To explore the advantages of traditional Chinese medicine （TCM） and integrative TCM-Western medicine approaches in the treatment of diabetic microvascular complications （DMC）， refine key pathophysiological insights and treatment principles， and promote academic innovation and strategic research planning in the prevention and treatment of DMC. The 38th session of the Expert Salon on Diseases Responding Specifically to Traditional Chinese Medicine， hosted by the China Association of Chinese Medicine， was held in Beijing， 2024. Experts in TCM， Western medicine， and interdisciplinary fields convened to conduct a systematic discussion on the pathogenesis， diagnostic and treatment challenges， and mechanism research related to DMC， ultimately forming a consensus on key directions. Four major research recommendations were proposed. The first is addressing clinical bottlenecks in the prevention and control of DMC by optimizing TCM-based evidence evaluation systems. The second is refining TCM core pathogenesis across DMC stages and establishing corresponding "disease-pattern-time" framework. The third is innovating mechanism research strategies to facilitate a shift from holistic regulation to targeted intervention in TCM. The fourth is advancing interdisciplinary collaboration to enhance the role of TCM in new drug development， research prioritization， and guideline formulation. TCM and integrative approaches offer distinct advantages in managing DMC. With a focus on the diseases responding specifically to TCM， strengthening evidence-based support and mechanism interpretation and promoting the integration of clinical care and research innovation will provide strong momentum for the modernization of TCM and the advancement of national health strategies.

ObjectiveHepatocellular carcinoma (HCC) represents 90% of all primary liver cancers. The main risk factors associated with HCC include viral hepatitis (B and/or C), alcohol abuse, and metabolic dysfunction-associated steatotic liver disease (MASLD), which progressively advance to liver fibrosis, cirrhosis, and ultimately evolve into HCC. Surgical resection represents the most effective treatment for HCC, while recent advances in immunotherapy, including immune checkpoint inhibitors and adoptive cell therapies, have provided improved treatment prospects for patients with unresectable HCC. However, the complex metabolic heterogeneity of HCC limits the therapeutic efficacy. Metabolic intermediates acyl-CoA not only provide energy and substrates for numerous biochemical reactions but also serve as donors for protein lysine acylation, a major class of post-translational modification (PTM). Therefore, a deeper understanding of the molecular mechanisms underlying protein lysine acylation and hepatocarcinogenesis is urgently needed. MethodsThe levels of protein lysine acylation and silence information regulator 5 (SIRT5) expression levels in clinical HCC samples were analyzed by Western blot. Quantitative malonylome and succinylome of HCC samples were analyzed by antibody-based affinity enrichment coupled with tandem mass spectrometry. The proliferation of HCC cells was analyzed with Cell Counting Kit-8 (CCK-8) assays, the apoptosis was quantified by Annexin V-FITC/propidium iodide (PI) staining coupled with flow cytometry, and the ability of cells to migrate was assayed by Transwell assays. The enzymatic activity of glutathione S-transferase Mu 1 (GSTM1) was quantified. Transgenic mice with hepatic overexpression of SIRT5 were constructed using CRISPR-Cas9, and primary hepatocarcinogenesis was induced by administration of diethylnitrosamine. ResultsWestern blot analysis indicated that the expression level of SIRT5 was elevated in clinical samples from HCC patients, and the levels of lysine malonylation, glutarylation, and succinylation were significantly reduced in HCC tissues. Knockout of SIRT5 in MHCC-97H and MHCC-97L hepatoma cells suppressed cell proliferation, and increased the percentage of apoptotic cells significantly. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the differentially malonylome and succinylome of HCC samples revealed significant enrichment in two major classes of biological processes: core energy metabolism (e.g., glycolysis/gluconeogenesis, tricarboxylic acid metabolic process, fatty acid beta oxidation) and detoxification and oxidative stress response (e.g., response to toxic substance, chemical carcinogenesis, reactive oxygen species (ROS)). SIRT5 removes malonylation from lysine residues in GSTM1 and restores its detoxification activity, which is crucial for the survival of hepatocytes under stressed conditions. More importantly, in vivo experiment indicated that hepatic-specific overexpression of SIRT5 in mice accelerated diethylnitrosamine-induced liver fibrosis and hepatocarcinogenesis, indicating the critical role of SIRT5 in HCC progression. ConclusionThis study highlights the previously unrecognized SIRT5-GSTM1 axis as a key regulator in hepatocarcinogenesis, and suggests a potential target for the treatment of patients with HCC.

