Purpose To summarize the clinicopathological features of pheochromocytoma and paraganglioma(PPGL)and discuss the potential correlation between SDHB immunophenotype and prognosis in PPGLs.Methods A retrospective analysis was conducted on 30 samples of PPGL along with their corresponding clinicopathological informa-tion,SDHB immunophenotype characteristics,and the risk of recurrence and metastasis.Results The study included 20 extra-adrenal paragangliomas and 10 pheochromocytoma cases.The male-to-female ratio was 13∶17,with a mean age of 56(range from 21 to 79).Four cases recurred,one case resulted in death and five cases failed to follow-up.All recurrent or fatal cases were paraganglioma patients.Among the 30 cases,3 had multiple nodular lesions,and the re-maining cases were single nodule.The neck was the most frequent site for paraganglioma(6/20),followed by retroper-itoneum(5/20).Histologically,the tumors displayed a variable"zellballen"architecture with a highly vascularized stroma.The chief cells had abundant pale eosinophilic cytoplasm and slightly to moderately atypical nuclei,and pe-ripherally located sustentacular cells.Positive immunoreactivity with markers of neuroendocrine cells,including Syn,CgA,and GATA3,was found in tumor chief cells,which were nonreactive for CK.The sustentacular cells exhibited positive immunoreactivity for the S-100 protein.SDHB deficiency was demonstrated in 12 of 30 cases,with only one case being pheochromocytoma.The recurrence rate in SDHB-deficient group was higher than that in the positive group(33.3％vs 6.7％).Only one case of paraganglioma developed distant metastasis and death.Conclusion SDHB de-ficiency was predominantly observed in paragangliomas and serverd as an indipentent factor for metastatic risk in PPGLs.It was closely associated with younger age at onset,invasiveness,extra-adrenal tumorgenesis,and a high rate of tumor recurrence.

Colorectal cancer stands as a leading cause of cancer-related morbidity and mortality globally,with liver metastases being a significant determinant of patient prognosis.Conventional diagnostic methods,includ-ing imaging studies and biomarker testing,frequently exhibit inadequate sensitivity and specificity,underscoring the necessity for more advanced technologies.Recent advancements in genomics,transcriptomics,proteomics,me-tabolomics,and epigenomics have revolutionized our understanding of the biological mechanisms driving colorectal cancer.These methodologies enable comprehensive analyses of genetic mutations,gene expression profiles,protein modifications,and metabolic reprogramming,all of which are pivotal to the metastatic process.This article high-lights the advanced capabilities of artificial intelligence(AI)technologies in processing complex multi-omics data,thereby enhancing diagnostic accuracy and supporting personalized treatment strategies.It also addresses the challenges AI encounters in multi-omics analyses,such as ensuring data quality,improving model interpretability,and facilitating clinical translation.Additionally,it explores the potential integration of emerging technologies like single-cell sequencing and spatial omics into large-scale,multicenter studies to further enhance the clinical utility of these tools.

