OBJECTIVE To investigate the causal relationships between gut microbiota， blood metabolites and antidepressant treatment response from a genetic perspective， and to assess the potential mediating role of blood metabolites. METHODS This study utilized a two-sample Mendelian randomization （MR） design. Exposure data were derived from four large-scale gut microbiome genome-wide association study （GWAS） datasets and two blood metabolite GWAS datasets. The inverse variance weighted method was used as the primary method to evaluate the causal relationships between gut microbiota， blood metabolites and antidepressant effects. The robustness， heterogeneity and horizontal pleiotropy of the results were evaluated through various sensitivity analyses. Additionally， the false discovery rate （FDR） was applied to correct type Ⅰ errors caused by multiple hypothesis testing. Finally， MR mediation analysis was conducted to test the potential mediating effect of blood metabolites. RESULTS The s_ Bilophila was negatively associated with the effectiveness of antidepressant treatment （ P ＝8.030×10 －5 ， then P ＝0.033 after FDR correction）， and the f_Bacteroidales was positively associated with the effectiveness of antidepressant treatment （ P ＝3.275×10 －4 ， then P ＝0.034 after FDR correction）. Over a hundred blood metabolites were also screened out as being associated with antidepressant response， but after FDR correction， no significant causal relationship was observed. The P value of the mediation effect proportion of blood metabolites in the “gut microbiota-blood metabolites-antidepressant efficacy” pathway was greater than 0.05. CONCLUSIONS The s_ Bilophila may represent a risk factor for antidepressant effects， whereas the f_Bacteroidales may serve as a protective factor for antidepressant effects. The correlation between blood metabolites and antidepressant efficacy is not strong， and no genetic evidence is found to support that the investigated blood metabolites play a key mediating role between the gut microbiota and antidepressant response.

Serotonin-selective reuptake inhibitors （SSRIs）， as widely used antidepressants in clinical practice， exhibit significant individual differences in antidepressant efficacy. Gut microbiota plays an important role in the development and progression of depression， and the use of SSRIs exerts a significant impact on the gut microbiota of patients with depression. Based on this， this article reviews the research progress on the interactions between the antidepressant effects of SSRIs and gut microbiota. It has been found that SSRIs can influence the diversity， abundance， and function of the gut microbiota directly or indirectly. Conversely， the composition of the gut microbiota and differences in its functional metabolic pathways， and other factors， can in turn affect the antidepressant effects of SSRIs. Therefore， in clinical practice， gut microbiota diversity can be utilized as a predictive indicator for the antidepressant effects of SSRIs. Probiotics can be employed as an adjunct therapy alongside SSRIs， and dietary adjustments， as well as fecal microbiota transplantation， can be used to enhance the therapeutic efficacy of SSRIs. In the future， large-scale， multicenter clinical studies should be conducted， enrolling a broadly representative cohort of patients with depression， to uncover the true association between the antidepressant effects of SSRIs and gut microbiota， thereby opening up more effective avenues for the comprehensive treatment of depression.

Lipidomics is an emerging discipline that systematically studies the various types, functions, and metabolic pathways of lipids within living organisms. This field compares changes in diseases or drug impact, identifying biomarkers and molecular mechanisms present in lipid metabolic networks across different physiological or pathological states. Through employing analytical chemistry within the realm of lipidomics, researchers analyze traditional Chinese medicine (TCM). This analysis aids in uncovering potential mechanisms for treating diverse physiopathological conditions, assessing drug efficacy, understanding mechanisms of action and toxicity, and generating innovative ideas for disease prevention and treatment. This manuscript assesses recent literature, summarizing existing lipidomics technologies and their applications in TCM research. It delineates the efficacy, mechanisms, and toxicity research related to lipidomics in Chinese medicine. Additionally, it explores the utilization of lipidomics in quality control research for Chinese medicine, aiming to expand the application of lipidomics within this field. Ultimately, this initiative seeks to foster the integration of traditional medicine theory with modern science and technology, promoting an organic fusion between the two domains.