Objective To evaluate the efficacy and safety of 450 nm blue laser vaporization enucleation of the prostate in the treatment of benign prostatic hyperplasia(BPH)complicated with urinary retention, so as to promote its clinical application. Methods A retrospective analysis was conducted on the clinical data of 60 patients with BPH and urinary retention who underwent 450 nm blue laser vaporization enucleation of the prostate in our hospital during Feb. 2023 and Apr. 2024. All patients had urinary catheters indwelt preoperatively due to urinary retention. The perioperative indicators and complications were recorded. The maximum urinary flow rate(Qmax), postvoid residual(PVR), international prostate symptom score(IPSS), and quality of life score(QoL)were compared before surgery and 3 months after surgery. Results All procedures were completed successfully without conversion to transurethral resection of the prostate(TURP). No cases of severe intraoperative bleeding or transfusion were reported. The average operation time was(60.5±21.5)min, postoperative hemoglobin reduction(3.2±0.8)g/L, catheterization time(3.1±0.4)days, and hospital stay(3.2±0.4)days. No bladder perforation or urethral injury occurred. At 3 months postoperatively, Qmax [(19.2±4.9)mL/s vs.(3.5±2.3)mL/s], PVR [(50.8±20.1)mL vs.(369.2±163.2)mL], IPSS [(9.7±0.9)vs.(21.8±3.2)], and QoL [(1.4±0.5)vs.(4.9±0.1)]were significantly improved compared with preoperative values(P＜0.001). Urinary retention occurred in 2 patients after catheter removal on postoperative day 3, which was resolved one week after re-catheterization. Conclusion The 450 nm blue laser vaporization enucleation of the prostate is a safe and effective treatment for BPH complicated with urinary retention. It can significantly improve the short-term voiding function and quality of life with a low incidence of postoperative complications, demonstrating promising potential for clinical adoption.

Objective The aim of the study is to analyze the incidence patterns and epidemiological characteristics of parasitic and vector-borne diseases in the Minhang and Jinshan districts of Shanghai, and provide evidence-based information for optimizing prevention and control measures. Methods We collected information from epidemic reports and epidemiological investigation forms for cases of parasitic and vector-borne diseases from 2005 to 2024 in Shanghai's Minhang and Jinshan districts. Descriptive epidemiological method were adopted to conduct a comparative analysis of incidence trends, epidemic characteristics, and infection sources. Results A total of 229 cases in 7 categories were reported between 2005 and 2024, with an average annual incidence rate of 0.36/100 000. The average annual incidence rate in Minhang District was significantly higher than that in Jinshan District. The most prevalent diseases were malaria and dengue fever, followed by Japanese encephalitis. Monthly case reports were available, predominantly from June to October, with a peak in July-August. A statistically significant difference was observed between the two districts in case distribution during June-October (P＜0.001), whereas no significant difference was found for July-August (P=0.331). The majority of cases were young men (111/229,48.47%), aged 20-39 years. Migrant workers/farmers constituted the largest occupational group (55/229, 24.02%). Registered residents of other provinces and cities (147/229,64.19%), and the main source of infection was overseas importation (112/229,48.91%). There were no statistically significant differences in gender and household-registration composition between the two districts (P＞0.05). Significant differences existed in age, occupation, and source of infection (P＜0.05). The imported diseases were malaria and dengue fever, with Africa and Southeast Asia being the primary source locations. Malaria was the predominant disease imported from other provinces and cities, with cases having been imported from abroad since 2012. Local infections were mainly Japanese encephalitis, followed by malaria (with the last local case reported in 2010). Cases between 2005 and 2009 were predominantly imported from other provinces and cities. The proportion of cases imported from abroad increased sharply after 2010, particularly in Minhang District. Local infections sometimes arise in Jinshan District, with Japanese encephalitis serving as the primary type. Conclusions Incidence rates of parasitic and vector-borne diseases in Minhang and Jinshan districts have generally remained low. To further reduce this disease burden, it will be necessary to strengthen joint measures for prevention and control, eliminate the environmental risk factors of vector organisms, enhance monitoring and precise control of the environment and inbound personnel to prevent the occurrence and transmission of parasitic and vector-borne diseases.

