Objective: To investigate the objective characteristics of tongue manifestation in different stages of damp-heat syndrome in diabetic kidney disease (DKD). Methods: A cross-sectional study enrolled 134 patients with DKD G3-5 stages who met the diagnostic criteria for damp-heat syndrome in DKD. The patients were treated at Dongzhimen Hospital, Beijing University of Chinese Medicine, from May 2023 to January 2024. The patients were divided into three groups: DKD G3, DKD G4, and DKD G5 stage, with 53, 33, and 48 patients in each group, respectively. Clinical general data (gender, age, and body mass index) and damp-heat syndrome scores were collected from the patients. The YZAI-02 traditional Chinese medicine (TCM) AI Tongue Image Acquisition Device was used to capture tongue images from these patients. The accompanying AI Open Platform for TCM Tongue Diagnosis of the device was used to analyze and extract tongue manifestation features, including objective data on tongue color, tongue quality, coating color, and coating texture. Clinical data and objective tongue manifestation characteristics were compared among patients with DKD G3-5 based on their DKD damp-heat syndrome status. Results: No statistically significant difference in gender or body mass index was observed among the three patient groups. The DKD G3 stage group had the highest age (P<0.05). The DKD G3 stage group had a lower score for symptoms of poor appetite and anorexia(P<0.05) than the DKD G5 group. No statistically significant difference was observed in damp-heat syndrome scores among the three groups. Compared with the DKD G5 stage group, the DKD G3 stage group showed a decreased proportion of pale color at the tip and edges of the tongue (P<0.05). The DKD G4 stage group exhibited an increased proportion of crimson at the root of the tongue, a decreased proportion of thick white tongue coating at the root, a decreased proportion of pale color at the tip and edges of the tongue, an increased hue value (indicating color tone) of the tongue color in the middle, an increased brightness value (indicating color lightness) of the tongue coating color in the middle, and an increased thickness of the tongue coating (P<0.05). No statistically significant difference was observed in other tongue color proportions, color chroma values, body characteristics, coating color proportions, coating color chroma values, and coating texture characteristics among the three groups. Conclusion Tongue features differ in different stages of DKD damp-heat syndrome in multiple dimensions, enabling the inference that during the DKD G5 stage, the degree of qi and blood deficiency in the kidneys, heart, lungs, liver, gallbladder, spleen, and stomach is prominent. Dampness is more likely to accumulate in the lower jiao, particularly in the kidneys, whereas heat evil in the spleen and stomach is the most severe. These insights provide novel ideas for the clinical treatment of DKD.

OBJECTIVES: Metastasis is the primary cause of death in osteosarcoma, and current clinical treatments remain limited. BRD4, a key epigenetic regulator, has shown therapeutic promise in various cancers through its inhibition. However, the mechanistic role of BRD4 in osteosarcoma remains poorly understood. This study aims to elucidate the molecular mechanisms by which BRD4 regulate osteosarcoma progression and to explore novel therapeutic strategies. METHODS: Immunofluorescence was used to assess BRD4 expression levels in a tissue microarray containing 80 osteosarcoma samples from different patients. The Gene Expression Omnibus (GEO) dataset (GSE42352, containing survival data from 88 osteosarcoma patients) was downloaded to perform Kaplan-Meier survival analysis based on BRD4 gene expression levels. In vivo, an orthotopic intramedullary osteosarcoma model was established using HOS cells in C57 mice, followed by treatment with varying doses of the BRD4 inhibitor (+)-JQ1. Micro-CT, 3D reconstruction of bone tissue, and HE staining were employed to evaluate pathological changes in bone and intestinal lymph nodes. In vitro, cell viability was measured using the methyl thiazolyl tetrazolium (MTT) assay, while colony formation and Transwell assays assessed proliferative and invasive capacities. Chromatin-bound BRD4 was analyzed via co-immunoprecipitation combined with mass spectrometry (Co-IP/MS), and O-GlcNAc glycosylation sites and glycan chains of BRD4 were identified using Co-IP with Nano-LC MS/MS. Real-time PCR and Western blotting were used to analyze the relative mRNA and protein expression levels of target genes, respectively. RESULTS: BRD4 was positively expressed in 61.25% (49/80) of osteosarcoma tissues. Patients with high BRD4 expression exhibited significantly shorter survival times (P<0.05). In the orthotopic mouse model, intervention with (+)-JQ1, a potent and commonly used BETi, significantly inhibited tumor growth in vivo and reduced bone destruction (P<0.05). (+)-JQ1 treatment significantly suppressed the proliferation (P<0.001), invasion (P<0.001), and migration (P<0.05) of HOS cells. In osteosarcoma cells, BRD4 exhibited O-GlcNAc modifications at both N- and C- C-termini, particularly at Thr73, which is essential for protein stability. This modification also contributed to the activation of the EGFR tyrosine kinase inhibitor resistance pathway (KEGG Pathway: hsa01521). (+)-JQ1 treatment displaced BRD4 from enhancers and downregulated the transcription of pathway-related genes, such as EGFR and PDGFC, thereby suppressing the malignant behavior of osteosarcoma cells. CONCLUSIONS BRD4 promotes osteosarcoma progression via O-GlcNAc modification at Thr73 and plays a crucial role in tumor growth and metastasis.
Osteosarcoma/drug therapy* ; Humans ; Transcription Factors/metabolism* ; Animals ; Cell Cycle Proteins ; Mice ; Bone Neoplasms/drug therapy* ; Azepines/pharmacology* ; Cell Line, Tumor ; Cell Proliferation/drug effects* ; Triazoles/pharmacology* ; Mice, Inbred C57BL ; Nuclear Proteins/metabolism* ; Gene Expression Regulation, Neoplastic ; Male ; Bromodomain Containing Proteins

