Objective:To investigate the mechanism of ursolic acid regulating HMGB1/TLR4 pathway in reducing intestinal barrier injury in a rat model of ulcerative colitis(UC).Methods:Rats were randomly divided into control group,model group,glycyr-rhizic acid(HMGB1 inhibitor)group,ursolic acid group and glycyrrhizic acid+ursolic acid group,with 12 rats in each group.UC rat model was induced by tritrobenzene sulfonate enema.After drug administration,body weight and disease activity index(DAI)score were performed of rats in each group;pathological morphology of colonic mucosa was detected by HE staining,the thickness of mucosa and height of villi were compared;levels of catalase(CAT),superoxide dismutase(SOD),malondialdehyde(MDA)in colon tissue,levels of serum diamine oxidase(DAO),and intestinal fatty acid binding protein(I-FABP),TNF-α,IL-18,IL-6 were detected by kits;expression levels of tight junction proteins(Claudin-1,ZO-1,Occludin)and HMGB1/TLR4 pathway proteins(HMGB1,TLR4,MyD88)in colon tissues were detected by Western blotting.Expression levels of HMGB1,TLR4 and MyD88 in colonic tissue were detected by immunohistochemistry.Results:Compared with control group,colonic mucosal tissue of model group had severe pathological injury,the body weight,mucosal thickness,villus height,CAT,SOD,Claudin-1,ZO-1 and Occludin levels in colon tis-sue were significantly reduced,while DAI score,serum DAO,I-FABP,TNF-α,IL-18 and IL-6 levels,colon tissue MDA,HMGB1,TLR4 and MyD88 levels were significantly increased(P<0.05);compared with model group,pathological injury of colonic mucosal tissue of rats in ursolic acid group,glycyrrhizic acid group and glycyrrhizic acid+ursolic acid group were reduced,body weight,muco-sal thickness,villus height,colon tissue CAT,SOD,Claudin-1,ZO-1 and Occludin levels were significantly increased,while DAI score,serum DAO,I-FABP,TNF-α,IL-18 and IL-6 levels,colon tissue MDA,HMGB1,TLR4 and MyD88 levels were significantly reduced(P<0.05);combined intervention of glycyrrhizic acid and ursolic acid could enhance the influence of ursolic acid on the above indexes(P<0.05).Conclusion:Ursolic acid can inhibit inflammation,reduce the level of oxidative stress,reduce the colonic mucosal injury of UC rats,repair the intestinal mucosal barrier function,and improve the clinical symptoms of rats,which may be achieved by down-regulating the HMGB1/TLR4 pathway.

Objective To explore the value of MRI quantitative parameters and free/total prostate-specific antigen ratio(f/tPSA)for diagnosing prostate imaging reporting and data system(PI-RADS)3-point clinically significant prostate cancer(csPCa).Methods Totally 57 patients with PI-RADS 3-point prostate lesions were retrospectively enrolled,including 18 prostate cancer(PCa)(PCa group)and 39 benign hyperplasia with chronic prostatitis(non-PCa group).The former included 12 cases of csPCa and 6 cases of clinically insignificant PCa(ciPCa).Taken non-PCa and ciPCa into non-csPCa group(n=45),laboratory and MRI parameters(apparent diffusion coefficient[ADC],T1,T2,proton density[PD]values)were compared between PCa and non-PCa groups,also between csPCa and non-csPCa groups.Based on laboratory and MRI parameters being statistically different between groups according to univariate analysis,combined models were established using logistic regression.The efficacy of laboratory,MRI parameters and combined models for differentiating PCa and non-PCa as well as csPCa and non-csPCa were evaluated.Results ADC,T1,T2,PD values in PCa group were all lower those in non-PCa group(all P＜0.05),and f/tPSA,ADC,T1,T2 and PD values in csPCa group were all lower than those in non-csPCa group(all P＜0.05).AUC of ADC,T1,T2 and PD values for differentiating PCa from non-PCa was 0.662,0.755,0.793 and 0.729 respectively,while of ADC-T1-T2-PD combined model was 0.839,higher than that of ADC alone(P＜0.05)but not significantly different with T1,T2 and PD values alone(all P＞0.05).AUC of f/tPSA,ADC,T1,T2 and PD values for differentiating csPCa from non-csPCa was 0.692,0.759,0.741,0.805 and 0.737,respectively,while of ADC-T1-T2-PD combined model was 0.889,higher than that of f/tPSA,ADC and T1 values alone(all P＜0.05)but not significantly different with that of T2 and PD value alone(both P＞0.05).AUC of f/tPSA-ADC-T1-T2-PD combined model was 0.898,higher than that of f/tPSA,ADC,T1 and PD values alone(all P＜0.05)but not significantly different with T2 value and ADC-T1-T2-PD combined model(both P＞0.05).Conclusion MRI quantitative parameters combined with f/tPSA could effectively diagnose PI-RADS 3-point csPCa.