Two novel diketopiperazines (1 and 5), along with ten known compounds (2-4, 6-12) demonstrating significant skin inflammation inhibition, were isolated from a marine-derived fungus identified as Aspergillus sp. FAZW0001. The structural elucidation and configurational reassessments of compounds 1-5 were established through comprehensive spectral analyses, with their absolute configurations determined via single crystal X-ray diffraction using Cu Kα radiation, Marfey's method, and comparison between experimental and calculated electronic circular dichroism (ECD) spectra. Compounds 1, 2, and 8 exhibited significant anti-inflammatory activities in Propionibacterium acnes (P. acnes)-induced human monocyte cell lines. Compound 8 demonstrated the ability to down-regulate interleukin-1β (IL-1β) expression by inhibiting Toll-like receptor 2 (TLR2) expression and modulating the activation of myeloid differentiation factor 88 (MyD88), mitogen-activated protein kinase (MAPK), and nuclear factor κB (NF-κB) signaling pathways, thus reducing the cellular inflammatory response induced by P. acnes. Additionally, compound 8 showed the capacity to suppress mitochondrial reactive oxygen species (ROS) production and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome activation, thereby reducing IL-1β maturation and secretion. A three-dimensional quantitative structure-activity relationships (3D-QSAR) model was applied to compounds 5-12 to analyze their anti-inflammatory structure-activity relationships.
Humans ; Aspergillus/chemistry* ; Diketopiperazines/isolation & purification* ; Anti-Inflammatory Agents/isolation & purification* ; Interleukin-1beta/genetics* ; Toll-Like Receptor 2/immunology* ; Propionibacterium acnes/drug effects* ; NF-kappa B/genetics* ; Molecular Structure ; Myeloid Differentiation Factor 88/immunology* ; Monocytes/immunology* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Cell Line

Objective To assess the clinical value of prognostic nutritional index(PNI)in predicting the prognosis of patients with advanced liver cancer treated with transarterial chemoembolization(TACE)combined with ablation therapy.Methods A total of 112 patients with advanced liver cancer,who received TACE combined with ablation at the Lishui Municipal Central Hospital of China from January 2020 to January 2024,were enrolled in this study.The general data,survival status,and survival time were collected.The Youden index of PNI was calculated using the receiver operating characteristic(ROC)curve model,and the optimal cutoff value was determined.Based on the optimal cutoff value,the patients were divided into low-PNI group and high-PNI group.The progression-free survival(PFS)and overall survival(OS)time were compared between the two groups,and the independent risk factors affecting PFS and OS were analyzed.Results The Youden index for PNI was 0.43,and the optimal cutoff value of PNI was 43.95.The low-PNI group included 65 patients,and the high-PNI group included 47 patients.There were no statistically significant differences in the baseline data between the two groups.The median PFS and the median OS in the high-PNI group were 13.21 months(95％CI=4.37-22.03)and 40.80 months(95％CI=31.55-50.05)respectively,which were longer than 9.20 months(95％CI=6.58-11.82)and 21.37 months(95％CI=16.56-26.17)respectively in the low-PNI group,the differences were statistically significant(both P＜0.05).The 6-month,one-year and 2-year PFS in the high-PNI group was 56.95％,47.25％and 33.87％respectively,which were higher than 43.95％,32.56％and 16.31％respectively in the low-PNI group.The one-year,2-year and 3-year cumulative survival rates in the high-PNI group were 80.77％,66.66％and 39.40％respectively,which were higher than 63.79％,34.31％and 27.75％respectively in the low-PNI group.Multivariate regression analysis indicated that the number of nodules,metastasis and PNI significantly affected OS,and metastasis and PNI strikingly affected PFS.High PNI was a protective factor for both PFS and OS.Conclusion For patients with advanced liver cancer treated with TACE combined with ablation therapy,PNI is an effective indicator for predicting the prognosis.