Objective To understand the changing profiles of antimicrobial susceptibility of the bacterial strains isolated from patients at Liuzhou Workers'Hospital in Guangxi from 2020 to 2022.Methods The bacteria were isolated,identified,and underwent antimicrobial susceptibility testing using VITEK 2 Compact,disk diffusion method,or E-test.The results were interpreted according to the breakpoints recommended by CLSI M100 32nd Edition in 2022.The data were analyzed using WHONET 5.6 software.Results A total of 26 254 nonduplicate strains were collected from 2020 to 2022,including Gram-positive bacteria(27.9％)and gram-negative bacteria(72.1％).The prevalence of methicillin-resistant strains was 20.0％in SS.aureus(MRSA),and 72.2％in coagulase-negative Staphylococcus(MRCNS).Methicillin-resistant staphylococcal strains were more resistant to most antimicrobial agents than methicillin-susceptible strains(MSSA and MSCNS).None of the staphylococcal strains was resistant to vancomycin,linezolid or tigecycline.Enterococcus faecium strains showed higher resistance rates to most antimicrobial agents than Enterococcus faecalis.None of enterococcal strains was resistant to vancomycin.A few enterococcal strains were resistant to linezolid.Overall,691 strains of the non-meningitis Streptococcus pneumoniae were isolated from children and 123 strains were isolated from adults.The prevalence of penicillin-resistant SS.pneumoniae(PRSP)was 0.4％in the strains from children and 1.6％in the strains from adults.None of S.pneumoniae strains was intermediate to penicillin.The prevalence of carbapenem-resistant Klebsiella pneumoniae(CRKpn)was 1.2％,1.2％,and 13.8％in 2020,2021,and 2022,respectively.The prevalence of carbapenem-resistant P.aeruginosa(CRPae)and carbapenem-resistant Acinetobacter baumannii(CRAba)was 10.7％and 68.4％in 2020,17.5％and 75.2％in 2021,14.3％and 77.3％in 2022,respectively.About 84.6％of the 1 269 strains of Haemophilus influenzae were isolated from children and 15.4％isolated from adults.The prevalence of beta-lactamase-producing strains was 39.4％in the isolates from children and 46.8％in the isolates from adults.The β-lactamase-producing H.influenzae was resistant to ampicillin.Furthermore,some β-lactamase-nonproducing ampicillin-resistant(BLNAR)H.influenzae strains(27.0％)were also identified.Conclusions Antimicrobial resistance is still serious in this hospital,especially high prevalence of carbapenem-resistant organisms(CRO).Hospital infection prevention and control measures,antibiotic stewardship,and proactive CRO screening should be strengthened.More clinical specimens should be collected for suspected infections.Antimicrobial treatment should be prescribed empirically in time and adjusted when the results of antimicrobial susceptibility testing are available.

Objective:To investigate the effects of sampling methods on pathological assessment of resected non-small cell lung cancer (NSCLC) specimen with tumor maximum diameter >3 cm after neoadjuvant therapy.Methods:NSCLC patients with a large tumor (diameter >3 cm) that were resected after neoadjuvant therapy from June 2020 to July 2023 were retrospectively collected in the Department of Pathology, Shanghai Pulmonary Hospital, Shanghai, China. Sampling methods of the tumor bed were performed in accordance with the international and Chinese experts recommendations for resection specimens following neoadjuvant therapy (recommended sampling method, RSM), and all remaining tumor bed lesions were completely sampled after recommended sampling (complete sampling method, CSM). The difference of pathological response assessment of residual viable tumor (RVT) between RSM and CSM was examined.Results:A total of 90 cases were identified and analyzed, including 39 cases of squamous cell carcinoma and 51 cases of adenocarcinoma, treated with neoadjuvant therapy including chemotherapy in 22 cases (24.4%), targeted therapy in 14 cases (15.6%), and chemoimmunotherapy in 54 cases (60.0%). There were 62 males and 28 females with an average age of (62.7±17.9) years. The average tumor maximum diameter was 4.3 cm (range, 3.1-8.0 cm). The average number of sampled blocks was 8 blocks (range, 5 to 16) and 15 blocks (range, 8 to 36) per case by RSM and CSM, respectively. According to the definition of major pathological response (MPR) in which RVT is ≤10%, the numbers of patients with MPR were 34 cases by RSM and 30 cases by CSM, respectively. Four cases showed inconsistent RVT between the two methods, including one case of squamous cell carcinoma and three cases of adenocarcinoma. The RVT of the four inconsistent cases was 7%, 7%, 5% and 9% (MPR by RSM), and 15%, 15%, 15% and 20% (non-MPR by CSM), respectively. The kappa values of MPR consistency evaluated by the two sampling methods were 0.893 for all cases, 0.906 for squamous cell carcinoma cases and 0.751 for adenocarcinoma cases. According to MPR cut-off of 65% for invasive primary adenocarcinoma, 24 cases and 20 cases achieved MPR by RSM and CSM, respectively. Of the four inconsistent cases, the RVT by RSM was 60% in three cases and 65% in one case (MPR), whereas the RVT by CSM was 70% in three cases and 75% in one case (non-MPR). The kappa value of the two sampling methods was 0.741.Conclusions:There is high consistency between RSM and CSM in the pathological assessment of post-treatment responses in resected NSCLC specimens with tumor maximum diameter larger than 3 cm. When the percentage of RVT cells is close to MPR, re-evaluation of the specimen is required and CSM may be necessary to accurately evaluate the degree of pathological remission, assist in clinical postoperative treatment, and predict patient prognosis.