Objective To explore the value of MRI quantitative parameters and free/total prostate-specific antigen ratio(f/tPSA)for diagnosing prostate imaging reporting and data system(PI-RADS)3-point clinically significant prostate cancer(csPCa).Methods Totally 57 patients with PI-RADS 3-point prostate lesions were retrospectively enrolled,including 18 prostate cancer(PCa)(PCa group)and 39 benign hyperplasia with chronic prostatitis(non-PCa group).The former included 12 cases of csPCa and 6 cases of clinically insignificant PCa(ciPCa).Taken non-PCa and ciPCa into non-csPCa group(n=45),laboratory and MRI parameters(apparent diffusion coefficient[ADC],T1,T2,proton density[PD]values)were compared between PCa and non-PCa groups,also between csPCa and non-csPCa groups.Based on laboratory and MRI parameters being statistically different between groups according to univariate analysis,combined models were established using logistic regression.The efficacy of laboratory,MRI parameters and combined models for differentiating PCa and non-PCa as well as csPCa and non-csPCa were evaluated.Results ADC,T1,T2,PD values in PCa group were all lower those in non-PCa group(all P＜0.05),and f/tPSA,ADC,T1,T2 and PD values in csPCa group were all lower than those in non-csPCa group(all P＜0.05).AUC of ADC,T1,T2 and PD values for differentiating PCa from non-PCa was 0.662,0.755,0.793 and 0.729 respectively,while of ADC-T1-T2-PD combined model was 0.839,higher than that of ADC alone(P＜0.05)but not significantly different with T1,T2 and PD values alone(all P＞0.05).AUC of f/tPSA,ADC,T1,T2 and PD values for differentiating csPCa from non-csPCa was 0.692,0.759,0.741,0.805 and 0.737,respectively,while of ADC-T1-T2-PD combined model was 0.889,higher than that of f/tPSA,ADC and T1 values alone(all P＜0.05)but not significantly different with that of T2 and PD value alone(both P＞0.05).AUC of f/tPSA-ADC-T1-T2-PD combined model was 0.898,higher than that of f/tPSA,ADC,T1 and PD values alone(all P＜0.05)but not significantly different with T2 value and ADC-T1-T2-PD combined model(both P＞0.05).Conclusion MRI quantitative parameters combined with f/tPSA could effectively diagnose PI-RADS 3-point csPCa.

Objective:To explore the value of metanephrine, normetanephrine, and some steroid hormones in the assessment of adrenal venous sampling (AVS).Methods:This retrospective study enrolled 101 patients with primary aldosteronism who underwent AVS at Peking Union Medical College Hospital between June 1, 2021, and October 1, 2024. Multiple hormones, including aldosterone, cortisol, metanephrine, normetanephrine and steroid hormone profiles, were measured in samples from the inferior vena cava and bilateral adrenal veins during AVS. Selectivity index and lateralization index were calculated based on the levels of different hormones to determine successful AVS cannulation (selectivity index≥2) and aldosterone hypersecretion lateralization (lateralization index≥2). Patients who underwent unilateral adrenalectomy were followed for at least 6 months. Clinical and biochemical outcomes were assessed according to the Primary Aldosteronism Surgical Outcome (PASO) criteria, with biochemical remission defined as achieving complete or partial biochemical remission postoperatively. The efficacy of different hormones relative to cortisol for calculating selectivity index and lateralization index was evaluated for subtype classification.Results:The age at diagnosis of the enrolled patients was (50.5±9.6) years, including 77 males. Regarding the selectivity index, five hormones including metanephrine, normetanephrine, androstenedione, 17α-hydroxypregnenolone, and dehydroepiandrosterone demonstrated significantly higher selectivity index compared to cortisol (all P<0.05). Based on the cortisol-derived selectivity index, AVS cannulation was unsuccessful in 8 patients; using the five indices, unsuccessful cannulation occurred in 2, 2, 3, 4, and 5 patients, respectively. Based on postoperative follow-up, 55 patients were identified as having unilateral surgically relievable primary aldosteronism. In identifying these patients, the performance of metanephrine, normetanephrine, androstenedione, 17α-hydroxypregnenolone, and dehydroepiandrosterone was non-inferior to cortisol, correctly identifying 95% (52/55), 93% (51/55), 91% (50/55), 87% (48/55), and 89% (49/55) of cases, respectively. However, among these patients, there were no statistically significant differences in the success rate of intubation in AVS and the ability to identify patients with unilateral primary aldosteronism between the five indicators and cortisol (all P>0.05). Using cortisol-based lateralization as the reference standard, androstenedione and dehydroepiandrosterone both achieved an accuracy of 90% (84/93) for determining the lateralized side, while 17α-hydroxypregnenolone, normetanephrine, and metanephrine achieved accuracies of 89% (83/93), 81% (74/93), and 80% (73/93), respectively. Conclusion:Metanephrine, normetanephrine, androstenedione, 17α-hydroxypregnenolone and dehydroepiandrosterone could increase the success rate of intubation in AVS, with a high ability to identify patients with unilateral primary aldosteronism, and are expected to replace cortisol as new indicators of AVS.