Objective To evaluate the combination score of albumin-bilirubin index(ALBI)and alkaline phosphatase(ALP)in predicting the prognosis of patients with cirrhosis complicated by portal hypertension after receiving transjugular intrahepatic portosystemic shunt(TIPS).Methods A total of 61 patients with cirrhosis complicated by portal hypertension,who received TIPS treatment at the Lishui Municipal Central Hospital of China from January 2016 to June 2024,were retrospectively collected.According to the Youden index of ALBI and ALP,the optimal cut-off values were calculated,and the patients were divided into low ALBI-low ALP group(0-point group),high ALBI-high ALP group(2-point group),and high ALBI-low ALP or low ALBI-high ALP group(one-point group).The efficacy of ALBI-ALP score in predicting the prognosis of patients was evaluated,and the survival rate and median survival time were compared between each other among the three groups.The independent risk factors affecting the survival time of patients were analyzed.Results The maximum Youden indexes of ALBI and ALP were 0.31 and 0.34 respectively,and the optimal cut-off values were-1.56 and 108.50 respectively.There were statistically significant differences in MELD score,Child-Pugh classification,and alanine aminotransferase level between each other among the three groups(all P＜0.05).The area under the ROC curve(AUC)of ALBI-ALP score was 0.77(95％ CI:0.66-0.89,P=0.000 2),which was better than 0.52 of the MELD score(95％ CI:0.37-0.67,P=0.77)as well as better than 0.57 of the Child-Pugh classification(95％ CI:0.43-0.72,P=0.34).The total mortality of patients was 49.18％.The mortality in the 0-point group was 11.11％(2/18),which was significantly lower than 59.46％(22/37)in the one-point group as well as than 100％(6/6)in the 2-point group,and the differences were statistically significant(x2=18.20,P＜0.001).In the 0-point group,as a large number of patients were still alive at the end of the study,the median survival time was unable to be calculated.The median survival time in the one-point group was 38.00 months(95％ CI:23.01-52.99 months),which in the 2-point group was only 1.00 month(95％ CI=0.00-2.60 months),the difference was statistically significant(x2=33.08,P＜0.000 1).In the 0-point group,one-point group and 2-point group,the one-year survival rates were 100％,66％ and 17％respectively,the 2-year survival rates were 100％,64％ and 17％ respectively,and the 3-year survival rates were 90％,53％ and 0％ respectively.Cox multivariate regression analysis showed that the combination score of ALBI and ALP(HR=7.11,95％ CI:2.95-17.15)was an independent risk factor for the survival time of patients with cirrhosis complicated by portal hypertension after receiving TIPS.Conclusion The combination score of ALBI and ALP can effectively predict the prognosis of patients with cirrhosis complicated by portal hypertension after receiving TIPS,and this score is an independent risk factor affecting the survival time of patients.

Lipidomics is an emerging discipline that systematically studies the various types,functions,and metabolic pathways of lipids within living organisms.This field compares changes in diseases or drug impact,identifying biomarkers and molecular mechanisms present in lipid metabolic networks across different physiological or pathological states.Through employing analytical chemistry within the realm of lipidomics,researchers analyze traditional Chinese medicine(TCM).This analysis aids in uncovering potential mechanisms for treating diverse physiopathological conditions,assessing drug efficacy,un-derstanding mechanisms of action and toxicity,and generating innovative ideas for disease prevention and treatment.This manuscript assesses recent literature,summarizing existing lipidomics technologies and their applications in TCM research.It delineates the efficacy,mechanisms,and toxicity research related to lipidomics in Chinese medicine.Additionally,it explores the utilization of lipidomics in quality control research for Chinese medicine,aiming to expand the application of lipidomics within this field.Ultimately,this initiative seeks to foster the integration of traditional medicine theory with modern science and technology,promoting an organic fusion between the two domains.