Objective To explore the impact of irregular shape of head CT hematomas on postoperative re-bleeding and prognosis of patients with spontaneous intracerebral hemorrhage(ICH)who undergo craniotomy for hematoma evacuation.Methods We retrospectively enrolled consecutive patients with ICH who underwent craniotomy for hematoma evacuation in the Department of Neurosurgery of the Second People's Hospital of Guiyang Affiliated to Guizhou Medical University from January 2019 to June 2024.Baseline and clinical data were collected form the patients,including age,gender,smoking history,drinking history,hypertension,diabetes,history of anticoagulant use,admission systolic and diastolic blood pressure,admission National Institutes of Health stroke scale(NIHSS)score,Glasgow coma scale(GCS)score,time from onset to the first head CT,neutrophil-to-lymphocyte ratio(NLR),and platelet-to-lymphocyte ratio(PLR).Admission head CT scans were used to assess hematoma shape(regular or irregular),hematoma location(basal ganglia,lobar,multifocal),hematoma volume,perihematomal edema volume,the presence of midline shift,and intraventricular extension.Volume of the hematoma was assessed 2 days after surgery.Postoperative re-bleeding is defined as an increase in the volume of the hematoma by 12.5 ml compared to the previous postoperative CT scan within 2 weeks after surgery,or the reappearance of high-density areas in the focal area of the head CT scan during follow-up after complete hematoma clearance.Conduct patients follow-ups via telephone at 6 months postoperatively to assess their modified Rankin scale(mRS)scores.The sliding dichotomy method was applied to define prognosis based on the patients' baseline characteristics and disease severity.The prognostic score was calculated using formula:10 × admission GCS score-age-0.64 × admission hematoma volume.A prognostic score＞27.672 was considered potentially favorable,while a score ≤ 27.672 was considered potentially unfavorable.For patients with a potentially favorable prognosis,an mRS score of 0-2 was defined as a good outcome,and a score of 3-6 as a poor outcome.For those with a potentially unfavorable prognosis,an mRS score of 0-3 was defined as a good outcome,and a score of 4-6 as a poor outcome.In the comparison of baseline and clinical data between patients with regular and irregular hematoma shapes,factors with P＜0.05 were included in propensity score matching(PSM)to adjust for confounding variables.A 1∶1 matching was performed using the nearest neighbor method with a caliper value set to 0.25.Variables with statistically significant differences between groups after PSM matching were included in the multivariate Logistic regression analysis to identify influencing factors for postoperative re-bleeding and poor prognosis in ICH patients undergoing craniotomy hematoma evacuation.The predictive value of irregular hematoma shape for postoperative rebleeding and poor prognosis in ICH patients was analyzed using receiver operating characteristic(ROC)curve analysis.Results(1)A total of 440 ICH patients were enrolled,including 342 males and 98 females,aged from 20 to 84 years with a mean age of(56±12)years.Statistically significant differences were observed in baseline and clinical data between patients with regular and irregular hematoma shapes before