Objective:To evaluate the safety, efficacy, advantages and disadvantages of the modified double-orifice valve plasty via total thoracoscopy for partial atrioventricular septal defect(PAVSD) through a retrospective analysis of early postoperative results.Methods:Patients diagnosed with PAVSD who underwent the standardized modified double-orifice valve plasty via total thoracoscopy between September 2023 and August 2024 were retrospectively enrolled. Baseline characteristics, surgical parameters, and follow-up outcomes were systematically analyzed.Results:A total of 14 patients(6 males, 8 females) were included, with a mean age of(32.9±15.5) years old and body weight of(55.1±11.6) kg. All procedures were successfully completed. The mean operative time, cardiopulmonary bypass time, and aortic cross-clamp time were(266.6±67.2) min, (160.7±34.2) min, and(97.0±31.1) min, respectively. Postoperative ICU stay, hospital stay, and total hospitalization duration were(1.7±1.1) days, (6.4±4.2) days, and(12.6±4.5) days, respectively. The mean follow-up duration was(7.9±3.6) months. Preoperatively, left atrioventricular valve regurgitation(LAVVR) was graded as mild, moderate, or severe in 5, 4, and 5 patients. Postoperatively, 13 patients exhibited mild or less LAVVR, with 1 case of moderate regurgitation. By 3 months, all patients demonstrated LAVVR of mild or lower severity, which remained stable through follow-up. Peak LAVV gradients were(4.6±2.7) mmHg(1 mmHg=0.133 kPa)(range: 1.8-10.2 mmHg) postoperatively, improving to(3.6±0.6) mmHg(3.2-4.0) mmHg at 1 year. Right atrioventricular valve regurgitation improved from preoperative moderate-severe(50.0%) to LAVVR of mild or lower severity in all patients by 3 months. No mortality, residual shunts, or high-grade atrioventricular block occurred through follow-up. By 1 month, NYHA functional class improved to Ⅰ in all patients, which remained stable through follow-up.Conclusion:Standardized modified double-orifice valve plasty via total thoracoscopy for PAVSD demonstrates safety, minimal invasiveness, and rapid recovery, with favorable early outcomes.

Objective The study aims to investigate the immunological functions of the nucleocapsid (N) protein of the novel coronavirus Omicron (BA.1, BA.2) and evaluate the differences among different N proteins of mutant strains in immunogenicity. Methods By aligning sequences, the mutation sites of the Omicron (BA.1, BA.2) N protein relative to prototype strain of the novel coronavirus (Wuhan-Hu-1) were determined. The pET-28a-N-Wuhan-Hu-1 plasmid was used as template to construct pET-28a-BA.1/BA.2-N through single point mutation or homologous recombination. The three kinds of N protein were expressed in prokaryotic system, purified through Ni-NTA affinity chromatography, and then immunized into mice. The titer and reactivity of the polyclonal antibody, as well as the expression level of IL-1β and IFN-γ in mouse spleen cells, were detected using indirect ELISA and Western blot assay. Results The constructed prokaryotic expression plasmids were successfully used to express the Wuhan-Hu-1 N, BA.1 N, and BA.2 N proteins in E.coli BL21(DE3) at 37 DegreesCelsius for 4 hours. The indirect ELISA test showed that the titers of polyclonal antibody prepared by three N proteins were all 1:51 200. All three N proteins can increase the expression of IFN-γ and IL-1β cytokines, but the effect of Omicron N protein in activing two cytokines was more obvious than that of Wuhan-Hu-1 N protein. Conclusion The study obtained three new coronavirus N proteins and polyclonal antibodies, and confirmed that mutations in the amino acid sites of the N protein can affect its immunogenicity. This provides a basis for developing rapid diagnostic methods targeting N protein of different novel coronavirus variants.
Animals ; Mice ; SARS-CoV-2/genetics* ; Coronavirus Nucleocapsid Proteins/immunology* ; Nucleocapsid Proteins/isolation & purification* ; COVID-19/immunology* ; Antibodies, Viral/immunology* ; Mice, Inbred BALB C ; Interferon-gamma/metabolism* ; Interleukin-1beta/metabolism* ; Female ; Escherichia coli/metabolism* ; Mutation ; Humans

