Coronary atherosclerotic heart disease is a major cardiovascular condition driven by atherosclerosis, distinguished by chronic inflammation and dysregulated lipid metabolism. The gut microbiota plays an essential role in human health and disease, with research indicating a strong association between gut microbial metabolism and the development and progression of coronary heart disease. This article provides a review of the relationship between gut microbiota and coronary heart disease, as well as the mechanisms by which traditional Chinese medicine regulates digestive tract microbiota to treat coronary heart disease, which systematically explains how the gut microbiota, through metabolic products and immune regulation, contributes to the occurrence and progression of coronary heart disease, and summarizes recent advances in research on traditional Chinese medicine's regulation of gut microbiota for treating coronary heart disease. It aims to provide further reference and insights for exploring the relationship between gut microbiota and coronary heart disease, as well as traditional Chinese medicine approaches for treating coronary heart disease.

Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.

Objective:To uncover alterations in the metabolic microenvironment of lymph node metastasis (LNM) in oral squamous cell carcinoma (OSCC) and identify potential metabolic biomarkers for the early diagnosis of LNM using desorption electrospray ionization mass spectrometry imaging (DESI-MSI) spatial metabolomics.Methods:Six OSCC patients with LNM, who underwent neck dissection surgery at the Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Jiangsu University between October 2020 and October 2022, were enrolled. Matched metastatically involved (positive) and benign (negative) lymph node tissue samples were collected and analyzed using DESI-MSI. Univariate and multivariate statistical analyses were employed to identify differentially abundant metabolites. The diagnostic efficacy of these metabolites was evaluated using receiver operating characteristic (ROC) curve analysis. Finally, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was performed to determine the implicated metabolic pathways.Results:A total of 62 and 29 differentially abundant metabolites were identified in the metastatically involved lymph nodes compared to benign lymph nodes under positive-ion mode and negative-ion mode, respectively. These metabolites were predominantly amino acids and lipids. Four metabolites common to both ionization modes were selected for ROC curve analysis: phenylalanine, phosphoethanolamine, histidine, and taurine. The area under the curve values were 0.861, 0.802, 0.729, and 0.722, respectively, indicating promising diagnostic performance. Metabolic pathway analysis revealed significantly heightened activity in Amino acid metabolism ( P=0.469) and Glycerophospholipid metabolism ( P=0.006) within the LNM microenvironment. Conclusions:This DESI-MSI-based study identified disruptions in amino acid and glycerophospholipid metabolism within OSCC metastatic lymph node tissues. The associated differentially abundant metabolites represent potential candidate molecules for diagnosing OSCC LNM.

Oropharyngeal squamous cell carcinoma(OPSCC)is a malignant tumor originating from the squamous epithelium of the oro-pharyngeal mucosa,accounting for more than 90％of oropharyngeal malignancies.In recent years,human papillomavirus(HPV)infec-tion has become one of the primary etiological factors of oropharyngeal squamous carcinoma.The incidence of HPV-associated oropharyn-geal squamous carcinoma has been rising annually,with a noticeable trend toward younger populations,posing a significant threat to hu-man health.Due to the distinct biological behavior and clinical characteristics of HPV-associated oropharyngeal squamous carcinoma com-pared to its non-HPV-related counterpart,the diagnostic and treatment strategies for oropharyngeal squamous carcinoma have undergone substantial changes.Prevention and screening for oropharyngeal squamous carcinoma are of critical importance.The diagnostic and treat-ment process involves multi-disciplinary collaboration,including oral and maxillofacial surgery,otolaryngology,head and neck surgery,oncology,radiology and pathology.Based on evidence from clinical practice,a comprehensive,integrated diagnostic and therapeutic ap-proach has been established,centered around the concept of"prevention,screening,diagnosis,treatment,and rehabilitation",covering the entire patient lifecycle and providing a valuable reference for clinical practice.