Objective:To evaluate the efficacy of preoperative prediction of regional lymph node (RLN) metastasis in renal cell carcinoma (RCC) using a machine learning model based on habitat imaging radiomics from renal MRI.Methods:This cross-sectional study retrospectively analyzed 220 patients with RCC who underwent nephrectomy and RLN dissection at four medical centers of Chinese PLA General Hospital from January 2010 to August 2023. The cohort included 65 patients with RLN metastasis and 155 without. A stratified random sampling method was used to divide 175 patients from the first medical center into a training set ( n=140) and an internal test set ( n=35) in an 8∶2 ratio, while 45 patients from the third, fourth, and fifth medical centers constituted the external test set. The primary RCC lesions were categorized into 15 habitat subregions based on corticomedullary-phase enhancement and T 2WI signal intensity on MRI, and the volume fractions of different subregions were analyzed. In the training cohort, radiomics features derived from the habitat subregions were used to construct a radiomics model employing various machine learning algorithms, including extremely random trees (ET), gradient boosting decision trees (GBDT), random forest (RF), and support vector machine (SVM). The optimal model was selected and combined with RLN short-axis diameter to develop a combined model. The efficacy of each model in predicting RLN metastasis was evaluated using the receiver operating characteristic (ROC) curve. Results:The volume fraction of hyper-enhanced hyper-intense regions in the non-metastatic group was significantly higher than that in the metastatic group (0.05±0.09 vs. 0.02±0.03; t=3.00, P=0.003). Among the machine learning models constructed using 15 optimal habitat radiomics features, the SVM model demonstrated the best performance, with area under the ROC curve (AUC) values of 0.85 (95% CI 0.72-0.98) in the internal test set and 0.82 (95% CI 0.67-0.98) in the external test set, surpassing those of the ET, GBDT, and RF models. The combined model, integrating the SVM model with RLN short-axis diameter, achieved AUC values of 0.94 (95% CI 0.85-1.00) in the internal test set and 0.89 (95% CI 0.78-1.00) in the external test set, with RLN short-axis diameter contributing AUC values of 0.81 (95% CI 0.66-0.96) and 0.81 (95% CI 0.68-0.94), respectively. The diagnostic sensitivity of the combined model was 91.7% in the internal test set and 85.7% in the external test set, with specificities of 78.3% and 67.7%, respectively. Conclusion:The combined model based on MRI habitat imaging radiomics and RLN short-axis diameter demonstrates excellent preoperative assessment capability for RLN metastasis in RCC.

Aim To elucidate the molecular mecha-nism underlying the inhibitory effect of liquidambaric acid(LDA)targeting TNF receptor associated factor 6(TRAF6)in colorectal cancer.Methods This study employed microscale thermophoresis(MST),drug af-finity responsive target stability assay(DARTS)and cellular thermal shift assay(CETSA)to confirm the direct binding of LDA to TRAF6.Additionally,we generated TRAF6 knockout colorectal cancer HCT116 cells using CRISPR/Cas9 technology,and assessed the impact of LDA on TRAF6-regulated Hippo/YAP and Wnt signaling pathways through immunofluorescence a-nalysis and TOPFlash/Renilla luciferase reporter sys-tem.Co-IP and proximity ligation assays(PLA)were conducted to investigate LDA-regulated TRAF6 pro-tein-protein interactions and elucidate molecular mech-anisms.Results The direct binding of LDA to TRAF6 was confirmed in cell lysates and living cells.LDA promoted TRAF6-dependent nuclear translocation of YAP in colorectal cancer cells,and inhibited Wnt signaling by overexpressing TRAF6.Co-IP and PLA revealed that TRAF6 formed a tripartite complex with YAP and β-catenin in colon cancer cells,where TRAF6 was a key scaffolding protein of the tripartite complex.LDA disrupted the interactions between the TRAF domain of TRAF6 and YAP,as well as YAP and β-catenin.Conclusion LDA regulates Hippo/YAP signaling pathway by targeting TRAF6 and inhib-its colorectal cancer.