Lung cancer, particularly non-small cell lung cancer (NSCLC), is a leading cause of cancer-related mortality worldwide. In recent years, metabolomics has emerged as a key systems biology approach for analyzing small-molecule metabolites in cells, tissues and organisms. It provides new strategies for early diagnosis and metabolic profiling. Additionally, metabolomics plays a crucial role in studying resistance mechanisms in lung cancer. Tumor cell metabolic reprogramming is a key driving factor in the initiation and progression of lung cancer. Metabolomics studies have revealed how lung cancer cells regulate critical pathways such as energy metabolism, lipid metabolism, and amino acid metabolism to adapt to the demands of rapid proliferation and invasive metastasis. This review summarizes the latest advances in metabolomics research in lung cancer, focusing on the characteristics of metabolic reprogramming, the identification of potential metabolic biomarkers, and the prospects of metabolomics in early diagnosis and the elucidation of resistance mechanisms in lung cancer.
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Humans ; Metabolomics/methods* ; Lung Neoplasms/pathology* ; Animals ; Biomarkers, Tumor/metabolism*

Objective To explore the current situation and experience of the development of multi-hospital areas in foreign medical institutions,and to analyze its enlightenment to the construction of"one hospital with multiple campuses"in public hospitals in China.Methods Through the combing of relevant literature,it systematically analyzes the development status of multi-hospital construction of medical institutions in typical countries such as the United States,the United Kingdom,and Germany,summarizes the relevant experience of different countries,and analyzes the current situation of the construction of"one hospital with multiple campuses"in China's public hospitals.Results At present,the orderly development of multiple hospitals of foreign medical institutions mainly depends on the homogenization of medical care,the scientific management of human resources and the improvement of information construction.China can learn from its experience and technical means to build a development pattern of"one hospital with multiple campuses"suitable for China's national conditions.Conclusion In the future,the construction of"one hospital with multiple campuses"in China's public hospitals should focus on"rationalization of human resource allocation,homogenization of medical service quality,and intelligent information system construction",improve"human resource allocation",establish and improve"information sharing mechanism",differentiate the layout of"hospital functions",and strengthen"quality supervision and patient feedback",aiming to improve the construction effect of"one hospital with multiple campuses"in China's public hospitals.

