OBJECTIVE To explore a synergistic medication strategy integrating stage-specific modifications of Bushen huoxue decoction with hormone replacement therapy （HRT） for premature ovarian insufficiency （POI）. METHODS The connotation of Academician Tong Xiaolin’s “state-target differentiation and treatment” theory and the disease stage characteristics of POI were summarized. The latent stage， subclinical stage， clinical stage and exhaustion stage of POI were classified into corresponding core pathogenesis “states” and key objective indicator “targets”. Taking Bushen huoxue decoction as the basic prescription， its staged modification scheme and its sequential combination with HRT were analyzed. RESULTS & CONCLUSIONS The four stages of POI correspond to four pathogenic states respectively： kidney yin deficiency， kidney deficiency and blood stasis， heart-kidney disharmony， and deficiency of both yin and yang. Follicle-stimulating hormone （FSH）， anti-Müllerian hormone （AMH）， antral follicle count （AFC） and Kupperman score were taken as the evaluation targets of staging. Combined with the “state-target” characteristics of each stage， a medication principle based on Bushen huoxue decoction with syndrome differentiation modification and stage-adjusted administration was established： traditional Chinese medicine dominates in the latent stage， a sequential collaborative regimen is adopted in the subclinical stage， HRT is dominant supplemented by traditional Chinese medicine in the clinical stage， and integrated traditional Chinese and Western medicine is applied to consolidate the root cause in the exhaustion stage.

AIM To evaluate the quality of Croci Stigma from different producing areas.METHODS The analysis was performed on a 25 ℃ thermostatic Waters Acquity UPLC HSS T3 column(2.1 mm× 100 mm,1.8μm),with the mobile phase comprising of 0.1％phosphoric acid-acetonitrile flowing at 0.35 mL/min in a gradient elution manner,and the detection wavelengths were set at 254,440 nm.The UPLC fingerprints were established,after which orthogonal partial least squares discriminant analysis was performed,picrocrocin,crocin-Ⅰ,crocin-Ⅱ,crocin-Ⅲ,crocin-Ⅳ contents and chromaticity values(L*,a*,b*,E*ab)were determined,Pearson correlation analysis was adopted in the investigation of correlations between chromaticity values and internal constituent contents.RESULTS There were 14 common peaks in the fingerprints for 22 batches of medicinal materials with the similarities of more than 0.98.Various batches of medicinal materials were clustered into 2 types,7 quality difference components were screened.crocin-Ⅰ content in medicinal materials from different producing areas demonstrated significant differences(P＜0.05);the redder the color of medicinal material,the higher the contents of crocins.Picrocrocin,crocin-Ⅰ,crocin-Ⅱ,crocin-Ⅳ contents displayed highly significant correlations with colorimetric values(P＜0.01),while crocin-Ⅲ content exhibited no significant correlation with the latter(P＞0.05).CONCLUSION This accurate and reliable method can provide references for the quality control and color-quality relationship elucidation of Croci Stigma.

Objective To screen genes associated with poor prognosis of colorectal cancer(CRC)through bioinformatics analysis.Methods The gene expression profiles of GSE74602,GSE110223,GSE113513 and GSE141174 were obtained from Gene Expression Omnibus(GEO)database,including samples from 65 CRC tissues and 65 normal tissues.Differentially expressed genes(DEGs)between CRC tissues and normal tissues were screened out by GEO2R tool and Venn software,and the consistent genes were extracted from DEGs by Venn software.A protein-protein interaction(PPI)network was constructed by the STRING database to identify key genes,which were analyzed by Kaplan-Meier Plotter and GEPIA.Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis was conducted on the 13 selected genes.Results There were 171 DEGs obtained from the four datasets,including 148 up-regulated genes and 23 down-regulated genes.Up-regulated DEGs were enriched in the redox processes,bicarbonate transport,digestion,ion trans-membrane transport,and one-carbon metabolism;and down-regulated DEGs were enriched in the positive regulation of cell proliferation.The survival curve analysis showed that 30 of the 87 genes were significantly associated with poor survival prognosis.GEPIA showed that 13 of the 30 genes were highly expressed in CRC tissues compared to normal tissues,among which MYC and FGFR3 markedly enriched in the CRC pathway.Conclusion This study identifies that MYC and FGFR3 are significantly up-regulated in CRC and closely associated with poor prognosis,suggesting that they may serve as potential prognostic markers and therapeutic targets for CRC patients.

