group， the Zishen Tongguan formula group showed a significant decrease in transforming growth factor（TGF）-β₁ expression level（P<0.05） and a significant increase in IgM expression level（P<0.01）. The results of gut microbiota analysis showed that， compared with the PCC-AR group， at the order level， the Zishen Tongguan formula group significantly reduced the relative abundance of conditional pathogens such as Bacteroidales， Acidaminococcales， Rhodospirillales， Clostridiales， and Elusimicrobiales（P<0.01）. And at the genus level， the Zishen Tongguan formula group significantly decreased the relative abundance of pathogenic microbiota such as Lachnospira and Bacteroides（P<0.01） and significantly increased the relative abundances of beneficial microbiota such as Ruminococcus and Lactobacillus（P<0.01）. ConclusionZishen Tongguan formula can reduce the level of harmful intestinal bacteria， increase the level of beneficial intestinal bacteria， down-regulate the expression of serum inflammatory factors， and the small amount of Cinnamomi Cortex in the formula may play a key role in the treatment of CNP with this formula.

ObjectiveBased on the theory of "gut-prostate" axis， this study explored the effects and mechanisms of Zishen Tongguan formula and Cinnamomi Cortex in the formula in treating rats with chronic non-bacterial prostatitis（CNP） by detecting the levels of inflammatory factors， and the composition and structure of intestinal flora in CNP rats. MethodsEight out of 42 SD rats were randomly selected as the normal group， and the remaining rats were injected with carrageenan to prepare the CNP model. After successful modeling， 32 rats were randomly divided into the model group， Ningmitai capsule group（0.50 g·kg^-1）， Zishen Tongguan formula group（2.00 g·kg^-1）， and the Phellodendri Chinensis Cortex-Anemarrhenae Rhizoma pair group（PCC-AR group， 2.00 g·kg^-1）， with 8 rats in each group. The administered groups were given the corresponding medicinal solution by gavage， and the normal and model groups were intragastrically administered with an equal volume of normal saline， once a day for 14 consecutive days. The prostate tissues of rats were collected and subjected to hematoxylin-eosin（HE） staining and Masson staining to observe the pathological changes of the tissues in each group. Enzyme-linked immunosorbent assay（ELISA） was used to detect the levels of related inflammatory factors in rat serum， and 16S rDNA sequencing was used to analyze the abundance and diversity changes of gut microbiota before and after administration， and species difference analysis was performed. ResultsAll the administered groups could alleviate the inflammatory symptoms of CNP rats， increase the expression levels of anti-inflammatory factors and decrease the expression levels of pro-inflammatory factors， with the most sIgnificant effect observed in the Zishen Tongguan formula group. Compared with the normal group， the expression levels of interleukin（IL）-8， hypersensitive C-reactive protein（hs-CRP）， immunoglobulin（Ig）M， secretory IgA （sIgA）， and inducible nitric oxide synthase（iNOS） were sIgnificantly increased in the model group（P<0.01）. Compared with the model group， the expression levels of the above inflammatory factors in all administered groups were significantly reduced（P<0.01）. When compared with the PCC-AR group， the Zishen Tongguan formula group showed a significant decrease in transforming growth factor（TGF）-β₁ expression level（P<0.05） and a significant increase in IgM expression level（P<0.01）. The results of gut microbiota analysis showed that， compared with the PCC-AR group， at the order level， the Zishen Tongguan formula group significantly reduced the relative abundance of conditional pathogens such as Bacteroidales， Acidaminococcales， Rhodospirillales， Clostridiales， and Elusimicrobiales（P<0.01）. And at the genus level， the Zishen Tongguan formula group significantly decreased the relative abundance of pathogenic microbiota such as Lachnospira and Bacteroides（P<0.01） and significantly increased the relative abundances of beneficial microbiota such as Ruminococcus and Lactobacillus（P<0.01）. ConclusionZishen Tongguan formula can reduce the level of harmful intestinal bacteria， increase the level of beneficial intestinal bacteria， down-regulate the expression of serum inflammatory factors， and the small amount of Cinnamomi Cortex in the formula may play a key role in the treatment of CNP with this formula.