PSM,including age,admission GCS score,NIHSS score,NLR,proportion of patients with hematoma rupture into ventricles,preoperative hematoma volume,proportion of patients with midline shift,preoperative volume of hematoma surrounding edema,proportion of patients with hematoma located in multiple sites,and postoperative 2-day hematoma volume(all P＜0.05).After propensity score matching of these factors,298 ICH patients were included in the statistical analysis,comprising 228 males and 70 females,with an age range of 20 to 84 years and a mean age of(57±12)years.Following PSM,no statistically significant differences were observed in the baseline and clinical characteristics between patients with irregular and regular hematoma shapes(all P＞0.05).(2)After propensity score matching,28 patients experienced postoperative re-bleeding while 270 did not.Significant differences were observed between the two groups in the following factors:proportion of patients with a history of anticoagulant use,admission PLR,NLR,irregular hematoma shape,and hematoma volume at 2 days after operation(all P＜0.05).No statistically significant differences were found in the remaining baseline and clinical characteristics(all P＞0.05).Using postoperative re-bleeding as the dependent variable and incorporating factors with P＜0.05 from the univariate analysis as independent variables,multivariate Logistic regression analysis identified irregular hematoma shape(OR,2.821,95％CI 1.142-6.968,P=0.025)and larger hematoma volume at 2 days post-operation(OR,1.062,95％CI 1.026-1.099,P＜0.01)as independent risk factors for re-bleeding following intracranial hematoma evacuation in ICH patients.ROC curve analysis demonstrated that irregular hematoma shape predicted postoperative re-bleeding with an area under the curve(AUC)of 0.62,showing a sensitivity of 71.4％and a specificity of 52.2％.(3)After propensity score matching,174 patients had poor prognosis while 124 had good prognosis.Significant intergroup differences were observed in age,admission GCS score,NIHSS score,irregular hematoma shape,proportion of patients with hematomas located in the basal ganglia and cerebral lobes,and hematoma volume at 2 days post-operation(all P＜0.05).No statistically significant differences were found in the remaining baseline and clinical characteristics(all P＞0.05).Using poor prognosis as the dependent variable and incorporating factors with P＜0.05 from univariate analysis as independent variables,multivariate Logistic regression analysis revealed that advanced age(OR,1.039,95％CI 1.015-1.064,P=0.002),high admission NIHSS score(OR,1.068,95％CI 1.025-1.113,P=0.002),irregular hematoma shape(OR,2.675,95％CI 1.582-4.524,P＜0.01),and larger hematoma volume at 2 days post-operation(OR,1.033,95％CI 1.002-1.064,P=0.038)were independent risk factors for poor prognosis.Conversely,lobar hematoma location(OR,0.192,95％CI 0.073-0.504,P＜0.01)was identified as a protective factor.ROC curve analysis showed that irregular hematoma shape predicted poor prognosis after intracranial hematoma evacuation with an AUC of 0.61,demonstrating a sensitivity of 59.2％and specificity of 62.9％.Conclusion Irregular hematoma shape on head CT is an independent risk factor for both postoperative re-bleeding and poor prognosis in ICH patients undergoing craniotomy for hematoma evacuation.