Objective To investigate the clinical value of serum hsa_circRNA_0002980 and hsa_circRNA_104348 expression in the diagnosis and prognosis evaluation of liver cancer patients.Methods From April 2020 to April 2022,a total of 105 liver cancer patients and 105 liver cirrhosis patients admitted in the hospital were selected as the liver cancer group and cirrhosis group,and another 105 healthy volunteers who underwent physical examinations in the hospital were selected as the control group.Real-time fluorescence quantitative PCR(qPCR)was applied to detect the expression of serum hsa_circRNA_0002980 and hsa_circRNA_104348.Receiver operating characteristic(ROC)curve was applied to evaluate the diagnostic value and prognostic val-ue of serum hsa_circRNA_0002980 and hsa_circRNA_104348 expression in liver cancer.Multivariate COX re-gression was performed to analyze the influencing factors of prognosis in liver cancer.Results The expression levels of serum hsa_circRNA_0002980 in the liver cancer group,liver cirrhosis group,and control group in-creased sequentially(P＜0.05),while the expression levels of serum hsa_circRNA_104348 decreased sequen-tially(P＜0.05).The levels of alanine aminotransferase and aspartate aminotransferase in the liver cancer group and the liver cirrhosis group were higher than those in the control group(P＜0.05),and the level of al-bumin was lower than that in the control group(P＜0.05).The area under the curve(AUC)for the diagnosis of liver cancer by hsa_circRNA_0002980 combined with hsa_circRNA_104348 was 0.888(95％CI:0.838-0.928),which was obviously higher than those of hsa_circRNA_0002980(Z=3.526,P＜0.001)and hsa_cir-cRNA_104348 alone(Z=2.184,P=0.029).The expression level of serum hsa_circRNA_0002980 in the poor prognosis group was lower than that in the good prognosis group(P＜0.05),and the expression level of ser-um hsa_circRNA_104348 and the proportion of TNM stage Ⅲ+Ⅳ were higher than those in the good progno-sis group(P＜0.05).The AUC for predicting prognosis in liver cancer patients by the combination of hsa_cir-cRNA_0002980 and hsa_circRNA_104348 was 0.870(95％CI:0.790-0.928),and there was no statistically significant difference compared to the AUC predicted separately by hsa_circRNA_0002980 and hsa_circRNA_104348(P＞0.05).The expression of serum hsa_circRNA_0002980,hsa_circRNA_104348 and TNM stage were influencing factors for the prognosis of liver cancer patients(P＜0.05).Conclusion The expression lev-el of hsa_circRNA_0002980 in the serum of liver cancer patients is relatively low,while the expression level of hsa_circRNA_104348 is relatively high.Both have certain clinical significance in the diagnosis and prognosis e-valuation of liver cancer.