Oral squamous cell carcinoma(OSCC)is a malignant lesion originating from the oral mucosal squamous epithelium,account-ing for over 80％of oral and maxillofacial malignancies.Key etiological factors include tobacco,alcohol abuse,and betel quid chewing.In China,its incidence has shown an overall upward trend,posing a significant threat to public health.OSCC exhibits high local invasive-ness,making early diagnosis critical for improving prognosis.Its clinical management requires close multidisciplinary collaboration among oral and maxillofacial surgery,head and neck surgery,radiation oncology,medical oncology,reconstructive surgery,radiology,patholo-gy,and nutritional support teams.Given the increasing disease burden of OSCC and rapid development of multidisciplinary collaborative models,an expert panel has formulated this integrated management consensus based on evidence-based medicine and extensive deliber-ation.Centered on the'Prevention-Screening-Diagnosis-Treatment-Rehabilitation'framework,the consensus provides comprehensive guidance for the entire disease course of OSCC patients,aiming to standardize clinical practice.

Objective To explore the molecular mechanism of plasmalemmal vesicle-associated protein(PLVAP)regulating high glucose(HG)induced endocytosis dysfunction in human liver sinusoidal endothelial cells(HLSECs)through Kelch-like epichlorohydrin ECH-associated protein 1(Keap1)/nuclear factor erythroid 2-related factor 2(Nrf2)/Maf protein.Methods HLSECs were cultured in vitro and divided into normal control(NC)group,high glucose(HG)group,PLVAP overexpression recombinant vector(LV-PLVAP)group,lentivirus empty vector(LV-CON)group,HG+LV-PLVAP+Nrf2 inhibitor(ML385)group,HG+LV-PLVAP+Maf inhibitor(Mafenide)group,HG+LV-CON+ML385 group and HG+LV-CON+Mafenide group.Cell activity was detected by CCK-8 assay.The transfection efficiency of LV-PLVAP was observed by fluorescence microscopy.The fluorescence expression of PLVAP and Nrf2 was detected by immunofluorescence.RT-PCR and western blot were used to detect the mRNA and protein expression of PLVAP,Keap1,Nrf2,and Maf,Caveolin-1(CAV-1).Results A lot of green fluorescence appeared in LV-PLVAP and LV-CON groups,however,no green fluorescence was shown in NC group.Immunofluorescence results showed that PLVAP was expressed in cell membrane;Nrf2 was expressed in cytoplasm,and in HG group,Nrf2 was expressed in nucleus.Compared with NC group,the expression of PLVAP,Keap1 mRNA and protein decreased in HG group(P<0.05 or P<0.01),while the expression of Nrf2,Maf and CAV-1 mRNA and protein increased in HG group(P<0.01).Compared with HG group,the expression of PLVAP,Keap1,Nrf2 mRNA and protein increased in HG+LV-PLVAP group(P<0.01),while the expression of Maf,CAV-1 mRNA and protein decreased in HG+LV-PLVAP group(P<0.01).Compared with HG+LV-PLVAP group,the expression of CAV-1 mRNA and protein increased in HG+LV-PLVAP+ML385 and HG+LV-PLVAP+Mafenide groups(P<0.05 or P<0.01).Conclusions PLVAP regulates the expression of CAV-1 through the Keap1/Nrf2/Maf pathway and then regulates HG induced endocytosis dys-function in HLSECs.Over expression of PLVAP alleviates this pathological reaction.