OBJECTIVE: To explore the clinical and genetic characteristics of two children diagnosed with two rare genetic diseases simultaneously. METHODS: Two children with comorbidity of two genetic diseases due to dual genetic mutations diagnosed at the Third Affiliated Hospital of Zhengzhou University respectively in May 2022 and March 2023 were selected as the study subjects. Clinical and genetic data of the two children were retrospectively analyzed. This study has been approved by the Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethic No. 2021-062-01). RESULTS: Child 1 was a 2-year-and-4-month-old boy whose clinical manifestations included facial dysmorphism, developmental delay, short stature, microcephaly, cleft palate, cryptorchidism, hypospadias, recurrent infections and immunological abnormalities. Whole exome sequencing revealed that he had harbored a heterozygous c.6595delT (p.Y2199Ifs*65) variant of the KMT2D gene and a heterozygous c.1892G>A (p.R631Q) variant of the PIK3R1 gene. This has led to a dual genetic diagnosis of Kabuki syndrome and PI3Kδ-related immunodeficiency type 36. Child 2 was a 15-year-old girl whose clinical manifestations included epilepsy, Albright's hereditary osteodystrophy, long body trunk, short limbs, hypocalcemia, hyperphosphatemia and hyperparathyroidism. The child also had a family history of short stature. Whole exome sequencing revealed that she had harbored a heterozygous c.2T>C (p.Met1?) variant of the GNAS gene and deletion of exons 2 to 6 of the SHOX gene. The two variants have led to dual diagnose of pseudohypoparathyroidism and X-linked idiopathic short stature. CONCLUSION When the clinical phenotype of a genetic disease is complex and cannot be fully explained with a single genetic variant, multiple pathogenic variants should be considered, and this may lead to the diagnosis of co-morbid genetic diseases. To adopt or supplement corresponding genetic testing in time and re-analyze the genetic data may facilitate accurate diagnosis of co-morbid genetic diseases.
Child, Preschool ; Female ; Humans ; Male ; Class Ia Phosphatidylinositol 3-Kinase/genetics* ; Comorbidity ; Exome Sequencing ; Mutation ; Rare Diseases/genetics* ; Retrospective Studies ; Adolescent

OBJECTIVE: To explore the impact of age on the genetic variant spectrum and prognosis of patients with previously untreated Diffuse large B-cell lymphoma (DLBCL). METHODS: A retrospective analysis was conducted on the clinical data and follow-up information of 254 previously untreated DLBCL patients from 14 hospitals in the Jiangsu Cooperative Lymphoma Group (JCLG) enrolled from July 2018 and July 2023. Following extraction of DNA from tumor tissue samples, next-generation sequencing (NGS) technique was employed to analyze the genetic variant spectrum of the DLBCL patients, with an evaluation of the relationship between age and genetic variants as well as prognosis. This study was approved by the Medical Ethics Committee of the Affiliated Hospital of Nantong University (Ethics No.: 2023-K048-01). RESULTS: The median age of the 254 DLBCL patients was 62 years old, with 55% of patients aged 60 years or above. Clinical evaluation showed that younger (< 60 years) patients had higher complete response (CR) (70% vs. 59%), and objective response rate (ORR) (88% vs. 79%) than older patients, though the difference between the two groups was not statistically. Survival analysis indicated that both the five-year overall survival (OS) (82.7% vs. 71.7%, P = 0.006) and progression-free survival (PFS) (70.6% vs. 50.2%, P < 0.05) rates were significantly higher in younger patients. NGS showed that 99.6% of the patients harbored genetic variants, with PIM1, KMT2D, TP53, MYD88, and CD79B being the most common genes. Age significantly affected the variant frequency of certain genes, with MYC variants serving an adverse prognostic factor for OS in younger patients (P = 0.002), while TP53 (P = 0.024) and BCL2 (P = 0.002) variants significantly impacted OS in older patients. Prognostic analysis identified age ≥ 60 years (HR = 3.439, 95%CI: 1.318~9.874), presence of B symptoms (HR = 2.871, 95%CI = 1.133~7.307), and elevated lactate dehydrogenase (HR = 3.528, 95%CI = 1.231~10.66) as independent adverse prognostic factors. CONCLUSION Age, genetic variants, and clinical factors may significantly affect the prognosis of the DLBCL patients. Younger patients have better survival compared to older patients. Variants of the MYC, BCL2, and TP53 genes are closely associated with poor prognosis.
Humans ; Lymphoma, Large B-Cell, Diffuse/diagnosis* ; Middle Aged ; Female ; Male ; Retrospective Studies ; Aged ; Prognosis ; Adult ; Aged, 80 and over ; High-Throughput Nucleotide Sequencing ; Young Adult ; Adolescent ; Genetic Variation