Objective To develop and validate a transgenic mouse model enabling specific and inducible optogenetic activation of oligodendrocyte precursor cells(OPCs).Methods A conditional allele for the photosensitive opsin chicken opsin 5(cOpn5)(Rosa26-LSL-cOpn5)was generated using CRISPR/Cas9 technology.These mice were subsequently crossed with NG2-CreERT transgenic mice to produce NG2-CreERT;cOpn5 animals.In this model,tamoxifen administration induces Cre-mediated recombination,leading to specific expression of cOpn5 in NG2-positive OPCs.The specificity and efficiency of cOpn5 expression in OPCs were confirmed by immunofluorescent staining.Functional validation of light-induced OPC activation was performed by using calcium imaging in acute brain slices after stimulation with 470 nm blue light.Results Immunofluorescence analysis confirmed robust and specific expression of cOpn5 within NG2-positive OPCs in the brains of tamoxifen-treated NG2-CreERT;cOpn5 mice.Crucially,calcium imaging of acute brain slices from these mice demonstrated a significant increase in intracellular calcium levels in cOpn5-expressing OPCs upon stimulation with 470 nm blue light,indicating successful optogenetic activation.Conclusion We have successfully generated and validated a novel transgenic mouse model(NG2-CreERT;cOpn5)that permits specific and inducible optogenetic activation of OPCs.This model provides a novel tool for subsequent in vivo studies of the role and regulating mechanisms of OPCs in the central nervous system.

Objective:To summarize and analyze the clinical features of patients with inflammatory bowel disease (IBD) accompanied by axial spondyloarthritis (ax-SpA) .Methods:A descriptive case series study was conducted. Consecutive IBD patients with ax-SpA admitted to Peking Union Medical College Hospital from January 2012 to December 2023 were enrolled, and the clinical data were collected and analyzed descriptively.Results:A total of 21 IBD patients with ax-SpA were enrolled, including 14 males (66.7%) and 7 females (33.3%). The median age at IBD diagnosis was 29 (24, 42) years. Among them, 10 had ulcerative colitis (UC) and 11 had Crohn's disease (CD). In 11 patients (52.4%), ax-SpA was diagnosed before IBD, while in 7 patients (33.3%), IBD was diagnosed before ax-SpA; the remaining 3 patients (14.3%) were diagnosed simultaneously. Thirteen patients (61.9%) had other extraintestinal manifestations, with 12 involving mucocutaneous manifestations. Nineteen patients including 9 UC and 10 CD were followed up for a median duration of 34 (12, 57) months. Among UC patients, 5 (55.6%) were escalated from conventional therapy to biologics or small-molecule drugs, and 6 (66.7%) developed opportunistic infections. Among CD patients, 3 (30.0%) were escalated to biologic therapy, and 2 (20.0%) developed opportunistic infections. Three patients (15.8%) underwent intestinal resection surgery.Conclusions:IBD patients with ax-SpA are predominantly male, with a similar proportion of UC and CD. There is no clear sequential pattern in the diagnosis timing of IBD and ax-SpA. These patients often present with other extraintestinal manifestations of IBD, primarily mucocutaneous manifestations.

Objective To explore the abnormal expression of the MT-ND family in pan-cancers and its prognostic value.Methods Transcriptome expression and clinical data of 33 cancers were downloaded from the TCGA database,thereby analyzing the expression differences of the MT-ND family in tissuesof different types of cancers and normal tissues.The prognostic role of the MT-ND family in pan-cancers was explored by univariate Cox regression analysis and Kaplan-Meier survival analysis.Results The expression of the MT-ND family was upregulated in the kidney chromophobe,acute myeloid leukemia and thymoma,and downregulated in the remaining tumors.The expression of the MT-ND family was associated with the overall survival rate of different types of cancers.In addition,the MT-ND family were significantly correlated with the immune invasion subtypes,and were correlated with stromal cell invasion and tumor cell stemness to varying degrees.The expression of MT-ND4 was downregulated in brain lower grade glioma,which was a protective factor for prognosis;while the expression of MT-ND4 in thymoma was upregulated,which was a risk factor for prognosis.Conclusion Pan-cancer analysis has confirmed that the MT-ND family can predict the tumor prognosis,which provides new ideas and strategies for the precision treatment and prognostic management of cancer.

Objective To study the damage effect of high-voltage electric shock on skin based on metabolomics,analyze its metabolic differences,and explore its injury mechanism.Methods A total of 16 SPF C57BL/6J male mice were divided into the electric shock group(head skin received electric shock treatment)and control group(head skin received electric shock acoustic-optical stimulation),and the skin appearance after treatment of mice in the two groups was observed.The histopathological changes caused by electric shock were analyzed by HE staining,EVG staining and Masson staining.GC-MS and LC-MS metabonomics were used to analyze the changes of skin metabolism spectrum and tissue metabolites after electric shock exposure,and the differential metabolites were analyzed.The obtained differential metabolites were combined and KEGG enrichment analysis was conducted.Results After high-voltage electric shock,the skin of mice could be damaged to the dermis,and the epidermis was partially thickened,lifted and separated.The structure of skin appendages in the dermis was destroyed,with a large number of inflammatory cells infiltrating and obvious swelling,accompanied by congestion,which led to severe skin inflammatory reaction and impaired skin barrier function.Metabonomics analysis suggested that the metabolites changed after electric shock exposure.KEGG enrichment analysis showed that electric shock significantly affected the central carbon metabolism pathway of cancer,pentose phosphate pathway,purine metabolism,glycine,serine and threonine metabolism processes,amino acid tRNA biosynthesis mechanism,glycerophospholipid metabolism pathway,pyrimidine metabolism pattern,glycolysis/gluconeogenesis,alanine metabolism process,glucagon signal pathway and so on.Conclusion High voltage electric shock can cause deep skin damage,disturb its energy metabolism and amino acid metabolism,and seriously interfere with its antioxidant and DNA repair system functions.