Objective:To investigate the correlation between rectal colonization of carbapenem resistant Klebsiella pneumoniae（CRKP）and bloodstream infections（BSI）using molecular epidemiological analysis. Methods:Patients admitted to the Intensive Care Unit（ICU），Hematology Department，and Neurosurgery Department of the First Hospital of Jiaxing from January 2022 to December 2024，were enrolled. Rectal CRKP colonization screening was performed for all participants，with concurrent monitoring for BSI.Whole genome sequencing of CRKP strains in the intestine and blood flow of patients with CRKP rectal colonization and CRKP-BSI was performed using the Illumina NovaSeq PE150 sequencing platform，and samples were genotyped based on the PubMLST database. MLST 2.0 was applied for multi site sequence typing，VFDB online database was used to analyze virulence genes，ResFinder was used to analyze resistance genes，and whole genome sequences were imported into BioNumerics software for core genome multi site sequence typing and clustering analysis. Using the BacWGSTdb database to construct a phylogenetic tree based on genomic SNPs，and the homology between CRKP rectal fixed plants and corresponding BSI-CRKP infected plants were analyzed.Results:A total of 772 patients were included，including 78 cases with positive results in rectal CRKP colonization screening（10.1%）and 694 cases without rectal CRKP colonization（89.9%）. The CRKP-BSI rate in rectal CRKP colonization patients was significantly higher than that in non-CRKP colonization patients［19.2%（15/78） vs. 5.5%（38/694）， χ2=20.749， P<0.001］. Analysis of CRKP rectal colonization strains and bloodstream infection strains in 15 patients with CRKP rectal implantation and CRKP-BSI revealed that ST11 type was the main strain（ n=10），followed by ST37 type（ n=3），with all carrying multiple β-lactam and carbapenem producing enzyme resistance genes.The distribution of virulence genes showed that CRKP strains carried multiple virulence genes，with iroE being ubiquitous，followed by iucA/ B/ C/ D， rmpA2，rmpA，and iroN. All ST11-type CRKP strains exhibited hypervirulent characteristics. Capsular serotyping analysis showed that the predominant type of CRKP colonization and infection strains was KL64. The results of cgMLST and SNP clustering analysis showed that CRKP rectal fixed plants exhibited homology with blood flow infected plants. Moreover，two clusters of CRKP rectal colonization strains with significant homology were found to cluster together among 15 patients. Conclusions:Rectal colonization of CRKP is an important risk factor for the occurrence of BSI-CRKP in hospitals，and ST11 hypervirulent CRKP is the main type. It is recommended to screen high-risk patients for CRKP to reduce the risk of BSI-CRKP.

Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.

Objective:To uncover alterations in the metabolic microenvironment of lymph node metastasis (LNM) in oral squamous cell carcinoma (OSCC) and identify potential metabolic biomarkers for the early diagnosis of LNM using desorption electrospray ionization mass spectrometry imaging (DESI-MSI) spatial metabolomics.Methods:Six OSCC patients with LNM, who underwent neck dissection surgery at the Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Jiangsu University between October 2020 and October 2022, were enrolled. Matched metastatically involved (positive) and benign (negative) lymph node tissue samples were collected and analyzed using DESI-MSI. Univariate and multivariate statistical analyses were employed to identify differentially abundant metabolites. The diagnostic efficacy of these metabolites was evaluated using receiver operating characteristic (ROC) curve analysis. Finally, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was performed to determine the implicated metabolic pathways.Results:A total of 62 and 29 differentially abundant metabolites were identified in the metastatically involved lymph nodes compared to benign lymph nodes under positive-ion mode and negative-ion mode, respectively. These metabolites were predominantly amino acids and lipids. Four metabolites common to both ionization modes were selected for ROC curve analysis: phenylalanine, phosphoethanolamine, histidine, and taurine. The area under the curve values were 0.861, 0.802, 0.729, and 0.722, respectively, indicating promising diagnostic performance. Metabolic pathway analysis revealed significantly heightened activity in Amino acid metabolism ( P=0.469) and Glycerophospholipid metabolism ( P=0.006) within the LNM microenvironment. Conclusions:This DESI-MSI-based study identified disruptions in amino acid and glycerophospholipid metabolism within OSCC metastatic lymph node tissues. The associated differentially abundant metabolites represent potential candidate molecules for diagnosing OSCC LNM.

Oral squamous cell carcinoma(OSCC)is a malignant lesion originating from the oral mucosal squamous epithelium,account-ing for over 80％of oral and maxillofacial malignancies.Key etiological factors include tobacco,alcohol abuse,and betel quid chewing.In China,its incidence has shown an overall upward trend,posing a significant threat to public health.OSCC exhibits high local invasive-ness,making early diagnosis critical for improving prognosis.Its clinical management requires close multidisciplinary collaboration among oral and maxillofacial surgery,head and neck surgery,radiation oncology,medical oncology,reconstructive surgery,radiology,patholo-gy,and nutritional support teams.Given the increasing disease burden of OSCC and rapid development of multidisciplinary collaborative models,an expert panel has formulated this integrated management consensus based on evidence-based medicine and extensive deliber-ation.Centered on the'Prevention-Screening-Diagnosis-Treatment-Rehabilitation'framework,the consensus provides comprehensive guidance for the entire disease course of OSCC patients,aiming to standardize clinical practice.