Objective:Using Mendelian randomization analysis to investigate the unidirectional causal effects of gut microbiota on gout and serum uric acid levels.Methods:The Mendelian randomization analysis was conducted using summary statistics from genome-wide association studies (GWAS). The gut microbiota was used as the exposure factor, with gout and serum uric acid levels as the outcomes, utilizing the MiBioGen Consortium, FinnGen GWAS, and CKDGen Consortium meta-analysis databases. The analysis was performed using inverse variance weighted (IVW) method, MR-Egger, and weighted median (WM) approach. Additionally, sensitivity analysis was conducted by excluding heterogeneity and horizontal pleiotropy. This study used RStudio 4.3.1 software for analysis.Results:The IVW results confirmed that 17 microbiota taxa were associated with gout, including class Verrucomicrobiaceae [ OR(95% CI)=1.162(1.004, 1.344), P=0.044], family Verrucomicrobiaceae [ OR(95% CI)=1.161(1.004, 1.344), P=0.044], genus Akkermansia [ OR(95% CI)=1.162(1.004, 1.344), P=0.044], genus Collinsella [ OR(95% CI)=1.257(1.043, 1.516), P=0.016], genus Eubacterium hallii group [ OR(95% CI)=1.226(1.022, 1.471), P=0.027], genus Howardella [ OR(95% CI)=1.094(1.001, 1.195), P=0.046], genus Ruminococcaceae UCG010 [ OR(95% CI)=1.317(1.089, 1.593), P=0.004], order Clostridiales [ OR(95% CI)=1.182(1.007,1.387), P=0.041], order Verrucomicrobiales [ OR(95% CI)=1.162(1.004, 1.344), P=0.044], class Melainabacteria [ OR(95% CI)=0.894(0.804, 0.994), P=0.038], family Streptococcaceae [ OR(95% CI)=0.851(0.727, 0.996), P=0.044], unknown family [ OR(95% CI)=0.890(0.800, 0.989), P=0.030], genus Streptococcus [ OR(95% CI)=0.836(0.710, 0.983), P=0.030], unknown genus [ OR(95% CI)=0.890(0.800, 0.989), P=0.030], genus Victivallis [ OR(95% CI)=0.857(0.736, 0.998), P=0.046], order Gastranaerophilales [ OR(95% CI)=0.890(0.800,0.989), P=0.030], and phylum Bacteroidetes [ OR(95% CI)=0.827(0.692, 0.989), P=0.037]. Additionally, 5 microbiota taxa were associated with serum uric acid levels: phylum Actinobacteria [ OR(95% CI)=0.963(0.925, 0.992), P=0.027], family ⅩⅢ [ OR(95% CI)=0.965(0.932, 1.008), P=0.035], genus Escherichia Shigella [ OR(95% CI)=1.047(1.005,1.089), P=0.034], genus Lachnospiraceae FCS020 group [ OR(95% CI)=0.974(0.941, 1.003), P=0.028], and genus Lachnospiraceae NC2004 group [ OR(95% CI)=0.966(0.943, 0.995), P=0.018]. No abnormalities in SNPs were found in the sensitivity analysis. Conclusion:An increase in the levels of class Verrucomicrobiae, family Verrucomicrobiaceae, genus Akkermansia, and genus Escherichia Shigella is associated with an increased risk of gout or serum uric acid levels, while an increase in the levels of class Melainabacteria, family Streptococcaceae, unknown family, phylum Actinobacteria, and family ⅩⅢ is associated with a decreased risk of gout or serum uric acid levels.

Objective:To explore the value of metanephrine, normetanephrine, and some steroid hormones in the assessment of adrenal venous sampling (AVS).Methods:This retrospective study enrolled 101 patients with primary aldosteronism who underwent AVS at Peking Union Medical College Hospital between June 1, 2021, and October 1, 2024. Multiple hormones, including aldosterone, cortisol, metanephrine, normetanephrine and steroid hormone profiles, were measured in samples from the inferior vena cava and bilateral adrenal veins during AVS. Selectivity index and lateralization index were calculated based on the levels of different hormones to determine successful AVS cannulation (selectivity index≥2) and aldosterone hypersecretion lateralization (lateralization index≥2). Patients who underwent unilateral adrenalectomy were followed for at least 6 months. Clinical and biochemical outcomes were assessed according to the Primary Aldosteronism Surgical Outcome (PASO) criteria, with biochemical remission defined as achieving complete or partial biochemical remission postoperatively. The efficacy of different hormones relative to cortisol for calculating selectivity index and lateralization index was evaluated for subtype classification.Results:The age at diagnosis of the enrolled patients was (50.5±9.6) years, including 77 males. Regarding the selectivity index, five hormones including metanephrine, normetanephrine, androstenedione, 17α-hydroxypregnenolone, and dehydroepiandrosterone demonstrated significantly higher selectivity index compared to cortisol (all P<0.05). Based on the cortisol-derived selectivity index, AVS cannulation was unsuccessful in 8 patients; using the five indices, unsuccessful cannulation occurred in 2, 2, 3, 4, and 5 patients, respectively. Based on postoperative follow-up, 55 patients were identified as having unilateral surgically relievable primary aldosteronism. In identifying these patients, the performance of metanephrine, normetanephrine, androstenedione, 17α-hydroxypregnenolone, and dehydroepiandrosterone was non-inferior to cortisol, correctly identifying 95% (52/55), 93% (51/55), 91% (50/55), 87% (48/55), and 89% (49/55) of cases, respectively. However, among these patients, there were no statistically significant differences in the success rate of intubation in AVS and the ability to identify patients with unilateral primary aldosteronism between the five indicators and cortisol (all P>0.05). Using cortisol-based lateralization as the reference standard, androstenedione and dehydroepiandrosterone both achieved an accuracy of 90% (84/93) for determining the lateralized side, while 17α-hydroxypregnenolone, normetanephrine, and metanephrine achieved accuracies of 89% (83/93), 81% (74/93), and 80% (73/93), respectively. Conclusion:Metanephrine, normetanephrine, androstenedione, 17α-hydroxypregnenolone and dehydroepiandrosterone could increase the success rate of intubation in AVS, with a high ability to identify patients with unilateral primary aldosteronism, and are expected to replace cortisol as new indicators of AVS.