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.

Hypercholesterolemia is a significant risk factor for the development of atherosclerosis. 2',3',5'-Tri-O-acetyl-N ⁶-(3-hydroxyphenyl) adenosine (IMM-H007), a novel AMPK agonist, has shown protective effects in metabolic diseases. However, its impact on cholesterol and triglyceride metabolism in hypercholesterolemia remains unclear. In this study, we aimed to elucidate the effects and specific mechanisms by which IMM-H007 regulates cholesterol and triglyceride metabolism. To achieve this goal, we used Apoe ^-/- and Ldlr ^-/- mice to establish a hypercholesterolemia/atherosclerosis model. Additionally, hepatocyte-specific Ampka1/2 knockout mice were subjected to a 5-week high-cholesterol diet to establish hypercholesterolemia, while atherosclerosis was induced via AAV-PCSK9 injection combined with a 16-week high-cholesterol diet. Our results demonstrated that IMM-H007 improved cholesterol and triglyceride metabolism in mice with hypercholesterolemia. Mechanistically, IMM-H007 modulated the AMPKα1/2-LDLR signaling pathway, increasing cholesterol uptake in the liver. Furthermore, IMM-H007 activated the AMPKα1-FXR pathway, promoting the conversion of hepatic cholesterol to bile acids. Additionally, IMM-H007 prevented hepatic steatosis by activating the AMPKα1/2-ATGL pathway. In conclusion, our study suggests that IMM-H007 is a promising therapeutic agent for improving hypercholesterolemia and atherosclerosis through the activation of AMPKα.

Purpose To investigate the diagnostic value of immunohistochemical(IHC)and molecular markers in diffuse pleural mesothelioma(DPM).Methods A total of 114 cases of DPM were retrospectively analyzed for clinical and imaging manifestations,histologic subtype and tumor grade.The positivity rates of Calretinin,WT-1,CK5/6,MC,D2-40,UPK3B,and GATA3 were assessed by IHC,and the loss rates of BAP-1 and MTAP were determined.The concordance between MTAP IHC and p16 gene fluorescence in situ hybridization(FISH)status was calculated,a-long with the sensitivity and specificity of MTAP IHC relative to p16 FISH.Results Among the 114 DPM patients,66(57.9％)were male and 48(42.1％)were female,with a mean age of 58.1 years(range 16-85 years).Imaging predominantly demonstrated pleural effusion and multiple pleural nodules(55.3％,63/114).Histologically,epitheli-oid,sarcomatoid and biphasic subtypes accounted for 88(77.2％),17(14.9％)and 9(7.9％)cases,respectively.Within the epithelioid group,low and high-grade tumors numbered 69(78.4％)and 19(21.6％),respectively.In epithelioid DPM,the highest IHC positivity rates were observed for Calretinin(92.4％,81/88),D2-40(90.0％,79/88)and WT-1(90.0％,79/88).In sarcomatoid DPM,D2-40(76.5％,13/17),WT-1(64.7％,11/17),and Cal-retinin(29.4％,5/17)showed the greatest positivity.UPK3B was positive in epithelioid(59.1％,39/66)and bi-phasic cases(66.7％,4/6),but was absent in sarcomatoid tumors(0/12).Among all DPM cases,loss rates were 47.3％(53/112)for BAP-1 and 19.2％(20/104)for MTAP by IHC,p16 gene deletion by FISH was 31.5％(34/108);Concordance between MTAP IHC and p16 FISH was 81.0％(81/100);MTAP IHC had a specificity of 95.5％(64/67)and sensitivity of 51.5％(17/33)relative to p16 FISH.Additionally,GATA3 was highly expressed in sarco-matoid DPM(76.5％,13/17).UPK3B positivity differed significantly between thoracoscopic DPM(59.2％,32/54)and percutaneous biopsy samples(36.7％,11/30)in epithelioid DPM(P＜0.05).WT-1 positivity was higher in thoracoscopic than percutaneous samples of sarcomatoid DPM(90.0％ vs 28.6％,P=0.009).Conclusion Calreti-nin,D2-40,and WT-1 are highly sensitive mesothelial markers and should serve as first-line IHC stains in DPM diag-nosis.UPK3B is diagnostically valuable in epithelioid DPM,GATA3 may complement the diagnosis of sarcomatoid DPM,and MTAP IHC can be used as a surrogate or adjunct to p16 FISH.

Objective:To investigate the clinical, pathological, and molecular biological characteristics of gastric hepatoid adenocarcinoma (HAS) in order to provide reference for clinical treatment.Methods:Thirty-two patients diagnosed with hepatoid adenocarcinoma after radical gastrectomy for gastric cancer at Shanxi Cancer Hospital were included from January 2019 to December 2021. Immunohistochemistry, in situ hybridization, and next-generation sequencing (NGS) methods were used to analyze immune markers and molecular characteristics in the pathological tissues from 32 patients with HAS. Cox regression analysis and Kaplan-Meier method were used to analyze the prognostic factors of overall survival and disease-free survival.Results:Among the 32 patients with HAS, 26 were male, 6 were female; aged 28-77 years, with an median age 62.0 (53.8, 67.2) years. Fifteen cases of HAS were located in the cardia, 10 cases in the antrum, and 7 cases in the body of the stomach. The maximum diameter of the mass was 3-10 cm, and mainly ulcerative in gross. The immunohistochemistry and in situ hybridization results showed that the positive rates of AFP, SALLA4, and Glypican-3 were 68.8% (22/32), 68.8% (22/32), 78.1% (25/32), respectively; Seven patients had microsatellite status of dMMR. Two cases of HER2 gene amplification and 2 cases of EB virus positivity. The NGS results showed that HAS was often accompanied by multiple gene mutations, with 23 cases having ≥ 2 gene mutations and 6 cases having ≥10 gene mutations. The TP53 gene had the highest mutation frequency; 4 cases had genetic structural variations; 28 cases had copy number variation. In addition, there were 7 cases of MSI-H and 9 cases of TMB-H. Follow-up results showed that 12 cases died, 9 cases developed metastasis, and the shortest survival time was 5 months.Conclusions:Gastric HAS is a type of tumor with high invasiveness and poor prognosis. The combined detection of AFP, SALLA4 and Glypican-3 can improve the diagnostic rate of tumors. dMMR/MSI-H and TMB-H patients in HAS are significantly higher than those in ordinary gastric cancer, and the high frequency mutation genes in HAS are often accompanied by multiple potential therapeutic targets. Immunotherapy combined with chemotherapy and targeted therapy are expected to become the treatment direction of HAS.