Objective:To explore the impacts of different frequencies of orthogonal image-guided verification on set-up error correction and the reference values of planning target volume (PTV) margins in postoperative radiotherapy for breast cancer, in order to provide recommendations of the verification frequency in clinical practice.Methods:A total of 80 breast cancer patients who received postoperative intensity-modulated radiotherapy for breast cancer at the Affiliated Union Hospital of Fujian Medical University from January 2021 to January 2022 were enrolled. Orthogonal image-guided verification was conducted before each radiation treatment to determine initial and residual set-up errors. The error data were statistically analyzed by categorizing patients into groups A, B, C, D, E, and F, based on assumed verification frequencies (daily, every 2, 3, 4, and 5 d, and no correction). The magnitude, distribution, and differences of set-up errors of various groups were analyzed, and the PTV margins were calculated using a reference formula.Results:The collected initial set-up errors of the 80 patients were (3.49±3.43), (2.87±2.88), and (2.75±2.35) mm, in x, y, and z directions, respectively. The residual set-up errors decreased gradually with increasing verification frequency. In the case of daily image-guided verification, the residual set-up errors in x, y, and z directions decreased to (1.63±0.90), (1.63±0.93), and (1.55±0.90)mm, respectively. The reference values of PTV margins calculated under different verification frequencies decreased with an increase in the verification frequency. Under daily verification, the reference values of PTV margins calculated based on set-up errors decreased from initial 6.60, 6.29, and 4.22 mm (without correction) to 1.27, 1.37, and 1.28 mm, respectively. Differences in the reference values under verification frequencies every 3, 4, and 5 d were less than 0.81 mm. Conclusions:Daily image-guided verification (including correction) can effectively reduce set-up errors in image-guided radiotherapy for breast cancer. The set-up errors differ under varying verification frequencies, with a higher frequency corresponding to better correction effects and smaller PTV margins required.

Objective To study the clinical characteristics and medication patterns of Wangbi Tablets in treating patients with knee osteoarthritis(KOA)in the real world and to analyze the advantages and specific features of Chinese patent medicines in treating advantage disease.Methods A prospective case registry study was conducted,registering 3 000 patients from 30 TCM and Western medicine hospitals across China from April 2019 to December 2021.Data on gender,age,BMI,Chinese medicine staging(CMS),K-L grading,medication duration,VAS score,medical history and combined medication were collected for descriptive analysis.Comparisons were made between different stages and between single-use and combined-use groups.The Apriori algorithm was used for association analysis of combined medications.Results A total of 2 999 patients were included,with 2 063 females(68.79%)and 936 males(31.21%).The average age was(56.89±8.90)years.The average BMI was(23.80±2.88)kg/m2.The proportion of patients in CMS I was 512(17.07%),with a VAS median score of 8,while the proportion of patients in CMS Ⅱ was 2 181(72.73%),with a VAS median score of 6.The proportion of patients in CMS Ⅲ was 306(10.20%),with a VAS median score of 3;316 cases(10.54%)were classified as K-L grade I,2 477 cases(82.59%)as grade Ⅱ,204 cases(6.80%)as grade Ⅲ,and 2 cases(0.07%)as grade Ⅳ.Medication analysis indicated that the single-use group(1507 cases,50.25%)was larger than the combined-use group(1 492 cases,49.75%).In terms of the number of drugs used in combination,one(39.01%)and two(38.14%)were the main types;in terms of medication types,combination therapy with Western medicine(62.27%)and simultaneous use of Western medicine and other Chinese materia medica(26.14%)were the main methods;the top three drugs with the highest frequency of combination use were glucosamine capsules,imrecoxib tablets and sodium hyaluronate injection.The top three drug combinations with the highest support were"Huoxue Zhishang Powder+imrecoxib tablets","glucosamine capsules+imrecoxib tablets"and"glucosamine capsules+sodium hyaluronate injection".Inter-group comparisons showed that the medication duration for Wangbi Tablets in CMS I was longer than in CMS Ⅱ and CMS Ⅲ(P<0.01).The proportion of patients on monotherapy in CMS I(62.11%)was higher than in CMS Ⅱ(46.54%)and CMS Ⅲ(56.86%)(P<0.001).Among patients in CMS I(16.41%)and CMS Ⅲ(21.24%),the highest proportion used one combined medication,whereas in CMS Ⅱ,the highest proportion was for those using two combined medications(20.50%).In all three groups,CMS I(19.53%),CMS Ⅱ(33.70%)and CMS Ⅲ(30.72%),the highest proportion of combined medications was Western medicine.Conclusion More than half of the patients treated KOA with Wangbi Tablets alone.Approximately one-fifth of the patients were in CMS I,with a median pain score of 8.The average duration of medication for patients in CMS I,CMS Ⅱ and CMS Ⅲ decreases,and there is no obvious pattern in the medication method at different stages;combination therapy is represented by"Huoxue Zhishang Powder+imrecoxib tablets"and"glucosamine capsules+imrecoxib tablets".