Objective To investigate the distribution and evolutionary patterns of traditional Chinese medicine(TCM)syndromes and syndrome elements during the malignant transformation from chronic pancreatitis(CP)to pancreatic intraepithelial neoplasia(Pan IN)and pancreatic ductal adenocarcinoma(PDAC).Methods A retrospective analysis was conducted on 710 patients(330 of CP,104 of Pan IN,276 of PDAC)diagnosed pathologically or clinically at Shanxi Institute of Traditional Chinese Medicine from January 2021 to June 2024.Data including demographics,laboratory results,and TCM diagnostic information were recorded using EpiData 3.1.Syndrome and syndrome-element patterns were determined via factor analysis and K-means clustering using SPSS 27.0.Results The study identifies seven TCM syndrome types in CP,Pan IN,and PDAC.Among CP patients,the syndrome distribution was primarily liver-gallbladder damp-heat syndrome(22.42％)and gastrointestinal excess-heat syndrome(20.91％),with excess syndromes accounting for a higher proportion(43.33％);the syndrome elements were mainly heat(51.52％)and dampness(35.15％),with the disease location in the pancreas,related to the liver,spleen,and stomach.In Pan IN patients,the syndrome distribution was mainly spleen deficiency with dampness obstruction(23.08％)and liver-gallbladder damp-heat syndrome(17.31％),with mixed deficiency-excess syndrome accounting for a higher proportion(30.00％);the syndrome elements were mainly heat(41.35％),dampness(40.38％),and qi deficiency(37.50％),with the disease location in the pancreas,related to the spleen and liver.In PDAC patients,the syndrome distribution was mainly spleen deficiency with dampness obstruction(29.71％)and qi-blood deficiency syndrome(20.29％),with deficiency syndromes accounting for a higher proportion(49.82％);the syndrome elements were mainly qi deficiency(50.00％)and dampness(36.23％),with the disease location in the pancreas,related to the spleen,kidney,and liver.Chi-square tests revealed significant differences in syndrome types(TCM syndromes:x2=100.419,P＜0.001;deficiency-excess syndromes:x2=73.722,P＜0.001),syndrome elements(x2=117.384,P＜0.001),and disease locations(x2=127.191,P＜0.001)across different stages of CP malignant transformation.During CP malignant progression,the proportion of excess syndromes gradually decreased(43.33％→12.32％),while deficiency syndromes increased(26.67％→49.82％).Excess syndrome elements(fire,heat,qi stagnation,blood stasis)decreased(53.48％→25.36％),whereas deficiency syndrome elements(qi deficiency,yin deficiency,yang deficiency,blood deficiency)increased(25.15％→49.64％).The disease location shifted from primarily the liver,spleen,and stomach in the inflammatory stage to the spleen and kidney in the cancerous stage.Conclusion The malignant transformation of CP basically involves the pancreas,is correlated early with liver and spleen-stomach and later with kidney,and exhibits a progression from excess to deficiency in the pattern of"deficiency interweaved with excess syndrome,transition from excess to deficiency,and progressive spleen deficiency".

Objective:To investigate the effects of sampling methods on pathological assessment of resected non-small cell lung cancer (NSCLC) specimen with tumor maximum diameter >3 cm after neoadjuvant therapy.Methods:NSCLC patients with a large tumor (diameter >3 cm) that were resected after neoadjuvant therapy from June 2020 to July 2023 were retrospectively collected in the Department of Pathology, Shanghai Pulmonary Hospital, Shanghai, China. Sampling methods of the tumor bed were performed in accordance with the international and Chinese experts recommendations for resection specimens following neoadjuvant therapy (recommended sampling method, RSM), and all remaining tumor bed lesions were completely sampled after recommended sampling (complete sampling method, CSM). The difference of pathological response assessment of residual viable tumor (RVT) between RSM and CSM was examined.Results:A total of 90 cases were identified and analyzed, including 39 cases of squamous cell carcinoma and 51 cases of adenocarcinoma, treated with neoadjuvant therapy including chemotherapy in 22 cases (24.4%), targeted therapy in 14 cases (15.6%), and chemoimmunotherapy in 54 cases (60.0%). There were 62 males and 28 females with an average age of (62.7±17.9) years. The average tumor maximum diameter was 4.3 cm (range, 3.1-8.0 cm). The average number of sampled blocks was 8 blocks (range, 5 to 16) and 15 blocks (range, 8 to 36) per case by RSM and CSM, respectively. According to the definition of major pathological response (MPR) in which RVT is ≤10%, the numbers of patients with MPR were 34 cases by RSM and 30 cases by CSM, respectively. Four cases showed inconsistent RVT between the two methods, including one case of squamous cell carcinoma and three cases of adenocarcinoma. The RVT of the four inconsistent cases was 7%, 7%, 5% and 9% (MPR by RSM), and 15%, 15%, 15% and 20% (non-MPR by CSM), respectively. The kappa values of MPR consistency evaluated by the two sampling methods were 0.893 for all cases, 0.906 for squamous cell carcinoma cases and 0.751 for adenocarcinoma cases. According to MPR cut-off of 65% for invasive primary adenocarcinoma, 24 cases and 20 cases achieved MPR by RSM and CSM, respectively. Of the four inconsistent cases, the RVT by RSM was 60% in three cases and 65% in one case (MPR), whereas the RVT by CSM was 70% in three cases and 75% in one case (non-MPR). The kappa value of the two sampling methods was 0.741.Conclusions:There is high consistency between RSM and CSM in the pathological assessment of post-treatment responses in resected NSCLC specimens with tumor maximum diameter larger than 3 cm. When the percentage of RVT cells is close to MPR, re-evaluation of the specimen is required and CSM may be necessary to accurately evaluate the degree of pathological remission, assist in clinical postoperative treatment, and predict patient prognosis.