Objective To investigate the effect of field angle on the results of in vivo dose validation of electronic portal imaging device(EPID)in patients.Methods Design the mold test and analyze the influence of different mold thicknesses and different frame angles on the 2D γ pass rate.Twenty-three patients who un-derwent radiotherapy in the Department of Radiotherapy of Jinhua Municipal Central Hospital from January to June 2023 were selected as the research object.In vivo dose verification was carried out during treatment to obtain 2D γ pass rate using same-day sector beam CT(FBCT)of planned CT and executive image guided(IG-RT)as reference images,and the influence of field angle on pass rate was analyzed.Results When the frame angle was unchanged,the area of the shooting field was larger than 17 cm×17 cm,and the 2D γ passing rate decreased with the increase of the thickness.The frame angle had no effect on the 2D γ pass rate when the mold thickness was constant.In clinical treatment data,the passage rate of 2D γ near 0°/180° was higher than that near 90°/270°(P＜0.05),and the passage rate near 90°/270° in the FBCT group was higher than that in the IGRT group(P＜0.05).The median passing rate of 3 mm 2D γ was 97.97％in 3％of the 23 patients.The non-IGRT group was 96.81％,the IGRT group was 97.89％,the FBCT group was 98.94％.There was a statistically significant difference in 2D γ passing rate between the non-IGRT group and the IGRT group(Z=-5.083,P＜0.05),and there was a statistically significant difference in 2D γ passing rate between the IGRT group and the FBCT group(Z=-10.657,P＜0.05).Conclusion Clinically,the difference of pass rate in vi-vo dose verification at different rack angles is mainly due to the difference of images within and between ses-sions.Using same-day FBCT as the reference image for in-vivo dose verification can improve the accuracy of pass rate and eliminate the influence of image difference between sessions.

Objective:To explore the clinical and genetic characteristics of two children diagnosed with two rare genetic diseases simultaneously.Methods:Two children with comorbidity of two genetic diseases due to dual genetic mutations diagnosed at the Third Affiliated Hospital of Zhengzhou University respectively in May 2022 and March 2023 were selected as the study subjects. Clinical and genetic data of the two children were retrospectively analyzed. This study has been approved by the Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethic No. 2021-062-01).Results:Child 1 was a 2-year-and-4-month-old boy whose clinical manifestations included facial dysmorphism, developmental delay, short stature, microcephaly, cleft palate, cryptorchidism, hypospadias, recurrent infections and immunological abnormalities. Whole exome sequencing revealed that he had harbored a heterozygous c.6595delT (p.Y2199Ifs*65) variant of the KMT2D gene and a heterozygous c. 1892G>A (p.R631Q) variant of the PIK3R1 gene. This has led to a dual genetic diagnosis of Kabuki syndrome and PI3Kδ-related immunodeficiency type 36. Child 2 was a 15-year-old girl whose clinical manifestations included epilepsy, Albright′s hereditary osteodystrophy, long body trunk, short limbs, hypocalcemia, hyperphosphatemia and hyperparathyroidism. The child also had a family history of short stature. Whole exome sequencing revealed that she had harbored a heterozygous c. 2T>C (p.Met1? ) variant of the GNAS gene and deletion of exons 2 to 6 of the SHOX gene. The two variants have led to dual diagnose of pseudohypoparathyroidism and X-linked idiopathic short stature. Conclusion:When the clinical phenotype of a genetic disease is complex and cannot be fully explained with a single genetic variant, multiple pathogenic variants should be considered, and this may lead to the diagnosis of co-morbid genetic diseases. To adopt or supplement corresponding genetic testing in time and re-analyze the genetic data may facilitate accurate diagnosis of comorbid genetic diseases.