Background and Aims:Whether to close mesenteric fissures during laparoscopic radical resection of colorectal cancer remains controversial.Traditional suture closure is technically demanding and may injure mesenteric vessels.This study aimed to evaluate the safety and efficacy of using α-cyanoacrylate medical glue to close mesenteric fissures during laparoscopic colorectal cancer surgery.Methods:A retrospective analysis was conducted on patients who underwent laparoscopic radical resection of colorectal cancer in the Department of Colorectal Surgery,the Sixth Affiliated Hospital of Sun Yat-sen University,from January 2022 to December 2023.Seventy-eight patients who received intraoperative α-cyanoacrylate glue closure of mesenteric fissures were included as the observation group,and 74 patients without fissure closure were selected as the control group using the propensity score matching method.Perioperative parameters,postoperative recovery,and complications were compared between the two groups.Results:No significant differences were observed in baseline characteristics or main intraoperative variables between groups(all P>0.05).The observation group had significantly less ascitic drainage within 3 days after operation[(203.14±116.44)mL vs.(384.53±243.89)mL,P<0.01]and shorter postoperative gas passage,defecation,and drainage tube removal times(all P<0.01).The incidence of postoperative complications and intestinal obstruction was comparable between groups(all P>0.05).Multivariate analysis showed that intraoperative application of α-cyanoacrylate glue was an independent promoting factor for intestinal exhaust within 3 days after surgery(OR=5.739,P=0.000).Conclusion:The use of α-cyanoacrylate medical glue for closing mesenteric fissures during laparoscopic radical resection of colorectal cancer is safe and feasible.It effectively reduces postoperative ascitic drainage and accelerates bowel recovery,offering a simple and reliable alternative to traditional suture closure.

Purpose To develop and validate a nomogram incorporating high-resolution MRI and clinicopathological indicators for predicting distant metastasis after curative resection of mid-low rectal cancer.Materials and Methods This retrospective study analyzed 219 patients with pathologically confirmed mid-low rectal cancer from Tianjin Union Medical Center(December 2016 to December 2021).Patients were categorized into metastasis(n=46)and non-metastasis(n=173)groups based on postoperative distant metastasis occurrence.All patients underwent preoperative pelvic MRI with measurement of posterior mesangial thickness(PMT),mesentery fat area(MFA)and mesenteric fascia envelopment volume(MFEV)on high-resolution T2WI.Clinicopathological and imaging data were collected.Cox proportional hazards model identified predictive factors for distant metastasis,and a risk probability nomogram was constructed.Predictive performance,goodness-of-fit and clinical applicability were evaluated.Results Kaplan-Meier analysis demonstrated significantly higher distant metastasis risk in patients with PMT≤1.43 cm,MFA≤19.31 cm2 and MFEV≤137.46 cm3 compared to those with higher values(χ2=29.07,8.71,19.05;all P<0.05).Cox regression identified tumor differentiation(HR=0.536,95％CI 0.290-0.990),pathological N stage(HR=0.397,95％CI 0.210-0.747),perirectal structure invasion(HR=0.242,95％CI 0.068-0.865)and PMT(HR=0.334,95％CI 0.168-0.664)as independent predictors.The nomogram achieved a concordance index of 0.775 with good calibration.Decision curve analysis demonstrated substantial net benefit across wide probability thresholds,indicating excellent clinical applicability.Conclusion Patients with PMT≤1.43 cm,MFA≤19.31 cm2 and MFEV≤137.46 cm3 exhibit elevated distant metastasis risk.The nomogram incorporating tumor differentiation,pathological N stage,perirectal structure invasion and PMT effectively predicts distant metastasis after curative resection of mid-low rectal cancer.

Objective:To explore the impacts of different frequencies of orthogonal image-guided verification on set-up error correction and the reference values of planning target volume (PTV) margins in postoperative radiotherapy for breast cancer, in order to provide recommendations of the verification frequency in clinical practice.Methods:A total of 80 breast cancer patients who received postoperative intensity-modulated radiotherapy for breast cancer at the Affiliated Union Hospital of Fujian Medical University from January 2021 to January 2022 were enrolled. Orthogonal image-guided verification was conducted before each radiation treatment to determine initial and residual set-up errors. The error data were statistically analyzed by categorizing patients into groups A, B, C, D, E, and F, based on assumed verification frequencies (daily, every 2, 3, 4, and 5 d, and no correction). The magnitude, distribution, and differences of set-up errors of various groups were analyzed, and the PTV margins were calculated using a reference formula.Results:The collected initial set-up errors of the 80 patients were (3.49±3.43), (2.87±2.88), and (2.75±2.35) mm, in x, y, and z directions, respectively. The residual set-up errors decreased gradually with increasing verification frequency. In the case of daily image-guided verification, the residual set-up errors in x, y, and z directions decreased to (1.63±0.90), (1.63±0.93), and (1.55±0.90)mm, respectively. The reference values of PTV margins calculated under different verification frequencies decreased with an increase in the verification frequency. Under daily verification, the reference values of PTV margins calculated based on set-up errors decreased from initial 6.60, 6.29, and 4.22 mm (without correction) to 1.27, 1.37, and 1.28 mm, respectively. Differences in the reference values under verification frequencies every 3, 4, and 5 d were less than 0.81 mm. Conclusions:Daily image-guided verification (including correction) can effectively reduce set-up errors in image-guided radiotherapy for breast cancer. The set-up errors differ under varying verification frequencies, with a higher frequency corresponding to better correction effects and smaller PTV margins required.