Objective:To investigate the clinical pathological features, immunophenotypes, diagnosis, and differential diagnosis of non-small cell lung carcinoma (NSCLC) with trophoblastic differentiation in males, and to improve the understanding of this rare disease.Methods:The clinical and pathological features of 16 NSCLC with trophoblastic differentiation in males diagnosed in Shanghai Pulmonary Hospital from January 2017 to December 2023 were retrospectively analyzed. Relevant literature was reviewed.Results:All 16 patients were male, with an onset median age of 66.5 (56.8, 68.8) years. They had no known personal history of cancer. Among the 8 resected NSCLC with trophoblastic differentiation, 3 showed concurrent lung adenocarcinoma, and 1 showed concurrent lung squamous cell carcinoma. Among the 10 patients who underwent serum β human chorionic gonadotropin (β-HCG) testing after the surgery or biopsy, 7 had significantly increased β-HCG. On gross examination, the tumors were hemorrhagic and necrotic, resembling a hematoma, with a medium texture, clear boundaries and no capsules. At low magnification, tumor cells were arranged in a nested or solid pattern. Those cells often showed massive bleeding, necrosis, and vascular infiltration. They were composed of two types of cells, namely cytotrophoblast and syncytiotrophoblast cells. At high magnification, the tumor cells showed large nuclei and hyperchromatia. They also had rich purple blue to bichromatic cytoplasm, eosinophilic nucleoli, and sometimes bizarre nuclei. The syncytiotrophoblast cells expressed β-HCG, CKpan, GATA3, CD10, and SALL4. Fourteen patients were followed up for 1-37 months. Two of them died, while three showed distant metastasis.Conclusions:NSCLC with trophoblastic differentiation in males is a rare and highly malignant tumor, poorly understood with difficulty in diagnosis. It requires comprehensive histological analysis in combination with clinical and imaging studies. Properly diagnosing this disease relies on recognition of its histopathological characteristics, including large areas of bleeding and necrosis, large and peculiar syncytial trophoblast cells, and varying degrees of β-HCG expression. It seems that β-HCG expression is very valuable for diagnosing this rare tumor.

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: 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.

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.

Objective: To investigate the epidemiological characteristics of pertussis in Harbin City from 2015 to 2024, so as to provide the basis for formulating pertussis prevention and control measures. Methods: The incidence data of pertussis in Harbin City from 2015 to 2024 were collected through the Infectious Disease Reporting Information System of Chinese Disease Prevention and Control Information System, and the vaccination data were collected through the Immunization Program Information System of Heilongjiang Province. Descriptive epidemiological methods were used to analyze the temporal, regional and population distribution characteristics of pertussis incidence as well as the immunization history of pertussis cases. Results: A total of 417 cases of pertussis were reported in Harbin City from 2015 to 2024, with an average annual reported incidence of 0.41/100 000. The reported incidence increased from 0.18/100 000 in 2015 to 0.64/100 000 in 2024, showing an overall upward trend (P<0.05). The peak incidence period was from August to November, with 253 cases, accounting for 60.67%. The average annual reported incidences of pertussis in Shuangcheng District, Nangang District and Daoli District were relatively high, at 1.09/100 000, 0.93/100 000 and 0.52/100 000, respectively. There were 223 male cases and 194 female cases, with a male-to-female ratio of 1.15∶1. The average annual reported incidence of pertussis was 0.45/100 000 in males and 0.39/100 000 in females, with no statistically significant difference (P>0.05). Cases were predominantly distributed among children under 6 months and those aged 6 to under 10 years, with 176 and 144 cases, accounting for 42.21% and 34.53% respectively. The majority of cases were scattered children, with 266 cases (63.79%). There were 175 cases (41.97%) without diphtheria-tetanus-pertussis (DTP) vaccine and 172 cases (41.25%) who had completed the full course of immunization. Conclusions The incidence of pertussis in Harbin City showed an upward trend from 2015 to 2024. Autumn was identified as the peak season for disease onset. Shuangcheng District and Nangang District were the high-incidence areas. Children under 6 months, those aged 6 to under 10 years, scattered children, and those who had not received the DTP vaccine were the high-risk groups. It is recommended to improve pertussis surveillance strategies and strengthen childhood immunization programs.

Aiming at the problem that the amount of Oxygen remaining and available time can not be accurately predicted while an astronaut conducting extravehicular activities(EVAs)in EVA spacesuit.Research the oxygen consumption process of EVA spacesuit.The model and algorithm of oxygen consumption are established by the gas state equation including compressibility and temperature coefficient,combined with human metabolism and micro leakage characteristics of spacesuit.Experimental data show that the orecast model and algorithm hasing high accuracy and practicability.