BACKGROUND: Exploring the underlying mechanism of rituximab resistance is critical to improve the outcomes of patients with diffuse large B-cell lymphoma (DLBCL). Here, we tried to identify the effects of the axon guidance factor semaphorin-3F (SEMA3F) on rituximab resistance as well as its therapeutic value in DLBCL. METHODS: The effects of SEMA3F on the treatment response to rituximab were investigated by gain- or loss-of-function experiments. The role of the Hippo pathway in SEMA3F-mediated activity was explored. A xenograft mouse model generated by SEMA3F knockdown in cells was used to evaluate rituximab sensitivity and combined therapeutic effects. The prognostic value of SEMA3F and TAZ (WW domain-containing transcription regulator protein 1) was examined in the Gene Expression Omnibus (GEO) database and human DLBCL specimens. RESULTS: We found that loss of SEMA3F was related to a poor prognosis in patients who received rituximab-based immunochemotherapy instead of chemotherapy regimen. Knockdown of SEMA3F significantly repressed the expression of CD20 and reduced the proapoptotic activity and complement-dependent cytotoxicity (CDC) activity induced by rituximab. We further demonstrated that the Hippo pathway was involved in the SEMA3F-mediated regulation of CD20. Knockdown of SEMA3F expression induced the nuclear accumulation of TAZ and inhibited CD20 transcriptional levels via direct binding of the transcription factor TEAD2 and the CD20 promoter. Moreover, in patients with DLBCL, SEMA3F expression was negatively correlated with TAZ, and patients with SEMA3F low TAZ high had a limited benefit from a rituximab-based strategy. Specifically, treatment of DLBCL cells with rituximab and a YAP/TAZ inhibitor showed promising therapeutic effects in vitro and in vivo . CONCLUSION Our study thus defined a previously unknown mechanism of SEMA3F-mediated rituximab resistance through TAZ activation in DLBCL and identified potential therapeutic targets in patients.
Humans ; Animals ; Mice ; Rituximab/therapeutic use* ; Hippo Signaling Pathway ; Lymphoma, Large B-Cell, Diffuse/pathology* ; Prognosis ; Semaphorins/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Membrane Proteins/genetics* ; Nerve Tissue Proteins/genetics*

Objective:This study aims to analyze of the quality of diagnosis and treatment data of community medical institutions on the national health information platform in a district of Beijing from the perspective of scientific research informatization, to provide experience and reference for promoting the informatization construction of primary medical units and tapping the scientific research potential of the regional data platform.Methods:Based on the data backup database of the national health information platform in the region, the data quality was analyzed and evaluated mainly in three dimensions: integrity, integration, and consistency.Results:Through the construction of the national health information platform, the district successfully achieved the effective collection of diagnosis and treatment data from community medical institutions, covering the main data such as patients′ basic information, visit information, test information, prescription information, etc. However, the data collected so far were still insufficient in terms of data integration and consistency.Conclusions:A regional medical data center is suggested to construct to break down the barriers between data systems, conduct pre-structuring of diagnosis and treatment data, improve data integration and consistency, and at the same time, carry out effective scientific research prospective design to promote the effective transformation of clinical data to scientific research data.

The first rate-limiting enzyme of the serine synthesis pathway (SSP), phosphoglycerate dehydrogenase (PHGDH), is hyperactive in multiple tumors, which leads to the activation of SSP and promotes tumorigenesis. However, only a few inhibitors of PHGDH have been discovered to date, especially the covalent inhibitors of PHGDH. Here, we identified withangulatin A (WA), a natural small molecule, as a novel covalent inhibitor of PHGDH. Affinity-based protein profiling identified that WA could directly bind to PHGDH and inactivate the enzyme activity of PHGDH. Biolayer interferometry and LC-MS/MS analysis further demonstrated the selective covalent binding of WA to the cysteine 295 residue (Cys295) of PHGDH. With the covalent modification of Cys295, WA blocked the substrate-binding domain (SBD) of PHGDH and exerted an allosteric effect to induce PHGDH inactivation. Further studies revealed that with the inhibition of PHGDH mediated by WA, the glutathione synthesis was decreased and intracellular levels of reactive oxygen species (ROS) were elevated, leading to the inhibition of tumor proliferation. This study indicates WA as a novel PHGDH covalent inhibitor, which identifies Cys295 as a novel allosteric regulatory site of PHGDH and holds great potential in developing anti-tumor agents for targeting PHGDH.