Purpose To develop and validate a nomogram incorporating high-resolution MRI and clinicopathological indicators for predicting distant metastasis after curative resection of mid-low rectal cancer.Materials and Methods This retrospective study analyzed 219 patients with pathologically confirmed mid-low rectal cancer from Tianjin Union Medical Center(December 2016 to December 2021).Patients were categorized into metastasis(n=46)and non-metastasis(n=173)groups based on postoperative distant metastasis occurrence.All patients underwent preoperative pelvic MRI with measurement of posterior mesangial thickness(PMT),mesentery fat area(MFA)and mesenteric fascia envelopment volume(MFEV)on high-resolution T2WI.Clinicopathological and imaging data were collected.Cox proportional hazards model identified predictive factors for distant metastasis,and a risk probability nomogram was constructed.Predictive performance,goodness-of-fit and clinical applicability were evaluated.Results Kaplan-Meier analysis demonstrated significantly higher distant metastasis risk in patients with PMT≤1.43 cm,MFA≤19.31 cm2 and MFEV≤137.46 cm3 compared to those with higher values(χ2=29.07,8.71,19.05;all P<0.05).Cox regression identified tumor differentiation(HR=0.536,95％CI 0.290-0.990),pathological N stage(HR=0.397,95％CI 0.210-0.747),perirectal structure invasion(HR=0.242,95％CI 0.068-0.865)and PMT(HR=0.334,95％CI 0.168-0.664)as independent predictors.The nomogram achieved a concordance index of 0.775 with good calibration.Decision curve analysis demonstrated substantial net benefit across wide probability thresholds,indicating excellent clinical applicability.Conclusion Patients with PMT≤1.43 cm,MFA≤19.31 cm2 and MFEV≤137.46 cm3 exhibit elevated distant metastasis risk.The nomogram incorporating tumor differentiation,pathological N stage,perirectal structure invasion and PMT effectively predicts distant metastasis after curative resection of mid-low rectal cancer.

Background and Aims:Whether to close mesenteric fissures during laparoscopic radical resection of colorectal cancer remains controversial.Traditional suture closure is technically demanding and may injure mesenteric vessels.This study aimed to evaluate the safety and efficacy of using α-cyanoacrylate medical glue to close mesenteric fissures during laparoscopic colorectal cancer surgery.Methods:A retrospective analysis was conducted on patients who underwent laparoscopic radical resection of colorectal cancer in the Department of Colorectal Surgery,the Sixth Affiliated Hospital of Sun Yat-sen University,from January 2022 to December 2023.Seventy-eight patients who received intraoperative α-cyanoacrylate glue closure of mesenteric fissures were included as the observation group,and 74 patients without fissure closure were selected as the control group using the propensity score matching method.Perioperative parameters,postoperative recovery,and complications were compared between the two groups.Results:No significant differences were observed in baseline characteristics or main intraoperative variables between groups(all P>0.05).The observation group had significantly less ascitic drainage within 3 days after operation[(203.14±116.44)mL vs.(384.53±243.89)mL,P<0.01]and shorter postoperative gas passage,defecation,and drainage tube removal times(all P<0.01).The incidence of postoperative complications and intestinal obstruction was comparable between groups(all P>0.05).Multivariate analysis showed that intraoperative application of α-cyanoacrylate glue was an independent promoting factor for intestinal exhaust within 3 days after surgery(OR=5.739,P=0.000).Conclusion:The use of α-cyanoacrylate medical glue for closing mesenteric fissures during laparoscopic radical resection of colorectal cancer is safe and feasible.It effectively reduces postoperative ascitic drainage and accelerates bowel recovery,offering a simple and reliable alternative to traditional suture closure.