Objective To investigate the anatomical structure and surface location of the Lieque(LU7)acupoint.Methods Firstly,the anatomical localization descriptions of the Lieque(LU7)acupoint from classical medical literature were reviewed and summarized.A total of 21 participants were recruited from Shandong Provincial Hospital Affiliated to Shandong First Medical University from January to March 2025.A Cartesian coordinate system was established over the Lieque(LU7)region on the right forearm.Following standardized manual pressure stimulation,the coordinates of the participant′s reported acupoint sensations were recorded.Based on surface pressure mapping result,10 participants were arbitrarily selected for acupuncture intervention.Upon elicitation of acupoint sensation,the ultrasound imaging was used for real-time visualization of anatomical spatial relationships between the needle tip and distal radial osseous landmarks.Five red latex-perfused adult upper limb specimens were selected for microdissection of the Lieque(LU7)regions pre-localized via ultrasonography,achieving definitive structural characterization of its anatomical strata.Another 10 participants were arbitrarily selected to find the physical structure of the Lieque(LU7)acupoint using ultrasound,and the similarities and differences of acupoint sensation responses were verified using acupuncture needle insertions into both the demarcated zone and peripheral tissues.Results The descriptions of the localization of the Lieque(LU7)acupoint in ancient books can be summarized as"one and a half cun above the wrist side"longitudinally,and"at the intersection head,between two tendons and two bones in the hollow"transversely.During surface pressure application,the sites of the participant′s elicited acupoint sensation were anatomically concentrated in the proximal depression adjacent to the radiopalmar ridge,specifically at the transitional interface between the extensor pollicis brevis tendon and scaphoid bone.During acupuncture-induced acupoint sensation,ultrasound imaging demonstrated that the location of the needle tip was located within the proximal depression adjacent to the radiopalmar ridge,accompanied by arterial hemodynamic perfusion signals into adjacent osseous interfaces.Microdissection findings revealed perforating branches of the radial artery traversing the cortical bone interface within the Lieque(LU7)acupoint region.Acupuncture stimulation at the proximal depression adjacent to the radiopalmar ridge elicited consistent acupoint sensations in all 10 participants,and the acupoint sensations differed from those of other surrounding tissues.Conclusion The anatomical structure of Lieque(LU7)acupoint is located within the proximal depression adjacent to the radiopalmar ridge,characterized by the presence of"hilus of bone"structure.