OBJECTIVE: To explore the genetic basis of a child with Chanarin-Dorfman syndrome (CDS) manifesting as ichthyosis. METHODS: A child who had presented at Henan Provincial People's Hospital in June 2023 was selected as study subject. Clinical data of the child was collected. Peripheral blood samples were collected from the child and her parents. Following extraction of genomic DNA, whole-exome sequencing (WES) was carried out. Candidate variants were verified by Sanger sequencing. Relevant literature was searched in databases using key words "Chanarin-Dorfman syndrome" and "ABHD5 gene". The clinical manifestations and variant sites of previously reported cases were compiled and analyzed for correlations. This study was approved by the Medical Ethics Committee of Henan Provincial People's Hospital [Ethics No.: (2019) Jun Shen No. (134)]. RESULTS: WES revealed that the child has harbored compound heterozygous variants of the ABHD5 gene, namely c.99_103del (p.H34*) in exon 2 and c.770C>G (p.P257R) in exon 5, which were inherited from her father and mother, respectively. Bioinformatic analysis suggested that both variants were pathogenic. Literature review indicated that the affected organs in CDS are ranked from most to least including liver, eyes, ears, nervous system, muscles, spleen, and kidneys. The c.594insC and c.594dupC variants are most common. CONCLUSION The identification of the two novel ABHD5 gene variants has enriched the mutation spectrum of CDS. c.594insC or c.594dupC are hotspot mutations of this disease, albeit with no definitive correlation between the genotype and phenotype.
Humans ; Female ; Ichthyosiform Erythroderma, Congenital/genetics* ; Lipid Metabolism, Inborn Errors/genetics* ; Phenotype ; 1-Acylglycerol-3-Phosphate O-Acyltransferase/genetics* ; Mutation ; Muscular Diseases/genetics* ; Exome Sequencing ; Child ; Male ; Child, Preschool

This study retrospectively analyzed data from 25 patients with paroxysmal nocturnal hemoglobinuria (PNH) admitted to Peking Union Medical College Hospital and Dongfang Hospital of Beijing University of Chinese Medicine from January 2023 to June 2024. Patients receiving sufficient eculizumab treatment for at least 3 months and who completed hemolytic complex (CH50) level testing pre- and post-treatment for 3 and 6 months were selected. Blood routine, biochemistry, and the 50% CH50-related indicators were monitored pre- and post-treatment. Among these patients, 24 completed 6 months of treatment and CH50 testing. After 3 and 6 months of eculizumab treatment, all patients with PNH showed significant improvement in symptoms, with lactate dehydrogenase (LDH) levels decreasing from a baseline of (1 814.4 ± 924.8) U/L to (248.5 ± 61.0) U/L and (239.3 ± 44.8) U/L. Hemoglobin levels increased from a baseline of (73.9±14.4) g/L to (99.9 ± 21.3) g/L and (99.6 ± 19.8) g/L. The baseline CH50 level was (32.4±14.7) %, which decreased to 2.0% (1.0% –8.0% ) and 1.0% (1.0% –4.0% ) at 3 and 6 months posttreatment, respectively. At baseline, a linear correlation was found between CH50 and LDH levels ( P<0.001), and the trend of CH50 changes was significantly lower than LDH at 3 and 6 months post-treatment with eculizumab, with similar trends. However, no linear correlation was observed between CH50 and LDH levels or other parameters at 3 and 6 months of medication. Our case demonstrates that eculizumab is effective for PNH hemolysis treatment. The serum CH50 level may be a biomarker for complement blockade induced by eculizumab, which can, to some extent, reflect the intravascular hemolysis of PNH and the efficacy of eculizumab.

Objective:To assess the implementation status of Internet-Plus Nursing Services from patient experience perspectives and analyze influencing factors in Putuo District, Shanghai.Methods:A cross-sectional study on Internet-Plus Nursing Services was conducted from January to March 2024. The study enrolled 502 patients from 12 community health centers and 4 social nursing stations in Shanghai Putou District via convenience sampling. Using Internet-Plus Nursing Services for ≥ 6 months were defined as having received the services. Service implementation and quality perception were evaluated using satisfaction assessments and SERVQUAL-based quality perception scales. Data analysis included descriptive statistics and binary logistic regression.Results:The service adoption rate was 73.71% (370/502), with 66.93%(336/502) policy awareness. The logistic regression analysis indicated that the application of services was significantly influenced by age ( OR=0.660, 95% CI: 0.512-0.850), self-care ability ( OR=0.384, 95% CI: 0.257-0.574), and policy awareness ( OR=0.344, 95% CI:0.210-0.564) (all P<0.05). Among the service types, specimen collection/monitoring (80.27%, 299/370) and home health guidance (64.86%,240/370) were most utilized. Injection services had the highest satisfaction (4.10/5), while the special type of care had the lowest satisfaction rate (2.45/5). Quality perception was highest for Assurance and Empathy dimensions (both 4.74/5). Conclusion:The application rate and satisfaction of Internet-Plus Nursing Service in Shanghai Putuo District is high, which is associated with effective integration of clinical needs and perceptual drivers. Targeted expansion of specialized care services is recommended to enhance service diversification.