Poly(lactic-co-glycolide)(PLGA)is a key excipient in long-acting sustained-release preparations,and its degradation properties directly affect the drug release behavior.In this study,PLGA microspheres were prepared by microfluidic techniques,and the morphology changes of the microspheres were observed by scanning electron microscopy(SEM).In alkaline environment,due to the accelerated hydrolysis of ester bonds,the surface of the microspheres was rapidly dissolved and eroded,and the degradation rate was significantly higher than that in acidic environment.High temperature accelerated the degradation of PLGA microspheres.Under neutral and alkaline conditions,the microspheres showed aggregation and adhesion.Under acidic conditions,the microspheres gradually decomposed into irregular fragments.The high ionic strength further promoted the surface corrosion of the microspheres,especially under extreme pH conditions.Simultaneously,PLGA microspheres encapsulating coumarin were prepared to simulate the microsphere formulation.The release rate of coumarin after degradation of the microspheres under different conditions was observed by measuring the absorbance with ultraviolet-visible spectrophotometry.The results were consistent with those of the blank microspheres.This study revealed that the degradation of PLGA microspheres was significantly pH-dependent,temperature sensitive and ion strength responsive.These findings not only helped to understand and optimize the long-term stability and controlled release performance of drug-carrying microspheres,but also provided a theoretical basis for further improvement of PLGA-based drug carrier design.

Objective:To summarize and analyze the clinical features of patients with inflammatory bowel disease (IBD) accompanied by axial spondyloarthritis (ax-SpA) .Methods:A descriptive case series study was conducted. Consecutive IBD patients with ax-SpA admitted to Peking Union Medical College Hospital from January 2012 to December 2023 were enrolled, and the clinical data were collected and analyzed descriptively.Results:A total of 21 IBD patients with ax-SpA were enrolled, including 14 males (66.7%) and 7 females (33.3%). The median age at IBD diagnosis was 29 (24, 42) years. Among them, 10 had ulcerative colitis (UC) and 11 had Crohn's disease (CD). In 11 patients (52.4%), ax-SpA was diagnosed before IBD, while in 7 patients (33.3%), IBD was diagnosed before ax-SpA; the remaining 3 patients (14.3%) were diagnosed simultaneously. Thirteen patients (61.9%) had other extraintestinal manifestations, with 12 involving mucocutaneous manifestations. Nineteen patients including 9 UC and 10 CD were followed up for a median duration of 34 (12, 57) months. Among UC patients, 5 (55.6%) were escalated from conventional therapy to biologics or small-molecule drugs, and 6 (66.7%) developed opportunistic infections. Among CD patients, 3 (30.0%) were escalated to biologic therapy, and 2 (20.0%) developed opportunistic infections. Three patients (15.8%) underwent intestinal resection surgery.Conclusions:IBD patients with ax-SpA are predominantly male, with a similar proportion of UC and CD. There is no clear sequential pattern in the diagnosis timing of IBD and ax-SpA. These patients often present with other extraintestinal manifestations of IBD, primarily mucocutaneous manifestations.

Objective To explore the abnormal expression of the MT-ND family in pan-cancers and its prognostic value.Methods Transcriptome expression and clinical data of 33 cancers were downloaded from the TCGA database,thereby analyzing the expression differences of the MT-ND family in tissuesof different types of cancers and normal tissues.The prognostic role of the MT-ND family in pan-cancers was explored by univariate Cox regression analysis and Kaplan-Meier survival analysis.Results The expression of the MT-ND family was upregulated in the kidney chromophobe,acute myeloid leukemia and thymoma,and downregulated in the remaining tumors.The expression of the MT-ND family was associated with the overall survival rate of different types of cancers.In addition,the MT-ND family were significantly correlated with the immune invasion subtypes,and were correlated with stromal cell invasion and tumor cell stemness to varying degrees.The expression of MT-ND4 was downregulated in brain lower grade glioma,which was a protective factor for prognosis;while the expression of MT-ND4 in thymoma was upregulated,which was a risk factor for prognosis.Conclusion Pan-cancer analysis has confirmed that the MT-ND family can predict the tumor prognosis,which provides new ideas and strategies for the precision treatment and prognostic management of cancer.