Objective To understand the changing profiles of antimicrobial susceptibility of the bacterial strains isolated from patients at Liuzhou Workers'Hospital in Guangxi from 2020 to 2022.Methods The bacteria were isolated,identified,and underwent antimicrobial susceptibility testing using VITEK 2 Compact,disk diffusion method,or E-test.The results were interpreted according to the breakpoints recommended by CLSI M100 32nd Edition in 2022.The data were analyzed using WHONET 5.6 software.Results A total of 26 254 nonduplicate strains were collected from 2020 to 2022,including Gram-positive bacteria(27.9％)and gram-negative bacteria(72.1％).The prevalence of methicillin-resistant strains was 20.0％in SS.aureus(MRSA),and 72.2％in coagulase-negative Staphylococcus(MRCNS).Methicillin-resistant staphylococcal strains were more resistant to most antimicrobial agents than methicillin-susceptible strains(MSSA and MSCNS).None of the staphylococcal strains was resistant to vancomycin,linezolid or tigecycline.Enterococcus faecium strains showed higher resistance rates to most antimicrobial agents than Enterococcus faecalis.None of enterococcal strains was resistant to vancomycin.A few enterococcal strains were resistant to linezolid.Overall,691 strains of the non-meningitis Streptococcus pneumoniae were isolated from children and 123 strains were isolated from adults.The prevalence of penicillin-resistant SS.pneumoniae(PRSP)was 0.4％in the strains from children and 1.6％in the strains from adults.None of S.pneumoniae strains was intermediate to penicillin.The prevalence of carbapenem-resistant Klebsiella pneumoniae(CRKpn)was 1.2％,1.2％,and 13.8％in 2020,2021,and 2022,respectively.The prevalence of carbapenem-resistant P.aeruginosa(CRPae)and carbapenem-resistant Acinetobacter baumannii(CRAba)was 10.7％and 68.4％in 2020,17.5％and 75.2％in 2021,14.3％and 77.3％in 2022,respectively.About 84.6％of the 1 269 strains of Haemophilus influenzae were isolated from children and 15.4％isolated from adults.The prevalence of beta-lactamase-producing strains was 39.4％in the isolates from children and 46.8％in the isolates from adults.The β-lactamase-producing H.influenzae was resistant to ampicillin.Furthermore,some β-lactamase-nonproducing ampicillin-resistant(BLNAR)H.influenzae strains(27.0％)were also identified.Conclusions Antimicrobial resistance is still serious in this hospital,especially high prevalence of carbapenem-resistant organisms(CRO).Hospital infection prevention and control measures,antibiotic stewardship,and proactive CRO screening should be strengthened.More clinical specimens should be collected for suspected infections.Antimicrobial treatment should be prescribed empirically in time and adjusted when the results of antimicrobial susceptibility testing are available.

Objective: The precise mechanisms driving intervertebral disc degeneration (IVDD) development remain unclear, but evidence suggests a significant involvement of gut microbiota (GM) and blood metabolites. We aimed to investigate the causal relationships between GM, IVDD, and blood metabolites using Mendelian randomization (MR) analysis. Methods: We utilized the summary statistics of GM from the MiBioGen consortium, 1400 blood metabolites from the genome-wide association studies (GWAS) Catalog, and IVDD data from the FinnGen repository, which are sourced from the largest GWAS conducted to date. Employing bidirectional MR analyses, we investigated the causal relationships between GM and IVDD. Additionally, we conducted 2 mediation analyses, 2-step MR and multivariable MR (MVMR), to identify potential mediating metabolites. Results: Five bacterial genera were causally associated with IVDD, while IVDD did not show a significant causal effect on GM. In the 2-step MR analysis, Eubacteriumfissicatenagroup, RuminococcaceaeUCG003, Lachnoclostridium, and Marvinbryantia genera, along with metabolites X-24949, Pimeloylcarnitine/3-methyladipoylcarnitine (C7-DC), X-24456, histidine, 2-methylserine, Phosphocholine, and N-delta-acetylornithine, were all significantly associated with IVDD (all p < 0.05). MVMR analysis revealed that the associations between Eubacteriumfissicatenagroup genus and IVDD were mediated by X-24949 (8.1%, p = 0.024); Lachnoclostridium genus and IVDD were mediated by histidine (18.1%, p = 0.013); and RuminococcaceaeUCG003 genus and IVDD were mediated by C7-DC (-7.5%, p = 0.041). Conclusion The present MR study offers evidence supporting the causal relationships between several specific GM taxa and IVDD, as well as identifying potential mediating metabolites.